Effects of ryanodine on ouabain-induced spontaneous mechanical and electrical oscillations in guinea-pig heart

Zakharov, Sergey I.

doi:10.1016/0022-2828(91)90022-e

Cited by 7 publications

(2 citation statements)

References 21 publications

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“…In addition, ryanodine has demonstrated efficacy in reducing early afterdepolarizations and Torsades de Pointes in a canine model of chronic AV nodal block (Verduyn et al, 1995). Similar to the findings in canines, ryanodine has been shown to reduce ouabain-induced arrhythmias in guinea pigs (Golovina et al, 1988; Zakharov et al, 1991). There is also evidence suggesting that ryanodine may reduce reperfusion-induced arrhythmias (Thandroyen et al, 1988; Hayashi et al, 1996).…”

Section: Therapeutic Strategiessupporting

confidence: 76%

Dysregulated sarcoplasmic reticulum calcium release: Potential pharmacological target in cardiac disease

Györke

Carnes

2008

Pharmacology & Therapeutics

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In the heart, Ca 2+ released from the intracellular Ca 2+ storage site, the sarcoplasmic reticulum (SR), is the principal determinant of cardiac contractility. SR Ca 2+ release is controlled by dedicated molecular machinery, composed of the cardiac ryanodine receptor (RyR2) and a number of accessory proteins, including FKBP12.6, calsequestrin (CASQ2), triadin (TRD) and junctin (JN). Acquired and genetic defects in the components of the release channel complex result in a spectrum of abnormal Ca 2+ release phenotypes ranging from arrhythmogenic spontaneous Ca 2+ releases and Ca 2+ alternans to the uniformly diminished systolic Ca 2+ release characteristic of heart failure. In this article, we will present an overview of the structure and molecular components of the SR and Ca 2+ release machinery and its modulation by different intracellular factors, such as Ca 2+ levels inside the SR as well as phosphorylation and redox modification of RyR2s.We will also discuss the relationships between abnormal SR Ca 2+ release and various cardiac disease phenotypes, including, arrhythmias and heart failure, and consider SR Ca 2+ release as a potential therapeutic target.

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Section: Therapeutic Strategiessupporting

confidence: 76%

Dysregulated sarcoplasmic reticulum calcium release: Potential pharmacological target in cardiac disease

Györke

Carnes

2008

Pharmacology & Therapeutics

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“…, 1988). Zakharov, Bogdanov & Golovina (1991) showed that ouabain‐induced ventricular arrhythmias were terminated after intravenous injection of ryanodine and sinus rhythm was completely restored in guinea‐pigs. This antiarrhythmic effect of ryanodine is probably related to a cellular effect and alteration of sarcoplasmic reticulum function.…”

Section: Calcium Channelsmentioning

confidence: 99%

Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels

Demiryürek

2005

Auton Autocoid Pharmacol

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1 Cardiac glycosides have been used for centuries as therapeutic agents for the treatment of heart diseases. In patients with heart failure, digoxin and the other glycosides exert their positive inotropic effect by inhibiting Na(+)-K(+)-ATPase, thereby increasing intracellular sodium, which, in turn, inhibits the Na(+)/Ca(2+) exchanger and increases intracellular calcium levels. As the therapeutic index of digitalis is narrow, arrhythmias are common problems in clinical practice. The mechanisms and mediators of these arrhythmias, however, are not completely understood. 2 The involvement of the sympathetic and parasympathetic nervous system in digitalis cardiac toxicity is reviewed. 3 Receptors, channels, exchange systems or other cellular components involved in digitalis-induced cardiotoxicity are also reviewed. 4 Possible mediators of digitalis-induced cardiac toxicity are discussed. 5 Management of digitalis toxicity in patients is summarized. 6 The determination of the possible mediators of digitalis-induced cardiac toxicity will enhance our knowledge and lead to the development of new therapeutic strategies to treat these lethal arrhythmias.

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Effects of cromakalim or glibenclamide on arrhythmias and dispersion of refractoriness in chronically infarcted anesthetized dogs

DʼAlonzo

Sewter

Darbenzio

et al. 1995

Naunyn-Schmiedeberg's Arch Pharmacol

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The proarrhythmic effects of the ATP-sensitive potassium channel modulators cromakalim (n = 10; 0.01 to 0.3 mg/kg i.v.), glibenclamide (n = 10; 0.3 to 10 mg/kg i.v.) or volume equivalents of vehicle (n = 10) were evaluated in post-infarcted anaesthetised dogs. Dogs were anaesthetised, subjected to an anterior-apical myocardial infarction, and allowed to recover. At 7.4 +/- 0.7 days post infarction, animals were anaesthetised again, electrophysiologic measurements (effective refractory periods, QT-intervals and ventricular fibrillation thresholds) were taken, and animals were tested for arrhythmias using a programmed electrical stimulation protocol. Only animals that did not have programmed electrical stimulation-inducible arrhythmias were used. Ventricular fibrillation thresholds were determined twice, once before the first dose then after the last dose of drug. At the end of the experiment, animals were subjected to ligation of the left circumflex coronary artery and survival was measured over the next two hours. Cromakalim significantly increased heart rate and decreased blood pressure. Although cromakalim significantly reduced effective refractory periods, it neither increased electrical dispersion, as determined by the standard deviation or coefficient of variance of the effective refractory period, nor did it enhance inducibility (0 out of 10 in both vehicle and cromakalim treated animals), change ventricular fibrillation thresholds, or reduce sudden death survival relative to vehicle. Glibenclamide did not increase electrical dispersion, but slightly increased the incidence of programmed electrical stimulation-induced arrhythmias (3 out of 10), and lowered ventricular fibrillation thresholds values. However, these changes were not statistically significant. Glibenclamide did not significantly affect survival relative to vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effects of ryanodine on ouabain-induced spontaneous mechanical and electrical oscillations in guinea-pig heart

Cited by 7 publications

References 21 publications

Dysregulated sarcoplasmic reticulum calcium release: Potential pharmacological target in cardiac disease

Dysregulated sarcoplasmic reticulum calcium release: Potential pharmacological target in cardiac disease

Cardiotoxicity of digitalis glycosides: roles of autonomic pathways, autacoids and ion channels

Effects of cromakalim or glibenclamide on arrhythmias and dispersion of refractoriness in chronically infarcted anesthetized dogs

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