Potassium as an electro-metabolic signal for local coronary vasodilation

Abstract

This study tested the hypothesis that K⁺ serves as an in vivo signal coupling coronary blood flow with the oxidative requirements of the myocardium. Experiments were performed in swine in which coronary parameters and arterial and coronary venous [K⁺] were measured under baseline conditions, during exogenous administration of K⁺ (1-5 mM; n = 4), during increases in myocardial oxygen consumption (MVO₂) to dobutamine (n = 7) and exercise (n = 6), alterations in coronary perfusion pressure (CPP; n = 8), and systemic hypoxemia (PaO₂ to ~ 30 mmHg; n = 7). Exogenous intracoronary K⁺ increased blood flow (~ 20%) in direct proportion to the coronary venous [K⁺] up to the lethal limit of ~ 10 mM. Dobutamine increased coronary flow and MVO₂ ~ threefold but the coronary venous-arterial [K⁺] gradient (i.e., a surrogate index of myocardial release of K⁺ into the coronary circulation) did not change. Similarly, exercise increased coronary flow and MVO₂ ~ 2.5-fold without a change in the coronary venous-arterial [K⁺] gradient. The coronary venous-arterial [K⁺] gradient did not change over the CPP range of 140-40 mmHg. Hypoxemia increased coronary blood flow ~ twofold and coronary vascular resistance was weakly associated with < 0.5 mM change in the coronary venous-arterial [K⁺] gradient. Intracoronary glibenclamide dose-dependently (1-3 mg/min; n = 4) increased coronary resistance but did not affect the coronary venous-arterial [K⁺] gradient. Intracoronary pinacidil dose-dependently (0.3-3.0 µg/kg/min; n = 3) increased coronary blood flow but did not affect the coronary venous-arterial [K⁺] gradient. Similarly, intravenous glibenclamide (3 mg/kg; n = 6) increased coronary resistance but did not affect the coronary venous-arterial [K⁺] gradient in exercising swine. These findings fail to support the concept that myocardial interstitial [K⁺] couples coronary blood flow to MVO₂ during physiologic increases in cardiac work or when oxygen delivery is constrained.

Keywords: ATP-sensitive potassium channel; Conducted responses; Coronary blood flow; Local metabolic control.