The role of ischemic neurodegeneration of the nodose ganglia on cardiac arrest after subarachnoid hemorrhage: An experimental study Mehmet D. Aydin a, ⁎, Ayhan Kanat b, ⁎, Adem Yilmaz c , Murteza Cakir d , Mucahit Emet e , Zeynep Cakir e , Sahin Aslan e , Sare Altas f , Cemal Gundogdu f a Ataturk University Medical Faculty, Department of Neurosurgery, Erzurum, Turkey b Rize University Medical Faculty, Department of Neurosurgery, Rize, Turkey c Sisli Research and Education Hospital, Department of Neurosurgery, Istanbul, Turkey d Research and Education Hospital, Department of Neurosurgery, Erzurum, Turkey e Ataturk University Medical Faculty, Department of Emergency Medicine, Erzurum, Turkey f Ataturk University Medical Faculty, Department of Pathology, Erzurum, Turkey abstract article info Article history: Received 24 March 2010 Revised 12 September 2010 Accepted 18 September 2010 Available online 29 September 2010 Keywords: Subarachnoid hemorrhage Vagal ischemia Nodose ganglion Cardiac arrest Background: The heart is innervated by several systems that contribute to the control of the heart's rhythm. The cardiac fibers of the vagus nerve have an important role in the regulation of heart rhythm under many emotional and physical conditions. Severe electrocardiographic disturbances have been reported following subarachnoid hemorrhage (SAH), but ischemic neuronal degeneration of the nodose ganglion of the vagus nerve has not been previously investigated. We examined if there is a relationship between ischemic injury of the nodose ganglion of the vagus nerve and the severity of heart rhythm disorders after subarachnoid hemorrhage. Methods: This study was conducted on 20 rabbits. Four rabbits were used as a baseline group. Experimental subarachnoid hemorrhage was applied to half of the remaining animals (n = 8) by injecting homologous blood into the cisterna magna, and the others (SHAM group, n = 8) were injected with isotonic saline solution in the same manner. For 20 days after the injection, heart rhythm changes were observed daily. After the experiment, normal and ischemic neuron densities in the nodose ganglia of the vagus nerves were examined stereologically. The number of heart rhythm irregularities and the number of degenerated neurons in the nodose ganglia were compared statistically. Results: The normal heart rhythm rate was 280 ± 45/min. At the beginning of the SAH, the average heart rate was 220 ± 30/min; about 10 hours later, it decreased to 189 ± 30/min, indicating severe bradycardia. However, after 7 days, the average heart rate had increased to 350 ± 30/min. Six animals died due to irregularities in cardiac function and respiration. Histopathological examinations showed that the average density of normal neurons in the nodose ganglion was 10,500 ± 2500 in the baseline animals and the SHAM group, but the normal neuron density was 8250 ± 1500 in survivors and 6450 ± 1330 in dead animals. The ischemic neuronal degeneration in the nodose ganglia was more severe in the dead animals than in the survivors (p b 0.0001). Conclusion: Afferent vagus nerves originating from the nodose ganglia have an important role in regulating heart rhythm via their afferent fibers and efferent connections. If neurons of the nodose ganglia are lesioned due to ischemic insult during subarachnoid hemorrhage, heart rhythm regulation by vagus afferent reflexes is disturbed. Vagus pathway paralysis may result in indirect sympathetic overactivity. The development of tachycardia causes depletion of the heart's reserves, and cardiac arrest may be inevitable following extensive subarachnoid hemorrhage. © 2010 Elsevier Inc. All rights reserved. Introduction The functional relationship between the heart and brain is an ancient topic (Cannon, 1942; Wolf, 1967). Hemodynamic changes after subarachnoid hemorrhage (SAH) were recognized by Cushing in 1900 (Cushing, 1901). As early as the 1940s and 1950s, a high incidence of cardiac problems, particularly electrocardiographic (ECG) abnormali- ties, was described in patients with SAH, especially in those with aneurysmal SAH. SAH serves as a good model for the study of heart– brain interactions because it is associated with both a high incidence of arrhythmia and a low prevalence of coronary heart disease (Mashaly and Provencio, 2008). Initial theories focused on the sustained stimulation of sympathetic nerve endings on cardiomyocytes, but recent data suggest that dysfunction of the parasympathetic nervous system may also contribute to these processes. Mashaly and Provencio (2008) believe that catecholamine release during parasympathetic Experimental Neurology 230 (2011) 90–95 Abbreviations: bpm, beats/min; ECGm, electrocardiography; SAH, subarachnoid hemorrhage. ⁎ Corresponding authors. E-mail addresses: nmda11@hotmail.com (M.D. Aydin), ayhankanat@yahoo.com (A. Kanat). 0014-4886/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2010.09.018 Contents lists available at ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr