Protection against ischaemic ventricular fibrillation by blocking agents of myocardial cell calcium influx. Electrophysiological study in the pig in situ heart

Timour, Quadiri; Larbre, JP; Jf, Aupetit; Gerentes-Chassagne, I.; Loufoua-Moundanga, J; Kioueh, I.; Faucon, G

doi:10.1111/j.1472-8206.1991.tb00753.x

Cited by 9 publications

(8 citation statements)

References 6 publications

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“…A longer time is then required for the fall to 0 mA. Conceivably, the results provided by time to fibrillation [11,12] are consistent with those of VFT.…”

Section: Discussionsupporting

confidence: 75%

“…In fact, since the initial finding of Kaumann and Aramendia [23], all experimental studies have concluded that calcium blockers are undoubtedly effective in preventing ischemic ventricular fibrillation [7][8][9][10][11][12], with differences depending on the compound used in terms of potency, tolerance, and persistence of the effects. Neither the bradycardia that occurs with verapamil and, occasionally, with diltiazem, nor the tachycardia that occurs with other dihydropyridines was observed with amlodipine [13].…”

Section: Control By Amlodipine Of the Onset Of Ischemic Ventricular Fmentioning

confidence: 99%

“…With the progression of ischemia, the increase in excitability is such that the activity of the ventricular fibers tends to become spontaneous, while the conduction of the stimulus from one fiber to another becomes more and more difficult. Fibrillation is just an activity originating from each fiber without propagation to the surrounding fibers [11,20].…”

Section: Control By Amlodipine Of the Onset Of Ischemic Ventricular Fmentioning

confidence: 99%

“…These conditions are reproduced in animals by the transient occlusion of a large coronary artery and the prophylactic administration of the drug just before the occlusion [4,5]. It is therefore of no surprise that most studies involving calcium entry blocking agents have used such an experimental setting to provide evidence of their efficacy against ischemic ventricular fibrillation [7][8][9][10][11][12].…”

mentioning

confidence: 99%

“…The time to fibrillation, which varies between 1 and 3 minutes, enables the assessment of vulnerability to fibrillation and its variations due to a drug; a number of determinations may be achieved in the course of an experiment. Since amlodipine seems to be only moderately negatively inotropic [13], better results might be expected from amlodipine than from other compounds previously studied [7][8][9][10][11][12], as heart failure in clinical settings appears to be an obstacle to favorable effects of calcium antagonists [14,15].…”

mentioning

confidence: 99%

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Delay by a calcium antagonist, amlodipine, of the onset of primary ventricular fibrillation in myocardial ischemia

Timour

Bui‐Xuan

Faucon

et al. 1996

Cardiovasc Drug Ther

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Calcium antagonists have been reported to counteract the increase by ischemia of vulnerability to ventricular fibrillation. This ability might be especially of interest in the prevention of sudden death subsequent to a major, but transitory, inadequacy between myocardial oxygen requirements and available coronary blood flow produced by exercise, emotion, etc., because death is then not related to irreversible damage of myocardial fibers. This study has been undertaken to examine the protective effect of a calcium antagonist on an animal model of this type of ischemia. This model used complete, but transient occlusion of the left anterior descending coronary artery near its origin during pacing at a constant high rate (180 beats/min) in anesthetized, open-chest pigs, most often resulting in fibrillation within 1-2 minutes after a progressive fall of the electrical fibrillation threshold. Amlodipine was the preferred calcium antagonist for this study because it is only moderately negatively inotropic. The results of the preventive administration of amlodipine was assessed by the time to onset of fibrillation. Amlodipine 0.30 mg/kg prolonged this time by 50-100% (p < 0.05) without appreciable impairment of blood pressure or myocardial contractility. Concurrently, amlodipine delayed the shortening of the monophasic action potential duration, the lengthening of conduction time, and the alterations of ST segments and T waves linked to ischemic depolarization. Consequently, when given experimentally before the occurrence of major, but transitory ischemia, amlodipine protected against fibrillation. Similarly, in clinical settings it ought to delay sudden death that may occur as a result of a major but transitory inadequacy between myocardial oxygen requirements and available coronary blood flow.

