Treatment of ventricular fibrillation and other acute arrhythmias with bretylium tosylate

Bacaner, Marvin B.

doi:10.1016/0002-9149(68)90286-5

Cited by 122 publications

(23 citation statements)

References 4 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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“…93,140,141 It also suggests a need in vulnerable patients for total norepinephrine transmitter blockade as achieved with bretylium, which certainly reduces the risk of SCD from VF. 150,[153][154][155][156][157][158][159][160][161][162][163][164][165][166][167] This protective effect of adrenergic blockade against vascular disease is not surprising because catecholamines activate phospholipases that have an important impact on lipid metabolism. 96,[119][120][121][122][123][124] This further links the development of atherosclerotic disease to adrenergic actions 2,74,79 since it can be antagonized by adrenergic blockade.…”

Section: Connecting the Dots Leading To The Concept Of Adcvhd And Neumentioning

confidence: 99%

“…The introduction of bretylium into cardiac therapy in the early 1960s specifically to suppress VF 153,[155][156][157][158][159][160] slowly forced recognition by the cardiac community in latter decades of the past century that VF was not simply an extension of a nonlife-threatening hemodynamically stable arrhythmia such as a premature ventricular contraction (PVC) (as postulated by Lown et al 161 in their warning arrhythmia hypothesis) that VF could be suppressed by Na + channel blocking antiarrhythmic drugs (like lidocaine) by suppressing PVCs. 160 However, it is now finally a widely accepted fact that suppression of VF does indeed require specific antifibrillatory drug actions exerted by so-called class 3 drugs 1 5 3 , 1 5 5 -1 6 0 , 1 6 2 (action potentiallengthening agents) to restore the normal spatial and temporal homogeneity of electrical parameters abnormally dispersed by cardiac disease, primarily IHD, 163,164 which makes the heart vulnerable to undergo and sustain VF by lowering VF threshold (VFT).…”

Section: Cardiac Therapy With Bretyliummentioning

confidence: 99%

Prevention of Ventricular Fibrillation, Acute Myocardial Infarction (Myocardial Necrosis), Heart Failure, and Mortality by Bretylium

Bacaner

Brietenbucher²,

LaBree³

2004

American Journal of Therapeutics

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It is widely, but mistakenly, believed that ischemic heart disease (IsHD) and its complications are the sole and direct result of reduced coronary blood flow by obstructive coronary artery disease (CAD). However, cardiac angina, acute myocardial infarction (AMI), and sudden cardiac death (SCD) occur in 15%-20% of patients with anatomically unobstructed and grossly normal coronaries. Moreover, severe obstructive coronary disease often occurs without associated pathologic myocardiopathy or prior symptoms, ie, unexpected sudden death, silent myocardial infarction, or the insidious appearance of congestive heart failure (CHF). The fact that catecholamines explosively augment oxidative metabolism much more than cardiac work is generally underappreciated. Thus, adrenergic actions alone are likely to be more prone to cause cardiac ischemia than reduced coronary blood flow per se. The autonomic etiology of IsHD raises contradictions to the traditional concept of anatomically obstructive CAD as the lone cause of cardiac ischemia and AMI. Actually, all the signs and symptoms of IsHD reflect autonomic nervous system imbalance, particularly adrenergic hyperactivity, which may by itself cause ischemia as in rest angina. Adrenergic activity causing ischemia signals cardiac pain to pain centers via sympathetic efferent pathways and tend to induce arrhythmogenic and necrotizing ischemic actions on the cardiovascular system. This may result in ischemia induced metabolic myocardiopathy not unlike that caused by anatomic or spasmogenic coronary obstruction. The clinical study and review presented herein suggest that adrenergic hyperactivity alone without CAD can be a primary cause of IsHD. Thus, adrenergic heart disease (AdHD), or actually adrenergic cardiovascular heart disease (ACVHD), appears to be a distinct entity, most commonly but not necessarily occurring in parallel with CAD. CAD certainly contributes to vulnerability as well as the progression of IsHD. This vicious cycle, which explains the frequent parallel occurrence of arteriosclerosis and IHD, an association that appears to be linked by the same cause, comprises a common vulnerability to deleterious adrenergic actions on the myocardium, lipid metabolism, and vascular system alike, rather than viewing CAD and IsHD as having a putative cause and effect relationship as commonly thought. Adrenergic actions can also cause the abnormal lipid metabolism that is associated with CAD and IsHD by catecholamine-induced metabolic actions on lipid mobilization by activation of phospholipases. This may also be part of toxic catecholamine hypermetabolic actions by enhancing deleterious cholesterol and lipid actions in damaging coronary vessels by plaque formation as well as inducing obstructive coronary spasm and platelet aggregation. This may also cause direct toxic necrosis on the myocardium as well as atherosclerosis in blood vessels. In fact, drugs that inhibit adrenergic actions like propranolol, reserpine, and guanethidine all inhibit arteriosclerosis induced by hypercholestero...

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“…However, almost every controlled study has failed to show a reduction in the incidence of ventricular fibrillation by prophylactic administration of lidocaine even when arrhythmias per se were suppressed (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). In contrast, ventricular fibrillation can be suppressed by bretylium tosylate and its pharmacologic analog, bethanidine sulphate (2,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Both drugs (termed class 3) increase ventricular fibrillation threshold manyfold, facilitate electrical defibrillation, and induce episodes of pharmacologic (spontaneous) defibrillation under conditions where it does not normally occur (refs.…”

Section: Introductionmentioning

confidence: 99%

Potassium channel blockade: A mechanism for suppressing ventricular fibrillation.

Bacaner¹,

Clay²,

Shrier³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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The suppression of ventricular fibrillation by antidysrhythmic drugs is well correlated with their ability to block potassium channels in nerve and cardiac membranes. Blockade of potassium channels reduces electrical inhomogeneities in action potential and conduction parameters that lead to ventricular fibrillation. These actions tend to effectively decrease the electrical size of the heart, which suggests a mechanism for antifibrillatory drug action. The receptor sites for antifibrillatory drug action (IK blockade) appear to be on the outside of the cardiac membrane whereas receptors for antiarrhythmic drug action (INa blockade) appear to be on the inside of the cardiac membrane.

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Treatment of ventricular fibrillation and other acute arrhythmias with bretylium tosylate

Cited by 122 publications

References 4 publications

Antifibrillatory effects of clofilium in the rabbit isolated heart

Antifibrillatory effects of clofilium in the rabbit isolated heart

Prevention of Ventricular Fibrillation, Acute Myocardial Infarction (Myocardial Necrosis), Heart Failure, and Mortality by Bretylium

Potassium channel blockade: A mechanism for suppressing ventricular fibrillation.

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