Although acidosis has long been known to cause vasodilation in certain systemic vascular beds (1-3), its effect on the pulmonary vessels remains unsettled. This uncertainty stems from the inconsistent effects of an acute change in blood pH on the pulmonary circulation of the isolated lung (4-8) and of the lung perfused in situ (9), and the lack of observations on intact animals and man.Liljestrand, on the basis of experiments involving the exposure of the isolated lung to severe hypoxia, recently proposed that the release of lactic acid from the cells of the lung is responsible for the increase in pulmonary arterial pressure during acute hypoxia (10). However, it is not clear to what extent this hypothesis, based on the behavior of an artificial preparation during drastic experimental conditions, applies to the behavior of the normal pulmonary circulation of either the intact animal or man during less severe hypoxia.The present study was designed to assess the role of acidosis in the regulation of the pulmonary circulation of intact animals and man. We found that acidosis can increase pulmonary vascular resistance. Experiments were then undertaken: 1) to distinguish between the effects of the hydrogen ion and the effects of the associated anions on the pulmonary circulation, and 2) to determine the role of acidosis in the pulmonary arterial pressor responses to acute hypoxia and to acute hypercapnia.
SUBJECTS AND METHODSAcute acidosis. In order to avoid the increase in minute ventilation which acidosis evokes in unanesthetized * Supported in part by Grant H-2299 (C3) from the National Heart Institute, with additional support from the American Heart Association and the New York Heart Association. Presented in part at the Conference on In-Vitro and In-Vivo Effects of Amine Buffers, The New York Academy of Sciences, December 12, 1960. t Senior Fellow of the New York Heart Association. Each type of experiment consisted of four periods; each period lasted for 15 to 20 minutes. The first type of experiment, involving the comparison of the effects of lactic with hydrochloric acid, consisted of the following periods: 1) control, i.e., ambient air breathing during the intravenous infusion of normal saline at a rate of 4 ml per minute; 2) the infusion of 0.3 M lactic acid at the same rate; 3) repeat control, 30 minutes after the second period, when the arterial blood pH had returned toward normal; and 4) the infusion of 0.3 M hydrochloric acid at the same rate. The second type of experiment, which compared the effects of lactic acid and acute hypercapnia, was the same as the first, except for the fourth period, when an inspired mixture containing 5 per cent CO. in air was substituted for ambient air, and normal saline was infused at the standard rate of 4 ml per minute. For the third type of experiment, which tested the effects of acute acidosis during acute hypoxia, the first two periods were the same as the first two periods of the previous experiments; during the third period, an inspired mixture of 12 per cent 0, in...