Ca 2 /calmodulin-dependent protein kinase inhibition suppresses post-ischemic arrhythmogenesis and mediates sinus bradycardic recovery in reperfusion

Abstract

Background: Ca 2+/calmodulin-dependent protein kinase (CaMKII) activation is known to be associated with conditions where the incidence of arrhythmias is increased, and where cardiomyocyte Ca 2+-overload occurs. The goal of this study was to determine whether CaMKII inhibition in the intact heart may be linked to the suppression of ventricular arrhythmias occurring during reperfusion after an ischemic insult. Methods: Non-paced male rat hearts (n = 8-11) were treated with a CaMKII inhibitor (KN93, 2.5 μmol/L) 10 min prior to global ischemia (20 min) and for the initial 10 min of reperfusion. Cardiac mechanical and arrhythmic responses were evaluated under constant pressure perfusion conditio..