Amlodipine, a long-acting calcium antagonist drug reduces ischemia-induced ventricular conduction delay in pig hearts

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 subepicardal left ventricular sites. After intravenous injection of amlodipine (0.3 mg/kg, n = 6), subsequent periods of ischemia greatly reduced (p < 0.01) all indexes of subepieardial conduction delay. In the subendocardium, amlodpine decreased only time to onset (-25 ± 4%, p < 0.01) within the ischemie zone. Significant delays in all indexes were present during repeated ischemic periods in the placebo-treated control group (n = 5). Amlodpine also Increased regional myocardial blood flow within the nonischemic myocardium by 25 ± 10% and deceased 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. This effect may help to reduce the likelihood of development of lethal ventricular arrhythmias in the early stage of myocardial ischemia in the clinical setting.