PART XI — HUMAN ADAPTATION TO ENVIRONMENTAL STRESS 



oxygen (Oj) and carbon dioxide 

 (COj) in the air he breathes. The 

 native highlander is relatively less 

 sensitive to low levels of O- in alveo- 

 lar air than is the lowlander; it is not 

 clear whether this decrease in sensi- 

 tivity is an advantage or a disadvan- 

 tage at altitude. 



Analysis of the important adaptive 

 respiratory process should include 

 study of: age and sex differences, 

 neurological factors, acid-base fac- 

 tors, chemoreceptor sensitivity and 

 thresholds, as well as tissue responses 

 to hypoxia. In addition, it would be 

 of importance f o study regulation of 

 ventilation during the performance 

 of physical work at altitude and dur- 

 ing sleep. Sleep and associated peri- 

 odic hypoventilization, as well as 

 performance of hard exercise, in- 

 crease hypoxic exposure. 



Circulatory Mechanisms of Alti- 

 tude Acclimatization — Although cir- 

 culatory responses in man at altitude 

 have received more study than other 

 physiological responses, we do not 

 know the criteria upon which we 

 could advise healthy people whether 

 they should or should not live at high 

 altitude, or at what stage of mor- 

 phological or functional alterations 

 they should move to low altitude. 

 The following areas of investigation 

 are of importance in answering this 

 problem: 



1. Epidemiology: Much needs to 

 be known about the prevalence 

 and incidence of cardiovascular 

 disease at altitude. Ecological 

 factors other than altitude 

 should be identified which af- 

 fect normal cardiac function in 

 highlanders. In addition, we 

 do not know the circulatory 

 response to physical work at 

 different ages. 



2. Cardiac Muscle Metabolism: 

 The basic inability of cardiac 

 muscle to work under anaerobic 

 conditions makes it vulnerable 

 to hypoxia induced by high 

 work loads at altitude. Before 



optimal and maximal levels for 

 work at altitude could be rec- 

 ommended, further studies are 

 necessary on coronary blood 

 flow and cardiac muscle metab- 

 olism during work and rest at 

 altitude. 



3. Microcirculation: Whether in- 

 creased capillarity and anasto- 

 motic vascularity in cardiac or 

 skeletal muscle is an anatomical 

 feature of the acclimatization 

 process needs further study. 

 The possible role of changes 

 in the microcirculation in the 

 development of chronic moun- 

 tain sickness has not been de- 

 termined. 



4. Pulmonary Hypertension: Lon- 

 gitudinal observations are 

 needed in highlanders who de- 

 velop pulmonary hypertension 

 and right heart hypertrophy. 

 Control measurements are 

 needed that cover both sexes 

 and a wide age range. Special 

 study is needed of the factors 

 that lead to high-altitude pul- 

 monary edema. 



5. Circulation Dynamics: More 

 information is needed on the 

 expected changes in cardiac dy- 

 namics at altitude. Included 

 under this heading are observa- 

 tions on cardiac output, car- 

 diac work, peripheral resistance, 

 heart rate, stroke volume, blood 

 pressure as well as the role 

 of changes in blood volume, 

 hematocrit levels, and pulmo- 

 nary circulation. Partitioning 

 of blood flow through vital 

 organs under various condi- 

 tions at altitude is also an im- 

 portant area to be studied. 



Cellular and Tissue Mechanism of 

 Altitude Acclimatization — The bi- 

 ochemical mechanisms underlying 

 high-altitude acclimatization are in- 

 adequately understood. Respiratory 

 and vascular adaptations to altitude 

 that permit an adequate delivery of 

 O- and removal of metabolites at the 



cellular level during rest may not be 

 adequate for sustained hard work 

 by healthy men or, for that matter, 

 sedentary life in the elderly and 

 infirm. There is a need to determine 

 the adaptive processes at the cellular 

 level in the highlander as well as in 

 newcomers to altitude. 



We need to know what role is 

 played in these cellular responses by 

 changes in the amount of myoglobin, 

 the number of mitochondria, and the 

 capacity of the cytochrome and elec- 

 tron transporting system. More in- 

 formation is needed on possible adap- 

 tive increases in enzymes favoring 

 both aerobic and anaerobic metabo- 

 lism. We need to know the degree 

 to which rate-limiting neurohumoral- 

 endocrine mediators affect these cel- 

 lular functions. And finally, we need 

 to know whether genetic factors are 

 operative in the adaptation at the 

 cellular and subcellular level. 



Other Areas of Altitude Physiology 

 Requiring Further Study — Available 

 knowledge is inadequate concerning 

 nutritional requirements of those 

 with natural or acquired acclimatiza- 

 tion or in those acutely exposed to 

 altitude. Further nutritional and 

 metabolic studies are necessary to 

 establish optimal nutritional allow- 

 ance for high-altitude residents and 

 for those who wish to reside at al- 

 titude. 



The factors regulating redistribu- 

 tion of fluid and electrolytes among 

 the various fluid compartments need 

 further elaboration. 



In the long-time resident at altitude 

 we need to know more about the 

 possible role of adaptive tissue and 

 vascular responses in the aging proc- 

 ess. It is also possible that high- 

 altitude residence has an effect on 

 man's immunological responses and 

 on the types and frequency of in- 

 fections that he harbors. 



The sequential changes that occur 

 during the period of adaptation of 

 the newcomer to high altitude are 



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