CARDIOPROTECTIVE EFFECT OF K-7259, A NOVEL DILAZEP DERIVATIVE, AGAINST ISCHEMIA-REPERFUSION DAMAGE IN ISOLATED, WORKING RAT HEARTS

Global ischemia (15 min) followed by reperfusion (10, 20 or 30 min) wa s performed in isolated, working rat hearts. Ischemia depressed mechan ical function, which was not restored by reperfusion of 20 min. Preisc hemic administration of K-7259 (N, N'-bis [4-(3,4, 5-trimethoxyphenyl) butyl] homopiperazine dihydrochloride) (1, 5 or 10 mu M) decreased the function before ischemia, but it attenuated the ischemia-induced dysf unction during reperfusion (20 min). Postischemic administration of K- 7259 (10 mu M) or dilazep (20 mu M) also attenuated the ischemia-induc ed dysfunction during reperfusion (30 min). Ischemia-reperfusion (10 m in) increased the tissue malondialdehyde level, and postischemic admin istration of K-7259 (10 mu M) or dilazep (20 mu M) attenuated the malo ndialdehyde accumulation. K-7259 has a cardioprotective effect when gi ven either before or after ischemia.