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Increased heart tolerance to hypoxia at high altitude

Prof. Gustavo Zubieta-Castillo performed isolated dog heart perfusion in order to study heart function at high altitude. He then observed that the hearts of high altitude residents were more tolerant to hypoxia than those at sea level, around 1961. This is considered one of the first observations with this concept. Ever since and gradually it has been further studied and applied practically with distinguished colleagues such as Dr. Emilio Marticorena from Peru that showed that high altitude cardiac rehabilitation is faster at high altitude. Frantisek Kolar from the Czech Academy of Sciences Institute, has performed extraordinary advance in research of hearts in rats exposed to hypoxia, further advancing in this concept. We have heard that Alberto Hurtado from Peru had similar ideas. Here is the Newspaper “Ultima Hora” publication back in 1964:

 

 

Scientific articles ranking in high altitude domain

ranked scientific articles this way:

Wednesday, June 1 , 2011

List 2: Top 10 Articles Published in the Same Domain Since Your Publication

Zubieta-Calleja GR, Paulev PE, Zubieta-Calleja L, Zubieta-Calleja N, Zubieta-Castillo G: Hypoventilation in chronic mountain sickness: a mechanism to preserve energy. J Physiol Pharmacol; 2006 Sep;57 Suppl 4:425-30

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León-Velarde F, Villafuerte FC, Richalet JP: Chronic mountain sickness and the heart. Prog Cardiovasc Dis; 2010 May-Jun;52(6):540-9
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Moore LG, Niermeyer S, Vargas E: Does chronic mountain sickness (CMS) have perinatal origins? Respir Physiol Neurobiol; 2007 Sep 30;158(2-3):180-9
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Rivera-Ch M, Huicho L, Bouchet P, Richalet JP, León-Velarde F: Effect of acetazolamide on ventilatory response in subjects with chronic mountain sickness. Respir Physiol Neurobiol; 2008 Aug 31;162(3):184-9
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Jafarian S, Gorouhi F, Ghergherechi M, Lotfi J: Respiratory rate within the first hour of ascent predicts subsequent acute mountain sickness severity. Arch Iran Med; 2008 Mar;11(2):152-6
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Zubieta-Castillo G Sr, Zubieta-Calleja GR Jr, Zubieta-Calleja L: Chronic mountain sickness: the reaction of physical disorders to chronic hypoxia. J Physiol Pharmacol; 2006 Sep;57 Suppl 4:431-42
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Maignan M, Rivera-Ch M, Privat C, León-Velarde F, Richalet JP, Pham I: Pulmonary pressure and cardiac function in chronic mountain sickness patients. Chest; 2009 Feb;135(2):499-504
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Penaloza D, Arias-Stella J: The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness. Circulation; 2007 Mar 6;115(9):1132-46
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Yan JH, Li ZQ, Ji LH, Chai KX, Ge RL: [Changes of serum angiogenesis in patients with chronic mountain sickness]. Zhongguo Ying Yong Sheng Li Xue Za Zhi; 2009 Nov;25(4):457-60
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Huicho L, Xing G, Qualls C, Rivera-Ch M, Gamboa JL, Verma A, Appenzeller O: Abnormal energy regulation in early life: childhood gene expression may predict subsequent chronic mountain sickness. BMC Pediatr; 2008;8:47
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List 3: Top 10 Articles Published in the Same Domain, All Time

Zubieta-Calleja GR, Paulev PE, Zubieta-Calleja L, Zubieta-Calleja N, Zubieta-Castillo G: Hypoventilation in chronic mountain sickness: a mechanism to preserve energy. J Physiol Pharmacol; 2006 Sep;57 Suppl 4:425-30
Go to the article

Sun S, Oliver-Pickett C, Ping Y, Micco AJ, Droma T, Zamudio S, Zhuang J, Huang SY, McCullough RG, Cymerman A, Moore LG: Breathing and brain blood flow during sleep in patients with chronic mountain sickness. J Appl Physiol; 1996 Aug;81(2):611-8
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Sun SF, Huang SY, Zhang JG, Droma TS, Banden G, McCullough RE, McCullough RG, Cymerman A, Reeves JT, Moore LG: Decreased ventilation and hypoxic ventilatory responsiveness are not reversed by naloxone in Lhasa residents with chronic mountain sickness. Am Rev Respir Dis; 1990 Dec;142(6 Pt 1):1294-300
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Erba P, Anastasi S, Senn O, Maggiorirni M, Bloch KE: Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation. Eur Respir J; 2004 Aug;24(2):303-8
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Richalet JP, Rivera M, Bouchet P, Chirinos E, Onnen I, Petitjean O, Bienvenu A, Lasne F, Moutereau S, León-Velarde F: Acetazolamide: a treatment for chronic mountain sickness. Am J Respir Crit Care Med; 2005 Dec 1;172(11):1427-33
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León-Velarde F, Arregui A, Vargas M, Huicho L, Acosta R: Chronic mountain sickness and chronic lower respiratory tract disorders. Chest; 1994 Jul;106(1):151-5
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León-Velarde F, Villafuerte FC, Richalet JP: Chronic mountain sickness and the heart. Prog Cardiovasc Dis; 2010 May-Jun;52(6):540-9
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Moore LG, Niermeyer S, Vargas E: Does chronic mountain sickness (CMS) have perinatal origins? Respir Physiol Neurobiol; 2007 Sep 30;158(2-3):180-9
Go to the article

Ge RL, Shai HR, Takeoka M, Hanaoka M, Koizumi T, Matsuzawa Y, Kubo K, Kobayashi T: Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness. Wilderness Environ Med; 2001;12(1):2-7
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Rivera-Ch M, Huicho L, Bouchet P, Richalet JP, León-Velarde F: Effect of acetazolamide on ventilatory response in subjects with chronic mountain sickness. Respir Physiol Neurobiol; 2008 Aug 31;162(3):184-9
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Read more »
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List 4: Top 10 Articles, with Free Full-Texts, Published in the Same Domain Since Your Publication

Zubieta-Calleja GR, Paulev PE, Zubieta-Calleja L, Zubieta-Calleja N, Zubieta-Castillo G: Hypoventilation in chronic mountain sickness: a mechanism to preserve energy. J Physiol Pharmacol; 2006 Sep;57 Suppl 4:425-30
Go to the article

Jafarian S, Gorouhi F, Ghergherechi M, Lotfi J: Respiratory rate within the first hour of ascent predicts subsequent acute mountain sickness severity. Arch Iran Med; 2008 Mar;11(2):152-6
Go to the article

Zubieta-Castillo G Sr, Zubieta-Calleja GR Jr, Zubieta-Calleja L: Chronic mountain sickness: the reaction of physical disorders to chronic hypoxia. J Physiol Pharmacol; 2006 Sep;57 Suppl 4:431-42
Go to the article

Maignan M, Rivera-Ch M, Privat C, León-Velarde F, Richalet JP, Pham I: Pulmonary pressure and cardiac function in chronic mountain sickness patients. Chest; 2009 Feb;135(2):499-504
Go to the article

Penaloza D, Arias-Stella J: The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness. Circulation; 2007 Mar 6;115(9):1132-46
Go to the article

Huicho L, Xing G, Qualls C, Rivera-Ch M, Gamboa JL, Verma A, Appenzeller O: Abnormal energy regulation in early life: childhood gene expression may predict subsequent chronic mountain sickness. BMC Pediatr; 2008;8:47
Go to the article

Gonzales GF, Gasco M, Tapia V, Gonzales-Castañeda C: High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men. Am J Physiol Endocrinol Metab; 2009 Jun;296(6):E1319-25
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Stuber T, Sartori C, Schwab M, Jayet PY, Rimoldi SF, Garcin S, Thalmann S, Spielvogel H, Salmòn CS, Villena M, Scherrer U, Allemann Y: Exaggerated pulmonary hypertension during mild exercise in chronic mountain sickness. Chest; 2010 Feb;137(2):388-92
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Moore JP, Claydon VE, Norcliffe LJ, Rivera-Ch MC, Lèon-Velarde F, Appenzeller O, Hainsworth R: Carotid baroreflex regulation of vascular resistance in high-altitude Andean natives with and without chronic mountain sickness. Exp Physiol; 2006 Sep;91(5):907-13
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Bailey DM, Evans KA, James PE, McEneny J, Young IS, Fall L, Gutowski M, Kewley E, McCord JM, Møller K, Ainslie PN: Altered free radical metabolism in acute mountain sickness: implications for dynamic cerebral autoregulation and blood-brain barrier function. J Physiol; 2009 Jan 15;587(Pt 1):73-85
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Chronic Hypoxia Symposium IV

Dear colleagues from around the world:

After 3 successful Chronic Hypoxia Symposiums held in La Paz, Bolivia, we are very proud to announce that the IV Chronic Hypoxia Symposium will be held in India under the direction of Prof. Thuppil Venkatesh.

Please stayed tunned for the preliminaries that will soon surface.

In the meantime, we want to thank all those that participated and attended our III Chronic Hypoxia Symposium held in La Paz in Oct 2010. Our President Larry Silver was able to find support from CISCO that transmitted via Webex to all the participants  live presentations from around the world.

Gustavo Zubieta-Calleja
Vice-President
International Society of Chronic Hypoxia

Chronic Hypoxia Symposium III ABSTRACTS

The III Symposium on the Effect of Chronic Hypoxia on Diseases at High Altitude

October 16-23, 2010
click here to go to the website

ABSTRACTS

BREATH-HOLD DIVING AND DECOMPRESSION SICKNESS.

Hans Christian Møller Thorsen, Poul-Erik Paulev & Gustavo Zubieta-Calleja

The Panum Institute, University of Copenhagen &

High Altitude Pathology Institute (IPPA), Zubieta University.

La Paz, Bolivia.                                                                           www.altitudeclinic.com

Breath-hold diving is used in many parts of the world as a sport, in order to get pearls and as a record breaking activity. The Pearl divers in the South Pacific typically perform repetitive BH dives to depths of 30 m or more for 1.5–2.5 minutes for about 6 hours a day. Some of the divers developed what was called “Taravana,” a disease similar to DCS and suspected to be due to nitrogen accumulation. The divers who developed “Taravana” primarily were having symptoms from the central nervous system, including nausea, dizziness, and partial or complete hemiplegia. Paulev argued for a connection between DCS and BH diving (1965, 1967). Paulev himself and three other divers developed symptoms of DCS after a series of BH dives in a submarine escape-training tank in Norway. In each case, severe neurological symptoms and signs were present.

One of the objectives has been to develop a suitable computer model and calculate the amount of nitrogen—expressed as nitrogen tissue tensions—accumulated in the body during diving profiles.

Symmetric accumulation and elimination of an inert gas is described by a differential equation:

dII/dt = 0.693 ( Pamb.t  – II)/T½

where II is the tissue pressure of the inert gas, Pamb is the ambient pressure at the actual depth and T½ is the half time period of the tissue. The differential equation is solved by numerical approximation:

II1 = II0 + 0.693 ( Pamb.t  – II)/T½.

