Endogenous VIP May Contribute to Vagally Induced Electrophysiological Changes in Canine Atria

Background: There has been increasing evidence that complex interactions among the various components of intracardiac neural network play an important role in atrial fibrillation (AF). Perfusion of vasoactive intestine polypeptide (VIP), a neural polypeptide, co-released with acetylcholine from intrinsic cardiac neurons during vagal stimulation, was shown to shorten the action potential duration (APD), decrease the intraatrial conduction velocity (CV), and promote induction of AF. However, the effect of endogenous VIP remains unclear. Methods: In 6 isolated arterially perfused canine left atria, high-resolution optical mapping techniques with di-4-ANEPPS and blebbistatin were used to measure APD and CV during fat-pad ganglion plexus stimulation (GPS, 30Hz, 10.2±2.3Volt validated with blockage of atrioventricular conduction), at during H9935, a VIP antagonist (1 μM) perfusion. The atria were paced at 200beats per minute. Metoprolol (1.8μM) was used to block the sympathetic effects. Results: Average APD was shorter (21%) during GPS compared to the baseline (100±8ms vs. 126±7ms, p<0.05), and average CV was slower than baseline (87±10cm/sec vs. 103±13cm/sec, p<0.05), which recovered within 2 min (APD: 128±8ms, p<0.05; CV: 105±13cm/sec, p<0.05). With H9335, the APD shortening effect (17%) of GPS persisted (GPS, 105±14ms, vs. 127±8ms at baseline and 125±10ms after recovery, p<0.05) with a trend towards being less pronounced as compared to GPS effect without H9335 (−18±6ms vs. −29±3ms, p=0.07). However, the GPS-induced CV slowing was abolished by H9335 (97±14cm/sec, vs. 103±15cm/sec at baseline and 101±16cm/sec after recovery, p=0.23). The effects of endogenous VIP were eliminated by atropine during GPS, indicating VIP release from intrinsic cardiac neurons may be mediated by muscarinic recpetors. Conclusion: Neuronally released VIP could contribute vagal effects and is primarily responsible for CV slowing during GPS. Neuronal release of VIP is likely mediated by muscarinic receptors in the intrinsic cardiac neurons.