Cisapride-Induced Transmural Dispersion of Repolarization and Torsade de Pointes in the Canine Left Ventricular Wedge Preparation During Epicardial Stimulation
Key result
Cisapride exhibited a biphasic response, inducing Torsade de pointes only at low concentrations (0.2 micromol/L) when transmural dispersion of repolarization was maximally prolonged.
Why the study?
Does cisapride induce torsade de pointes and alter transmural dispersion of repolarization in the canine left ventricular wedge preparation?
Population
Isolated arterially perfused canine left ventricular wedge preparation
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Cautions against assuming low-dose cisapride safety from QT data alone in models; leaves open clinical translation of transmural dispersion mechanisms.
Structured PICO
Does cisapride induce torsade de pointes and alter transmural dispersion of repolarization in the canine left ventricular wedge preparation?
P
Population
Isolated arterially perfused canine left ventricular wedge preparation
I
Intervention
Cisapride (0.1 to 5 micromol/L) added to the coronary perfusate
O
Outcome
Transmembrane action potentials, pseudo-ECG, QT interval, transmural dispersion of repolarization (TDR), and induction of torsade de pointes (TdP)surrogate
Cisapride exhibits a biphasic concentration-response for inducing torsade de pointes, which is driven by increased transmural dispersion of repolarization rather than QT prolongation alone, and is facilitated by epicardial activation.
Cite This Study
Diego et al. (2003) studied Torsade de pointes. Cisapride was evaluated on Transmural dispersion of repolarization and induction of Torsade de pointes. Cisapride exhibited a biphasic response, inducing Torsade de pointes only at low concentrations (0.2 micromol/L) when transmural dispersion of repolarization was maximally prolonged.