The structural-functional basis of spontaneous ventricular defibrillation

Manoach, Mordechai; Basat, Mina Ben

doi:10.1016/0167-5273(90)90029-5

Cited by 18 publications

(9 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results correlate very well with previous morphological studies [25,32,33] showing that susceptibility of the myocardium to arrhythmias is closely related to its viability and that the incidence of VF coincides with maximum heterogeneity of ultrastructural alterations of electrically active myocytes.…”

Section: Discussionsupporting

confidence: 91%

“…Reduced intercellular coupling is significantly arrhythmogenic. While in searching for the mechanisms involved in ventricular spontaneous defibrillation, we found that TVF requires a high degree of intercellular synchronization [13,24,25]. Since intercellular synchronization depends on intercellular coupling and conduction, we hypothesized that any defibrillating drug should increase intercellular synchronization, preserve excitation-contraction coupling, and prevent the hypoxia-induced intercellular electrical uncoupling [6,13,14,26].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

1996

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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

1996

Self Cite

View full text Add to dashboard Cite

show abstract

“…Such "synchronized fibrillation" may occur only in hearts with good intercellular coupling, where electrical signals spread through the cells of both ventricles in a manner that brings the cells to act almost in unison [12]. This would require a low intercellular resistance, high intercellular propagation velocity, and tight gap junctions [11][12][13][14][15].…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence of such a transient VF has been commonly observed in young animals [9] and also in adults pretreated with various defibrillating compounds, including tricyclic antidepressants and phenothiazines [10]. The ability of the hearts of young animals to defibrillate spontaneously has been correlated to their predominantly sympathetic autoregulation, as well as to their tight intercellular gap junctions [11], whereas the mechanism of these compounds to transform sustained VF to transient VF has been attributed to an improvement in cellular synchronization [12][13][14].…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Sotalol facilitates spontaneous ventricular defibrillation by enhancing intercellular coupling. An entirely new mechanism for its antiarrhythmic action

et al. 1995

View full text Add to dashboard Cite

We have previously shown that sotalol, a class III antiarrhythmic agent, helps spontaneous ventricular defibrillation in various mammalian species. Since we hypothesized that self ventricular defibrillation depends on a high degree of intercellular synchronization, and since the major electrophysiological action of sotalol causing prolongation of action potential duration (APD), cannot fully explain its defibrillating property, we carried out a series of studies to examine the effect of sotalol on intercellular myocardial coupling. Guinea pig right ventricular muscle preparations were superfused in a tissue bath and the spread of intracellularly injected fluorescent dye (Lucifer yellow CH) to the neighboring cells was studied under various conditions. When either the Ca2+ concentration of Tyrode's solution was elevated to 6 mM or the solution was made hypoxic by not bubbling O2 (n = 3 each), no spread of the injected dye was observed. The addition of 1 microM sotalol to the high Ca2+ solution or 0.5 microM to the hypoxic superfusate (n = 3 each) caused a wide spreading of the dye, thus strongly suggesting a marked improvement in the intercellular coupling. These results show an entirely new property of sotalol, i.e., enhancement of cellular synchronization, which may better explain its ability to cause spontaneous ventricular defibrillation than its class III action. Our previous demonstration of successful spontaneous ventricular defibrillation by several other agents that are known to enhance intercellular coupling but have contrasting actions on APD further substantiates our hypothesis.

show abstract

Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes

Zinman

Shneyvays

Tribulová

et al. 2005

Journal Cellular Physiology

View full text Add to dashboard Cite

In this study, we examined the acute effects of thyroid hormones (TH) T(3) and T(4), leading to improvement of myocardial function through activation of Ca(2+) extrusion mechanisms and, consequently, prevention of intracellular calcium overload. Extracellular calcium elevation from 1.8 to 3.8 mM caused immediate increase in intracellular calcium level ([Ca(2+)](i)) in newborn cardiomyocyte cultures. Administration of 10 or 100 nM T(3) or T(4) rapidly (within 10 sec) decreased [Ca(2+)](i) to its control level. Similar results were obtained when [Ca(2+)](i) was elevated by decreasing extracellular Na(+) concentration, causing backward influx of Ca(2+) through Na(+)/Ca(2+) exchanger, or by administration of caffeine, releasing Ca(2+) from the sarcoplasmic reticulum (SR). Under these conditions, T(3) or T(4) decreased [Ca(2+)](i). T(3) and T(4) also exhibited protective effects during ischemia. T(3) or T(4) presence during hypoxia for 120 min in culture medium restricted the increase of [Ca(2+)](i) and prevented the pathological effects of its overload. An inhibitor of SR Ca(2+)-ATPase (SERCA2a), thapsigargin, increases [Ca(2+)](i) and in its presence neither T(3) nor T(4) had any effect on the [Ca(2+)](i) level. The reduction of [Ca(2+)](i) level by T(3) and T(4) was also blocked in the presence of H-89 (a PKA inhibitor), and by calmodulin inhibitors. The effect of TH on the reduction of [Ca(2+)](i) was prevented by propranolol, indicating that the hormones exert their effect through interaction with adrenergic receptors. These results support our hypothesis that TH prevent calcium overload in newborn rat cardiomyocytes, most likely by a direct, acute, and nongenomic effect on Ca(2+) transport into the SR.

show abstract

The structural-functional basis of spontaneous ventricular defibrillation

Cited by 18 publications

References 42 publications

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

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

Sotalol facilitates spontaneous ventricular defibrillation by enhancing intercellular coupling. An entirely new mechanism for its antiarrhythmic action

Acute, nongenomic effect of thyroid hormones in preventing calcium overload in newborn rat cardiocytes

Contact Info

Product

Resources

About