Department of Pathology, Fimlab Laboratories, Arvo Ylpön katu 4, 33520 Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland.
Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland; Division of Cardiothoracic Surgery, Tampere University Heart Hospital, Elämänaukio 1, 33520 Tampere, Finland.
Cardiovasc Pathol. 2022 Jul-Aug;59:107426. doi: 10.1016/j.carpath.2022.107426. Epub 2022 Mar 27.
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 µm/mm vs. 2391.01±1841.37 µm/mm; 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 µm/mm vs. 2132.89±1845.89 µm/mm; 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 µm/mm vs. 919.26±1677.58 µm/mm), CHAT-positive (180.8±532.9 µm/mm vs. 374.22±894.76 µm/mm), and GAP43-positive nerves (593.58±507.97 µm/mm vs. 1337.34±1747.69 µm/mm) 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 µm/mm vs. 1365.51±2149.10 µm/mm; CHAT: 256.18±666.86 µm/mm vs. 368.53±959.47 µm/mm; GAP43: 661.21±839.51 µm/mm vs. 1759.90±2008.80 µm/mm). Moreover, there was no association found in nerve densities between subjects with documented atrial fibrillation vs. sinus rhythm (TH: 235.07±425.69 µm/mm vs. 1166.08±1563.84 µm/mm; CHAT: 648.59±1017.33 µm/mm vs. 175.31±641.65 µm/mm; GAP43: 990.17±1315.18 µm/mm vs. 1039.86±1467.23 µm/mm).
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.
心脏自主神经系统的定量变化可能在各种心血管疾病的发病机制中起重要作用。在本形态学分析中，我们旨在研究心肌袖套和腔静脉周围纤维脂肪组织中的自主神经密度。我们将神经分布与心血管死亡率和心房颤动病史相关联。
共切除 24 例成人尸检心脏，与上、下腔静脉一起切除，并根据直接和根本死因（心血管与非心血管）分组，并记录心脏节律史（心房颤动与窦性节律）。通过测量交感神经（酪氨酸羟化酶，TH）和副交感神经（胆碱乙酰转移酶，CHAT）神经和神经节的免疫组织化学染色面积来量化自主神经密度。生长相关蛋白 43（GAP43）用作神经生长标志物。
记录到根本死因是心血管与非心血管的组间，上腔静脉心肌袖套中 TH 阳性神经的平均密度显著降低（平均密度±标准差（SD）：704.81±1016.41 µm/mm 与 2391.01±1841.37 µm/mm；P=.008）。同样，上腔静脉心肌袖套中 GAP43 阳性神经的密度在记录到根本心血管病因的患者中也显著降低（平均密度±SD：884.74±1240.16 µm/mm 与 2132.89±1845.89 µm/mm；P=.040）。记录到根本心血管与非心血管病因的患者的平均年龄显著较高（平均年龄±SD：69.2±11.9 岁与 57.5±11.2 岁；P=.016）。在记录到即时心血管与非心血管病因的组间，TH 阳性（953.01±1042.93 µm/mm 与 919.26±1677.58 µm/mm）、CHAT 阳性（180.8±532.9 µm/mm 与 374.22±894.76 µm/mm）和 GAP43 阳性神经（593.58±507.97 µm/mm 与 1337.34±1747.69 µm/mm）的密度没有差异。同样，在记录到根本心血管与非心血管病因的组间，TH 阳性（717.23±887.31 µm/mm 与 1365.51±2149.10 µm/mm）、CHAT 阳性（256.18±666.86 µm/mm 与 368.53±959.47 µm/mm）和 GAP43 阳性神经（661.21±839.51 µm/mm 与 1759.90±2008.80 µm/mm）的密度也没有差异。此外，在记录到心房颤动与窦性节律的患者之间，神经密度之间没有关联（TH：235.07±425.69 µm/mm 与 1166.08±1563.84 µm/mm；CHAT：648.59±1017.33 µm/mm 与 175.31±641.65 µm/mm；GAP43：990.17±1315.18 µm/mm 与 1039.86±1467.23 µm/mm）。
上腔静脉心肌袖套交感神经密度的降低可能与心血管死亡率和/或衰老有关。在记录到心房颤动与窦性节律的患者之间，自主神经支配没有差异。
