THE INFLUENCE OF CEREBRAL BLOOD-FLOW ON RESPIRATION

Abstract

I. A study of the means employed in measuring cerebral blood-flow, of the ways in which it can be altered, and of the respiratory responses to such alteration. No evidence of vasomotor nerves to cerebral vessels could be obtained by the methods used, but an intrinsic control by chemical influences was found: dilatation by increased CO2 or acid, decreased O, increased temp. of the blood, or by cerebral anemia; constriction by increased alkalinity, O, or cooling of the blood. Otherwise cerebral blood-flow followed passively a change in aortic pressure. Respiration was depressed by an increase in cerebral flow, stimulated by a decrease (within certain limits) no matter how produced, and no matter what the gas content of the blood or the aortic blood pressure; the respiratory responses are attributed to changes in content of stimulant material within the center. When cerebral flow was reduced too far, respiration was depressed, and now an increase in flow stimulated breathing; to this condition the term Reversal is applied. It appeared to be due to accumulation within the center of products of incomplete oxidation. II. A study of the gaseous metabolism of the brain of the anesthetized dog, cerebral blood-flow being maintained constant by auto-perfusion while respiration was altered by various measures. Apparent gaseous metabolism of the brain varied directly with respiratory activity as influenced by electrical stimulation or puncture of the medulla, central vagus stimulation, and drugs (morphine, atropine, caffeine, ether, ephedrine, cyanide); it was not increased during CO2 inhalation in 3 of 4 attempts. These results are regarded as evidence that the central respiratory mechanism has an active metabolism. The discrepancy in the case of CO2 may be due to dilatation of cerebral vessels. III. An attempt to evaluate the interplay of changes in blood reaction or acidity, changes in metabolism of the center, and changes in blood-flow through it, in the determination of respiratory responses. The response to change in cerebral flow is transitory, probably because intrinsic changes in cerebral vessels oppose the change in total flow, in either direction. Likewise change in blood reaction or gas-tension is opposed, in either direction, by cerebral vascular adjustments, so that O or bicarbonate may stimulate breathing, and blood of normal or increased CO2 content may depress breathing if the vessels are dilated by acute anemia; a similar antagonism probably is exerted upon increased acid or CO2 content of the blood under all conditions, so that the respiratory response is minimized. Vasomotor responses also dampen respiratory responses and tend to stabilize them. Metabolic activity of the center may be altered by afferent nervous influences and by drugs. Periodic breathing of 3 distinct types can be elicited by primary changes in blood-supply of the center. The general conclusion of all 3 papers is that the chief purpose of the respiratory mechanism is the maintenance within the center of a constant concentration of stimulant material. Factors concerned are: chemical changes in arterial blood; changes in cerebral vessels and in total cerebral flow; changes in metabolic rate of the center itself. Alteration of any of these factors causes a respiratory reaction. These results confirm those recently published by Gesell, and are a reversion to the theory of respiratory regulation developed many years ago by Rosenthal.