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Possible prevention by amlodipine of ventricular fibrillation related to brief ischemia episodes
Q Timour1, J F Aupetit, M Freysz
1Département de pharmacologie médicale, Université Claude Bernard, Lyon, France.
Insights
Calcium channel blockers, like amlodipine, can prevent sudden cardiac death by delaying the onset of ventricular fibrillation during temporary heart ischemia. This study shows amlodipine significantly prolongs the time to fibrillation in a pig model.
Area of Science:
- Cardiovascular Pharmacology
- Cardiac Electrophysiology
- Ischemic Heart Disease
Background:
- Ventricular fibrillation (VF) is a primary cause of sudden cardiac death, often triggered by transient myocardial ischemia.
- Calcium channel blockers (CCBs) may mitigate VF by optimizing coronary blood flow relative to myocardial metabolic demand.
- Amlodipine, a CCB with minimal negative inotropic effects, was chosen to investigate its anti-arrhythmic potential during ischemia.
Purpose of the Study:
- To determine if amlodipine can prolong the time to the onset of ventricular fibrillation in an animal model of transient myocardial ischemia.
- To evaluate the electrophysiological effects of amlodipine during ischemic conditions.
Main Methods:
- A transient ischemia model was created in anesthetized pigs via occlusion of the left anterior descending coronary artery during ventricular pacing.
- Amlodipine was administered intravenously at doses of 0.30 mg/kg and 0.60 mg/kg.
- Measurements included time to fibrillation, hemodynamic parameters (blood pressure, left ventricular dP/dtmax), and electrophysiological variables (action potential duration, conduction time, ST segments, T waves).
Main Results:
- Amlodipine significantly prolonged the time to fibrillation from 87 ± 10 s to 146 ± 16 s (0.30 mg/kg) and 201 ± 22 s (0.60 mg/kg) (p < 0.05).
- These effects were achieved without significant adverse impacts on blood pressure or cardiac contractility.
- Amlodipine limited ischemia-induced shortening of action potential duration, lengthening of conduction time, and ST-T wave alterations.
Conclusions:
- Amlodipine effectively increases the time to ventricular fibrillation onset during transient myocardial ischemia in pigs.
- The drug's electrophysiological stabilizing effects contribute to its anti-arrhythmic properties under ischemic stress.
- Amlodipine may reduce the incidence of sudden cardiac death by extending the time to fibrillation beyond the duration of ischemic episodes.
Abstract:
Calcium antagonists may reduce propensity to ventricular fibrillation, by altering the balance between coronary blood flow and metabolic demand, and thus may substantially prolong time to occurrence of fibrillations. This delay in the onset of fibrillation should be sufficient to prevent sudden death in the case of transitory episodes of myocardial ischemia. Therefore, this study was based on the determination of time to onset of fibrillation in an animal model of transitory ischemia. This model was achieved by the complete, but transitory occlusion of the left anterior descending coronary artery near its origin under ventricular pacing at a constant high rate (180 beats/min), in anesthetized, open-chest pigs. Amlodipine was preferred to another calcium antagonist for this study because it is among the least negatively inotropic of these drugs. It was intravenously infused at 0.02 mg.kg-1.min-1. Time to fibrillation was prolonged from 87 +/- 10 to 146 +/- 16 s (p < 0.05) with the 0.30 mg/kg dose and to 201 +/- 22 s (p < 0.05) with the 0.60 mg/kg dose, without serious impairment of blood pressure or left ventricular dP/dtmax in the absence of ischemia. Concurrently, amlodipine significantly limited the shortening of monophasic action potential duration (200 +/- 4 vs. 172 +/- 6 ms), the lengthening of conduction time (43 +/- 2 vs. 53 +/- 2 ms), and the alterations of ST segments and T waves induced by 60 s ischemic depolarization. Consequently, amlodipine might reduce the incidence of sudden death by lengthening time to onset of fibrillation beyond the duration of the ischemia, when transitory.