We have developed a dive table that may protect against decompression sickness, but its validity has to be evaluated in practice.

The danger is increased in mountain lake free diving, where breath-hold diving has not yet been practiced but will probably be done in the near future.

CHRONIC CONTINUOUS HYPOXIA INCREASES CARDIAC ISCHEMIC TOLERANCE VIA ACTIVATION OF MITOCHONDRIAL BKCa CHANNELS

Kolar F, Borchert GH, Neckar J, Ostadal B

Department of Developmental Cardiology, Institute of Physiology, Academy of Sciences of the Czech Republic, and Centre for Cardiovascular Research, Prague, Czech Republic

Chronic hypoxia increases cardiac tolerance against acute oxygen deprivation and its salutary effects persist for several weeks. Although several protective pathways have been identified, the mechanism of this long-lasting cardioprotective phenomenon is not fully understood. The aim of this study was to find out whether i) brief daily exposures to normoxia (reoxygenation) during the adaptation to hypoxia affects the induction of protected cardiac phenotype and ii) mitochondrial large conductance calcium-activated potassium channels (BKCa) contribute to its mechanism. Adult male Wistar rats were exposed to continuous normobaric hypoxia (CNH; FIO2 = 0.1) for 3–4 weeks; a subgroup of animals was allowed to recover at normoxia daily for a single 60-min period (CNH-R). CNH significantly reduced the size of myocardial infarction, induced by 20-min coronary artery occlusion and 3-h reperfusion, from 62% of the area at risk in normoxic controls to 42%. Protection by CNH was retained in subsequently isolated left ventricular cardiomyocytes subjected to 25-min metabolic inhibition followed by 30-min reenergization; it was detected as increased cell viability and reduced release of lactate dehydrogenase. These protective effects were completely absent in chronically hypoxic animals exposed to periodic reoxygenation (CNH-R). Pretreatment of cells with paxilline (BKCa channel blocker, 2 mM) significantly attenuated the improved resistance of cells from CNH rats without affecting normoxic controls. On the other hand, NS1619 (BKCa channel opener, 30 mM) protected cells from normoxic animals but no additional salutary effect occurred in the CNH group. However, myocytes isolated from CNH-R rats (that did not exhibit resistant phenotype) were protected by NS1619 similarly as normoxic controls. It is concluded that brief daily periods of normoxia during the adaptation to chronic hypoxia counteract the development of a cardioprotective mechanism which involves the activation of mitochondrial BKCa channels.

THE EFFECT OF PRENATAL HYPOXIA ON EXPRESSION OF TRX-1 AND LIPID PEROXIDATION PRODUCTS IN RAT HIPPOCAMPUS AT DIFFERENT PERIODS OF POSTNATAL ONTOGENESIS

Stroev S.A. 1,2, Tjulkova E.I. 2, Vataeva L.A. 2, Kislin M.S. 2, Samoilov M.O. 2, Pelto-Huikko M.T. 1

1 Tampere University Medical School, Tampere, Finland; 2 I.P. Pavlov Institute of Physiology RAS, St.Petersburg, Russia.

The effect of severe hypobaric hypoxia produced in a flow chamber (180 Torr, 3 times during 3 hours at 14th, 15th and 16th days of pregnancy) endured by pregnant Wistar rats on the thioredoxin-1 (Trx-1) expression was studied in hippocampal neurons of their descendants of the first generation at 3th, 14th and 80th-90th days of postnatal ontogenesis.

The expression of Trx-1 was studied in areas of cornu Ammonis-1, 2 and 3 (CA1, CA2, CA3) and dentate gyrus (DG) by immunocytochemistry that was assayed using two criteria: the total number of immunoreactive cells shown as a percent of control (Nt) and the number of intensely-labeled cells as a percent of control (Ni).

It was shown that hypoxia endured at the prenatal period significantly modifies the expression level of Trx-1 in hippocampal neurons of rats during their postnatal development. Herewith the direction of changes in Trx-1 expression may vary in different areas of the hippocampus and times of postnatal ontogenesis.

At the 3rd postnatal day in rats exposed to prenatal hypoxia, there was an statistically significant (P<0,05) decrease of Nt in CA1 (Nt = 74±9%) and Ni in CA2 (Ni = 47±13%) compared with the control rats of the same age. At the level of statistically non-significant but consistent trend (0,05<P<0,1) a reduction of Ni in CA1 (Ni = 60±8%) and increase Nt in DG (Nt = 122±4%) were also observed.

At the 14th day a statistically significant (P<0,01) decrease of Ni in the DG (Ni = 34±7%) and increase of Ni in the CA2 (Ni = 505±74%), were noted. At the level of trends (0,05<P<0,1) a decrease of Nt in CA1 (Nt = 79±7%) and increase of Nt in CA3 (Nt = 127±7%) were shown. Herewith the markers of lipid peroxidation level (Klein’s oxidation index, the level of diene and triene conjugates, thiobarbituric acid-reacting products (TBARP) and Schiff bases) were not perceptibly differ compared to control.

In adult age (80th – 90th days) a statistically significant decrease (P<0,01) of Nt in CA1   (Nt = 75±4%) and decrease (P<0,05) of Ni in CA3 (Ni = 43±17%) were noted. Nt in DG also tended to decrease (Nt = 84±7%; 0,05<P<0,1). Accordingly, the level of all lipid peroxidation products studied was markedly higher than in the controls.

These data suggest that severe hypoxia endured by maternal organism during the critical fetal development period, leads to a modification of pro- and antioxidant systems in hippocampal neurons of born rats throughout all their postnatal ontogenesis extending into adulthood. Along with the previously shown modifications of calcium and phosphoinositide systems of intracellular signal transduction, these changes reflect apparently one of the possible molecular mechanisms that underlie both adaptive and pathological modifications of cognitive and behavioral functions of animals exposed to prenatal hypoxia.

FOREVER: LOSS OF ADAPTATION, DOES NOT EXIST.

G Zubieta-Castillo & GR Zubieta-Calleja

High Altitude Pulmonary and Pathology Institute (IPPA), Zubieta University

La Paz, Bolivia.

zubieta@altitudeclinic.com

Chronic Mountain Sickness (CMS) is a term that does not explain the ethiopathogenesis of the disease in response to the effect of chronic hypoxia. There is no CMS, but rather pulmonary (mainly), cardiac, carotid, kidney, hematological or genetic disease. All these associated to an increase on the hematocrit or what is now known as polyerythrocythemia. CMS, was described by Carlos Monge Medrano close to 90 years ago. He was unable to find an explanation for the signs and symptoms and chose to use the term “LOSS OF ADAPTATION”.  This was originally accepted, but today it can be appreciated as lacking significance. And should stop being used.

Undoubtedly, CMS is a chronic hypoxic process resulting in an increase of hemoglobin, due to pulmonary lesions (fundamentally), that alter the pulmonary function, thereby reducing the oxihemoglobin saturation and stimulating the increase of red blood cells. This, essentially occurs due to pulmonary lesions that are sequelae of diverse lung disease giving rise to intra-pulmonary shunts or uneven ventilation-perfusion. The term “LOSS OF ADAPTATION”, is even semantically inadequate, because in nature, living beings tend to adapt to different environments and circumstances. These could be: going to high altitude, temperature changes, solar radiation, UV radiation, diet changes, etc, etc . Consequently, to insist in contemporary medicine on the use of “LOSS OF ADAPTATION”, is not only a mistake, but rather foolishness!

The arterial oxygen content of blood in polyerythrocythemia, appears to be increased. However this apparent increase refers to the maximum oxygen carrying capacity of hemoglobin in blood when fully saturated. This gives rise to two conclusions:

1)      that the hemoglobin in patients with polyerythrocythemia tends to be normal and is capable of full saturation when exposed to high oxygen pressures.

2)      Fundamentally lung disease that results in intra-pulmonary shunts and uneven ventilation-perfusion, reduce the alveolar pressure of oxygen and the most efficient mechanism to compensate for this ventilatory deficiency is polyerythrocythemia.

The misunderstanding of these concepts has led to wrong interpretations of CMS such as “Loss of adaptation”.

Throughout history, all living beings, go through  evolution, in order to adapt to different environmental conditions. Even aging is an evolution, that goes to finish a vital cycle.  It never goes in the reverse way. This concept of loss of adaptation is unacceptable.

Again, “The organic systems of human beings and all other species tend to adapt to any environmental change and circumstance within an optimal period of time, and  never tend towards regression (loss of adaptation), which would inevitably lead to death”.

ACID-BASE BALANCE AT HIGH ALTITUDES: A COMPREHENSIVE APPROACH USING THE MODIFIED VAN SLYKE EQUATION, TITRATABLE HYDROGEN ION DIFFERENCE (THID) AND OTHER ASPECTS.

G Zubieta-Calleja, PE Paulev, J Mehrishi* & G. Zubieta-Castillo.

High Altitude Pulmonary and Pathology Institute (IPPA), Zubieta University La Paz, Bolivia and *University of Cambridge, Cambridge, United Kingdom and The Cambridge Blood, Stem, Sperm Cells, Blood Doping and High Altitude Research.
The Acid-Base balance in the human body is calculated by the Van Slyke equation based on sea level measurements. The maintenance of blood pH within a fairly strict range at/around pH 7.4, with due consideration of the effect of hyperventilation, is essential for cellular function at any altitude. This is because various chemical processes occurring in the body, e.g., those involving proteins and enzymes, are pH-dependent. As is well known, oxygen and carbon dioxide partial pressures get lower as the altitude gets higher. At a permanent  low production of CO2, the acid-base balance begins to change. Mountaineering physiologists, sadly, assumed that the sea level equation for A-B balance would be equally applicable, without any critical thought, and never thought of appropriate equations valid for high altitudes calculations. The Van Slyke equation for sea level seems to have been used indiscriminately for high altitudes in order to calculate for Base Excess (BE). It is essential to become aware that BE is an obsolete term and has been previously replaced by the concept of Titratable Hydrogen Ion Difference (THID).
For some extraordinary reasons, the BE equation without any critical discussion received the approval of CLSI for calculations of A-B balance at high altitudes (where the gas pressures are most certainly considerably lower). (CLSI:Clinical Laboratory Standards Institute, (http://www.clsi.org)).
The validity of the Van Slyke equation used for high altitudes, originally meant for sea level conditions, would clearly seem to be rather incongruous when critically considered. In our opinion it is not going too far to say that this procedure is woefully inadequate being inappropriate and to achieve excellence, is unacceptable. The higher the altitude the bigger the mistake in calculation of Acid-Base parameters.

