The end-effectors of ischemic preconditioning (IPC) are not well known. It has been recently shown that transgenic mice underexpressing the
gap junction protein connexin43 (
Cx43) cannot be preconditioned. Because gap junctions allow spreading of cell death during
ischemia-reperfusion in different tissues, including myocardium, we hypothesized that the protection afforded by IPC is mediated by effects on gap junction-mediated intercellular communication. To test this hypothesis, we analyzed the effect of IPC (5 min
ischemia-5 min reperfusion x 2) on the changes in electrical impedance (four
electrode probe) and impulse propagation velocity (transmembrane action potential) induced by
ischemia (60 min) and reperfusion (60 min) in isolated rat hearts. IPC (n = 8) reduced reperfusion-induced
lactate dehydrogenase release by 65.8% with respect to control hearts (n = 9) (P = 0.04) but had no effect on the time of onset of rigor
contracture (increase in diastolic tension), electrical uncoupling (sharp changes in tissue resistivity and phase angle in impedance recordings), or block of impulse propagation during
ischemia. Normalization of electrical impedance during reperfusion was also unaffected by IPC. The lack of effect of IPC on ischemic rigor
contracture and on changes in tissue impedance during
ischemia-reperfusion were validated under in vivo conditions in pigs submitted to 48 min of
coronary occlusion and 120 min of reperfusion. IPC (n = 12) reduced
infarct size (
triphenyltetrazolium) by 64.9% (P = 0.01) with respect to controls (n = 17). We conclude that the protection afforded by IPC is not mediated by effects on electrical coupling. This result is consistent with recent findings suggesting that
Cx43 could have effects on cell survival independent on changes in cell-to-cell communication.