Ischemic postconditioning delays recovery of passive myocardial electrical properties independently of connexin 43 expression.

RODRÍGUEZ-SINOVAS A; DIEZ ER; SÁNCHEZ JA; RUIZ MEANA M; GARCÍA-DORADO D

Barcelona

Congreso; ESC Congress 2014; 2014

European Society of Cardiology

Background: Ventricular arrhythmias are acommonclinical manifestation in patientswith acute myocardial infarction submitted to coronary revascularizaton. Reperfusion arrhythmias have been associated with successful myocardial reperfusion during thrombolytic therapy, but they have been also suggested to be a marker of large infarct size and worse prognosis. Ischemic postconditioning (PostC) has been shown to reduce the incidence of reperfusion arrhythmias. However, the mechanisms involved in the antiarrhythmic effects of ischemic PostC are not well known. The aims of this study were (1) to analyze the electrophysiologycal effects of ischemic PostC on passive myocardial electrical properties, as a surrogate of gap junctional communication, in isolated rat hearts, and (2) to assess the involvement of connexin 43 (Cx43) in these effects, using isolated hearts from wild-type mice and from mice devoid of connexin 43. Methods and results: Isolated rat hearts were submitted to 20min of global ischemia followed by 25 min of reperfusion. Myocardial electrical impedance (tissue resistivity and phase angle) was assessed using a four-electrode probe, placed in the left ventricular free wall, at 7 kHz. Global ischemia induced a marked rise in resistivity and a decrease in phase angle (p≤0.05). Ischemic PostC (6 cycles of 10 seconds of reperfusion/ischemia, n=7), applied at the onset of reperfusion, slowed and delayed, by about 4 min, recovery of tissue resistivity as compared with recovery in control hearts. To analyze the involvement of Cx43 in these changes, isolated hearts from two Cx43-defficient mice (Cx43KI32 mice, in which the coding region for Cx43 is replaced by that of Cx32, and a inducible knock-out model, in which a marked reduction in Cx43 expression is achieved after 4-hydroxytamoxifen administration) were submitted to 30min of global ischemia followed by reperfusion. Hearts from wild-type Animals and from both homozygous Cx43KI32 mice (n=6-8) and Cx43Cre-ER(T)/fl mice (n=7-8), were protected against infarction by ischemic PostC (6 cycles of 10 seconds of reperfusion/ischemia). Similar to findings in isolated rat andmice wild-type hearts, ischemic PostC still delayed recovery of tissue resisitvity (about 3 min) in hearts from Cx43-defficient animals. Conclusions: Ischemic PostC delays recovery of tissue resistivity during reperfusion, but this effect is indepenent of Cx43 expression.. The mechanisms of the antiarrhythmic effect of ischemic postconditioning remain elusive.