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

Tyler D. Vermeulen, Lindsey M. Boulet, Mike Stembridge, Alexandra M. Williams, James D. Anholm, Prajan Subedi, Chris Gasho, Philip N. Ainslie, Eric O. Feig, Glen E. Foster*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review


    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 (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of MVO2. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV 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 LADV 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.

    Original languageEnglish
    Pages (from-to)H132-H140
    JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
    Issue number1
    Publication statusPublished - 1 Jul 2018


    • Coronary blood flow
    • Hypercapnia
    • Hypoxia
    • Myocardial oxygen demand
    • β-adrenergic blockade


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