Sympathetic innervation modulates ventricular impulse propagation and repolarisation in the immature rat heart

Objective: When cardiac sympathetic innervation in neonatal rats is retarded by antiserum to nerve growth factor, there is a corresponding increase in the QT interval on ECG. Since the propagation of the cardiac impulse and the repolarisation of cardiac cells both contribute to the QT interval, the aim of this study was to determine the role of sympathetic innervation in modulating ventricular impulse propagation and repolarisation. Methods: Neonatal rats were treated for the first 10 days of life with nerve growth factor (NGF), its antiserum (As), or placebo. Standard microelectrode techniques were used to study the transmembrane action potential characteristics of subendocardial (ventricular septal) and subepicardial ventricular myocardium. Bipolar surface electrograms were used to record the velocity of impulse propagation and electron microscopy to examine the intercalated discs. Results: In the subendocardium, the phase 0 upstroke velocity of the action potential (dV/dt_max) was lowest in the As treated rats. The latter group also showed the slowest conduction velocity. There were no differences in control action potential durations in the endocardium among the three groups, but in the epicardial tissues, action potential duration was longest in the As treated group. Thus the dispersion in action potential duration was smallest in the As treated animals. Electron microscopic studies of the intercalated discs of ventricular myocytes showed significant enhancement of nexal junction formation in NGF treated rats, whereas As treated animals showed a retarded pattern of both nexal and desmosomal junction formation. Conclusions: The differences in ultrastructure, conduction, and repolarisation seen in As and NGF treated animals may explain the prolonged QT interval seen in the As treated group.