Abstract 13088: A Reduction in the Number of Gap Junction Channels or in Their Unitary Conductance Increases Ischemia-Reperfusion Arrhythmias in Isolated Mice Hearts
Introduction. A transient reduction of cell-to-cell coupling during reperfusion is known to limit myocardial necrosis, but little is known about its arrhythmogenic effects during ischemia-reperfusion (IR).
Aims. To analyze the incidence of ventricular arrhythmias during ischemia and reperfusion in mice hearts after both a reduction in gap junctional conductance, in Cx43KI32 mice, and an extreme reduction in Cx43 expression induced by 4-hydroxytamoxifen (4-OHT).
Methods. Isolated mice hearts from Cx43Cre-ER(T)/fl animals treated with 4-OHT (n=10), Cx43KI32 mice (n=14), in which Cx43 has been replaced by Cx32, and control animals (n=11-13) were submitted to 20 or 60 min of regional ischemia and reperfusion, and spontaneous and induced ventricular arrhythmias were monitored. In additional 47 hearts, changes in conduction velocity and electrical impedance during global IR were assessed.
Results. In contrast to ablation by 4-OHT, replacement of Cx43 by Cx32 did not modify baseline conduction velocity or electrical impedance. However, the number of premature ventricular beats and ventricular tachyarrhytmias was higher in Cx43KI32 and 4-OHT-treated Cx43Cre-ER(T)/fl animals vs. wild-type during normoxia, ischemia (12.29±3.26 and 52.17±22.51 spontaneous tachyarrhythmias vs. 3.00±1.46, p<0.05) and reperfusion. Impairment in conduction during ischemia was steeper in homozygous Cx43KI32 animals, whereas changes in myocardial impedance were attenuated during ischemia in both transgenic models, suggesting altered cell-to-cell coupling at baseline.
Conclusions. Both a reduction in the number of gap junction channels after 4-OHT treatment or in their conductivity after replacement of Cx43 by less conductive Cx32 were arrhythmogenic under normoxia and IR, despite no major effects on baseline electrical properties. These results suggest that modifications in gap junctional communication silent under normal conditions may be arrhythmogenic during ischemia-reperfusion.
- © 2011 by American Heart Association, Inc.