Effects of minoxidil on ischemia-induced mechanical and metabolic dysfunction in dog myocardium.
Effects of minoxidil on ischemia-induced myocardial mechanical and metabolic dysfunction were examined in anesthetized open-chest dogs. A regional portion of the left ventricle was made ischemic for 20 min by ligating the left anterior descending coronary artery, and then reperfused for 120 min. Dimethylsulfoxide or minoxidil (0.3, or 1.0 mg/kg) was injected intravenously 10 min before ligation. Ischemia decreased regional myocardial contraction, and reperfusion recovered it but incompletely. Myocardial metabolic derangement was observed during ischemia, such as decreases in the myocardial levels of ATP and creatine phosphate. These metabolic changes caused by ischemia were restored by reperfusion. Minoxidil injection at 0.3 and 1.0 mg/kg significantly decreased blood pressures but increased coronary flow. Pretreatment with minoxidil significantly enhanced the recovery of myocardial contraction during reperfusion after ischemia. The levels of ATP and creatine phosphate in the ischemic myocardium were significantly preserved by minoxidil at 0.3 mg/kg. No significant effect of minoxidil on the metabolism was observed in the 120 min reperfused myocardium. In conclusion, minoxidil improved the mechanical dysfunction in the reperfused heart and the drug at low dose preserved high-energy phosphates during ischemia.
Yamamoto
Atsuko
A
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Satoh
Kumi
K
Ichinosawa
Kenichi
K
Kaneta
Shigeru
S
Kano
Seiichiro
S
Ichihara
Kazuo
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D010725:Phosphocreatine / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism
D000959:Antihypertensive Agents; D015221:Potassium Channels; D010725:Phosphocreatine; D008914:Minoxidil; D000255:Adenosine Triphosphate; D004121:Dimethyl Sulfoxide