[Value of calcium channel blockers in the prevention of ventricular fibrillation of ischemic etiology: experimental arguments].

Abstract

The prevention of ventricular fibrillation raises a special problem when related to myocardial ischaemia, since class I antiarrhythmic drugs are then ineffective and may even behave as profibrillatory agents: the usual antifibrillatory properties of these drugs which are inhibitors of sodium channel, activated at high potentials, disappear with the disappearance of the role of sodium channel caused by ischaemic depolarization. Calcium channel then replacing sodium channel, calcium channel inhibitors should tend to prevent ischaemic ventricular fibrillation. Therefore, vulnerability to ventricular fibrillation was assessed in open-chest pigs by the threshold for fibrillation electrically induced with impulses of 100 ms duration at the rate of 180 beats/min. Ischaemia was produced by total occlusion of the left anterior descending coronary artery near its origin. Electrical fibrillation threshold was measured at the end of ischaemic period of increasing duration (30, 60, 120, 180, 240, 360 s) under control conditions and after i.v. administration of verapamil (50 micrograms/kg loading dose and 2 micrograms/kg/min infusion). Unaffected by verapamil when coronary circulation was normal, fibrillation threshold was raised by the drug when lowered by ischaemia, increasingly with the prolongation of ischaemia responsible for depolarization of the fibres, up to 500%. The rise of fibrillation threshold resulted in a delay in the triggering of fibrillation which occurs when the fibrillation threshold (6-8 mA) falls down to the pacing threshold (0.3-0.4 mA). These experiments tend to confirm the positive results recently obtained in man with verapamil in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, in these experiments, left ventricular dP/dt max was not reduced by more than 15%, even just after the loading dose and returned to its control values within a few minutes.

• Authors: Q Timour, M Freysz, J F Aupetit, J Loufoua, D Frassati, G Faucon
• Journal: Bulletin de l'Academie nationale de medecine (Bull Acad Natl Med) Vol. 180 Issue 1 Pg. 215-26; discussion 226-7 (Jan 1996) ISSN: 0001-4079 [Print] Netherlands
• Vernacular Title: Intérêt des inhibiteurs du canal calcique dans la prévention de la fibrillation ventriculaire d'origine ischémique: arguments expérimentaux.
• PMID: 8696877 (Publication Type: Comparative Study, English Abstract, Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Calcium Channel Blockers
• Vasodilator Agents
• Verapamil

Topics

• Animals
• Anti-Arrhythmia Agents (therapeutic use)
• Calcium Channel Blockers (therapeutic use)
• Death, Sudden, Cardiac (prevention & control)
• Hemodynamics
• Humans
• Myocardial Ischemia (complications, drug therapy, physiopathology)
• Swine
• Vasodilator Agents (therapeutic use)
• Ventricular Fibrillation (etiology, physiopathology, prevention & control)
• Verapamil (therapeutic use)