Preconditioning reduces tissue complement gene expression in the rabbit isolated heart

Both preconditioning and inhibition of complement activation have been show n to ameliorate myocardial ischemia-reperfusion injury. The recent demonstr ation that myocardial tissue expresses complement components led us to inve stigate whether preconditioning affects complement expression in the isolat ed heart. Hearts from New Zealand White rabbits were exposed to either two rounds of 5 min global ischemia followed by 10 min reperfusion (ischemic pr econditioning) or 10 mu M of the ATP-dependent K+ (K-ATP) channel opener pi nacidil for 30 min (chemical preconditioning) before induction of 30 min gl obal ischemia followed by 60 min of reperfusion. Both ischemic and chemical preconditioning significantly (P < 0.05) reduced myocardial C1q, C1r, C3, C8, and C9 mRNA levels. Western blot and immunohistochemistry demonstrated a similar reduction in C3 and membrane attack complex protein expression. T he KATP channel blocker glyburide (10 mu M) reversed the depression of C1q, C1r, C3, C8, and C9 mRNA expression observed in the pinacidil-treated hear ts. The results suggest that reduction of local tissue complement productio n may be one means by which preconditioning protects the ischemic myocardiu m.