Oral administration of nicorandil enhances the survival of ischemic skin flaps in rats

Nicorandil has an anti-apoptotic effect on ischemic myocardium through the activation of ATP-sensitive potassium (KATP) channel. We tested the hypothesis that oral administration of nicorandil had a protective effect on ischemic skin flaps. A cranially based skin flap measuring 3 × 7 cm in full thickness was made on the back of rats. The rats were divided into a control group and 8 nicorandil groups (group 1-8) according to different doses and timings of administration. On day 7 at 5 cm, groups 1 to 6 (10 or 30 mg/kg twice per day for 3 days starting at 24 h before, 0.5 h before or 0.5 h after the operation) showed significantly higher blood perfusion change rate (73.3 ± 2.9%-79.1 ± 4.1% vs. 25.9 ± 8.6%, P < 0.01), and significantly higher survival rate (68.8 ± 4.8-75.2 ± 8.2% vs. 47.0 ± 2.8%, P < 0.05) than the control group. Many more surviving blood vessels were also observed in these groups. In contrast, no significant effects were found either in group 7 (30 mg/kg twice per day for 3 days starting 24 h after the operation) or group 8 (30 mg/kg once at 0.5 h after the operation). We did not find an angiogenic effect of nicorandil in vitro. Therefore, our results confirmed that the oral administration of nicorandil could protect tissues from necrosis in ischemic skin flaps. In addition, its protective effect depends on the time of first administration and the duration.