Targeting the carotid arteries for neuromodulation therapy – Human nerve distribution and density

H. Struthoff (Homburg/Saar)¹, L. Lauder (Basel)², J. Federspiel (Homburg/Saar)³, M. Hohl (Homburg/Saar)¹, M. Böhm (Homburg/Saar)¹, T. Tschernig (Homburg)⁴, F. Mahfoud (Basel)^2
1Universitätsklinikum des Saarlandes Innere Medizin III - Kardiologie, Angiologie und internistische Intensivmedizin Homburg/Saar, Deutschland; ²Universitätsspital Basel Abt. für Kardiologie Basel, Schweiz; ³Universitätsklinikum des Saarlandes Institut für Rechtsmedizin Homburg/Saar, Deutschland; ⁴Universität des Saarlandes Zellbiologie und Anatomie Homburg, Deutschland

Background: Modulating the autonomic nervous system is an attractive treatment target for cardiovascular diseases, including hypertension and heart failure. Knowledge about the nerves running along the carotid arteries is essential to identify treatment targets and further refine existing technologies and techniques.
Objective: To assess the nerve distribution along carotid arteries in human body donors.Methods: Carotid arteries and adjacent tissue from nine body donors were excised and examined histologically. Immunohistochemical staining was used to analyze nerve size and distribution and to identify afferent (calcitonin gene-related peptide [CGRP]-positive) and efferent (tyrosine hydroxylase [TH]-positive) sympathetic nerve fibers.
Results: A total of 17 carotid arteries were examined. The investigated vessels had an average diameter of 6.3±1.1 mm pre-bifurcation, 7.9±2.3 mm at bifurcation, 4.3±1.4 mm post-bifurcation, 5.1±1.3 mm in the internal carotid artery, and 3.6±1.2 mm in the external carotid artery. The absolute number of nerves was lowest in the bifurcation region (n=408) and highest in the post-bifurcation region (n=1714). The mean lumen-to-nerve distance was smaller in the post-bifurcation segment (2.45±1.48 mm) than in the pre-bifurcation (2.85±1.40 mm) and bifurcation segments (2.91±1.38 mm; p<0.001). The overall nerve density was 46±51 nerves/cm². There was no significant difference in nerve density when comparing the left and right (p=1.000) or the internal and external carotid arteries (p=0.076). The number of nerve fibers per cm² increased from 33±38 in the pre-bifurcation and 35±33 in the bifurcation segments to 58±60 in the post-bifurcation segment (p<0.001 for pre-bifurcation vs post-bifurcation; p=1.000 for pre-bifurcation vs bifurcation; and p=0.127 for bifurcation vs post-bifurcation). The TH/CGRP ratio was similar across all vessel segments, including pre-bifurcation (39±62), bifurcation (45±70), and post-bifurcation (45 ±70, p=0.922).
Conclusion: The absolute number of nerves along the carotid arteries was highest in the post-bifurcation segment. Nerves converge to the carotid artery’s lumen from proximal to distal, resulting in the lowest lumen-to-nerve distance in the distal post-bifurcation segments. Efferent nerves occur predominantly, and their ratio to afferent nerves is similar across all vessel segments.