Effects of dantrolene sodium in rodent models of cardiac arrhythmia

Brooks, Robert R.; Carpenter, John F.; Jones, Scott; Gregory, Cinda M.

doi:10.1016/0014-2999(89)90260-4

Cited by 22 publications

(8 citation statements)

References 18 publications

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“…Because of these fast repetitive activations, intracellular Na + and Ca 2+ overload occurs contributing to Ca 2+ oscillations, the consequent electrical instability and myocardial dysfunction even after successful defibrillation (Zaugg et al, 1998). An early study showing the increased fibrillation threshold after dantrolene administration in rats (Brooks et al, 1989) has been followed by a recent study demonstrating that cessation of the abnormal Ca 2+ cycling by applying dantrolene to inhibit RyR effectively ameliorated the postfibrillatory ventricular dysfunction in pigs in vivo (Zamiri et al, 2014). In addition, dantrolene facilitated the success of defibrillation and decreased the number of refibrillation episodes.…”

Section: Antiarrhythmic Effect Of Ryr Inhibitionmentioning

confidence: 99%

Role of the dysfunctional ryanodine receptor - Na+-Ca2+exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies?

Acsai

Ördög

Varró

et al. 2016

European Journal of Pharmacology

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Abnormal Ca(2+)homeostasis is often associated with chronic cardiovascular diseases, such as hypertension, heart failure or cardiac arrhythmias, and typically contributes to the basic ethiology of the disease. Pharmacological targeting of cardiac Ca(2+)handling has great therapeutic potential offering invaluable options for the prevention, slowing down the progression or suppression of the harmful outcomes like life threatening cardiac arrhythmias. In this review we outline the existing knowledge on the involvement of malfunction of the ryanodine receptor and the Na(+)-Ca(2+)exchanger in disturbances of Ca(2+)homeostasis and discuss important proof of concept pharmacological studies targeting these mechanisms in context of hypertension, heart failure, atrial fibrillation and ventricular arrhythmias. We emphasize the promising results of preclinical studies underpinning the potential benefits of the therapeutic strategies based on ryanodine receptor or Na(+)-Ca(2+)exchanger inhibition.

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Section: Antiarrhythmic Effect Of Ryr Inhibitionmentioning

confidence: 99%

Role of the dysfunctional ryanodine receptor - Na+-Ca2+exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies?

Acsai

Ördög

Varró

et al. 2016

European Journal of Pharmacology

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“…The class 111 electrophysiologic action was manifested in vitro at concentrations equal to or greater than those required for skeletal muscle-relaxant activity. An antianhythmic action of dantrolene sodium in vivo was established in a rat occlusion-reperfusion model of ventricular arrhythmias (7).…”

Section: Introductionmentioning

confidence: 99%

Pharmacology of Azimilide Dihydrochloride (NE‐10064), A Class III Antiarrhythmic Agent

Salata

Brooks

1997

Cardiovascular Drug Reviews

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“…On the other hand, enhanced automaticity has been reported to be the dominant mechanism of VPBs in post-IR injury hearts [ 22 ]. The lack of a VPB suppressing effect by dantrolene could be due to its inability to suppress automaticity [ 23 , 24 ]. Second, if triggered activity is the dominant mechanism of VPBs, it implies that dantrolene could not ameliorate the Ca i overload condition effectively in these IR hearts.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dantrolene on Arrhythmogenicity in Isolated Regional Ischemia-Reperfusion Rabbit Hearts with or without Pacing-Induced Heart Failure

Chou

Lee

Chang

et al. 2015

BioMed Research International

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Dantrolene was reported to suppress ventricular fibrillation (VF) in failing hearts with acute myocardial infarction, but its antiarrhythmic efficacy in regional ischemia-reperfusion (IR) hearts remains debatable. Heart failure (HF) was induced by right ventricular pacing. The IR rabbit model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo in both HF and non-HF groups (n = 9 in each group). Simultaneous voltage and intracellular Ca2+ (Cai) optical mapping was then performed in isolated Langendorff-perfused hearts. Electrophysiological studies were conducted and VF inducibility was evaluated by dynamic pacing. Dantrolene (10 μM) was administered after baseline studies. The HF group had a higher VF inducibility than the control group. Dantrolene had both antiarrhythmic (prolonged action potential duration (APD) and effective refractory period) and proarrhythmic effects (slowed conduction velocity, steepened APD restitution slope, and enhanced arrhythmogenic alternans induction) but had no significant effects on ventricular premature beat (VPB) suppression and VF inducibility in both groups. A higher VF conversion rate in the non-HF group was likely due to greater APD prolonging effects in smaller hearts compared to the HF group. The lack of significant effects on VPB suppression by dantrolene suggests that triggered activity might not be the dominant mechanism responsible for VPB induction in the IR model.

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Effects of dantrolene sodium in rodent models of cardiac arrhythmia

Cited by 22 publications

References 18 publications

Role of the dysfunctional ryanodine receptor - Na+-Ca2+exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies?

Role of the dysfunctional ryanodine receptor - Na+-Ca2+exchanger axis in progression of cardiovascular diseases: What we can learn from pharmacological studies?

Pharmacology of Azimilide Dihydrochloride (NE‐10064), A Class III Antiarrhythmic Agent

Effects of Dantrolene on Arrhythmogenicity in Isolated Regional Ischemia-Reperfusion Rabbit Hearts with or without Pacing-Induced Heart Failure

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