UCLA

The autonomic nervous system regulates cardiac excitability and genesis of ventricular tachyarrhythmias (VT/VF). Myocardial infarction leads to sympathetic activation and parasympathetic dysfunction, which act in concert to increase risk of sudden death due to VT/VF. The mechanism behind parasympathetic dysfunction and the electrophysiological effects of vagal nerve stimulation are poorly characterized.

The vago-symapthetic trunks carries both efferent cardiomotor as well as cardiac afferent fibers that transduce mechano-chemical changes. To better delineate and compare their functional effects, in normal porcine hearts in vivo, right and left vagal nerve stimulation (VNS) was performed and hemodynamic parameters and activation recovery interval mapping (ARI) performed. ARI is a validated surrogate of local action potential duration. Subsequently, role of afferent fiber activation during VNS on efferent control of cardiac function was assessed by transection of right and/or left, and ispilateral, contralateral, and/or bilateral trunks. Finally, mechanism behind neural parasympathetic remodeling due to myocardial infarction (MI) and the anti-arrhythmic effects of VNS were assessed in a chronic porcine infarct model.

In normal porcine hearts, right and left VNS significantly decreased heart rate and dP/dt max and prolonged regional ARI. No anterior-posterior-lateral ventricular regional differences in prolongation of ARI were found. However, endocaridal ARI increased more than epicardial ARI, and apical ARI more than basal ARI, during right and left VNS. With regards to afferent fiber activation during VNS, an augmentation in hemodynamic and electrophysiological effects of right VNS after ipsilateral vagal nerve transection was observed. Similar changes were suggested by left VNS after left vagal nerve transection, however, contralateral vagal nerve transection did not modify VNS response. Finally, measurement of regional acetylcholine, the primary neurotransmitter of cardiac parasympathetic neurons, showed that this neurotransmitter is primarily preserved in infarcted hearts. However, direct neural recordings from intrinsic cardiac ganglia showed significant alterations in the basal activity of parasympathetic efferent neurons that receive input from the left vagal trunk, suggesting a decrease in central parasympathetic drive. Augmentation of parasympathetic drive with VNS reduced ventricular tachy-arrhythmia inducibility by decreasing dispersion of repolarization in border zone regions of infarcted hearts.

In conclusion, both right and left vagi provided significant innervation to the ventricular myocardium, modulating both cardiac electrical and mechanical function. VNS activated both afferent and efferent fibers in the ispilateral vagal trunk, and afferent fiber activation reduced efferent physiological effects. Myocardial infarction led to significant neural remodeling and alteration in the behavior of parasympathetic neurons in the cardiac ganglia, changes that were suggestive of decreased central parasympathetic drive. VNS restored this drive and electrically stabilized infarct border zones, reducing ventricular arrhythmias.