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) 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.
Hoque
A N
AN
Department of Pharmacology, Asahikawa Medical College, Japan.
Hoque
N
N
Hara
A
A
Hashizume
H
H
Ichihara
K
K
Abiko
Y
Y
D000818:Animals; D004109:Dilazep / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
C092019:K 7259; D014665:Vasodilator Agents; D008315:Malondialdehyde; D004109:Dilazep