Delayed remote preconditioning induces cardioprotection: role of heme oxygenase-1.

The role of heme oxygenase-1 (HO-1) in the cardioprotection induced by delayed remote ischemic preconditioning (DRIPC) has not been investigated. Therefore, this study was designed to investigate whether HO-1 is involved in DRIPC-mediated cardioprotection in an isolated perfused rat heart model. Isolated rat hearts were subjected to 30 min ischemia followed by 60 min reperfusion. DRIPC (four cycles 5-min occlusion and 5-min reflow at the unilateral hind limb once per day for 1, 2, or 3 d before heart isolation, abbreviated as D1RIPC, D2RIPC, or D3RIPC respectively). Infarct size, myocardial troponin levels, and heart function were measured. The protein and messenger RNA levels of HO-1 were determined. DRIPC facilitated postischemic cardiac functional recovery and decreased cardiac enzyme release. The infarct size-limiting effect of DRIPC was more pronounced in the D3RIPC group (10.22 ± 2.57%) than the D1RIPC group (22.34 ± 4.02%, P < 0.001) or the D2RIPC group (14.60 ± 3.13%, P = 0.034). These effects in the D1RIPC group could be blocked by Zinc Protoporphyrin IX (ZnPP) (an HO-1 specific inhibitor). DRIPC-mediated cardioprotection was associated with enhanced HO-1 protein expression (D1RIPC, 0.11 ± 0.03; versus 0.15 ± 0.06 in the D2RIPC group, P = 0.06; versus 0.20 ± 0.04 in the D3RIPC group, P = 0.04) and messenger RNA levels of HO-1 expression. Our findings suggest that HO-1 is involved in the cardioprotection induced by DRIPC, and that increase in the number of preconditioning stimuli may enhance cardioprotective effects accompanied with increased HO-1 level.