Therefore, we took measurements and gathered information of the various parameters at high altitudes (2,500 3,500, 4,500m) to derive the urgently needed modified Van Slyke for quantifying Acid-Base balance at high altitudes. These are the key points and the thrust of our presentation. Consequently, we developed a modified Van Slyke equation for A-B balance and the adequate Ole Siggaard-Andersen nomograms adapted to different altitudes. We also discuss the point about the necessity of the adaptation factor according to the formula already developed and described in deriving the modified Van Slyke equation. The normal hemoglobin values for completely adapted individuals is likewise presented.

Acid-Base balance at any altitude can thus be adequately interpreted and, in fact, becomes crucial for the correct and precise interpretation of metabolic function. Furthermore, it is a life saving knowledge for mountaineers and high altitude residents around the world.
CLINICAL AND PROGNOSTIC VALUE OF INTERLEUKIN-12 IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Barbarash OL., Kashtalap VV., Zykov MV.

Research Institute for Complex Issues of Cardiovascular Diseases

Siberian Branch of the Russian Academy of Medical Sciences,

Kemerovo 650002, Russia

The research objective was to study clinical and prognostic value of  inflammation markers in patients after Q-wave myocardial infarction (MI). The study enrolled 214 patients diagnosed with ST segment elevation MI. Cytokine levels (interleukins (IL)-1α,-6,-8,-10,-12 and tumor necrosis factor alpha (TNF – α)) were measured in all of the patients on days 10-14 after MI onset, and C-reactive protein (CRP) levels were detected by an immunoenzymatic method. Out of all analyzed inflammation factors only TNF – α, IL-12 and CRP were significantly higher in patients with multivessel coronary artery disease compared to patients with an isolated lesion. There was a positive correlation between the levels of inflammation markers IL-12 and IL-6 and the severity of an atherosclerotic lesion of brachiocephalic arteries or lower limb arteries. Data regression analysis with step-by-step selection showed the age of ≥ 53 years and IL-12 levels of ≥87,1 pg/ml to be of the greatest predictive value in detecting a haemodynamically significant coronary lesion, and the age ≥ 65 years and IL-12 levels of 108,8 pg/ml, in detecting a haemodynamically significant non-coronary lesion. II and > Killip class of acute heart failure and IL-12 levels of > 90 pg/ml were identified to be independent variables for risk stratification of any cardiovascular event a year after MI. Thus, out of all studied inflammation indicators IL-12 possesses the greatest diagnostic value in defining patients at a high risk of severe coronary and polyvascular atherosclerosis and subsequent complications.

THE VENTILATORY HYPEROXIC SHUNT TEST AT 3510 m. OF ALTITUDE

L Zubieta-Calleja, G. Zubieta-Castillo & GR Zubieta-Calleja.

High Altitude Pathology Institute (IPPA), Zubieta University

La Paz, Bolivia.

www.altitudeclinic.com

We use a new method to test pulmonary shunt by hyperoxia at high altitude.  The subject is tested first breathing ambient air in the seated position. Using a face mask, ventilation, ETO2, ETCO2, ECG, pulse oximetry and blood pressure are measured. An arterial blood sample is taken from the radial artery. The whole procedure is repeated with the subject breathing 100 % O2 from a Douglas Bag. This technique allows for precise measurements that provide a clear picture of cardio-respiratory parameters. Furthermore it allows the possibility of observing when there is an equilibration of the PIO2 as it is observed on a breath by breath basis in the same wave that the ETO2 is observed. The average PIO2 was 421.7 mmHg.  For 3510 m, the altitude of our Laboratory, the test performed in 14 normal subjects(mean ± SD)   using t-students reports:

SpO2 in % VE BTPS ETCO2 mmHg ETO2 mmHg PaO2

mmHg

PaCO2 mmHg pH
Ambient Air 91.56

± 1.45

9.19

± 2.3

28.05

± 1.9

66.42

± 4.05

59.3

± 5.92

27.7

± 3.72

7.43

± 0.03

89% O2 98.15

± 0.73

8.26

± 2.06

26.17

± 2.2

337.59

± 14.7

237

± 25.8

27.25

± 3.6

7.46

± 0.06

p = <0.0001 NS <0.0001 <0.0001 <0.0001 NS NS

This tests permits the operator to observe when the PIO2 reaches the maximum level thereby making the precise observation of shunt, irrespective of uneven ventilation that can delay such equilibration of inspired gases. The intra-pulmonary shunts are essential for evaluation of patients with Chronic Mountain Sickness at high altitude.

EXTREME HYPOXIA IN NEWCOMERS TO HIGH ALTITUDE, HOW CAN IT BE TOLERATED?

G. Ardaya-Zubieta, G Zubieta-Calleja, N. Zubieta-DeUrioste & GR Zubieta-Castillo.

High Altitude Pulmonary and Pathology Institute (IPPA), Zubieta University

La Paz, Bolivia.

zubieta@altitudeclinic.com

Patients suffering from the acute effects of hypobaric hypoxia can have extremely low arterial oxygen tensions (PaO2), which are quite well tolerated. They come to consultation with a PaO2 between 30 and 40 mmHg. Their recovery after a few days is uneventful following the efficient treatment of the underlying cause. When the medical reports were sent to their sea level physician they were asked: “Were you conscious?”

At sea level these very low oxygen tensions are not tolerable. A patient presenting a PaO2 of 60 mmHg is sent to an intensive care unit, as his life is in peril. However at high altitude in the city of La Paz 3600m, the normal acid-base values are: PaO2 = 60 ± 2 mmHg. PaCO2 = 30 ± 2 mmHg and pH = 7.40 ± 0.02, SpO2 = 91% ± 1%. The later oscillates with irregular breathing and deep breaths can achieve even 98% as has been previously described.

One out of four subjects, arriving to La Paz, has some form of Acute Mountain Sickness.

Some can present extreme hypoxia. The pathologies that we have recently seen associated with this extreme hypoxia are: pneumonia upon ascent, pulmonary thromboembolism, high altitude pulmonary or cerebral edema and several others.

As example a young Frenchman 25 years old climbed Huayna Potosi at 6000m two days after arriving to La Paz 3600 m, from Paris. On the way down he feels very short of breath. He is unable to sleep over the night. He comes to consultation walking. A blood gas analyses reports a PaO2 = 35 mmHg, PaCO2 = 29 mmHg and a pH = 7.53. This is diagnosed as severe hypoxia and respiratory alkalosis in High Altitude Pulmonary Edema. Would he have been alive if at sea level?

What is the explanation for this extreme hypoxia tolerance?

The alkaline pH during acute high altitude exposure shifts the oxygen dissociation curve to the left, allowing more capture and transport of oxygen. The other variable that can allow for the tolerance to extremely low PaO2 values is the normal low (relative to sea level) PaCO2. These new concepts are analyzed and discussed.

GERIATRICS AND EXERCISE AT HIGH ALTITUDE

OF Murillo, GR Zubieta-Calleja,   G Zubieta-Castillo

High Altitude Pulmonary and Pathology Institute (IPPA), La Paz, Bolivia.

Hillside Internal Medicine, Hannover PA, USA

www.altitudeclinic.com

More and more, it becomes evident that exercise at sea level is essential, even for the elder. But at high altitude, there is little information on how much exercise can be performed by people above 65 years of age. At sea level, active 65 years old women have a life expectancy of 18.4 years compared to inactive at only 12.7 years. The NIH Consensus Conference on Physical Activity and Cardiovascular Health stated on exercise in the elder: “Benefits include reduction in mortality, reduction in symptoms, improvement in exercise tolerance and functional capacity, and improvement in quality of life”.  Furthermore, several pathologies improve with exercise: elevated cholesterol, chronic lung disease, diabetes mellitus, high blood pressure, knee osteo-arthritis, obesity and osteoporosis.  Exercise has been advised as being of two types by the American Geriatrics Society. 1) Vigorous = at least 20 minutes of vigorous physical activity on 3 or more days each week  and 2) Moderate = a brisk walk, or an equivalently intense aerobic activity, for at least 10 min at a time, for a total of at least 30 min a day, on at least 5 days/wk. Vigorous exercise seems more benefitial, however it has to be achieved gradually and regularly in order to avoid injury. Exercise performed at 3510m in 4 normal people with ages ranging from 65 to 84 has shown that they have comparable SpO2, pulse and ventilation to young men in their early 20’s. The only difference is that 3 of the 4 subjects could not achieve the last stage of the USAF modified exercise protocol on a treadmill. Intensive exercise is limited in the elderly, but could be achieved gradually through training even at high altitude.

The guidelines for exercise in the elders at sea level

, are suitable for elders at high altitude. However, these should be gradually performed in newcomers and can reach full intensity of exercise, only when complete adaptation to high altitude is achieved from the hematological aspect.

THE HIGH ALTITUDE AND LOW ALTITUDE ADAPTATION STUDIES AND ITS PRACTICAL APPLICATION TO TRAVEL IN HUMAN EXPLORATION OF SPACE

G Zubieta-Calleja, N. Zubieta-DeUrioste & GR Zubieta-Castillo.

High Altitude Pathology Institute (IPPA), Zubieta University

La Paz, Bolivia.

zubieta@altitudeclinic.com

When sea level dwellers ascend to high altitude environments, their organism adapts in three phases to chronic hypoxia. Acute adaptation, that lasts between one and two days and where acute mountain sickness can occur. High Altitude Pulmonary Edema and high Altitude Cerebral Edema can likewise begin and extend towards the next phase. Subacute adaptation is the phase between the second day and the day total adaptation is achieved at a fixed altitude. The length depends on the time to reach the stable hematocrit and varies depending on the altitude. It is calculated using the formula:

Adaptation =

In this subacute phase if the subject performs excessive exercise, he feels short of breath, and the right heart can become dilated, and evolve to what is known as subacute heart disease. A consequence of incomplete adaptation. Finally, in the third stage when the hematocrit no longer increases, complete high altitude adaptation is achieved. Several factors, such as previous ascents, genetic characteristics, dehydration, quality of the food, presence of previous lung disease, and yet to be described factors, may alter somewhat the time frames. During full adaptation and life in the mountains, the subjects are able to carry out a normal life comparable to sea level, reproduce and practice sports.

Inversely, if high altitude residents go to sea level, the organism is facing a “relative hyperoxia” and hence, an aggression of an abnormal environment (disregarding the other factors such as temperature and humidity, food, lodging and so on). The hematocrit decreases linearly through neocytolysis and an abrupt stop of RBC production until a plateau is reached. Sometimes there is an over-boost taking the hematocrit to very low levels. This is attributed to a highly efficient use of oxygen.

The knowledge achieved herein is applied to a proposal for a most efficient capsule environment for the human exploration of Space. Currently space vehicles use sea level barometric pressure (760 mmHg) with normoxia (21%). Astronauts suffer, among many other complex micro-gravity alterations, anemia, that upon return to sea level, has to be correspondingly normalized to pre-flight levels. The reason that anemia presents is in part due to a lower requirement of oxygen by orthostatic muscles in Earth’s gravity. Consequently, a cabin pressure 2/3 that of sea level, similar to the city of La Paz, would maintain a hematocrit for re-entry, and furthermore, could significantly accelerate the preparation for Extra Vehicular Activity that currently takes up several hours, in order to avoid decompression sickness, going from a sea level pressure to 1/3.

