Phasic effects of cardiac-synchronized vagus nerve stimulation on spatiotemporal behavior of the sinoatrial node in swine.

Background: Recent clinical trials of cervical vagus nerve stimulation (VNS) in heart failure patients failed to demonstrate the expected benefits seen in experimental studies, potentially due to subtherapeutic VNS levels. The timing and burst firing of VNS affects cardiac cycle length (CL) prolongation and the shift of the sinoatrial node (SAN) from a superior to inferior position in mammals, including humans. Objective: The study sought to determine if parasympathetic nerves of swine respond in a similar manner to other studies in mammals. Methods: Seven pigs were anesthetized using isoflurane for surgical instrumentation before the study. Once completed, the anesthesia was switched to α-chloralose. Cardiac-synchronized VNS was performed in bursts for 10 to 20 cardiac cycles. The synchronization of the bursts varied by 100-ms increments following sensed atrial depolarization. Epicardial mapping was performed to characterize the spatiotemporal behavior of the SAN during VNS in 6 of 7 animals. Results: The average cardiac CL before VNS was 517 ± 73 ms. Altering the synchronized delay of the VNS resulted in CL prolongations (range 16 ± 6% to 27 ± 18%) in pigs, similar to those observed in other mammals. Interestingly, the SAN shifted inferiorly in only 2 of 6 mapped animals during VNS regardless of the extent of CL prolongation. These shift sites, the superior SAN and inferior SAN, alternated between the 2 locations as the CL changed. Conclusion: The temporal behavior of the SAN during cardiac-synchronized VNS in swine is similar to that observed in other mammals, but its spatial behavior is different. Because burst firing of VNS is physiological, future work in swine on its effect on mitigating heart failure should be studied.