J Physiol. 2025 Dec 31. doi: 10.1113/JP290343. Online ahead of print.
ABSTRACT
We know that ischaemic cardiomyopathy leads to compensatory changes in the cardiovascular system to offset the reduction in cardiac output; there is a marked increase in cardiac sympathetic drive, as measured by noradrenaline spillover, and a marked increase in sympathetic vasoconstrictor drive to the skeletal muscle vascular bed, as measured by recording muscle sympathetic nerve activity from a peripheral nerve. Conversely based on assessment of heart rate variability there is believed to be a decrease in cardiac parasympathetic drive. Accordingly we might expect a decrease in ongoing neural activity in the vagus nerve. To test this we performed microelectrode recordings from the right vagus nerve in 14 patients with ischaemic cardiomyopathy and left ventricular ejection fractions ranging from 30%-48%. Multiple intrafascicular sites were analysed in each participant, with 57 multiunit sites being identified in which ongoing neural activity exhibited cardiac rhythmicity. Construction of cross-correlation histograms between the neural activity and the ECG demonstrated that there was no reduction in cardiac-modulated neural activity when compared to a group of healthy controls. Rather the magnitude of cardiac modulation of vagal activity was significantly elevated in ischaemic cardiomyopathy: 30.8% ± 13.7% (mean ± SD) vs. 18.1% ± 18.0% (P < 0.0001). Conversely there was no significant difference in the magnitude of respiratory modulation of vagal activity (48.0 ± 24.6% vs. 40.7% ± 22.7%, P = 0.1122). We conclude that ongoing cardiac-modulated activity in the right vagus nerve is elevated in ischaemic cardiomyopathy. Given that most of the vagus nerve is sensory we interpret this as reflecting an increase in afferent activity from the failing heart. KEY POINTS: Intraneural recordings from the cervical vagus were obtained in awake patients with ischaemic cardiomyopathy via tungsten microelectrodes inserted into the nerve through ultrasound guidance. Cross-correlation analysis of multiunit vagal activity revealed cardiac and respiratory modulation, from which the amplitude of modulation could be computed. We expected cardiac-locked vagal activity to be reduced, given the evidence for an overall reduction in heart rate variability in heart failure and the interpretation that this largely reflects an increase in cardiac sympathetic drive and a decrease in parasympathetic drive. However compared to data obtained in healthy participants the magnitude of cardiac modulation of vagal activity was significantly elevated in ischaemic cardiomyopathy (31% vs. 18%), but there was no significant difference in the magnitude of respiratory modulation of vagal activity (48% vs. 41%). We interpret this as reflecting an increase in afferent activity from the failing heart.
PMID:41474364 | DOI:10.1113/JP290343