RESUMEN
The effects of amlodipine (300 micrograms/kg administered intravenously), a new, long-acting, dihydropyridine class, calcium channel blocking drug, were studied in atrially paced (120 beats/min), autonomically blocked dogs. Hemodynamic and electrophysiologic parameters were measured before and up to 3 hours after amlodipine. Coronary blood flow was significantly increased 10 and 30 minutes after drug administration, whereas cardiac output and mean arterial pressure were unaffected. Coronary vascular resistance was decreased but total systemic vascular resistance did not change. Atrioventricular (AV) nodal conduction was slightly prolonged, as reflected by increases in atrial-His bundle and AV conduction times and PR interval, 30 minutes after administration. All parameters returned toward their control values within 3 hours after drug administration. Comparison of coronary vascular resistance and AV conduction changes with those previously reported for other calcium channel blocking drugs where autonomic blockade existed suggests that at equivalent levels of coronary vasodilation, amlodipine's effects more closely resemble the effects of diltiazem or verapamil than other dihydropyridines.
Asunto(s)
Sistema de Conducción Cardíaco/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Amlodipino , Animales , Bloqueo Nervioso Autónomo , Bloqueadores de los Canales de Calcio , Perros , Electrofisiología , Femenino , Sistema de Conducción Cardíaco/fisiología , Masculino , Nifedipino/farmacología , Factores de TiempoRESUMEN
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.