Kumi Satoh (1), Atsuko Yamamoto (1), Katsuji Hoshi (1) and Kazuo Ichihara
(1,2,*)
(1) Department of Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka,
Otaru 047-0264, Japan
(2) Department of Clinical Pharmacology (Tsumura), Asahikawa Medical College,
4-5 Nishikagura, Asahikawa 078-8510, Japan
(*) To whom correspondence should be addressed (1).
Abstract: 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.
Keywords: Azelnidipine, Dihydropyridine derivative, Ischemia, Myocardial
stunning