Ventricular arrhythmias upon reperfusion depend on Ca2+-Calmodulin protein Kinase (CaMKII) phosphorilations at the sarcoplasmic reticulum (SR) level”

SAID M. M., BECERRA R., MUNDIÑA- WEILENMANN C., KAETZEL M., DEDMAN J.R., VITTONE L., MATTIAZZI A.

Hotel Sheraton, Bs. As., Argentina

Congreso; International Society for Heart Research, XVII Meeting Latin American Section.; 2009

International Society for Heart Research, Latin American Section

Introduction: Reperfusion after ischemia, is particularly prone to arrhythmias. The type and mechanisms of reperfusion arrhythmias are still not clear and are the aim of the present work. Methods: Langendorff perfused spontaneously beating rat/mouse hearts were submitted to global ischemia/reperfusion (15-20/30min, 37º). Epicardial monophasic action potentials and left ventricular developed pressure were either alternatively or simultaneously recorded. Results: The onset of reperfusion (first 3min) caused ectopic beats. The arrhythmic pattern observed seems to be triggered at least in part by afterdepolarizations (DADs and EADs), that in many cases culminated in ventricular tachycardia or ventricular fibrillation. Triggered ectopic beats (EB) were significantly decreased by the CaMKII-inhibitior, KN-93 (EB: 46±6 Control vs 11±3 KN-93 p<0.05) and by  the inhibitor of the release SR Ca2+ channel, Ryanodine (EB: 46±6 Control vs 25±3 Ry p<0.05). Experiments in transgenic mice with targeted inhibition of CaMKII at the level of cardiac SR-membranes (SR-AIP), prevented reperfusion arrhythmias. Conclusion: We suggest that reperfusion arrhythmias are at least in part due to CaMKII dependent phosphorylations  at the SR levels.