'74^ 



11 WDHDllK Hi- 1'HYSIOLOGY 



NKl ROPHYSIOLOGY III 



arc protected against the lull impact ol these blood- 

 borne changes to an extent indicated by a decrease in 

 the corresponding; cerebral arteriovenous differences, 

 Opposite changes in the arterial blood produce 

 increases in cerebral vascular tonus, widening of the 

 cerebral arteriovenous differences and attenuation of 

 the concomitant changes within the brain cells. 



The extent to which these automatic adjustments 

 of the resistance of the human cerebral vessels to 

 induced alterations in arterial p('Oo and pO> can 

 compensate is greater than was expected from the 

 animal studies. As noted elsewhere (39), the changes 

 in cerebral venous pCO-> of man during inhalation of 

 carbon dioxide or hyperventilation are about half 

 those observed in the arterial blood. These were only 

 moderate shifts (inhalation of 5 to 7 per cent carbon 

 dioxide and hyperventilation short of overt tetany). 

 Studies of the effects of more marked changes in 

 arterial pC0 2 are complicated by the occurrence of 

 unconsciousness and convulsions which will have to 

 be obviated before definitive results can be obtained. 

 There is at present no means of knowing whether the 

 cerebral vascular readjustments to changes in arterial 

 pC() 2 progress steadily with the intensity of the stimu- 

 lus or are limited to a definite (presumably physio- 

 logical) range. The answer to this question might 

 have interesting implications. 



The corresponding observations with decreases and 

 increases of arterial pC) 2 in man have confirmed the 

 general concept outlined above, but they have also 

 yielded some unexpected food for thought. Mild 

 anoxemia (from inhalation of to per cenl oxygen in 

 nitrogen) in 111.111 decreased cerebral vascular resist- 

 ance about as much .is did inhalation of 5 or 7 per 

 cent carbon dioxide, although its effeel on total 

 cerebral blood flow was less because ofa simultaneous 



fall in arterial pressure instead of the rise produced bv 

 carbon dioxide (25). Since the arterial and cerebral 

 venous pCOj both fell because of concomitant hyper- 

 ventilation, it is clear that the vasodilator influence 

 of anoxia u.is preponderant over the opposing tend- 

 ency 11I hypocapnia. This conclusion is a little sur- 

 prising because the latter, when induced by amino- 

 phylline, apparently overshadows in man (42, 471 

 the distinct cerebral vasodilator effeel which this 

 drug exerts in animals (11). Furthermore, the cerebral 

 vasoconstrictor influence <>l hypocapnia overcame 

 the vasodilator trend of acid in postconvulsive states 

 in in. in < hi. z6) in experimental acidosis (36) and in 

 patients in diabetic acidosis short of coma (24, 31). 

 In comatose diabetics, however, there was cerebral 



v . isi.dil.il. 1 1 ion in spite of even 11 101c severe liv pocapnia 



1 j \, 31 I. The best explanation at present is that the 

 dilatation in diabetic coma represents a transition 

 from the physiological to the pathological range, in 

 which the normal mechanisms are overcome by the 

 beginning of irreversible changes. If this reasoning is 

 applied to the above-mentioned effects of anoxia, 

 these appear as a manifestation of the general prin- 

 ciple that "anoxia not only stops the machine, it 

 wrecks the machinery" (5), and the cerebral vaso- 

 dilator influence of anoxia becomes pathological 

 rather than physiological. Another observation point- 

 ing in this direction is the decreased effectiveness of 

 epinephrine as a circulatory stimulant in the presence 

 of anoxemia (45). 



IK pocapnia and norepinephrine are the only 

 agencies that have been shown to be capable of causing 

 distinct cerebral vasoconstriction in man, and, of 

 these, hypocapnia is by far the stronger. This also 

 fits into the simple concept of carbon dioxide as the 

 chief regulator of cerebral vascular tonus. The cere- 

 bral vasoconstrictor effect associated with oxygen 

 inhalation in animals (11, 37) also was confirmed in 

 man (25, 30), and during oxygen inhalation under 

 3.5 atm. pressure it became almost as marked as that 

 elicited by hyperventilation with air (30). This, 

 however, now appears not to be due to the oxygen, 

 but to the concomitant hyperpnea and hypocapnia; 

 when the latter is obviated by addition of carbon 

 dioxide to the inhaled oxygen in amounts appropriate 

 for the maintenance of a constant arterial pCO», 

 inhalation of oxygen produces no cerebral vaso- 

 constriction in man (4b). At the same time the cerebral 

 venous (and presumably tissue) pO_> rises markedly 

 and the convulsant effects of hvperoxia come on much 

 more rapidly than before (29). Thus the hyperventila- 

 tion induced bv oxygen inhalation, particularly under 

 pressures greater ill. in 1 atm., appears .is a potent 

 means lor protecting the brain cells against the lox- 

 icilv of exci'ssiv e o\v gen pressures 1 28) another man- 

 ifestation of the homeostatic role of intrinsic ad- 

 justments of cerebral vascular tonus in relation to 

 blood-borne changes in the respirator) gases 



CEREBRAL VASCl I VK ADJUSTMENTS In METABOLIC 



REQUIR] VII MS OF BRAIN GELLS 



Here the simple concept derived from experiments 

 on animal- ha- inn been substantiated hv studies on 

 man. Animal experiments indicated that an increase 

 in the functional activity of the entire brain (such as 

 that produced bv pentylenetetrazol or picrotoxin in 



