Cellular Mechanisms Underlying the Development of Catecholaminergic Ventricular Tachycardia
Key result
Isoproterenol combined with caffeine induced epicardial ventricular tachycardia in 56.25% (9 of 16) of canine ventricular wedge preparations compared to 21.43% (3 of 14) with isoproterenol alone.
Population
Arterially perfused canine ventricular wedge preparations
Comparison
Isoproterenol in the presence of low-dose caffeine vs Caffeine alone or Isoproterenol alone
Design
Preclinical
Authors
Discussion
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Implication
Offers no clinical guidance; extends animal models of calcium handling defects in CPVT.
Key Points
- This study investigates the cellular mechanisms underlying catecholaminergic ventricular tachycardia caused by RyR2 mutations.
- Simultaneous recording of transmural ECG and action potentials from epicardial, M, and endocardial cells in canine ventricular wedges.
- Low-dose caffeine was used to simulate defective calcium handling.
- Isoproterenol was applied to induce ventricular tachycardia under different conditions.
- Isoproterenol alone induced sustained monomorphic VT in 3 of 14 preparations.
- Caffeine enhanced the induction of epicardial VT from 9 of 16 wedge preparations.
- Propranolol and verapamil completely suppressed ectopic activity arising from the epicardium.
Structured PICO
P
Population
Arterially perfused canine ventricular wedge preparations (n=30 total: 14 for isoproterenol alone, 16 for isoproterenol + caffeine)
I
Intervention
Isoproterenol (100 nmol/L) in the presence of low-dose caffeine (100 to 300 micromol/L)
C
Comparator
Caffeine alone (10 to 300 micromol/L) or Isoproterenol alone (100 nmol/L)
O
Outcome
Induction of ventricular tachycardia (VT) and changes in transmural dispersion of repolarizationsurrogate
Main Result
Absolute Event Rate: 56.25% vs 21.43%
In a canine ventricular wedge model, defective calcium handling mimicked by caffeine combined with isoproterenol induces delayed afterdepolarizations and increases transmural dispersion of repolarization, leading to bidirectional and polymorphic VT.
Cite This Study
Nam et al. (2005) studied Catecholaminergic polymorphic ventricular tachycardia (n=30). Isoproterenol and caffeine vs. Isoproterenol alone was evaluated on Induction of epicardial ventricular tachycardia. Isoproterenol combined with caffeine induced epicardial ventricular tachycardia in 56.25% (9 of 16) of canine ventricular wedge preparations compared to 21.43% (3 of 14) with isoproterenol alone.