Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo

Protein kinase C (PKC) has been known to play an important role in ischemic preconditioning (IP). This study was designed to examine whether the trans location of PKC is associated with the cardioprotective effects of IP in vi vo on infarct size and ventricular arrhythmias in a rat model. Using anesthetized rats, heart rate, systolic blood pressure, infarct size and ventricular arrhythmias during 45 min of coronary occlusion were measur ed. PKC activity was assayed in both the cytosolic and cell membrane fracti on . Brief 3-min periods of ischemia followed by 10 min of reperfusion were used to precondition the myocardium. Calphostin C was used to inhibit PKC. Infarct size was significantly reduced by IP (68.1 (2.5)%, mean (S.E.) vs. 45.2 (3.4)%, p 0.01). The reduction in infarct size by IP was abolished by pretreatment with calphostin C. The total number of ventricular premature c omplex (VPC) during 45 min of coronary occlusion was reduced by IP (1474 (1 69) beats/45 min vs. 256 (82) beats/45 min, p 0.05). The reduction the tota l number of VPC induced by IP was abolished by the administration of calpho stin C before the episode of brief ischemia. The same tendency was observed in the duration of ventricular tachycardia and the incidence of ventricula r fibrillation. PKC activity in the cell membrane fraction transiently incr eased immediately after IP (100 vs. 142%, p 0.01) and returned to baseline 15 min after IP. Pretreatment with calphostin C prevented the translocation of PKC. The translocation of PKC plays an important role in the cardioprotective ef fect of IP on infarct size and ventricular arrhythmias in anesthetized rats .