A study on dilazep: I. Mechanism of anti-ischemic action of dilazep is not coronary vasodilation but decreased cardiac mechanical function in the isolated, working rat heart.
In the isolated, perfused working rat heart, ischemia (15 min) decreased the mechanical function and the tissue levels of adenosine triphosphate and creatine phosphate and increased the levels of lactate and free fatty acids. Reperfusion (20 min) did not restore the mechanical function, but restored incompletely the levels of metabolites, with the exception of free fatty acids, which increased further during reperfusion. Dilazep was given 5 min before starting ischemia until the end of ischemia. Dilazep at 5 or 10 microM decreased the cardiac mechanical function, but did not affect coronary flow in the pre-ischemic heart. Dilazep at 5 or 10 microM accelerated the recovery of mechanical function and coronary flow during reperfusion, and it attenuated metabolic changes induced by ischemia and reperfusion. Dilazep at 1 microM neither decreased the pre-ischemic mechanical function nor restored the mechanical function during reperfusion, although it attenuated the accumulation of free fatty acids during reperfusion. These results suggest that dilazep attenuates both ischemia- and reperfusion-induced myocardial damage and that the anti-ischemic action of dilazep is not due to coronary vasodilation but probably due to an energy-sparing effect and other effects that remain to be studied.
Hoque
A N
AN
Department of Pharmacology, Asahikawa Medical College, Japan.
Hoque
N
N
Hashizume
H
H
Abiko
Y
Y
D000818:Animals; D016718:Arachidonic Acid / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004109:Dilazep / Q000494:pharmacology* / Q000627:therapeutic use; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D007773:Lactates; D010710:Phosphates; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D019344:Lactic Acid; D004109:Dilazep