AT 4000m IN THE HIGHLAND ENVIRONMENT, REMISSION OF SEA LEVEL LIFESTYLE RELATED DISEASE IS POSSIBLE THROUGH QUANTUM BIOLOGY
Prof.Kunihiro Seki.,  Dr.Antonio Saravia, and  Prof.Takeo Nomura
Quantum Biology Institute, Japan
mail: seki822@yf7.so-net.ne.jp

In man, after the age of 20, cellular “redifferentiation” a form of cellular regeneration in 200 types  of cells, with few exceptions will occur. But when you live at around 4000m, the altitude of Titicaca Lake, the dividing cells in the body undergo “transdifferentiation”. This would automatically be induced by cell division through drinking deuterium depleted water(DDW) and ingestion of deuterium depleted food(DDF) a consequence of low humidity and hypoxia.
The highlands at 3812m altitude in the mountainous  regions of South America’s
Titicaca Lake, the UV radiation is 13 times that of sea level. At sea level, UV radiation increases the incidence of skin cancer by 3-6%. However at 4000m, high altitude residents – have apparently not suffered from skin cancer, however this needs to be further studied.
A subject was diagnosed suffering from a thyroid gland tumor at sea level. He migrated to La Paz Bolivia and stayed in the highlands at 4000m, and originally  few physiological changes were observed. Until the arrival to La Paz, he had been ingesting DDW but no DDF.  After 5 months, an ultrasonic diagnostic imaging practiced at the CiLap Hospital of La Paz  reported remission and calcification of the tumor.
The validity of my hypothesis about the possibility of overcoming cancer by means of DDW and DDF was thus verified. An extraordinary achievement!
Life at the high altitude of 4000m as well as daily consumption of DDW and
DDF led to the multiplication of cells in the body, which resulted in such a reinforcement of cell proliferation, immune function and power of spontaneous cure that cancer remitted.
Going from the lowlands to highlands at 4000m above sea level, the following environmental changes and symptoms take place:
1 Partial pressure of oxygen at highlands is 120hPa which is 60% of lowlands (sea level  PO2=206hPa).
2 Deuterium concentration of water and food is 138ppm while at sea level it is 150ppm.
3 The number of red blood cells increases by 1.6 times, and cardiopulmonary
function by 1.3 times  and some men and women can suffer from nosebleed.
4 Cell proliferation becomes vigorous resulting in improved sexual health with
daily ejaculation for men and monthly ovulation for women.

5 With the improvement in the faculty of spontaneous healing, normally considered incurable diseases can have their symptoms temporarily alleviated or be completely cured.
Living at 4000m during one week (a diabetic’s?) fasting glucose levels reported  100mg/dl. This is evidence that insulin has proliferating β cells that secrete insulin in the pancreas islet. Upon returning from 4000m to sea level, these conditions remained for a month. At 4000m, the altitude hypoxic environment with low temperature and dry air is a spontaneous cure and improves immune function and metabolism in type 2 diabetes-affected people at sea level.
In conclusion, quantum biology supplies a theoretical basis for the remission of cancer
which has been considered incurable.
1. In people exposed to high altitude hypoxia, low atmospheric pressure, low temperature and dry air, immediately stimulates cell division in their body enhancing cell proliferation, immune function becoming a power of spontaneous cure.
2. If one consumes DDW and DDF available at the altitude of 4000m above sea level, cell proliferation, immune function and power of spontaneous cure are all strengthened.
3. Healthy sexual life activates cell proliferation, immune function and power of spontaneous cure.
When all three above-mentioned conditions are met concurrently, owing to their synergistic effect, cancer in the human body can go into remission.

SIR CHRISTIAN JOHN STOREY BONINGTON

Interview by Jay Mehrishi

Cambridge University, UK

Sir Christian John Storey Bonington, CVO, CBE, DL (styles himself as ‘Chris’ Bonigton)  is a British mountaineer, born on August 6th, 1934 in Hampstead, an area of London, 4 miles (6.4 km) north-west of Charing Cross rail station. He was  educated at University College School in Hampstead, London and joined the Royal Fusiliers before attending Royal Military Academy Sandhurst. On graduation, in 1956 he was commissioned in the Royal Tank Regiment. After three years in Northern Germany, he spent two years at the Army Outward Bound School as a mountaineering instructor.

He is married to Wendy, who is a freelance illustrator of children’s books. The couple have two sons: Daniel and Rupert.

Following a request by Larry Silver (from California) to say a few words to the conference that arrived while he happened to be in Cambridge for delivering a lecture elsewhere, he kindly invited me to a breakfast meeting on Sep 23rd and an interview. It was an immense pleasure for me to meet Sir Chris Bonington in the courtyard of Corpus Christi College under the typical light English rain falling on us!

At breakfast he had 2 rashes of bacon and a sausage (can’t remember if he had any fried egg), grilled tomatoes, orange juice and a slice of toast (that he did not eat). Looking at my one tablet of weetabix, grilled tomatoe and some basked beans, he remarked on the type and small size of the breakfast.We had a most interesting discussion in the rooms after we both fiddled with the simple tripod mechanics, the digital camcorder that I had not used for four years and of course, the rather poor light.  Like a true experienced mountaineer taking things in his stride, Chris thought that the natural light would be fine and we got on. Fortunately, he had the same Apple Laptop  as mine, that had all the questions  I was asked by Gustavo and Larry to put to Chris.

Amongst other things about AMS, nausea, fatigue, rate of climb, adaptation (that he thinks varies from person to person), in particular, Chris recalled about the blood getting ‘thicker’. In a sentence I described to him how  oxygen getting rarer, the need for more oxygen, requests more Hb and thus more RBCs, triggered by  EPO to make more RBCs! He surprised me by the extraordinary story of a climber’s hematocrit remarkably reaching as high ~70% and the attending physical having to remove 2 litres of blood  ( that he, otherwise, believed, would have died) and administer saline!Because of  my interests since 1960 in the viscosities of human blood in cardiovascular disease and red cell mass increase in climbers at high altitudes, I found this of particular interest.

At the end of the interview, he finally packed his roller bag and we walked for 4 min to my car for the 10 min drive to the rail station to catch the train to London and his home in Cumbria. We talked  a little in the car about various things.Like any proud grandfather he showed me the photographs of his grand children and of course he asked me about my family.

His career has included nineteen expeditions to the Himalayas, including four to Mount Everest and the  Bonington was part of the party that made the first British ascent of the South West Pillar of the Aiguille du Dru in 1958, and the first ascent of the Central Pillar of Freney on the south side of Mont Blanc in 1961 with Don Whillans, Ian Clough and Jan Dlugosz. In 1960 he was part of the successful joint the British-Indian-Nepalese forces expedition to Annapurna II. On leaving the British Army in 1961, he joined Van den Berghs, a division of Unilever. But he left after nine months, and became a professional mountaineer and explorer. In 1966 he was given his first assignment by the Daily Telegraph magazine to cover other expeditions, including – climbing Sangay in Ecuador; hunting Caribou with Eskimos on Baffin Island. In 1968 he accompanied Captain John Blashford-Snell and his British Army team in the attempt to make the first ever descent of the Blue Nile.

He has written fifteen books, made many television appearances, and received many honours, including, since January 2005, the chancelloship of Lancaster University.

He is honorary president of the Hiking Club and Lancaster University Mountaineering Club and has a boat named after him among Lancaster University Boat Club’s fleet. Furthermore he is the Honorary President of the British Orienteering Federation. He has lived in Cumbria with his wife, Wendy since 1974. He is a patron, and former president (1988-91), of the British Mountaineering Council (BMC). He succeeded Sir Edmund Hillary as the Honorary President of Mountain Wilderness, an international NGO dedicated to the worldwide protection of mountains. Noteworthy:

1970 Annapurna (south face), successful, summit reached by Haston and Whillans death of Ian Clough

1972 Mount Everest, (south-west face), unsuccessful

1975 Mount Everest (south-west face), successful, summit reached by Scott, Haston, Boardman, Pertemba Sherpa and Mick Burke; death of Burke

1978 K2 (west face), unsuccessful; death of Nick Escourt

1982 Mount Everest (north-east ridge), unsuccessful; death of Boardman and Tasker

Parts of this description has made use of the biography of Sir Chris Bonington on the

Website http://en.wikipedia.org/wiki/Chris_Bonington  that is duly acknowledged and Sir Chris Bonington also will have been consulted for the accuracy for which the writer Jay Mehrishi, the Director of High Altitude Pulmonary and Pathology Institute IPPA (Gustavo Zubieta-Calleja), the Chairman of the III Symposium on Chronic Hypoxia (Gustavo Zubieta-Castillo) and the President of  International Society of Chronic Hypoxia ISCH, (Larry Silver)  are thankful.

Chronic Hypoxia Symposium III now live on the Internet

Hello dear friends and colleagues around the world:

You can now participate in our Symposium on the web, from your office or home with a Powerpoint presentation.

We are once more going to write history! And this time thanks to Larry Silver, President of the International Society of Chronic Hypoxia.

Why history? Because it is the first time a conference dealing with hypoxia will be held from high altitude sites through the internet. That is, from a chronic hypoxia environment where the PIO2 is 2/3 that of sea level in the city of La Paz, to all the scientists of the planet,through Webex, a CISCO Networking software, to environments where the oxygen tension is higher. This is of utmost importance as will be appreciated during the conferences.

Furthermore, you can easily imagine, the outstanding world exposure this will generate, a true leading edge future scientific trend!

We are working details with Larry and will get back to you with the rules of the game.

However, in the mean time, please prepare your abstracts in order to participate from your lab or your home anywhere on earth.

Send them to us as soon as possible as they will be available online at the symposium website.  So do not loose your seat and this unique opportunity to become famous!
The Abstract Deadline has been moved to accommodate this new technology to Monday Sept 8th !! So you have an extra week.

The III Symposium on the Effect of Chronic Hypoxia
on Diseases at High Altitude

October 16-23, 2010
click here to go to the website

Remember, we are a different kind of symposium. We are open to any presentation. We don’t reject anyone. Everyone has an opportunity to express their ideas. Many great ideas are buried due to peer reviewers and groups that only publish their teams and reject others in spite of their great talent and production. But talent and creation are like an unsinkable buoy. They always surface even if you try to keep them underwater.
Dr. Jitendra Mehrishi from Cambridge University has joined us as scientific advisor and is boosting further the symposium. The conference is dedicated to the memory of Haldane-Barcroft.

We will be honored with the attendance of Dr. Giridhar J. Gyani, Secretary General of the Quality Council of India. His visit and activities are being coordinated by Dr. Thuppil Venkatesh, from St.John’s Medical College in Bangalore, India.

