CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Ventricular arrhythmias upon reperfusion depend on Ca2+-calmodulin protein kinase (CaMKII) phosphorylations at the sarcoplasmic reticulum (SR) level.
SAID M; BECERRA R; MUNDIÑA-WEILENMANN C; KAETZEL M; DEDMAN JR; VITTONE L; MATTIAZZI A
Ciudad Autónoma de Buenos Aires - Buenos Aires - Argentina
Congreso; XVII Meeting of ISHR Latin American Section; 2009
ISHR sección Latinoamericana
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 (1520/30 min, 37 °C). Epicardial monophasic action potentials and left ventricular developed pressure were either alternatively or simultaneously recorded. Results: The onset of reperfusion (first 3 min) 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-inhibitor, KN-93 (EB: 46±6 control vs. 11±3 KN-93; pb0.05) and by the inhibitor of the release SR Ca2+ channel, ryanodine (EB: 46±6 control vs. 25±3 Ry; pb0.05). Experiments in transgenic mice with targeted inhibition of CaMKII at the level of cardiac SR-membranes (SRAIP) prevented reperfusion arrhythmias. Conclusion: We suggest that reperfusion arrhythmias are at least in part due to CaMKII dependent phosphorylations at the SR levels