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The role of catecholamines on intercellular coupling, myocardial cell synchronization and self ventricular defibrillation

  • Part III: Signal Transduction
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Abstract

Ventricular fibrillation (VF) is one of the most life threatening events. Although in humans VF is generally sustained (SVF) requiring artificial defibrillation, in various mammals and in some cases in humans VF terminates by itself, reverting spontaneously into sinus rhythm. Since VF is one of the main causes of sudden death, one of the important clinical problems today is if and how we can transform the fatal SVF into a self limited transient one (TVF).

From electrophysiological studies carried out on anaesthetized open chest animals, we have found that TVF requires a high degree of intercellular coupling and synchronization.

Cardiac myocytes are electrically coupled with adjacent cells. The intercellular coupling is a focus of low electrical resistance which allows rapid transmission of electrical impulses between cells. Any decrease in intercellular coupling decreases the ability of the heart for self defibrillation. The cell-to-cell coupling decreases with age, ischemia, VF and variations in physiological conditions probably due to an increase in intercellular resistance (Ri), widening in the internexal gaps, decrease in electrotonic space constant (λ) etc. All of these factors are known to be affected by intracellular concentration of free Ca++ ([Ca++]).

On the basis of studies carried out on various mammals at different ages, we hypothesized that the ability of the heart to defibrillate depends on the cardiac catecholamine level [CA], during VF. This hypothesis is supported by the facts, known from the literature, that increase in [CA] decreases intracellular free Ca++ concentration, decreases Ri and increases λ. By these effects, increase in [CA] enhances intercellular coupling and intercellular synchronization, and thereby, according to our hypothesis, leads to spontaneous ventricular defibrillation — TVF.

During VF the sympathetic activity is enhanced but in some cases the [CA] does not reach the level needed for TVF. In order to help the heart in its effort to elevate the [CA] during VF, we proposed to treat these cases with drugs which inhibit the reuptake of [CA]. The facts that administration of [CA] reuptake inhibitors, before the induction of VF, and/or intracoronary infusion of adrenaline, during VF, transforms SVF into TVF, emphasized the validity of our hypothesis.

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  1. Sackler School of Medicine, Department of Physiology and Pharmacology, Tel-Avic University, Tel-Aviv, Israel

    Mordechai Manoach, Dalia Varon & Mordechai Erez

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  1. Mordechai Manoach
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  2. Dalia Varon
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  3. Mordechai Erez
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Manoach, M., Varon, D. & Erez, M. The role of catecholamines on intercellular coupling, myocardial cell synchronization and self ventricular defibrillation. Mol Cell Biochem 147, 181–185 (1995). https://doi.org/10.1007/BF00944799

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