Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po 2 and Pco 2 or if coronary vascular responses are the result of concomitant increases in myocardial O 2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po 2 and Pco 2 would be attenuated in healthy men when [Formula: see text] was attenuated with β 1 -adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β 1 -adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LAD V ; Doppler echocardiography), heart rate, and arterial blood pressure. LAD V values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (ME LV ) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, ME LV , and LAD V , but only RPP and ME LV were attenuated (4–18%) after β 1 -adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and ME LV responses, β 1 -adrenergic receptor blockade did not attenuate the mean LAD V vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β 1 -adrenergic receptor blockade. These results indicate a direct influence of arterial Po 2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β 1 -Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O 2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O 2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β 1 -adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po 2 and Pco 2 during hypercapnic hypoxia.