Introduction: The importance of beta receptor blockade for the antiarrhythmic action of sotalol has not been completely elucidated. We determined how beta receptor blockade interacts with the effects of potassium channel blockade on reentrant circuits. Methods and Results: Sustained ventricular tachycardia was induced by programmed stimulation in dogs 4 days after left anterior coronary artery occlusion and reentrant circuits in the epicardial border zone (EBZ) mapped. The effects of the beta receptor-blocking drug, esmolol, the potassium channel-blocking drug d-sotalol, which lacks beta receptor-blocking effects, and the combination of the two drugs on the reentrant circuits that cause tachycardia were determined. Esmolol did not alter the ability to induce tachycardia. Small changes in the location or extent of lines of block in reentrant circuits accounted for small decreases or increases in tachycardia cycle lengths. d-Sotalol prolonged the lines of block in reentrant circuits, slowed propagation around the circuits, and prolonged tachycardia cycle length, but it did not stop tachycardia or prevent the induction of tachycardia. The combination of esmolol and d-sotalol prevented the initiation of sustained tachycardia. The stimulated premature impulse either blocked before reentering or traversed the circuit several times prior to blocking in a region of fractionated electrograms. The addition of esmolol to d-sotalol abolished the reverse use-dependent effects of d-sotalol alone on effective refractory period (ERP) and significantly prolonged ERP in the area of the reentrant circuit. Conclusion: Beta receptor blockade is important for the antiarrhythmic effects of d,1-sotalol on reentrant ventricular tachycardia in this model. The mechanism is speculative but may involve potentiation of d-sotalol actions to prolong ERP or effects on gap junctions.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
- Beta receptor blockade
- Potassium channel block
- Ventricular tachycardia