PART \I — HUMAN ADAPTATION TO ENVIRONMENTAL STRESS 



are long term and at concentrations 

 as low as from 0.8 to 4 parts per 

 million. The work has been reported 

 by Freeman and his colleagues and 

 has been demonstrated in rabbits, 

 rats, mice, and monkeys. 



Closely related is the finding of 

 Mueller, Buell, and Thomas, at the 

 California State Department of Public 

 Health, that structural changes in 

 proteins can be produced by ex- 

 posures to low levels (0.25 to 5 ppm) 

 of either nitrogen dioxide or ozone 

 for a short period of time, and that 

 these changes revert slowly. The 

 mast cells reversibly disappear from 

 the respiratory airways on exposure 

 to nitrogen dioxide; nitrogen dioxide 

 and ozone inhalation can lead to 

 lipid peroxidation in the pulmonary 

 parenchyma. These changes are all 

 presumably adaptive in nature, but 

 their consequences for long-term ef- 

 fects are certainly suggestive, since 

 lipid peroxidation has also been as- 

 sociated with the aging processes. 



Balchum, Armstrong, and Ury have 

 reported the impairment of respira- 

 tory function in persons already hav- 

 ing chronic respiratory diseases who 

 were exposed to elevated levels of 

 photochemical smog occurring in Los 

 Angeles. The lung-function test most 

 consistently responding was that of 

 airway resistance, and its increase 

 reflects the likelihood that persons 

 with chronic respiratory diseases 

 would have to expend more energy 

 to ventilate their lungs during smoggy 

 periods than during normal ones. 



Toyama in Japan and Holland, 

 Douglas, Waller, and Lunn in Eng- 

 land have shown that schoolchildren 

 exposed to pollution, mostly in the 

 forms of sulfur oxide and particu- 

 lates, have impaired respiratory func- 

 tion during periods in which the pol- 

 lution is elevated and have a greater 

 frequency of respiratory conditions. 

 The finding, which has been con- 

 firmed in Italy, should also be studied 

 in other countries. It seems quite 

 reasonable to assume that these 



changes in schoolchildren represent 

 adaptation, and with it the risk of 

 developing chronic respiratory dis- 

 ease. At a meeting in Geneva in 

 1969 of the Directors of Cooperating 

 Laboratories of the World Health 

 Organization's International Refer- 

 ence Center on Air Pollution, the 

 recommendation was adopted that 

 first priority for additional compara- 

 tive epidemiologic studies in air pol- 

 lution should be given to studies of 

 the effects of air pollution on school- 

 children. 



Impairment of Circulatory Func- 

 tion — Astrup has shown that the ex- 

 posure of rabbits on a high-choles- 

 terol diet to increasing amounts of 

 carbon monoxide will increase the 

 atherosclerotic changes in the large 

 blood vessels. Similar changes can 

 be produced by placing the animals 

 in a chamber with low oxygen ten- 

 sion. The findings that smokers with 

 atherosclerosis have higher levels of 

 carboxyhemoglobin, implying higher 

 or more intense exposures to carbon 

 monoxide or greater retention from 

 smoking, than do individuals with 

 similar smoking histories but without 

 atherosclerosis, is strongly suggestive 

 of the role of carbon monoxide in this 

 process. Yet human populations at 

 high altitude, where the oxygen ten- 

 sion is low, have a lower frequency of 

 atherosclerosis, lower blood pressure, 

 and lower cholesterol. Accordingly, 

 it has been most valuable to have an 

 experimental comparison of the ef- 

 fects of high altitude and of repeated 

 carbon monoxide exposures in healthy 

 experimental subjects reported by 

 Astrup and Pauli. 



They studied eight subjects divided 

 into two groups of four; each group 

 was exposed both to sufficient carbon 

 monoxide to produce 15 percent car- 

 boxyhemoglobin and to altitude at 

 11,225 feet (roughly equivalent in 

 terms of oxygen saturation). The 

 major findings were that with car- 

 to.ryhemoglobin exposure, the oxy- 

 hemoglobin saturation curve shifted 

 to the left (i.e., the available oxygen 

 would be given off less readily at the 



tissue level under these circum- 

 stances), whereas with altitude the 

 curve shifted to the right (i.e., the 

 hemoglobin would more readily give 

 up its oxygen at the tissue level). 

 Carboxyhemoglobin exposures did 

 not increase the respiratory rate, but 

 altitude did. Both types of exposure 

 increased the rapidity with which 

 new red blood cells were produced. 

 Both types of exposure, if sufficiently 

 intense and prolonged, are capable 

 of leading to an increase in the 

 hematocrit. Thus, the major differ- 

 ence in adaptation to altitude and 

 roughly equivalent carboxyhemoglo- 

 bin levels produced by exposure to 

 this agent is that men adapt to 

 changes in oxygen delivery in the 

 case of altitude; in the case of carbon 

 monoxide exposures, the changes 

 that occur in oxygen delivery appear 

 to be maladaptive. There is a res- 

 piratory volume compensation for 

 decreased oxygen-carrying capacity 

 in the case of altitude, but there is 

 none for carbon monoxide. 



Ayres, among others, has shown 

 that different portions of the circula- 

 tory system have different ways of 

 adapting to the impairment of oxygen 

 transport produced by carbon mon- 

 oxide exposures. (See Figure XI-9) 

 In particular, the myocardin adapts 

 to increased demand of the heart 

 by increasing the blood flow, since 

 its oxygen-extraction ratio is usually 

 much higher than other tissues. That 

 is to say, the heart normally takes 

 out of the blood that circulates 

 through it a high fraction of the 

 available oxygen in relation to the 

 pattern for other organs. Hence, im- 

 pairment in oxygen delivery by car- 

 bon monoxide requires an increase in 

 the blood flow through the heart 

 muscle. In the case of people with 

 coronary heart disease, however, 

 there is no way in which the heart 

 can increase its blood flow. Thus, 

 according to Ayres' data, it is demon- 

 strable that in persons with coronary 

 heart disease, carbon monoxide dras- 

 tically interferes with the metabolism 

 of the heart muscle, shifting it from 

 an oxidative to a less efficient form 



388 



