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 PO2 and P CO₂ or if coronary vascular responses are the result of concomitant increases in myocardial O₂ consumption/demand (MVO₂). We hypothesized that the coronary vascular response to PO₂ and P CO₂ would be attenuated in healthy men when MVO₂ was attenuated with β₁-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β₁-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 MVO₂. All gas manipulations augmented RPP, MELV, and LAD_V, but only RPP and ME_LV were attenuated (4–18%) after β₁-adrenergic receptor blockade (P ± 0.05). Despite attenuated RPP and MELV responses, β₁-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 β₁-adrenergic receptor blockade. These results indicate a direct influence of arterial PO₂ on coronary vascular regulation that is independent of MVO₂. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β₁-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O₂ demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O₂ consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β₁-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of PO₂ and P CO₂ during hypercapnic hypoxia.