Depolarizing cardiac arrest and endothelium-derived hyperpolarizing factor-mediated hyperpolarization and relaxation in coronary arteries: the effect and mechanism.

Abstract

Depolarizing (hyperkalemic) solutions are widely used to preserve organs for transplantation and for cardiac operations. We previously observed that exposure to hyperkalemia reduced endothelium-dependent, noncyclooxygenase- and non-nitric oxide-mediated relaxation. This study was designed to examine the mechanism of this effect with regard to K channels and the associated membrane potential changes. Porcine coronary artery rings were studied in organ chambers. After incubation of the tissue with 20 or 50 mmol/L doses of potassium for 1 hour, the endothelium-derived hyperpolarizing factor-mediated relaxation in the artery and the membrane hyperpolarization in a single coronary smooth muscle cell were studied. The endothelium-derived hyperpolarizing factor-mediated relaxation induced by substance P, which could be significantly inhibited by the Ca(2+)-activated K channel blocker tetraethylammonium but only to a lesser extent by the adenosine triphosphate-sensitive K channel blocker glibenclamide, was significantly reduced. Substance P-induced hyperpolarization of the membrane potential was also significantly reduced by the hyperkalemic incubation with a significantly elevated resting membrane potential. Depolarizing arrest reduces endothelium-derived hyperpolarizing factor-mediated membrane hyperpolarization and relaxation by affecting mainly the Ca(2+)-activated K channels and by depolarizing the membrane for a prolonged period. We suggest that this is one of the mechanisms for coronary dysfunction after exposure to depolarizing (hyperkalemic) cardioplegic and organ-preservation solutions and that, therefore, "perfect" protection of the heart or other organs should restore the endothelium-derived hyperpolarizing factor-related endothelial function.