Distribution of cardiac nerves in patients with diabetes mellitus: An immunohistochemical postmortem study of human hearts

Background: Autonomic neuropathy and functional cardiac denervation are complications of diabetes mellitus (DM). It is unknown if DM patients show histopathologic evidence of cardiac denervation. Methods and Results: Nine sites were sampled at fixed distances from the atrioventricular valves from 27 postmortem hearts. Sections were stained with antibodies to S100 protein and to neurofilament (NF). Samples were visualized by light microscopy using the avidin–biotin peroxidase technique. The amount of cardiac nerves was graded blindly using semiquantitative methods according to the following criteria: Grade 0=presence of nerves in the epicardium only; Grade 1=strictly perivascular nerves; Grade 2=Grade 1 and nerve sprouts between myocardial cells sporadically; Grade 3=Grade 2 and nerve sprouts throughout the myocardium and endocardium. Specimens were divided into four groups. Control group consisted of patients with neither myocardial infarction (MI) nor DM. Experimental groups consisted of MI (n=7), MI with DM (n=6), and DM without MI (n=8). Average age of all patients was 57.3±15.7 years. No age differences existed among groups. Heterogeneous nerve distribution existed in all groups. S100-positive nerve density for control, MI, DM and MI, and DM without MI are 1.95±0.40, 1.66±0.54, 1.54±0.37, and 1.81±0.14, respectively (P=ns). NF-positive nerve density in the same groups were 1.10±0.18, 1.31±0.24, 1.13±0.12, and 1.19±0.42, respectively (P=ns). No differences in nerve densities between anterior and inferoposterior sections of the left ventricle existed. Conclusion: In postmortem human hearts, cardiac nerve distribution was heterogeneous among normal, MI, and DM patients. No evidence of cardiac denervation in patients with DM was demonstrated.