Effects of azelnidipine, a dihydropyridine calcium antagonist, on myocardial stunning in dogs.
Effects of azelnidipine, a dihydropyridine derivative, on stunned myocardium were examined in anesthetized open-chest dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and then released for 60 min. Dimethyl sulfoxide (DMSO), the solvent of azelnidipine, or azelnidipine (0.03, 0.1 or 0.3 mg/kg) was injected i.v. 20 min before ligation. Segment shortening was determined by sonomicrometry. The levels of high-energy phosphate were measured in 60-min reperfused hearts. Azelnidipine at 0.1 and 0.3 mg/kg significantly decreased diastolic blood pressure and increased % segment shortening. The increase in % segment shortening due to azelnidipine appeared to be abolished by propranolol and atropine pretreatment. Ischemia significantly decreased % segment shortening in all groups. The % segment shortening that had been decreased by ischemia recovered during reperfusion, but did not reach its preischemic level in each group. In the 0.1 and 0.3 mg/kg of azelnidipine-treated dogs, a significant enhancement of % segment shortening recovery during reperfusion was observed, as compared with that in the DMSO-treated dogs. Azelnidipine did not affect the high-energy phosphate levels in 60-min reperfused hearts. In conclusion, azelnidipine improved the contractile dysfunction in stunned myocardium, without any preservation of high-energy phosphate.
Satoh
K
K
Department of Pharmacology, Hokkaido College of Pharmacy, Otaru, Japan.
Yamamoto
A
A
Hoshi
K
K
Ichihara
K
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D001383:Azetidinecarboxylic Acid; D001285:Atropine; C038806:1,4-dihydropyridine; D011433:Propranolol; C061679:azelnidipine