Coronary Blood Flow Velocity Responses to Oxygen and Carbon Dioxide in Humans
Authors: Boulet Lindsey M , Stembridge Mike , Tymko Michael M , Tremblay Josh C , Foster Glen E 
Published: November 2023

In humans, coronary blood flow (CBF) is tightly regulated by microvessels within the myocardium. While there is clear evidence that CBF rises to match myocardial workload, there is conflicting evidence regarding the inherent sensitivity of the coronary vasculature to changes in the partial pressure of arterial carbon dioxide (PaCO2) and oxygen (PaO2) within the physiological range. The purpose of this study was to investigate the changes in CBF associated with isooxic hypo‐ and hyper‐capnia and isocapnic hypoxia. We hypothesized that a modest systemic increase in end‐tidal partial pressure of CO2 (PetCO2) or decrease in end‐tidal partial pressure of O2 (PetO2) would result in a significant increase in coronary blood flow velocity (CBFV) due to downstream vessel dilatation. Likewise, we hypothesized that hypocapnia would cause a reduction in CBFV. Finally, we hypothesized that normalizing for cardiac workload (WC) or mechanical energy (EM) would diminish the observed reactivity. Young men free of cardiovascular disease (age = 23.4 ± 1.3 years, n=14) were exposed to two ventilatory challenges: (1) an isooxic CO2 test that consisted of six, 8‐min steps of PetCO2 (−8, −4, 0, +4, and +8 mmHg from baseline values) and (2) an isocapnic hypoxic test that involved three, 8‐min steps of hypoxia (PetO2 = 64, 52 and 45 mmHg). CBFV was measured using Doppler echocardiography in the mid segment of the left anterior descending coronary artery (LAD). WC and EM were estimated using the rate pressure product (RPP; systolic blood pressure × heart rate) and the area of a derived pressure‐volume loop (PVA) respectively. The PVA was calculated using volumes derived from echocardiographic measurements, a validated estimation of left ventricular end‐systolic elastance and beat‐by‐beat blood pressure from photoplethsmography. A PetCO2 of +8 mmHg evoked a 34.6 ± 8.5% increase in mean peak diastolic CBFV (P<0.01). CBFV increased by 38.3 ± 12.6% and 51.4 ± 8.8% in response to a PetO2 of 52 and 45 mmHg, respectively (P<0.05). RPP and PVA were significantly elevated during hypercapnia (+4, +8 mmHg PetCO2; P<0.05), hypoxia (52 and 45 mmHg PetO2; P<0.01) and were not different during hypocapnia (P>0.05). When CBFV was indexed against either measure of RPP and PVA, the CBFV responses to hypercapnia and hypoxia were abolished. Estimated coronary vascular resistance (CBFV/mean arterial pressure) did not change significantly across any protocols (P>0.05). With respect to absolute changes in CBFV, hypercapnia and hypoxia elicit increases in peak diastolic velocity; though when corrected for changes in RPP and PVA associated with each condition the changes in CBFV were absent (P>0.05). In summary, the lack of sensitivity of the coronary vasculature supplied by the LAD is underscored by the lack of both a CBFV and cardiac workload response in hypocapnia. It can be surmised that the regulation of coronary vessels is mediated primarily through metabolic changes within the heart rather than an inherent sensitivity to changes in arterial blood gases within a physiological range.

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Funding: NSERC, CFI