It will once more be an itinerant symposium, where talks are given in different altitude sites. You will learn of “life at high altitude” in different environments.

click here to read about it.

Forever: “Loss of Adaptation” does not exist!

Forever: “Loss of Adaptation” does not exist!

Prof. Dr. Gustavo Zubieta-Castillo (Sr)

Honorary Director                    Español (mas abajo)

Instituto Pulmonar y Patología de la Altura IPPA

La Paz, Bolivia

AltitudeClinic.com

Chronic Mountain Sickness (CMS) is a term that does not explain the ethiopathogenesis of the disease in response to the effect of chronic hypoxia. There is no CMS, but rather pulmonary (mainly), cardiac, carotid, kidney, hematological or genetic disease. All these associated to an increase on the hematocrit or what is now known as polyerythrocythemia.

CMS, was described by Carlos Monge Medrano close to 90 years ago, He was unable to find an explanation for the signs and symptoms and chose to use the term “LOSS OF ADAPTATION”.  This was originally accepted, but today it can be appreciated as lacking significance. And should stop being used.

Undoubtedly, CMS is a chronic hypoxic process resulting in an increase of hemoglobin, due to pulmonary lesions (fundamentally), that alter the pulmonary function, thereby reducing the oxihemoglobin saturation and stimulating the increase of red blood cells. This, essentially, in pulmonary lesions that are sequelae of diverse lung disease giving rise to intra-pulmonary shunts or uneven ventilation-perfusion. The term “LOSS OF ADAPTATION”, is even semantically inadequate, because in nature, living beings tend to adapt to different environments and circumstances. These could be: going to high altitude, temperature changes, solar radiation, UV radiation, diet changes, etc, etc . Consequently, to insist in contemporary medicine on the use of “LOSS OF ADAPTATION”, is not only a mistake, but rather foolishness!

On the other hand, if one is convinced as to the cause of a disease, where other scientists are in disagreement, it is futile to incur in the use of insults. In the International Chronic Mountain Sickness Consensus Group, you Fabiola Leon-Velarde, recurred to them in your e-mail on January 09, 2005 with the expression as follows:

“Third, we have agreed in Xining that any member of the group who have had a different opinion in any point, should send a letter to the Journal informing about the discrepancy. Of course, if any member of the group do not agreed at all with the Consensus, he should ask that his name is retired from the list of names, otherwise his letter will appear a little bit esquizofrenic.”

Please note that you misspelled the word…  “schizophrenia”. This is what happens when one is not a medical doctor and doesn’t have medical knowledge. You live in Lima, at sea level,and your brief visits to high altitude, give you no authority or experience on disease at high altitude. Through your attitude, you are confusing world researchers. This has to be said for the sake of truth. Your knowledge should be restricted to the spectrum provided by your occupations instead of persisting on the use of “loss of adaptation” in regards to CMS. To have written a book entitled “Desadaptation a las grandes Alturas” (Loss of adaptation to high altitude) is to insist and confirm that you hardly understand the basic concepts of nature. A grave mistake, with no return.

In reference to this article please read “Consensus statement on chronic and subacute high altitude diseases” (1) . where we participated as a minority with an opposite standing versus “Loss of Adaptation”. We stated our concepts in regards to CMS within the aforementioned group (comments are available, on-line (3,4).) In that group, there were many prestigious scientists, from around the globe, but most of them lacked knowledge about diseases at high altitude.

We urge the reader not to misinterpret us. We are not offended by the insult, and quite the contrary we laughed upon reading it as anecdotal. What we are doing here is setting things straight, for the sake of science. The term “loss of adaptation” is inadmissible as it does not explain an ethiopathogenesis.

We are so convinced, based on our fifty years of high altitude research and experience, that living beings not only adapt to life at 5000m, as it is well known, but rather even to  8842m at the summit of Monte Everest.  There can be no doubt.

Similarly, pulmonary and cardiac patients in chronic hypoxic environments at high altitude, also adapt, hand in hand with their disease. Polyerythrocythemia, is one of the resulting hematologic mechanisms that allows for an increase of the oxygen content.

You, on purpose, as you have done before, exclude us from participating in the  THE VIII WORLD CONGRESS ON HIGH ALTITUDE MEDICINE AND PHYSIOLOGY – CARLOS MONGE CASSINELLI. Congratulations for naming it after our dear friend Choclo.We remind you that we initiated these world congresses successfully, in Bolivia, back in 1994. We invited everyone dedicated to high altitude to attend, including yourself as you were Choclo’s collaborator.

We are now at our III CHRONIC HYPOXIA SYMPOSIUM in October 2010 in La Paz, Bolivia. You and everyone are invited to attend, with no restrictions, nor political interest groups, that often block the participation of some, that think different.

Throughout history, all living beings, go through  evolution, in order to adapt to different environmental conditions. Even aging is an evolution, that goes to finish a vital cycle.  It never goes in the reverse way. This concept of loss of adaptation is unacceptable.

Again, “The organic systems of human beings and all other species tend to adapt to any environmental change and circumstance within an optimal period of time, and  never tend towards regression which would inevitably lead to death” (2)

La Paz, March 11, 2010

———————————————————————————————-

Para siempre: La “Desadaptación a la Altura”: No existe !

Prof. Dr. Gustavo Zubieta-Castillo (Sr)

Director

Instituto Pulmonar y Patología de la Altura IPPA

La Paz, Bolivia

El Mal de Montaña Crónico  (CMS), es un término inadecuado porque no explica la etiopatogenia de la enfermedad. Las enfermedades en la altura sufren el efecto de la hipoxia crónica. No existe el mal de montaña crónico sino las enfermedades pulmonares de diferente etiopatologia que van asociadas al aumento del hematocrito o polieritrocitemia.

Carlos Monge Medrano, describió admirablemente los síntomas y signos del Mal de Montaña Crónico. Al no encontrar una etiología adecuada, para esa época, utilizó el termino DESADAPTACION. Este término aceptado al principio, se puede comprobar que actualmente no tiene significación.

El síndrome de Mal de Montaña Crónico, se sabe actualmente, sin que pueda hacerse objeciones, es fundamentalmente, un proceso crónico hipóxico con un aumento del hematocrito. Esto debido a lesiones pulmonares que alteran la función respiratoria y que impiden la adecuada saturación de la sangre estimulando el aumento de los glóbulos rojos. Sobretodo es debido a secuelas de lesiones pulmonares de diversa etiología con shunt pulmonar y/o ventilación no uniforme. El termino desadaptación, es incluso semánticamente inadecuado porque en la naturaleza los seres biológicos tienden a la adaptación a diferentes medios y circunstancias. Como ser: cambio de altura, de temperatura, radiación solar, radiación UV, cambio de alimentación, etc, etc. De manera que insistir en la medicina contemporánea con el termino desadaptación, no solo es un error, sino una insensatez!

Por otra parte si uno tiene la convicción sobre las causas de alguna enfermedad, con la cual no están de acuerdo otros científicos, no es esto motivo, para que se recurra al insulto. La ecuanimidad esta en reconocer que uno puede equivocarse pero no tratar de imponer criterios recurriendo al insulto como lo esta haciendo Ud. Fabiola Leon Velarde.

Para referencia está la publicación “Consensus statement on chronic and subacute high altitude diseases”(1) donde participamos minoritariamente con una posición contraria a la Desadaptación.(3,4).  Ese grupo de prestigiosos científicos de todo el mundo, tenian escaso conocimiento de las enfermedades en la altura.

Durante las reuniones previas en Jan09,2005, Ud. nos escribió (traducido al Español):

“Tercero, hemos acordado en Xining, que cualquier miembro del grupo que tuviera una opinión diferente, debería enviar una carta al Journal informando de esa discrepancia. Por supuesto, si algún miembro del grupo no esta de acuerdo con el Consenso, debe pedir que su nombre sea retirado de la lista de nombres, de otra manera su carta aparecería algo esquizofrénica. (esquizofrenic en la version en ingles)

Ojo,  en Inglés se escribe “schizophrenia”.

Su audacia no tiene limites, porque Ud. no es medico y por lo tanto no sabe medicina. Ud. vive en Lima, a nivel del mar, y sus visitas esporádicas a la altura no le dan ninguna autoridad ni experiencia y esta confundiendo a los investigadores presentando estos casos. Sus conocimientos deberían estar limitados al espectro que le permitan sus ocupaciones y no tratar de insistir de que el mal de montaña es debido a “desadaptacion”. Haber escrito un libro titulado “Desadaptación a las grandes alturas” es insistir y confirmar que no se entiende los conceptos básicos de la naturaleza. Error cometido irremediablemente.

No nos ofende, ni causa resentimiento que Ud. en esa oportunidad, nos llamó esquizofrenicos, y sentimos por el contrario que es motivo de buen humor y anecdotico. Lo que estamos haciendo es afirmar que el termino desadaptación es inadmisible porque no explica ni señala una etiopatologia.

Estamos tan convencidos que el ser biológico no solo se adapta a la vida a los 5000m, sino hasta los 8842m en la cima del Monte Everest. No cabe duda… De igual forma los enfermos pulmonares o cardiacos en el ambiente hipóxico de la altura, también se adaptan con su enfermedad, resultando la polieritrocitemia, un mecanismo para aumentar el contenido de oxígeno.

Ud. nos excluye intencionalmente del VIII Congreso Mundial de Medicina y Fisiología de la Altura, cuya serie, nosotros iniciamos exitosamente en Bolivia el año 1994, al que invitamos cordialmente a todos dedicados a la altura, incluyéndola a Ud. por ser la colaboradora de nuestro amigo Carlos Monge Casinelli. Nos alegramos que el VIII sea en honor a nuestro amigo Choclo.

Nosotros tenemos el III Simposio del Efecto de La Hipoxia Crónica en las Enfermedades en la Altura en Octubre 2010, al cual queda Ud. Cordialmente invitada, aquí en La Paz. Todos están invitados a participar, sin restricciones, ni grupillos de interés político común, como frecuentemente ocurre bloqueando intencionalmente la participación de algunos, que opinan diferente.

A través de la historia, todos los seres vivientes evolucionan, para adaptarse a diferentes condiciones ambientales. Incluso la edad es una forma de evolución, que se dirige a finalizar un ciclo. Nunca va en sentido contrario. Este concepto de Desadaptacion es inaceptable.

Nuevamente, “Los sistemas orgánicos  de los seres humanos y de las otras especies tienden a la adaptación a cualquier cambio ambiental, dentro de un periodo óptimo de tiempo, y nunca tienden hacia la regresión que inevitablemente daría curso a la muerte”.(2)

 

La Paz, 11 de marzo de 2010

References

1) León-Velarde F, Maggiorini M, Reeves JT, Aldashev A, Asmus I, Bernardi L, Ge RL, Hackett P, Kobayashi T, Moore LG, Penaloza D, Richalet JP, Roach R, Wu T, Vargas E, Zubieta-Castillo G, Zubieta-Calleja G.

