The role of the cardiac vagus in maintaining cardiac function during exercise
Authors: Shanks Julia , Pachen Mridula , Chang Joshua W-H , Ramchandra Rohit 
Published: May 2024

There is a strong association between parasympathetic nervous system activity (vagal tone) and physical fitness. High vagal tone is associated with increased capacity to exercise and overall cardiovascular health. Evidence for vagal withdrawal during exercise comes from historic studies examining heart rate control and the use of cholinergic blockers. However, more recent studies have challenged this assumption. We hypothesized that cardiac vagal activity increases during exercise and maintains cardiac function via neurotransmitters other than acetylcholine. The left cardiac vagal branch was identified in anesthetized open-chested sheep. Cardiac innervation of the left cardiac vagal branch was confirmed with lipophilic tracer dyes (DiO). Custom-built coil electrodes were placed around the left cardiac vagal branch. 3-10 days after surgery, conscious, direct recordings of cardiac vagal nerve activity (CVNA), cardiac output, coronary artery blood flow and heart rate were recorded in adult female sheep during whole-body treadmill exercise. Sheep were exercised with pharmacological blockers of acetylcholine (atropine, 250 mg), vasoactive intestinal peptide (VIP) ([4Cl−D-Phe6,Leu17]-VIP 25 μg), or saline control, randomized on different days. In a subset of sheep, the left cardiac vagal branch was denervated. Neural innervation from the cardiac vagal branch is seen at major cardiac ganglionic plexi, and within the fat pads associated with the coronary arteries. Directly recorded CVNA increased during exercise. CVNA increases during the lowest exercise intensity and plateaus as exercise intensity increases. Left cardiac vagal branch, denervation attenuated the maximum changes in coronary artery blood flow (maximum exercise, control: 63.5 ± 5.9 ml/min, n = 8, cardiac vagal denervated: 32.7 ± 5.6 ml/min, n = 6, mean ± SEM. P = 2.5x10−7. Two-way ANOVA-interaction), cardiac output and heart rate during exercise. Atropine did not affect any cardiac parameters during exercise, but VIP antagonism significantly reduced coronary artery blood flow during exercise to a similar level to vagal denervation (maximum exercise, paired: control: 68.2 ± 6.0 ml/min, VIP antagonism: 44.9 ± 3.9 ml/min, n = 6, mean ± SEM. P = 4.8x10−3. Two-way ANOVA-interaction). Our study challenges the conventional view and demonstrates that cardiac vagal nerve activity increases and is crucial for maintaining cardiac function during exercise. Furthermore, our findings show that the dynamic modulation of coronary artery blood flow during exercise is mediated by VIP and that acetylcholine has no role in modulating cardiac function during exercise. This work is supported by the Health Research Council of New Zealand 23/119 (Fellowship. JS) and the New Zealand Heart Foundation (JS, RR). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.