Pathophysiological study of arrhythmogenesis in ischemic heart

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To know how abnormal intracellular Ca^<2+> dynamics and gap junctional communication are integrated into arrhythmia, we visualized the intracellular Ca^<2+> dynamics by in situ Ca^<2+> imaging and expression of connexin 43 by GFP technique in ischemic rat hearts. Based on the hypothesis that Ca^<2+> waves would arise at the border zone of the infarction as a consequence of Ca^<2+> overload, we conducted in situ Ca^<2+> imaging. The subepicardial myocytes at the border zone showed abnormal intracellular calcium handling and gap junctional intercellular communication, such as stimulation-induced Ca^<2+> waves, which were evoked exclusively on electrical stimulation, instead of Ca^<2+> transients. These abnormal [Ca^<2+>]_i dynamics are supposed to be an important substrate for arrhythmias in ischemic hearts. We also made an EBV-based plasmid encoding connexin43-mRFP fusion protein for elucidating effects of abnormal gap junctional communication on ventricular conductivity. The EBV-based plasmid has different fluorescent wavelength spectrum from that of a calcium indicator, fluo-3,and were infused into the aortic root of rats. To maximize delivery, the aortic root was transiently occluded during a brief asystole. We concluded that these techniques could substantially contribute to our understanding of relationship between intracellular Ca^<2+> dynamics and expression of connexin 43 in ischemic rat hearts.