"Anatomic guidance to sympathetic denervation of the common hepatic artery." Rami Tzafriri, Fernando Garcia-Polite, John Keating, Raffaele Melidone, Jennifer Knutson, Peter Markham, Elazer R. Edelman, Felix Mahfoud.

Aims: Combined renal artery and common hepatic artery (CHA) denervation is being explored as a novel therapy for uncontrolled hypertension. As guidance for clinical studies, we quantified the distribution of nerves and adjacent anatomies surrounding human CHA in samples from diabetic and nondiabetic patients.

Methods and Results: Refrigerated CHA with attached aorta, celiac artery, and splenic artery were collected from 20 human anatomical samples within 72h of postmortem. Donors were 48–78 years old (65 ± 8.6) and distributed equally between male (n = 10) and females (n = 10). Per donor medical histories, eleven of the samples were designated diabetics, 9 non-diabetics. Diabetic and non-diabetic donors were similarly distributed in terms of sex, age, height, body mass index, hypertension, and renal disorders. Samples were perfusion-fixed, and the CHA dissected and marked for orientation, while leaving sufficient periarterial tissue to allow thorough histologic evaluation of the intact periarterial microanatomy. The entire CHA was sectioned in consecutive fashion into 3–5 mm blocks. Tissues were processed and paraffin embedded, slides were obtained from each block and stained with Hematoxylin and Eosin (H&E) for morphology assessment and immunohistochemical stains for nerve identification. Tissue sections all along the CHA exhibited abundant nerves within the loose adventitial/periarterial adipose and fibrovascular tissue that were often surrounded by lymph nodes, pancreas and vascular structures, including comparably sized portal veins and smaller arterial and venous branches. No associated ganglionic structures were present. Nerve abundance (82/section) and mean size (0.35 mm) were both high compared to published values in renal arteries (respectively, 38 nerves/section and 0.12 mm).
Tyrosine hydroxylase (TH), part of the norepinephrine synthetic pathway, was used as a specific immunohistochemical marker for efferent sympathetic nerve fibers and exhibited strong diffuse staining of periarterial nerves confirming their predominantly sympathetic nature. Calcitonin Gene Related Peptide (CGRP) was used as a marker for afferent (i.e., sensory) nerve fibers in representative CHA sections from each sample.
Overall nerve fiber positivity for CGRP was < 5%, and afferent fibers were therefore considered a negligible fraction within periarterial nerves. Nerve abundance decreased significantly with distance from the aortic ostium (P < 0.0001) and was higher in the Superior/Inferior compared to the Anterior/Posterior quadrants (P = 0.014). In each locational group, nerves were absent from the arterial media and only observed at radial distances > 0.5-1.0 mm from the CHA lumen. Further from the lumen, the abundance of nerves declined with radial distance. Median subject-averaged nerve distance to the lumen was 2.75 mm, ranging from 2.1-3.1 mm in different arterial segments and quadrants and 2.0-3.5 mm in individuals. Inter-individual variance was high, with certain individuals exhibiting 50th and 75th nerve distances of, respectively, 3.5 and 6.5 mm. The pancreas rarely approached within 4 mm of the lumen proximally and 2.5 mm more distally.

Conclusions: The CHA is a rich and accessible target for sympathetic denervation regardless of sex and diabetes, with efficacy and safety most optimally balanced proximally. Compared to published values for human cadaver renal arteries, CHA nerves were 2-fold more abundant and with a 3-fold larger diameter.