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Comparative effects of azelnidipine and amlodipine on myocardial function and mortality after ischemia/reperfusion in dogs.

Abstract
Effects of azelnidipine were examined and compared with those of amlodipine on stunned myocardium in dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and subsequently released for 60 min. A vehicle, azelnidipine (0.3 mg/kg), or amlodipine (0.3 or 1 mg/kg) was injected intravenously 20 min before LAD ligation. The heart rate increased after a depressor response in the presence of amlodipine, while it decreased despite a decrease in arterial pressures in the presence of azelnidipine. After reperfusion, the coronary flow (CF) significantly increased in the presence of azelnidipine, but did not change with amlodipine after reperfusion. A positive inotropic effect was observed after treatment with both calcium antagonists. Ischemia significantly decreased the percentage of segment shortening (%SS) in all groups. Treatment with both calcium antagonists significantly increased %SS after reperfusion, although high-energy phosphate levels did not improve in the presence of calcium antagonists 60 min after reperfusion. Mortality with azelnidipine was significantly lower than that with 0.3 mg/kg amlodipine immediately after reperfusion. In conclusion, improvement in myocardial stunning after pretreatment with azelnidipine is associated with an increase in CF after reperfusion. The negative chronotropic action may have contributed to decreased mortality due to reperfusion arrhythmias. Azelnidipine is more beneficial than amlodipine and may provide an additional advantage to patients with angina and hypertension.
AuthorsSeiichiro Kano, Kazuo Ichihara, Ken-ichi Komatsu, Kumi Satoh
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 116 Issue 2 Pg. 181-7 ( 2011) ISSN: 1347-8648 [Electronic] Japan
PMID21597238 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Calcium Channel Blockers
  • Dihydropyridines
  • Amlodipine
  • Azetidinecarboxylic Acid
  • azelnidipine
Topics
  • Amlodipine (pharmacology)
  • Animals
  • Azetidinecarboxylic Acid (analogs & derivatives, pharmacology)
  • Calcium Channel Blockers (pharmacology)
  • Dihydropyridines (pharmacology)
  • Dog Diseases (mortality, prevention & control)
  • Dogs
  • Energy Metabolism
  • Female
  • Male
  • Myocardium (metabolism)
  • Reperfusion Injury (mortality, prevention & control)

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