Consensus statement on chronic and subacute high altitude diseases.

High Alt Med Biol. 2005 Summer;6(2):147-57

2) Zubieta-Castillo G Sr, Zubieta-Calleja GR Jr, Zubieta-Calleja L.

Chronic mountain sickness: the reaction of physical disorders to chronic hypoxia.

J Physiol Pharmacol. 2006 Sep;57 Suppl 4:431-42.

3) http://altitudeclinic.com/blog/2010/07/chronic-mountain-sickness-discussion-part-1/

4) http://altitudeclinic.com/blog/2010/07/chronic-mountain-sickness-discussion-part-2/

Chronic Mountain Sickness Discussion Part 2

The following excerpts are from the E-mail discussion of the committee on chronic mountain sickness, prior to The 3rd World Congress on Mountain Medicine and High Altitude Physiology and The 18th Japanese Symposium on Mountain Medicine carried out in Matsumoto, Japan (May 20th – 24th, 1998). This is part 2/2

Hyperoxic-Hypoxic adaptation Chamber respiration studies

Respiratory studies in the Hyperoxic/Hypoxic Adaptation Chamber

Date: 31 Mar 1998 08:23:27 U From: “John Reeves” Subject: Re: CMS discussion To: “Gustavo Zubieta” Cc: “Ingrid Asmus” , “Linda Curran” , “Dr. Gerilli” , “GUSTAVO ZUBIETA, M.D. * IPPA *” , “Toshio Kobayashi” , “Fabiola Leon-Velarde” <106435.1365@compuserve.com>, “Shigeru Masuyama” , “Prof. Mirrakhimov” , “Carlos Monge” , “Hideki Ohno” , “Lorna G. Moore”3/31/98 8:20 AM

Thank you so much for the thoughtful remarks. They are extremely useful for the purposeof initiating discussion. As a bystander who does not see CMS patients, but who is interested in consensus, I do see differences of opinion that could and should be laid out on the table for friendly discussion, where everyone benefits. Getting these diverse opinions in ahead of the meeting should make people aware of the differences, and allow them to think about the problems. I hope you agree. Final answers may not come from the meeting, but the process of discussion will have been initiated. I am trying to keep Wu informed by fax of these discussions, but am not sure the faxes are getting through. I have taken the liberty of sending your thoughtful comments around, as I believe they deserve wide distribution. I hope that is O.K.

Jack

————————————–

Date: 3/30/98 4:05 PM To: John Reeves From: GUSTAVO ZUBIETA, M.D. * IPPA *

Jack:

Here goes the homework requested by you, Lorna Moore and her colleagues. We feel troubled by the subject of scoring CMS. As you can read from our publications, we are confident that there is no “loss of adaptation of life at altitude”, but rather an adaptation of pulmonary, cardiac, renal or other disease to the hypoxia at high altitude. (And to tell you the truth, CMS patients do remarkably well, provided their basic disease is treated or looked after).

In general, patients with CMS are examined while attending a regular consultation. Most often, after suffering the disease during many years and only when they and their family become aware of the change in the color of the skin, particularly in the face. Also, when the consultation is for another kind of disease and the routine laboratory tests report increased polycythemia. At this time, the signs and symptoms can be present in different degrees and are prominent or more evident in THS. The score will only be valid for some patients with CMS and exclude others.

Gastrointestinal ulcers, are frequent findings. Gastro-intestinal bleeding, will change the score. The same happens with Gout. Several patients with CMS have increased uric acid, and some with evident signs of Gout by deposits in the ear helix. Gout can lead to well known pulmonary alterations. Similarly, hypertension is also present in some of them. This generally implies kidney disease. Finger clubbing is present in some, even when they are very young.

In broncho-pulmonary lesions of smokers, for example, there can be severe cyanosis, low saturation, increased polycythemia and pulmonary hypertension. If they stop smoking there is significant improvement. This is the same as at sea level, but in chronic hypoxia they reach lower saturation. Another example are some patients with asthma. This shows that CMS patients have a different etiopathogenesis. If all these examples are not included, are they going to be considered a different kind of disease? It does not seem so.

At altitude, “cyanotic pulmonary diseases and asymptomatic high altitude polycythemia” (as defined by Hultgren) are, in our experience, CMS, and the later approaches more exactly CMS present at moderate altitude. If you use a score, you have to be aware that it will apply for that moment only and it will most probably change even within the next few days. Also, great differences in scoring will be found, depending on the degree of compromise of lung or cardiac function, the type of disease, and of course the altitude. Why? Because patients that have CMS are subject to viral diseases, bronchitis, colds or even seasonal climate changes (we have a CMS patient with allergies). This we described as triple hypoxia syndrome (THS), an acute condition overimpossed on CMS (please see further down and the article in our Web page below). So, if the score pretends to be used to access the moments’ clinical state of the patient with CMS, that is fine. About scoring CMS: In the score used by Dr. Wu in CMS, the signs are present particularly in AMS and the triple hypoxia syndrome, that we also call “sorojche (AMS) in bed”. With the exception of hyperaemia in conjunctivae and mucosae, which are chronic. The scores 0, 1, 2 and 3 for none, mild, moderate and severe, seem adequate.

We think that everybody agrees that the disorder regresses on descent to sea level, in around one month. Patients who reascend to high altitude, and are exposed again to hypoxia, develop CMS once more. This is a mechanism of adaptation, to supply the necessary oxygen to the tissues. The patients from low lands with chronic pulmonary diseases commonly unnoticed at sea level, develop CMS at altitude. Are we going to consider these cases as a loss of adaptation?. Certainly not, it is hard to think in such a way. We agree that the most appropriate approach to score the disease, are the laboratory findings: hemoglobin or hematocrit and oxygen saturation, with or without carbon dioxide retention, depending of the severity of the case. For over 15 years now, we have been using a classification by number of red blood cells (“El mal de montaña crónico y los mineros”, published in the magazine of the Academia Nacional de Ciencias de Bolivia,1985;4:109-116), and it has proved to be a good guide in our medical practice. Originally, diagnosis was based on clinical examination, chest x- rays film and hemogram only, due to the lack of equipment. It is as follows: moderate 6.5 to 7.5 million RBC/mm3 severe 7.5 to 8.5 million RBC/mm3 grave > 8.5 million RBC/mm3 For 3600 m. of altitude only. We feel now that it would have been better to name them as mild, moderate and severe and to use the hematocrit or hemoglobin, which amount to the same thing.

———————- With respect to your 7th question, (a very good one, indeed); yes, there is an altitude at which everyone gets CMS. Please see the abstract “Pulmonary disease, CMS and gender differences at high altitude” that we plan to present as a poster. When the respiratory frequency and ventilatory capacity are unable to compensate the extreme hypoxia, the last resort for the human being is to develop severe pulmonary hypertension (right heart hypertrophy) and increase the number of the red cells. All permanent residents will be sick with CMS at 5500 m, for example at the mine of Chorolque located at 5562 m. Since not everyone has equal capacity of adaptation, the CMS will be more severe in some than in others, and still they will survive. Of course, in miserable conditions. In terms of genetic predisposition, CMS is most probable for some individuals, over 40 years old, who have a tendency to gain weight, but this is due to the predisposition to get sick from respiratory disorders. Also, about impairment of intelligence in these patients, and intelligence itself in chronic hypoxia, we drop the subject for the moment. It is important to mention that chest X-rays films as a test of diagnosis of CMS is mandatory, (and now CAT scan or NMR) as is the clinical history of pulmonary diseases, and the pulmonary function tests.

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In summary, to answer the first question about Chronic Mountain Sickness, “What is it?”. We feel that the most simple description of CMS, is going to be the most adequate for the moment. In that respect we are closer to John Weil’s definition.

Our definition is: “CMS or Monge’s disease is found in residents at high altitude with some abnormal pulmonary function (increased shunt, impaired diffusion, uneven ventilation and/or hypoventilation), sequelae of diseases of diverse etiopathogenesis. These lead to a sustained (and variable) low oxygen saturation and cyanosis, giving rise to pulmonary hypertension and increased polycythemia as compensatory mechanisms of adaptation to the disease under chronic hypoxic conditions. The symptoms and signs are reversible by descent to sea level or by increasing the PIO2.”

Both of us (Gustavo Sr. and Jr.) discuss this subject profoundly and we only write down the subjects in which we are in full agreement. We are expectant of the discussion on the scoring system.

Gustavo Sr and Gustavo Jr.

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Received: from Pmail on IPPA_0 by PegWaf v0.24 93.03.15 id 3382 ; Mon, 30 Mar 98 18:10:51 To: “John Reeves” From: ZUBIETA@oxygen.bo (GUSTAVO ZUBIETA, M.D. * IPPA *) Date: 30 Mar 98 18:10:51 Subject: CMS discussion Priority: normal X-mailer: Pegasus Mail v2.3 (R5). ————————————————————- Date: 10 Apr 1998 16:47:23 +0100 From: “John Reeves” Subject: FWD>Comments, please To: “Inder Anand” , “Ingrid Asmus” , “Peter Bartsch” , “Buddha Basnyat”

, “Linda Curran” , “Marlowe Eldridge” , “Bob Grover” , “Peter Hackett” <75543.465@compuserve.com>, “Toshio Kobayashi” , “Fabiola Leon-Velarde” <106435.1365@compuserve.com>, “Shigeru Masuyama” , “Professor Mirrakhimov” , “Carlos Monge” , “Susan Niermeyer” , “Hideki Ohno” , “Akio Sakai” , “Tatiana Serebrovskaya” , “Peter Wagner” , “Gustavo Zubieta” , “Lorna G. Moore” Mail*Link(r) SMTP FWD>Comments, please

Very interesting and important comments from the Zubieta’s. Dr. Leon-Velarde and myself, the Zubieta’s and others would like to hear some comments on these points.

Jack Reeves

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Date: 4/10/98 8:59 AM From: GUSTAVO ZUBIETA, M.D. * IPPA *

Dear Jack:

We completely agree with you, that we should be aware of the differences in opinions and also of the similarity in the approach to clarify some aspects in CMS. The paramount point of this forthcoming congress, I am sure (Gustavo Sr.), is that the assistants, while enjoying the friendship, try to find out some clues that will benefit thousands of people, who live, get sick and are treated at high altitude, all around the world. We are sure that everything you are doing is OK and please feel free and confident to make us notice any illogical digression of our part. Regarding the difficulty in making sure lungs are normal in CMS, because severe polycythemia itself alters gas exchange, Dr. West points out: “I would like to add a small point. Jack Reeves stated that ‘severe polycythemia itself alters [pulmonary] gas exchange’. I do not think this issue is settled. We induced severe normovolemic polycythemia in dogs (hematocrits up to 76%) and found no broadening of the distribution of ventilation perfusion ratios (J. Appl Physiol. 65:1686-1692, 1988). In the introduction to that article we reviewed the published studies on whether polycythemia impairs pulmonary gas exchange and no clear message emerged.” These interesting remarks, show us that many people think that polycythemia (of unknown etiopathogenesis), affects pulmonary function in CMS. According to Dr. West’s research, this would not be so.

