Calcium channel blockers and early ischemic ventricular arrhythmias: Electrophysiological versus anti-ischemic effects

Coetzee, William A.; Dennis, Steven C.; Opie, Lionel H.; Müller, C.

doi:10.1016/s0022-2828(87)80006-8

Cited by 22 publications

(2 citation statements)

References 82 publications

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“…During each phase of the protocol (i.e., control, simulated ischemia, and reperfusion), we interrupted the basic drive cycle for 30 seconds to observe delayed afterdepolarizations or triggered activity or both. We then stimulated the preparations at cycle lengths of 500 and 300 msec (15)(16)(17)(18)(19)(20) beats/cycle) and interrupted the drive for 30 seconds before returning to the basic drive cycle of 800 msec. We performed three simulated ischemia and reperfusion protocols with three or four fibers for each protocol in this fashion.…”

mentioning

confidence: 99%

Alpha-adrenergic receptor stimulation during simulated ischemia and reperfusion in canine cardiac Purkinje fibers.

Hamra

Rosen

1988

Circulation

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confidence: 99%

Alpha-adrenergic receptor stimulation during simulated ischemia and reperfusion in canine cardiac Purkinje fibers.

Hamra

Rosen

1988

Circulation

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“…Two mecha nisms have been suggested to explain the antifibrillatory potential of calcium antagonists, such as verapamil. The first mechanism un derlying the antiarrhythmic activity of cal cium blockers involves inhibition of the cal cium currents in ventricular tissue [23,25] which could reduce the occurrence of trig gered activities [26]. The prominent role of the calcium current in rabbit ventricular myo cytes [27,28] may explain the greater efficacy of verapamil compared to zatebradine in the present study.…”

Section: Discussionmentioning

confidence: 67%

Effect of Zatebradine, a Specific Bradycardic Agent, on Ischemia-Induced Arrhythmias in Anesthetized Rabbits

Bril¹,

Forest²,

Cheval³

et al. 1994

Pharmacology

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The effects of the specific bradycardic agent, zatebradine (UL·FS 49), on ventricular arrhythmias occurring during an acute ischemia were compared to those of verapamil. Anesthetized rabbits were submitted to a ligation of the left circumflex coronary artery for 20 min. Zatebradine (150 and 750 µg/kg, i.v.) dose-dependently reduced heart rate, but changed neither the left ventricular pressure nor the (+)dp/dt_max. In comparison, verapamil (150 and 750 µg/kg, i.v.) reduced heart rate, systemic blood pressure, left ventricular pressure and (+)dp/dt_max. The incidence of ventricular premature beats occurring during acute ischemia was changed neither by zatebradine nor by verapamil. Ventricular fibrillation, occurring in 36% of the saline-treated rabbits, was reduced to 18% in the presence of 750 µg/kg of zatebradine and 0% with verapamil (750 µg/kg, p < 0.05). The action of zatebradine on ischemia-induced ventricular fibrillation, albeit limited, was completely reversed by atrial pacing to the predrug heart rate. To further investigate the mechanisms involved in the antiarrhythmic potential of both zatebradine and verapamil, their electrophysiological actions were compared in canine Purkinje fibers. Both zatebradine and verapamil induced a dose-dependent increase in action potential duration (APD) measured at 90% repolarization. The APDs measured during the plateau level (APD30) and at 50% of the repolarization (APD50) were shortened by verapamil and increased by zatebradine showing that at the concentrations used, zatebradine did not exhibit any calcium antagonistic activity when compared to verapamil. The results of the present study suggest that the specific bradycardic agent zatebradine showed a beneficial action mainly because of its anti-ischemic properties. However, the present studies performed in anesthetized rabbits suggest that in this species pure reduction in heart rate is not sufficient to entirely prevent ischemic arrhythmias.

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Myocardial Infarction Agents

Altschuld

2003

Burger's Medicinal Chemistry and Drug Discovery

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A myocardial infarction begins with the occlusion of a coronary artery, usually resulting from the rupture of an atherosclerotic plaque. Pharmacologic treatment begins with conventional pain relief and under appropriate circumstances thrombolytic agents are administered. Anticoagulants are used in conjunction with thrombolytic agents to assist thrombolysis and prevent reocclusion of the affected vessel. Lethal arrhythmias such as ventricular fibrillation are a major cause of death following myocardial infarction. β‐Adrenoceptor antagonists are used to reduce the incidence of this sudden cardiac death. Angiotensin converting enzyme inhibitors are used to reduce post‐infarction ventricular remodeling, which is a leading cause of congestive heart failure. Current therapy has significantly reduced in hospital mortality but acute myocardial infarction remains the leading cause of death in the United States. Congestive heart failure secondary to myocardial infarction is becoming an epidemic. Additional therapeutic agents and/or strategies are needed to reduce death and disability following myocardial infarction.

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Calcium channel blockers and early ischemic ventricular arrhythmias: Electrophysiological versus anti-ischemic effects

Cited by 22 publications

References 82 publications

Alpha-adrenergic receptor stimulation during simulated ischemia and reperfusion in canine cardiac Purkinje fibers.

Alpha-adrenergic receptor stimulation during simulated ischemia and reperfusion in canine cardiac Purkinje fibers.

Effect of Zatebradine, a Specific Bradycardic Agent, on Ischemia-Induced Arrhythmias in Anesthetized Rabbits

Myocardial Infarction Agents

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