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“…A longer time is then required for the fall to 0 mA. Conceivably, the results provided by time to fibrillation [11,12] are consistent with those of VFT.…”

Section: Discussionsupporting

confidence: 75%

Section: Control By Amlodipine Of the Onset Of Ischemic Ventricular Fmentioning

confidence: 99%

Section: Control By Amlodipine Of the Onset Of Ischemic Ventricular Fmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Delay by a calcium antagonist, amlodipine, of the onset of primary ventricular fibrillation in myocardial ischemia

Timour

Bui‐Xuan

Faucon

et al. 1996

Cardiovasc Drug Ther

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Prevention by Calcium Antagonists of Profibrillatory Effects of Class I Antiarrhythmic Drugs in Acute Myocardial Ischemia: Study in Pig Heart In Situ

Bui‐Xuan,

Aupetit,

Freysz

et al. 1997

Pharmacotherapy

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Class I antiarrhythmic drugs do not decrease, but increase, the risk of ventricular fibrillation in the ischemic myocardium. On the contrary, vulnerability to fibrillation related to ischemia appears to be substantially reduced by calcium antagonists. We assessed whether the calcium antagonist diltiazem (0.50 mg/kg bolus plus 0.02 mg/kg/min infusion) could prevent the profibrillatory effect or even partially restore the antifibrillatory effect of a class I antiarrhythmic drug, flecainide (1 mg/kg bolus plus 0.04 mg/kg/min infusion) in the ischemic myocardium of anesthetized, open‐chest pigs. Ischemia was obtained by completely occluding the left anterior descending coronary artery near its origin. Vulnerability to fibrillation was assessed by electrical fibrillation threshold (EFT), measured with diastolic impulses of 100 msec duration delivered at a rate of 180 beats/minute. Diltiazem did not oppose the rise in EFT induced by flecainide in the absence of ischemia (6.8 ± 1.2 to 9.9 ± 0.9 mA, p<0.001). It limited the fall in EFT observed under the dual influence of ischemia and flecainide (4.2 ± 0.9 vs 1.3 ± 0.6 mA, p<0.001). By reducing calcium entry into myocardial fibers, diltiazem delayed ischemic depolarization, as evidenced by reduced shortening of the monophasic action potential duration from 215 ± 7 to 200 ± 4 msec, instead of 178 ± 6 (p<0.001), and reduced lengthening of intraventricular conduction time from 33 ± 5 to 43 ± 4 msec, instead of 53 ± 4 (p<0.01). Therefore, diltiazem is likely to prevent the loss and even the reversal of the antifibrillatory properties of flecainide due to myocardial ischemia in dosages that do not adversely affect myocardial contractility or atrioventricular conduction to a large extent.

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Attenuation of the ischaemia-induced fall of electrical ventricular fibrillation threshold by a calcium antagonist, diltiazem

Timour

Chevrel

et al. 1993

Naunyn-Schmiedeberg's Arch Pharmacol

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Calcium antagonists have been reported to decrease the incidence of sudden death in postinfarction management and vulnerability to fibrillation secondary to experimental coronary occlusion. In order to confirm such beneficial results regarding ischaemic ventricular fibrillation, the threshold intensity for fibrillation electrically induced with impulses of 100 ms and 180 beats.min-1 was measured during the course of ischaemias obtained by total occlusion of the left anterior descending coronary artery near its origin in open-chest pigs. The variations of electrical fibrillation threshold with ischaemia duration (30, 60, 120, 180, 240, 360 s) were compared under control conditions and after i.v. diltiazem (0.50 mg.kg-1 plus 0.02 mg.kg-1.min-1 over 25 min). Electrical fibrillation threshold was not influenced by diltiazem before, but raised during ischaemia, particularly from the 60th s (1.7 to 4.0 mA), with delay in the triggering of fibrillation which occurs when the fibrillation threshold falls down to the pacing threshold (0.2 to 0.3 mA). In 6 pigs out of 8, fibrillation was even avoided in the longest of the ischaemic periods considered (360 s), for fibrillation threshold ceased falling before reaching the critical level. These experimental results obtained with diltiazem are consistent with the clinical effectiveness of calcium antagonists recently observed in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, left ventricular dP/dtmax was not reduced by more than 6.8% in the present experiments.

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Protection against ischaemic ventricular fibrillation by blocking agents of myocardial cell calcium influx. Electrophysiological study in the pig in situ heart

Cited by 9 publications

References 6 publications

Delay by a calcium antagonist, amlodipine, of the onset of primary ventricular fibrillation in myocardial ischemia

Delay by a calcium antagonist, amlodipine, of the onset of primary ventricular fibrillation in myocardial ischemia

Prevention by Calcium Antagonists of Profibrillatory Effects of Class I Antiarrhythmic Drugs in Acute Myocardial Ischemia: Study in Pig Heart In Situ

Attenuation of the ischaemia-induced fall of electrical ventricular fibrillation threshold by a calcium antagonist, diltiazem

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