Gustavo Sr, believes that those experiments resemble more what would happen in polycythemia Vera (Vaquez-Osler disease), where, according to the scarce bibliography, he has, there are no cardio-pulmonary alterations. If these experiments were repeated at high altitude, probably the results would be the same: No broadening of the distribution of ventilation-perfusion ratios. Some authors found that in polycythemia Vera, the pulmonary diffusing capacity was greater than in normals, attributed to increased hemoglobin concentrations (Journal of Clinical Investigation, Vol 4, NO. 7, 1963).

Polycythemia increases the total surface of red blood cells exposed to oxygen, which is another advantage. In Monge Medrano’s original paper, he thought that he found polycythemia Vera of high altitude (1928). Then he realized that it was not exactly the same so he changed his point of view to “loss of adaptation” and CMS (1937 & 1943).

The clinical description and observation of increased polycythemia was an important contribution to high altitude pathology, made 70 years ago. We look forward to the presentation by Carlos Monge and Fabiola Leon Velarde, our distinguished friends, on the history of how CMS was discovered . If the disease exists at high altitude, with the original description, Gustavo Sr. has not been able to see it in over 40 years of medical practice (and we were always looking for it). As you know there are thousands of people with increased polycythemia, in the Bolivian high plateau (abnormal), that can be easily diagnosed by simple observation in the streets, when there is the experience.

Some of the participants in the CMS discussion affirm that they have found people with CMS but with no anatomical or functional alterations. It seems to us that we are observing a different kind of pathology. By the way, we have neither seen one case of Polycythemia Vera. When one of us was in USA, nobody gave an adequate explanation about this last disease. The only thing I know for sure is that polycythemia vera is accompanied by leucocytosis, increased platelet count and can evolve to a very severe hematological disease.

As we previously pointed out, AFTER PROVING THAT THESE PEOPLE HAVE CARDIO-PULMONARY PATHOLOGY, ARE WE GOING TO EXCLUDE THEM FROM CMS OR MONGE’S DISEASE? For this reason, our point of view is that pulmonary diseases, that leave sequelae, give rise to low saturation and consequently CMS.

Lets suppose that 3 individuals, apparently normal, one 20 years old, and two 40 years old, move from the lower part of the city of La Paz, at 3000 m. They remain 3 months at 3500 m, and 3 months at 4100 m (in the city of El Alto, the highest part). The blood tests will show that the 20 years old and one of the 40 years old have their hemoglobin and hematocrit normal, for each altitude. The other has increased his hemoglobin to around 20 gm%. Can we say that this last one has “lost his adaptation”? and that the other two have adapted?. The last one has developed chronic mountain sickness. Do we call this: “adaptation” or “loss of adaptation” ?. This is not a hypothesis, it is a fact of common observation. Furthermore, if he has “lost his adaptation”, is he unable to live there any longer ?. Here, we are in the most critical point, in health problems. Should this man go to the lowlands, even though he feels well in the intellectual and physical conditions? When he becomes aware that he has CMS, it turns into a big economical and social problem. Of course, he will, from time to time, suffer from colds with headaches, lassitude, sleep disturbance and so on (as any healthy subject with a cold) that will be diagnosed by physicians as the CMS alteration, but in reality it is the triple hypoxia syndrome in CMS, that is transitory and treatable.

Since the participants are unable to go to discuss the cases in the different hospitals, clinics or laboratories, of each country, may we suggest that you ask each participant in the liberal discussion on CMS (if feasible), bring a color photograph of the patient, the clinical history, the laboratory findings, the cardio-pulmonary function tests or any additional data, to the meeting so that we can all see the differences and discuss them, in a friendly way. These results will show us more than a thousand words.

Gustavo Zubieta Sr. & Gustavo Zubieta Jr.

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To: “John Reeves” From: ZUBIETA@oxygen.bo (GUSTAVO ZUBIETA, M.D. * IPPA *) Date: 10 Apr 98 10:12:34 Subject: CMS discussion Priority: normal X-mailer: Pegasus Mail v2.3 (R5). ———————————————————– Date: 20 Apr 1998 08:47:15 -0600 From: “Lorna G. Moore” Subject: Re: Lorna’s questions on “adaptation” To: “GUSTAVO ZUBIETA, M.D. * IPPA *” Cc: john.reeves@UCHSC.edu Reply to: RE>Lorna’s questions on “adaptation” Thank you for your interesting reply. If I interpret your remarks correctly, you are asking if the effects of CMS on life expectancy (mortality) are similiar to those of COPD at sea level (or at altitude). That might be an interesting way to get at the seeming confusion over the uniqueness of CMS as a high-altitude condition. Looking forward to seeing you in Japan!

Lorna

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Date: 4/19/98 7:28 PM To: Lorna G. Moore From: GUSTAVO ZUBIETA, M.D. * IPPA *

Dear Lorna: Your fundamental points regarding the term “adaptation”, stimulated and gave an electrifying boost to everyone’s thoughts. Thank you for letting us know the interesting definition of “adaptation” by Theodosious Dobzhansky. We had not heard it previously. First of all, I (Gustavo Sr) am compelled to explain the importance of the term “adaptation”, which concerns me very strongly.

Any term in medicine implies a concept (knowledge) of the diseases which will set the rules for prevention and treatment (CMS in this case). I include in CMS many kinds of pulmonary disease in chronic hypoxia. By associating CMS with the term “loss of adaptation”, attention has been focused only in the increase of the number of red blood cells. This, mislead many studies. With such a concept, many people with pulmonary disorders have been sent to the lowlands in order to reduce their hematocrit and they die very soon. Due to the hot, humid and oxygen rich environment (an optimum medium for bacteria) there is worsening of infectious diseases (tuberculosis, for example). Some remain living their life as anyone in the lowlands in any part of the world, with unnoticed mild respiratory or ventilatory impairment.

Another form of treatment was targeted to decrease the hematocrit, by using radioactive compounds (such as phosphorous) or cytolytic drugs (such as fenilhidrazine). Nowadays, the pharmaceutical market is full of “medicines” announcing that they can “reduce” the number of red blood cells. Phlebotomy has to be revised, in lieu of the advance of knowledge in hypoxia, but we will not deal with this subject in this letter.

In relation to impaired fertility: We don’t know of any specific studies, however it is a common observation that the fastest growing city (over 600,000 inhabitants) in Bolivia happens to be El Alto “the high plateau” (4100 m). There, according to a presentation we will give in Matsumoto, about 52% of the males and 28 % of females that receive medical attention in all diseases, have a hematocrit above 58 %. The people of the city of El Alto, reproduce even in the most disadvantageous conditions of poverty, lack of adequate housing, lack of hygiene and so on.

On the other hand, I (Gustavo Sr.) have studied sick miners of high altitude mining centers in Bolivia, who had increased polycythemia with pulmonary diseases and several of them had over 8 children. Many of the children died, because of bad sanitary, nutritional and infectious conditions in the mines. They only stopped having children when the women reached menopause. Incidentally, it is well known that human fetuses live in hypoxic conditions (and that they are polycythemic! ). That is probably why they don’t die, and can tolerate very long apneas and extreme hypoxia during delivery. At high altitude, it surprises us more.

By the way, breath-holding in CMS is one of our subjects of presentation in Matsumoto. In dealing with hypoxia, environmental factors should never be overlooked. For example, impotence that has to do with fertility, is not a common complaint at high altitude, as it happens in developed countries (paradoxical?) About life expectancy: There are no great differences between disease at sea level and at high altitude, in the course of life. Again, we know of no studies on life expectancy in respiratory disease at high altitude. For example, at sea level, chronic obstructive pulmonary disease (COPD) and emphysema affect 20-30 % of the adult population, with more than 60,000 deaths/year. The predominant age is over 40 and the predominant sex is male. This is strongly similar to our clinical observations here (except the death incidence per year, that is not quantified).

If patients with CMS, have reduced life expectancies, it will probably be due to a reduced life expectancy of chronic lung disease, just as at sea level. Depending on the severity of the cases, naturally. We have followed patients with CMS, for over 14 years, into their 80’s and we have never looked after one, the moment he died. No one has reported, up to date, an autopsy of CMS. Probably, because when the pathological alterations were discovered, they were classified as cardio-pulmonary disease. By the way, malnutrition, cor-pulmonale, hypercapnia and a pulse > 100 are all poor prognostic indicators in COPD at sea level. The same happens at high altitude.

Furthermore, cor-pulmonale in patients with CMS is probably an advanced and untreated consequence of respiratory disease. Increased polycythemia can’t be absent in many cases. At sea level, supplemental oxygen, has been shown to increase survival. This is conflictive for us. It would imply that there is a shorter life expectancy for high altitude residents, but that does not seem to be so. Ever since the use of penicillin, life expectancy has expanded also at high altitude. Previously, many people died of pneumonia in their forties. With better nutrition, improved health care, and more hygiene, we are seeing people, more and more, that live well into their nineties. We are not saying that altitude is the best place to live in, but just that we live here. We are aware of how easy it is to make a mistake or fall into speculation, but what you just read comes from our on-site experience, a lot of hypoxia and its interpretation….

Gustavo Sr. & Gustavo Jr.

—————— RFC822 Header Follows —————— Received: by defiance.uchsc.edu with ADMIN;19 Apr 1998 19:27:58 -0600 Received: from unbol.bo (unbol.bo [166.114.1.32]) by essex.UCHSC.edu (8.6.12/8.6.9) with SMTP id TAA01496 for ; Sun, 19 Apr 1998 19:31:26 -0600 Received: from oxygen.UUCP by unbol.bo (8.6.12/1.35) id VAA24235; Sun, 19 Apr 1998 21:26:59 +0400 Message-Id: <199804191726.VAA24235@unbol.bo> Received: from Pmail on IPPA_0 by PegWaf v0.24 93.03.15 id 8078 ; Sun, 19 Apr 98 20:37:23 To: “Lorna G. Moore” From: ZUBIETA@oxygen.bo (GUSTAVO ZUBIETA, M.D. * IPPA *) Date: 19 Apr 98 20:37:22 Subject: Lorna’s questions on “adaptation” CC: john.reeves@UCHSC.edu Priority: normal X-mailer: Pegasus Mail v2.3 (R5).

Chronic Mountain Sickness discussion part 1

The following excerpts are from the E-mail discussion of the committee on chronic mountain sickness, prior to The 3rd World Congress on Mountain Medicine and High Altitude Physiology and The 18th Japanese Symposium on Mountain Medicine carried out in Matsumoto, Japan (May 20th – 24th, 1998). Part 1/2.

Inside the Hyperoxic/hypoxic adaptation chamber using the Bogomoletz helmet.

