Problem
The vagus nerve (VN), a key component of the parasympathetic nervous system, plays a vital role in regulating various bodily functions, including the promotion of the "rest and digest" response. Consequently, vagus nerve stimulation (VNS) has emerged as a significant area of interest for therapeutic applications across a wide range of medical conditions. One particularly compelling area of investigation is the potential use of VNS to address cardiovascular diseases, such as heart failure and atrial fibrillation. Nevertheless, our current understanding of the precise anatomical details, including the fascicular anatomy and topography of the cardiac branch (CB) of the vagus nerve, remains incomplete. This lack of detailed anatomical knowledge limits the potential for targeted cardiac neuromodulation, hindering its therapeutic effectiveness.
Notably, our research and focus have centered on the application of VNS to restore vagal cardiac control in heart transplant patients. Our aim is to reestablish a physiological resting heart rate, ultimately improving the overall quality of life for these patients while reducing adverse treatment outcomes.
Solution
Surgical dissections were performed in pigs and rabbits, and a species-comparative imaging approach was established using µCT and 3D rendering to map the cardiac autonomic innervation with emphasis on the cardiac vagal branches from the level of the nodose ganglion down to the cardiac branches of VN. In addition, anatomical key features such as fascicle numbers as well as the size and area of the nerve were quantitatively measured at different levels.
Our data showed that cardiac vagal fascicles remained separated from other VN fascicles up to 22.19 mm (IQR 14.02–41.30 mm) in pigs and 7.68 mm (IQR 4.06–12.77 mm) in rabbits from the CB point and then started merging with other fascicles. Exchanges of nerve fascicles between sympathetic trunk (ST) and VN were observed in 3 out of 11 nerves, which might cause additional unwanted effects in unselective VNS. Finally, the 3D rendered digital model of the cardiac fascicles that was generated showed that CB first remained on the medial side where it branched off the VN, as also shown in the µCT data of 11 pig nerves, and then migrated towards the ventromedial site the further it was traced cranially.
Furthermore, in conjunction with these anatomical findings, our team has also proposed a numerical model that can predict the acute cardiac responses to VNS and explain the underlying mechanisms on different levels. With this model - tested against published data from sheep - we found that the four most important parameters are related to vagus nerve anatomy (electrode-fiber distances, fiber diameters) and ACh kinetics in the vagal neuroeffector junction (rate of ACh release and -hydrolysis) which together explain >53% of the observed variability in acute cardiac responses to VNS.
Impact
Using microcomputed tomography imaging and subsequent 3D rendering, we revealed here different merging and branching patterns of the cardiac branches among species. Ultimately, this data provided an anatomical map of the cardiac vagal branches including cervical VN and ST for future approaches of selective cardiac neurostimulation, indicating the best position of selective cardiac VNS just above the CB point.
We have also proposed a model that can explain the cardiac responses to VNS on multiple levels. The model represents a substantial improvement in terms of comprehensibility of the underlying mechanisms of the acute cardiac responses to VNS. A tutorial - available here - explains how to use and re-use this model in further depth.
SPARC enhances FAIR data publication by promoting transparency and collaboration. The o²S²PARC platform facilitates seamless integration and analysis of physiological data, while its integration with EM-neuro nerve interface simulations offers valuable insights into neural connections, advancing neuroscientific research.
The anatomical data provides key findings on the species-related CBs, while the numerical model represents a substantial improvement in terms of comprehensibility of the underlying mechanisms of the acute cardiac responses to VNS. And together, they lay the groundwork for future characterization of the cardiac autonomic innervation. Revelations that will prove critical to improved stimulation patterns from selective cardiac VNS.
