CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CaMKII contributes to cardiac arrythmogenesis during early reperfusion of ischemic myocardium
Autor/es:
VALVERDE CA; SAID M; BECCERRA R; MUNDIÑA-WEILENMANN C; KAETZEL MA; DEDMAN JR; VITTONE L; MATTIAZZI A
Lugar:
New London, NH
Reunión:
Conferencia; Gordon Research Conferences- Cardiac regulatory Mechanisms; 2010
Institución organizadora:
Gordon Research Conferences
Resumen:
Introduction: Ventricular arrhythmias deteriorating into sudden cardiac death are the major cause of mortality in developed countries. Reperfusion after ischemia is particularly prone to arrhythmias. Experiments from our laboratory have shown a CaMKII-dependent phosphorylation of Thr17 residue of phospholamban (PLN) (Vittone, 2002) in close association with a cytosolic calcium overload (Valverde, 2006) and arrhythmias at the beginning of reperfusion. In the present work, we tested the hypothesis that CaMKII is involved in the arrhythmogenesis that occurs upon reperfusion after global ischemia in the heart. Methods: Langendorff perfused rat/mouse hearts were submitted to global ischemia (15-20min)/reperfusion(3min) at 37°C. Epicardial monophasic action potentials and mechanical parameters were simultaneously recorded. Results: Reperfusion of the ischemic hearts produced ectopic beats. Reperfusion arrhythmias appear to be triggered, at least in part, by afterdepolarizations (DADs and EADs), causing and electric alteration that in many cases culminated in ventricular tachycardia or ventricular fibrillation. Triggered ectopic beats (EB) during the 3 first min of reperfusion were significantly decreased by the CaMKII-inhibitor, KN-93 (EB number: 46 ± 6 control vs. 11 ± 3 KN-93; p<0.05) and by the inhibitor of the SR Ca2+ release channel, ryanodine 1mM (46 ± 6 control vs. 22.8 ± 6 Ry; p < 0.05). Experiments in transgenic mice with targeted inhibition of CaMKII at the SR level (SR-AIP) prevented reperfusion arrhythmias (2.7 ± 1.3 and 34.2 ± 10.1, SR-AIP vs. WT, respectively). Similar results were obtained in SR-AIP hearts loaded with DI-8-ANNEPS and mounted in a pulsed local field fluorescent microscopy, in order to measure transmembrane potential. Conclusion: The results presented herein indicate that arrhythmias induced by reperfusion are, at least in part, due to CaMKII-dependent phosphorylations at the SR level.
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