From: “GUSTAVO ZUBIETA M.D. * IPPA *” Date: 20 Mar 98 16:16:43 Subject: Re: CMS Symposium X-mailer: Pegasus Mail v2.3 (R5). To: “John Reeves”

Dear Jack: Thank you for your E-mail of march 15. We were out of town and just returned yesterday.

You wrote: > I have the abstract “Incidence of Disease at High Altitude in La Paz > Bolivia”. Will that be the subject of your presentation in the CMS session?

Yes, we consider this to be more adequate to our field than in the high altitude population in the world symposium. In fact we meant to deal more with CMS in this presentation.

> How long are you planning to talk? Would 20 minutes be fine? Keep in mind that we are hoping for as much  time as possible for discussion.  One of the main question that will require discussion is that  of the definition of CMS, so that we can all play from the same  sheet music. In your case, do you include or exclude persons with  chronic lung disease in the CMS group?

Following is the summary of the modest opinion of my father and myself, from many years of observations in the bowl-shaped city of La Paz to El Alto (between 3100m and 4100m), with much CMS in a population above 1.2 million:

1) In our concept, CMS or Monge’s disease are adequate denominations for a disease present only in hypoxic conditions due mainly to respiratory and ventilatory alterations of different etiopathogenesis, some complicated by other alterations such as kidney disease, arterial hypertension, and so on.

2) CMS at high altitude is expressed as cyanosis and low arterial saturation which gives rise to pulmonary hypertension and increased polycythemia, as compensatory mechanisms of adaptation to the disease under hypoxic conditions.

3) CMS is irreversible in diseases like pulmonary fibrosis, and reversible in chronic bronchitis, for example. If the arterial blood is completely saturated at 98%, as such is the case when the subject descends to sea level, there is a regression of the symptoms and signs. Giving continuous oxygen administration to a patient with COPD at sea level, will achieve similar results.

4) Respiratory diseases are the same at high altitude, in etiopathogenesis as those of sea level; but the impaired respiratory function, with low oxygen saturation, below the plateau of the saturation curve (in the steep part), shows us what we know as CMS or Monge’s disease.

5) Since CMS is a common denominator of diverse diseases of the respiratory system, each case should be diagnosed and treated according to the etiopathogenesis. It seems also evident that some subjects are more prone to suffer pulmonary diseases. Similarly, men have a greater tendency to develop pulmonary disease, than women and consequently are more susceptible to develop CMS. So, hoping to answer your question: The confusion arrives because the classical description of Monge’s disease in 1928, expressed that there is no pulmonary anatomical or functional alterations, not able to become evident at the time, due to the lack of modern technology that we have nowadays. Not all patients with respiratory disease at high altitude develop CMS. Some pulmonary diseases alter as a sequelae the pulmonary function, like impaired diffusion, uneven ventilation, increased shunt, or hypoventilation. These lead to low saturations in hypoxic conditions and to CMS. Please read our article New Concepts on Chronic Mountain Sickness.

We enjoyed preparing these comments, and if you should have any doubts, questions or comments please feel free to send us an E- mail. We were hoping to meet you in Cuzco, and inquired about you but they said you were in Russia. We were supposed to go the meeting in Ukraine invited by Beloshitsky. We ran into many problems. We couldn’t get to Ukraine from Moscow. We will tell you more when we meet in Japan.

Gustavo Sr. & Gustavo Jr. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Gustavo Zubieta, M.D. HIGH ALTITUDE PATHOLOGY INSTITUTE * IPPA * Av. Saavedra 2302 Tel: 591-2-368734 P.O. BOX 2852 Fax: 591-2-229504 La Paz, Bolivia E-mail: zubieta@oxygen.bo

New Human Physiology book on-line

New Human Physiology | Paulev-Zubieta 2nd Edition


We are proud to announce the launching of a new free on-line physiology book entitled “New Human Physiology” by Prof. Dr. Poul-Erik Paulev and Prof. Dr. Gustavo Zubieta-Calleja (Jr), where there is an important contribution of Prof. Dr. Gustavo Zubieta-Castillo (Sr.) in the chapter related to high altitude, where he gives the new concepts on high altitude physiology.


In this 2nd Edition of the Textbook in Medical Physiology And Pathophysiology Essentials and clinical problems, we decided to change the name in order to show that this new version is modified in form and becomes interactive. This digital book uses a new format in order to constantly evolve and improve. Hence the term “New” never becomes outdated, as it is permanently evolving. You are welcome to send us comments or additions in each section where the link comments are posted. Please be brief and try to fit in one sentence an essential concept in physiology. Remember this is a textbook for medical students. And due to the exponential growth of information, they are overwhelmed with data. If you agree your name and/or your affiliation can be included in the comments. This allows for a dynamic physiology book that is often updated with the new exponentially growing information. A new format for future scientific books.

As a comment is posted, we review it and proceed to include it in the book, if appropiate. We have an open mind and this has always been our standing with respect to science. It should be a common good, open to all around the globe. A true globalization of knowledge. That is why the 1st edition published by the first author in 2002 has been so popular. It was the first medical physiology book to be completely free on-line.

Please note that we are not obliged to publish the comments on-line, as we will peer review them first. But you can be sure that we are not biased or just publish your contribution if you are a member of a closed group (as some journals do). Quite the contrary, we are open for any sound, solid scientific contribution from any distinguished colleague (or student) around the world. We base our focus of science on two concepts: “The joy of seeing the light” and “Science, honor and Truth

Any suggestions as to how to improve this book are most welcome. Enjoy!

Poul-Erik Paulev & Gustavo Zubieta-Calleja

Click here to visit the NEW HUMAN PHYSIOLOGY


 

The Mountain Guru

Prof. Dr. Gustavo Zubieta-Castillo (Sr.) has received a most extraordinary distinction and honor in Bangalore, India at the St. John’s Medical College:

In response to an invitation by Prof. Thuppil Venkatesh to attend a meeting and present their recent scientific work, Prof. Dr. Gustavo Zubieta-Castillo (Sr) and Prof. Dr. Gustavo Zubieta-Calleja (Jr) travelled to Bangalore, India and on the way there stopped in Copenhagen, Denmark to visit and discuss scientific projects with Prof. Dr. Poul-Erik Paulev. Further news on this will follow soon.

Once in India, they were received by the most distinguished Shashidhara N. who became along with Prof. Thuppil Venkatesh their guides, and colleagues of profound phylosophical discussions during 10 days of a most memorable visit to incredible India.

Having arrived at the modern airport in Bangalore, they were then transported to Kochi, where the 36th National Conference of Clinical Biochemists was carried out Nov 5-8th, 2009 under the direction of Prof. D.M.Vasudevan. After their presentation both Zubietas were driven to Mysore to meet Prof. Virupasksha Hosur and visit the extraordinary Mysore Palace. Elephants, crocodiles and bird watching filled them with eco-nature and a profound understanding of the wisdom of the people from India.

Felicitation in Bangalore, IndiaUpon returning to Bangalore Prof. Zubieta-Castillo (Sr.) and Prof. Zubieta-Calleja (Jr.) were invited to give a talk at the St. John’s Medical College  (see the invitation on the left). Much to their surprise, Prof. Thuppil Venkatesh leaded in the presentation and introduced the Director of the St John’s National Academy of Health Sciences Dr. Lawrence D’Souza, along with very distinguished personalities of Bangalore.

Then upon the podium, starting with Dr. Lawrence D’Souza one by one the wicks of a large oil lamp, were lighted by each of the distinguished guests as a sign of friendship and cooperation (photo below).

DSC_3871

Shown at left: Dr. Prem Pais (Dean of St. John’s Medical College), Mr. A.S. Sadashivaiah, Chairman Karnataka State Pollution, Prof. Dr. Zubieta-Castillo (Sr.), Dr. Lawrence D’Souza, Director St. John’s National Academy of Health Sciences, Prof. Dr. Zubieta-Calleja(Jr) Padmashree Mahadevappa, Former Chancellor UAS and Prof. Thuppil Venkatesh, NRCLPI. (All photos courtesy of the distinguished colleagues from India)

Immediately afterwards, Dr. Lawrence D’Souza presented Prof. Dr. Gustavo Zubieta-Castillo (Sr) in a special ceremony a turbant, flowers and a gold plated oil lamp.

Guru1sThe special honors, the turbant, flowers, a gold plated oil lamp bestowed upon Prof. Dr. Gustavo Zubieta-Castillo at St. John’s National Academy of Health Sciences in Bangalore, India, Nov 11, 2009.

Then the honoree gave a talk on “Patho-Physiology of Adaptation to Hypoxia and Prof. Zubieta-Calleja (Jr) on ” The Current Status of Millions of Highlanders”.

The photo below shows the resemblance of Prof. Zubieta-Castillo with the late and famous legendary Indian Engineer-Statesman: Sir. Mokshagundam Visvesvarayya, as expressed by many distinguished attendees.

DSC_3942

Prof. VenkateshWith Prof. Thuppil Venkatesh, Principal Advisor Quality Council of India (QCI) &
National Referral Centre for Lead Poisoning in India (NRCLPI)
Professor- Department of Biochemistry & Biophysics
St. John’s Medical College

At a dinner in the Country Club in Bangalore, Prof. Venkatesh surrounded by very important people gave Prof. Zubieta-Castillo, the following distinction:

GuruTitle1

Furthermore, he was repeatedly mentioned as a candidate for the Nobel Price in Medicine for he has determined that Chronic Mountain Sickness is not a “Loss of Adaptation” but rather a consequence of pulmonary diseases with shunts that increase the number of red cells (polyerythrocythemia) thereby saving the life of thousands of high altitude residents that have been intoxicated with drugs like Phenylhidrazine with the wrong concept of destroying the “excessive” red blood cells. This drug damaged the liver cells producing jaundice and also the endothelium of all vessels in the system, and lesions to the kidneys. His theories of Adaptation to life at the hypoxic levels of Mt. Everest applying the high altitude adaptation  formula, following Ohm’s law, and the triple hypoxia syndrome were also mentioned.

They likewise were also honored by a visit to his excellency Governor Karnataka, H R Bhardwaj, at the Governor’s Palace in Bangalore,  below :

IMGShown here Shashidhara N, Gustavo Zubieta-Calleja (Jr), His excellency Governor of Karnataka H R Bhardwaj, Gustavo Zubieta-Castillo (Sr), Thuppil Venkatesh.

So those of different countries must be wondering but what is a Guru?

guru (Sanskritगुरु) is one who is regarded as having great knowledge, wisdom and authority in a certain area, and who uses it to guide others (teacher). As a principle for the development of consciousness it leads the creation from unreality to reality, from the darkness of ignorance to the light of knowledge.

The syllable gu means shadows
The syllable ru, he who disperses them,
Because of the power to disperse darkness
the guru is thus named.

– Advayataraka Upanishad 14—18, verse 5

from Wikipedia