Improved guinea pig model of cardiac tachyarrhythmias

Guinea pigs are frequently used as models for ventricular tachyarrhythmias, including polymorphic ventricular tachycardia (VT) and ventricular fibrillation. However, applications of the model for short-term therapies are limited because the arrhythmias are transient, typically lasting <5 sec. Thus, spontaneous termination cannot be easily distinguished from effective short-term therapy in standard models. Results of this study confirmed an improved induction method that consistently extends the arrhythmias to 30 sec or longer. In 10 (400- to 1200-g) male guinea pigs, a pacing electrode was advanced in the esophagus. The anode for pacing was a wire advanced through a 20-gauge needle across the diaphragm toward the ventricular apex. Two 12-mm-diameter electrodes were placed on the skin on opposing aspects of the thorax for T-wave stimulation. The blood pressure in the carotid artery was continuously monitored. Two traditional methods were used to induce VT: 2 sec of a 50-Hz square wave, and a single 200 V/5 ms transthoracic stimulus at the peak of the T-wave after pacing at 80% of the intrinsic R-R interval. A third novel method also was used: a single 200 V/5 ms transthoracic stimulus at the peak of the T-wave after a rapid pacing sequence. The rapid pacing sequence was a 25-stimulus sequence, which accelerated to end with 15 beats at the shortest pacing interval for which all pacing stimuli captured. A tachyarrhythmia was defined as any abnormally rapid surface electrocardiographic waveform lasting at least 2 sec after termination of the initiating stimulus. Between 5 and 23 attempts were made to induce tachyarrhythmias in each animal. In four additional animals (>800 g), the efficacy of an established short-term therapy for tachyarrhythmias was measured, using the proposed rapid pacing model. All arrhythmias induced by use of the three induction methods were polymorphic VT accompanied by complete hemodynamic collapse. In hearts weighing >2.5 g (body mass >800 g), 100% of arrhythmia episodes were sustained for 30 sec or longer when initiated after rapid pacing, as opposed to only 55% sustained by use of other induction methods (P < 0.01). The efficacy results for the established short-term therapy matched those previously reported for 100-kg calves. A brief period of rapid pacing facilitates initiation of consistent, sustained ventricular tachyarrhythmias in large guinea pigs, eliminating spontaneous termination as a confounding factor in the study of short-term therapies.