Jpn. J. Pharmacol. 73 (4), 365-369 (1997)


Cardioprotective Effect of K-7259, a Novel Dilazep Derivative, against Ischemia-Reperfusion Damage in Isolated, Working Rat Hearts

A.N. Ehsanul Hoque (1,#), Nina Hoque (1,#), Akiyoshi Hara (1), Hiroko Hashizume (1), Kazuo Ichihara (2) and Yasushi Abiko (1,*)

(1) Department of Pharmacology, Asahikawa Medical College, Asahikawa 078, Japan
(2) Department of Pharmacology, Hokkaido College of Pharmacy, Otaru 047-02, Japan
(#) Present address: Department of Pharmacology and Toxicology, Medical Sciences Building, University of Western Ontario, London, Ontario N6A 5CI, Canada
(*) To whom correspondence should be addressed.

Abstract: Global ischemia (15 min) followed by reperfusion (10, 20 or 30 min) was performed in isolated, working rat hearts. Ischemia depressed mechanical function, which was not restored by reperfusion of 20 min. Preischemic administration of K-7259 (N,N'-bis[4-(3,4,5-trimethoxyphenyl)butyl]homopiperazine dihydrochloride) (1, 5 or 10 microM) decreased the function before ischemia, but it attenuated the ischemia-induced dysfunction during reperfusion (20 min). Postischemic administration of K-7259 (10 microM) or dilazep (20 microM) also attenuated the ischemia-induced dysfunction during reperfusion (30 min). Ischemia-reperfusion (10 min) increased the tissue malondialdehyde level, and postischemic administration of K-7259 (10 microM) or dilazep (20 microM) attenuated the malondialdehyde accumulation. K-7259 has a cardioprotective effect when given either before or after ischemia.

Keywords: K-7259, Working rat heart, Ischemia


Copyrightę The Japanese Pharmacological Society 1997

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