In the course of previous studies in puppies 1-6 weeks old we have encountered a high incidence of spontaneous defibrillation occurring during the early weeks and decreasing with age. We have also found during the first weeks an increased vulnerability to fibrillation, as estimated by ventricular fibrillation thresholds, which increases with age. Thus, there might be a critical time during development (3rd-4th week in pups) during which the heart is still vulnerable to fibrillation, but it can no longer defibrillate spontaneously. Although a certain ventricular mass and weight are considered as prerequisites for the maintenance of ventricular fibrillation other postnatal developmental factors may also play a role. We have found so far, that vagal stimulation enhances the incidence of spontaneous defibrillation the first three weeks, while sympathetic stimulation prevents it. In the later weeks autonomic stimulation does not alter the incidence. Differences in the time course of the development of the autonomic innervation to the heart, as identified in previous studies, and their effect in certain electrophysiologic variables can be held responsible. We hypothesize that vagal innervation, which is more developed than the sympathetic, at birth, affects ventricular refractoriness and conduction velocity in a way that, combined with the small ventricular mass, facilitates the cessation of ventricular fibrillation. In contrast, sympathetic innervation, which develops later, by affecting the above variables in the opposite way and in combination with a growing ventricular mass facilitates the maintenance of fibrillation. The proposed studies will be conducted in puppies 1-6 weeks old, studied at weekly intervals. Activation (A) and recovery (R) times and (A-R) intervals, which closely correlate with refractory periods, will be obtained from unipolar epicardial electrograms using computer assisted techniques. The sequential and spatial distributions of the above events will be displayed in map form, to estimate conduction velocities. Data obtained weekly in the control state and during vagal, sympathetic and combined vagosympathetic stimulation will be analyzed for differences in conduction velocity and ventricular refractoriness occurring with autonomic manipulation and/or for age related differences. Ventricular weights will be compared to age and to the incidence of spontaneous defibrillation each week. The developing heart with its borderline mass constitutes a unique model for the study of the above factors.
