Hypoxemia Augments the Local Metabolic Error Signal and Improves Coronary Pressure-Flow Autoregulation

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2022

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Warne, Cooper M.
Essajee, Sal
Dick, Gregory
Tune, Johnathan

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Abstract

The local metabolic hypothesis proposes that myocardial oxygen tension, indexed by coronary venous PO2 (CvPO2), determines the degree of coronary pressure-flow autoregulation by increasing the production of vasodilator metabolites as coronary perfusion pressure (CPP) is reduced. We tested this hypothesis by examining the extent to which exaggeration of the metabolic error signal influences coronary autoregulatory capability. Experiments were performed in anesthetized, open chest swine (n = 8) in which the left anterior descending coronary artery was cannulated and connected to a servo-controlled roller pump system. This allowed CPP to be reduced from 140 to 40 mmHg in increments of 10 mmHg before and during hypoxemia (PaO2 from 138 ± 5 to 34 ± 1 mmHg). Under control-normoxic conditions, CvPO2 decreased from 33 ± 1 to 20 ± 1 mmHg and coronary blood flow fell from 0.81 ± 0.09 to 0.35 ± 0.04 ml/min/g as CPP was reduced from 140 to 40 mmHg. Hypoxemia augmented myocardial oxygen consumption (P < 0.01), increased coronary blood flow (P < 0.0001), and reduced CvPO2 (22 ± 1 to 14 ± 1 mmHg; P < 0.0001) over the same range of CPPs. Increases in coronary blood flow during hypoxemia were sufficient to maintain myocardial oxygen delivery at values equivalent to normoxic conditions (P = 0.20). Calculation of closed-loop autoregulatory gain (Gc) over a CPP range of 120 to 60 mmHg (value of 1 represents perfect autoregulation) demonstrated that Gc was improved from 0.18 ± 0.05 to 0.45 ± 0.14 under normoxic vs. hypoxemic conditions respectively (P = 0.02). Gc was also inversely related to CvPO2 and the slope increased ~4-fold by hypoxemia. These findings support that coronary pressure-flow autoregulatory capability is augmented by hypoxemia-induced increases in the local metabolic error signal.

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