Chemical ventricular defibrillation of the human heart with bretylium tosylate

Sanna, G; Arcidiacono, R

doi:10.1016/s0002-9149(73)80168-7

Cited by 93 publications

(21 citation statements)

References 26 publications

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“…It is novel however to find an agent that possesses not only an antiarrhythmic/antifibrillatory capacity, but a defibrillatory capacity. Reports in the past have ascribed this effect to bretylium (Bacaner, 1968;Sanna & Arcidiacono, 1973), but the effects of bretylium on the sympathetic nervous system, i.e., release of catecholamines from sympathetic nerve terminals (Boura & Green, 1959) and side effects of hypotension contributed to its lack of widespread use.…”

Section: Discussionmentioning

confidence: 99%

Antifibrillatory effects of clofilium in the rabbit isolated heart

Friedrichs¹,

Chi²,

Green³

et al. 1994

British J Pharmacology

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1 This study was designed to determine whether clofilium exhibits antifibrillatory activity in a pinacidil + hypoxia-induced model of ventricular fibrillation (VF) in Langendorff-perfused hearts.2 Ten minutes after exposure to vehicle or clofilium (0.1, 1.0 and 10.0 JIM), hearts were exposed to pinacidil (1.25 riM), then subjected to 12 min of hypoxia and reoxygenated. Onset to VF was recorded.Additional groups of hearts were pretreated with UK-68,798 (1.0, 3.0 and 10.0 pLM), a delayed rectifier channel blocker, and 5-hydroxydecanoate (1O iM), a known ATP-dependent K+ channel blocker, and subjected to an identical protocol. 3 Clofilium decreased the incidence of VF in a concentration-dependent manner; 7/9 control hearts developed VF vs 1/9 hearts (P = 0.007, Fisher's Exact) treated with 10.011M clofilium. In addition, 5-hydroxydecanoate protected hearts from VF, while UK-68,798 pretreatment did not. 4 In a separate group of hearts, electrically-induced VF was converted to sinus rhythm in 10/11 hearts after clofilium was introduced as a bolus. 5 Clofilium is capable of preventing VF in the rabbit isolated heart in a concentration-dependent manner. We have data to suggest that the ability of clofilium to attenuate the effects of pinacidil + hypoxia in our model may include blockade of metabolically active K+ channels, i.e., KATP (glibenclamide-sensitive) channel.

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Section: Discussionmentioning

confidence: 99%

Antifibrillatory effects of clofilium in the rabbit isolated heart

Friedrichs¹,

Chi²,

Green³

et al. 1994

British J Pharmacology

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“…During the last two decades, it has been established that spontaneous ventricular defibrillation appears in various mammals [1] and in humans [2] and that different drugs experimentally transform sustained VF (SVF) into a transient form (TVF) [3][4][5]. TVF exhibits slow and well organized electrical fibrillating activity, with a large part of the ventricular mass acting in synchrony, while SVF exhibits unorganized, less synchronized electrical activity, at a higher rate and with small, local fibrillating areas [6].…”

Section: Introductionmentioning

confidence: 99%

The Protective effect ofd-sotalol against hypoxia-induced myocardial uncoupling

1996

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The effects of D-sotalol on intercellular electrical coupling and ultrastructure under hypoxic conditions were investigated in myocardial samples from eight young (1-2 months) and four older (10-12 months) guinea pigs. A right ventricular muscle strip was kept simultaneously in two divided chambers and superfused with normoxic and/or hypoxic (97% N2+ 3% Co2) Krebs solution. Hypoxia caused shortening of action potential duration (APD) and electrical cell-to-cell uncoupling. If the uncoupling appeared after short-term hypoxia (less than 30 min), administration of 3.10(-7)M of D-sotalol to the hypoxic perfusate led to a recovery of electrical coupling. Transmission electron microscopy revealed moderate reversible ultrastructural alterations of the cardiomyocytes. No apparent changes in intercellular junctions were observed. The recoupling effect of sotalol decreased with the time of hypoxia as the ultrastructural damage progressed. After prolonged hypoxia (more than 30 min), cardiomyocytes were markedly injured, intercellular junctions were severely affected, and gap junctions occurred less frequently. In these cases, administration of D-sotalol caused only transient recoupling. After 1 h of hypoxia, no recoupling was observed. Pretreatment with D-sotalol prevented hypoxia-induced electrical uncoupling and markedly attenuated ultrastructural damage, although shortening of APD still persisted. Our results indicate that the cardioprotective effect of D-sotalol on electrical intercellular coupling is closely associated with sotalol-induced prevention of the ultrastructural damage. Considering previous results, we suggest that this protective effect of D-sotalol may be related to its ability to increase intracellular cyclic adenosine monophosphate and, thereby, to decrease cytosolic free Ca. These effects can explain the antiarrhythmic and defibrillating properties of D-sotalol.

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“…Although there have been occasional reports in the literature of chemical defibrillation in humans, e.g. with bretylium [27] and with dibenzepin [28], the concept of defibrillatory drugs is invoked only on rare occasions [29]. Manoach and colleagues [14] regard chemical defibrillation as a separate class of antiarrhythmic activity with considerable therapeutic potential.…”

Section: Reappraisal Of Proarrhythmic Effects Of Drugsmentioning

confidence: 99%

Torsades de pointes: Arrhythmia, syndrome, or chimera? A perspective in the light of the Lambeth Conventions

Curtis

1991

Cardiovasc Drug Ther

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What is torsades de pointes? Is it an arrhythmia or a syndrome? The distinction is critical. In this article I have attempted to explain why this is so. Both from the clinical and nonclinical standpoint, it is of overriding importance that torsades de pointes be amenable to measurement and quantification. This is the fundamental prerequisite for any variable to be of value as an endpoint in an investigation. Measurement and quantification require that a variable has an objective definition that is both inclusive and exclusive. In his seminal work, Dessertenne coined the term torsades de pointes to describe an arrhythmia with unusual features. However, torsades de pointes has been reinterpreted and redefined by Dessertenne's successors. It was originally described as occurring in certain settings (e.g., hypokalemia). However, this has been reinterpreted to mean that a specific set of antecedent conditions (such as hypokalemia) are part of the definition of torsades de pointes. If this is the case, then torsades de pointes is a syndrome, not an arrhythmia. For those more concerned with arrhythmias than with syndromes, the key issue to be determined is what to call the arrhythmia that is part of the syndrome. I have put forward some suggestions with the objective of answering this question, using the Lambeth Conventions as a guide. I believe that there is strong case for ventricular tachyarrhythmias to be classified simply as tachycardia or fibrillation, with the optional use of the term delayed repolarization syndrome in cases where a long QT interval is present. The latter term should be used as one might use the term acute myocardial ischemia, i.e., to denote an underlying condition; it should not be used to define the arrhythmia itself. Twenty-four years after its introduction, the term torsades de pointes has now become a chimera and is best abandoned.

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Chemical ventricular defibrillation of the human heart with bretylium tosylate

Cited by 93 publications

References 26 publications

Antifibrillatory effects of clofilium in the rabbit isolated heart

Antifibrillatory effects of clofilium in the rabbit isolated heart

The Protective effect ofd-sotalol against hypoxia-induced myocardial uncoupling

Torsades de pointes: Arrhythmia, syndrome, or chimera? A perspective in the light of the Lambeth Conventions

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