The autonomic nervous system is essential for the regulation of heart rhythm and contraction and for adaptation to cardiac load. Heart or heart–lung transplants or other surgical procedures that result in vagotomy reduce exercise tolerance and can contribute to cardiac dysfunctions. In small animal models of heart failure, stimulation of the right vagus nerve (RVN) has cardioprotective effects. However, the effects of RVN repair on the heart are not well explored. In Science Translational Medicine, Dushpanova et al. conducted a study in minipigs, a large animal model that mirrors human cardiac anatomy, to analyze whether repair of transected vagus nerve could preserve cardiac function. They found that the RVN is “not only a brake on sympathetic drive but also a guardian of cardiac youthfulness”, says corresponding author Lionetti.
The researchers used male minipigs and divided them into a sham-operated group (controls) and two fully operated groups. Operated animals received (treated) or did not receive (untreated) a biodegradable cuff-like nerve guidance conduit (C-NGC) composed of chitosan (Chi) and poly-ε-caprolactone (PCL) after the right vagotomy to reconnect the RVN. Findings showed that 4 months after surgery, the untreated group had impaired global left ventricle (LV) strain, and reduced LV ejection fraction and stroke volume compared with the control and treated groups, whereas hemodynamic parameters remained stable in all groups. The vagotomy caused a reduction in LV strain in the anterior LV regions and in the inferior and septal segments, sigmoidal early-diastolic septal motion, higher maximal diastolic dyssynchrony, and reduced the LV early peak filling rate, which were preserved by heart-RVN reconnection in the treated group. Although these differences were apparent 10 days or 1 month after vagotomy, they became significant after 4 months. The heart–RVN–reconnection through ChiPCL C-NGC restored the sympathetic–parasympathetic balance, prevented vagal fascicle degeneration and supported the regrowth of vagal fibers. In addition, the untreated pigs showed increased levels of oxidative stress, cellular senescence and macrophage infiltration in the dysfunctional cardiac regions, alongside higher levels of IL-10 and IL-11 than the controls and treated animals. Proteomics analysis showed that in the hearts of ChiPCL C-NGC-treated minipigs, proteins involved in complement activation, fibrinolysis and proinflammatory signaling were downregulated. Conversely, similar cardiac regions of untreated pigs showed altered, partly opposite expression patterns. In the hearts of treated pigs, proteins related to mitochondrial respiration, sarcomeric organization and calcium handling were upregulated and showed a similar expression pattern to the control group, and this pattern seemed to contribute to the cardiac ‘youthfulness’.
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