title: Amlodipine, a long-acting calcium antagonist drug reduces ischemia-induced ventricular conduction delay in pig hearts.
abstract: The effects of amlodipine, a novel, long-lasting calcium channel blocking agent, on ischemia-induced myocardial conduction delay was studied in anesthetized pigs paced at a constant heart rate. Acute coronary occlusion (3 minutes) significantly lengthened time to onset, time to peak and duration of bipolar electrograms recorded from both subendocardial and subepicardial left ventricular sites. After intravenous injection of amlodipine (0.3 mg/kg, n = 6), subsequent periods of ischemia greatly reduced (p less than 0.01) all indexes of subepicardial conduction delay. In the subendocardium, amlodipine decreased only time to onset (-25 +/- 4%, p less than 0.01) within the ischemic zone. Significant delays in all indexes were present during repeated ischemic periods in the placebo-treated control group (n = 5). Amlodipine also increased regional myocardial blood flow within the nonischemic myocardium by 25 +/- 10% and decreased mean aortic pressure by 7 +/- 2% without altering flow in the ischemic region. Left atrial pressure remained unchanged. Indexes of ischemia-induced conduction delay were more rapidly restored after reperfusion in amlodipine-pretreated than in control animals. In conclusion, amlodipine produced a beneficial blood flow-independent effect on ischemia-induced injury potentials. The effect may help to reduce the likelihood of development of lethal ventricular arrhythmias in the early stage of myocardial ischemia in the clinical setting.
authors.affiliation: Department of Pharmacology & Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575.
authors.forename: M P
authors.initials: MP
authors.lastname: Rämö
authors.forename: J S
authors.initials: JS
authors.lastname: Plowden
authors.forename: M
authors.initials: M
authors.lastname: Gabel
authors.forename: R W
authors.initials: RW
authors.lastname: Millard
authors.forename: D A
authors.initials: DA
authors.lastname: Lathrop
mesh_terms: D017311:Amlodipine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles; D009543:Nifedipine / Q000494:pharmacology; D015424:Reperfusion; D013552:Swine; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D017311:Amlodipine; D009543:Nifedipine