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Feasibility of Dantrolene to Study RyR2 Inhibition to Prevent Ventricular Arrhythmias

2019-10-28 13:57:22 | BioPortfolio

Summary

This is an open label trial (N=5 participants) to demonstrate the feasibility of using I.V. dantrolene to study the effect of RyR2 inhibition on cardiac electrophysiology, hemodynamics and ventricular arrhythmia inducibility in patients with structural heart disease referred for VT ablation. The investigators will also explore the pharmacokinetic/pharmacodynamic relationship of I.V. dantrolene and it short-term effect on specific cardiac electrophysiologic and hemodynamic parameters.

Description

Dantrolene inhibits RyR2-mediated Ca leak but does not block the Na channel. By reducing spontaneous Ca leak, dantrolene may reduce Ca mediated Na channel inactivation thereby reversing slowed conduction in abnormal tissues. It also may reduce SK channel activation thereby reversing shortened refractoriness in abnormal tissues. The investigators will test the idea that selective RyR2 inhibition with dantrolene will reduce VT/VF in structural heart disease by reversing proarrhythmic changes in conduction and refractoriness that promote scar-related reentry.

Study Design

Conditions

Ventricular Tachycardia

Intervention

Dantrolene

Location

Vanderbilt University Medical Center
Nashville
Tennessee
United States
37232

Status

Recruiting

Source

Vanderbilt University Medical Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-10-28T13:57:22-0400

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Medical and Biotech [MESH] Definitions

Implantable devices which continuously monitor the electrical activity of the heart and automatically detect and terminate ventricular tachycardia (TACHYCARDIA, VENTRICULAR) and VENTRICULAR FIBRILLATION. They consist of an impulse generator, batteries, and electrodes.

An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).

A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.

Cardiac electrical stimulators that apply brief high-voltage electroshocks to the HEART. These stimulators are used to restore normal rhythm and contractile function in hearts of patients who are experiencing VENTRICULAR FIBRILLATION or ventricular tachycardia (TACHYCARDIA, VENTRICULAR) that is not accompanied by a palpable PULSE. Some defibrillators may also be used to correct certain noncritical dysrhythmias (called synchronized defibrillation or CARDIOVERSION), using relatively low-level discharges synchronized to the patient's ECG waveform. (UMDNS, 2003)

A potentially lethal cardiac arrhythmia characterized by an extremely rapid, hemodynamically unstable ventricular tachycardia (150-300 beats/min) with a large oscillating sine-wave appearance. If untreated, ventricular flutter typically progresses to VENTRICULAR FIBRILLATION.

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