Experimental studies on the effects of nicorandil for the myocardial reperfusion injury

The cardioprotective effects of nicorandil （NIC） in isolated blood perfused rat hearts using support rat through the ischemia and the reperfusion were investigated. NIC （1mM） was administered with cardioplegia （group NIC-I, n=8） or at the time of reperfusion （group NICR, n=8） or both （group NIC-I+R, n=8）, and these groups were compared with a non-ischemic group （group C, n=8） and a vehicle group （group ISC, n=10）. After 20 minutes equilibration, the heart was arrested with St. Thomas solution （25℃） and put into 30-min global ischemia （37℃） followed by 40 minutes reperfusion. The parameters of LV function was taken with a intra-ventricular latex balloon （balloon volume: BV 40, 80, 140μl） before ischemia and after reperfusion. After this experiment, the heart was divided and the adenine nucleotides and water content of the tissues were measured. To investigate the effects of NIC during ischemia, tissues from hearts arrested using cardioplegia with NIC （group NI, n=6） were compared with those from hearts arrested without NIC （group NT, n=6）. To investigate the effects of NIC on cardiac functions, NIC was administered into the circuit for 10 minutes after 20 minutes equilibration, the parameters of LV function before and after NIC were compared with each other （n=6）. The recovery values of rate-pressure product （RPP） were better in NIC-I+R than in ISC at BV of 40 and 140, and the values of left ventricular developed pressure （LVDP）, peak positive dP/dt （+ dP/dt） and peak negative dP/dt （ -dP/dt） were also higher at BV of 40, μl. The recovery values of HR and CF in groups NIC-R and NIC-I+R were significantly higher than in ISC. The ATP/ADP ratio of NIC-R was significantly higher than that of ISC. The water content of the hearts in C was significantly smaller than in all other groups. There were no significant differences in the adenine nucleotides or water content between NI and NT. After perfusion with NIC for 10 minutes, the values of LVDP, RPP, +dP/dt （BV: 40, 80μl）,-dP/dt （in all BV） and HR （80, 140μl） were significantly increased. The level of CF was remarkedly increased, almost doubled. The administration of NIC 1mM during the ischemic period did not provide any cardioprotective effects. Administration in the reperfusion period also did not improve LV function, but it did appear to improve the energy status of the heart because it increased the ATP/ADP ratio. The administration of NIC in both ischemic and reperfusion periods significantly improved LV function. These results indicated that high doses of NIC effect on improvement of LV function in the isolated blood ?perfused rat heart, particularly when administered during ischemia and during reperfusion.departmental bulletin pape