Abstract 16378: Increased Extracellular Sodium and Calcium Modify the Extracellular Potassium and Cardiac Conduction Velocity Relationship in a Langendorff-perfused Guinea Pig Heart

Abstract

Background: Previous studies have demonstrated a biphasic relationship between extracellular potassium (K o ) and cardiac conduction velocity (CV). With moderate hyperkalemia, CV increases in what is referred to as supernormal conduction, but further increases in K o lead to severe conduction slowing and asystole. We recently demonstrated that altering extracellular sodium (Na o ) and extracellular calcium (Ca o ) modulates CV dependence on gap junctions (GJs). We have also shown that increasing Na o and Ca o can attenuate conduction loss caused by global ischemia ischemia. The purpose of this study was to determine if increasing Na o and Ca o would alter the K o -CV relationship and preserve CV at high K o . Hypothesis: Increasing Na o and Ca o will mitigate conduction slowing and the incidence of asystole associated with severe hyperkalemia in conditions of both normal and uncoupled GJs. Methods: Langendorff-perfused guinea pig hearts were optically mapped to measure CV. Na o was set to 145 or155mM and Ca o to 1.25 or 2.0mM. K o was varied from 4.6, 6.4, 8, to 10 mM in each experiment. Perfusion order was blinded and randomized. GJs were inhibited using carbenoxolone. Results: A biphasic K o -CV relationship was observed under all conditions. Maximum CV was achieved at either 6.4 or 8.0mM K o followed by a decrease in CV with increased K o . Importantly, the degree of CV slowing in the presence of 10mM K o was significantly reduced with the 155mM Na o / 2.0mM Ca o perfusate compared to all other Na o /Ca o combinations. Carbenoxolone reduced CV across all K o , but did not alter the K o -CV relationship. With 145mM Na o / 1.25mM Ca o , all hearts became asystolic at K o =10.0mM. Increasing Na o and Ca o significantly reduced the incidence of asystole at K o =10.0mM. Conclusions: Elevating Na o and Ca o preserves CV during severe hyperkalemia with or without strong GJ coupling. Increasing Na o and Ca o significantly reduces the incidence of asystole during severe hyperkalemia. These data suggest that non-linear and combinatorial effects of sodium, calcium, and GJ uncoupling can differentially modulate cardiac conduction during hyperkalemic perfusion. These results have important implications for cardioplegic arrest and ischemic heart disease when potassium and calcium homeostasis are disrupted.