Autonomic nerves in myocardial sleeves around caval veins: Potential role in cardiovascular mortality?

Quantitative changes in the cardiac autonomic nervous system may play an important role in the pathogenesis of various cardiovascular diseases. In the present morphological analysis, we aimed to study autonomic nerve density in myocardial sleeves and surrounding fibro-fatty tissue around caval veins. We correlated the nerve distribution with cardiovascular mortality and a history of atrial fibrillation.

A total of 24 autopsied adult hearts were excised together with the superior and inferior vena cava and grouped according to the immediate and underlying causes of death (cardiovascular vs. non-cardiovascular), and documented heart rhythm history (atrial fibrillation vs. sinus rhythm). The density of autonomic nerves was quantified by measuring the area of immunohistochemical staining for sympathetic (tyrosine hydroxylase, TH) and parasympathetic (choline acetyltransferase, CHAT) nerves and ganglia. Growth-associated protein 43 (GAP43) was used as a neural growth marker.

The mean density of TH-positive nerves in the superior vena cava myocardial sleeves was significantly decreased between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean density ± standard deviation (SD): 704.81±1016.41 µm²/mm² vs. 2391.01±1841.37 µm²/mm²; P = .008). Similarly, the nerve density of GAP43-positive nerves in the superior vena cava myocardial sleeves was significantly lower in subjects with documented underlying cardiovascular cause of death (mean density ± SD: 884.74±1240.16 µm²/mm² vs. 2132.89±1845.89 µm²/mm²; P = .040). The mean age was significantly higher in subjects with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean age ± SD: 69.2±11.9 years, vs. 57.5±11.2 years, P = .016). No differences were found in nerve densities of TH-positive (953.01±1042.93 µm²/mm² vs. 919.26±1677.58 µm²/mm²), CHAT-positive (180.8±532.9 µm²/mm² vs. 374.22±894.76 µm²/mm²), and GAP43-positive nerves (593.58±507.97 µm²/mm² vs. 1337.34±1747.69 µm²/mm²) in myocardial sleeves around the inferior vena cava between groups with documented immediate cardiovascular vs. non-cardiovascular cause of death. Similarly, no differences were found between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (TH: 717.23±887.31 µm²/mm² vs. 1365.51±2149.10 µm²/mm²; CHAT: 256.18±666.86 µm²/mm² vs. 368.53±959.47 µm²/mm²; GAP43: 661.21±839.51 µm²/mm² vs. 1759.90±2008.80 µm²/mm²). Moreover, there was no association found in nerve densities between subjects with documented atrial fibrillation vs. sinus rhythm (TH: 235.07±425.69 µm²/mm² vs. 1166.08±1563.84 µm²/mm²; CHAT: 648.59±1017.33 µm²/mm² vs. 175.31±641.65 µm²/mm²; GAP43: 990.17±1315.18 µm²/mm² vs. 1039.86±1467.23 µm²/mm²).

Decrease of superior vena cava myocardial sleeve sympathetic nerves may be associated with cardiovascular mortality and/or aging. No difference in autonomic innervation was found between subjects with documented atrial fibrillation vs. sinus rhythm.