The superior cervical ganglia modulate ventilatory responses to hypoxia independently of pre-ganglionic drive from the cervical sympathetic chain

Superior cervical ganglia (SCG) post-ganglionic neurons receive pre-ganglionic drive via the cervical sympathetic chain (CSC). The SCG projects to structures like the carotid bodies (e.g., vasculature, chemosensitive glomus cells), upper airway (e.g., tongue, nasopharynx) and to parenchyma and cerebral arteries throughout the brain. We previously reported that a hypoxic gas challenge elicited an array of ventilatory responses in sham-operated (SHAM) freely-moving adult male C57BL6 mice and that responses were altered in mice with bilateral transection of the cervical sympathetic chain (CSCX). Since the CSC provides pre-ganglionic innervation to the SCG, we presumed that mice with superior cervical ganglionectomy (SCGX) would respond similarly to hypoxic gas challenge as CSCX mice. However, while SCGX mice had altered responses during hypoxic gas challenge that occurred in CSCX mice (e.g., more rapid occurrence of changes in frequency of breathing and minute ventilation), SCGX mice displayed numerous responses to hypoxic gas challenge that CSCX mice did not, including reduced total increases in frequency of breathing, minute ventilation, inspiratory and expiratory drives, peak inspiratory and expiratory flows, and appearance of non-eupneic breaths. In conclusion, hypoxic gas challenge may directly activate sub-populations of SCG cells, including sub-populations of post-ganglionic neurons and small intensely fluorescent (SIF) cells, independently of CSC drive, and that SCG drive to these structures dampens the initial occurrence of the hypoxic ventilatory response, while promoting the overall magnitude of the response. The multiple effects of SCGX may be due to loss of innervation to peripheral and central structures with differential roles in breathing control.

Vagosympathetic imbalance induced thyroiditis following subarachnoid hemorrhage: a preliminary study

Introduction: This preliminary study evaluates the possible responsibility of ischemia-induced vagosympathetic imbalances following subarachnoid hemorrhage (SAH), for the onset of autoimmune thyroiditis. Methods: Twenty-two rabbits were chosen from our former experimental animals, five of which were picked from healthy rabbits as control (nG-I=5). Sham group (nG-II=5) and animals with thyroid pathologies (nG-III=12) were also included after a one-month-long experimental SAH follow-up. Thyroid hormone levels were measured weekly, and animals were decapitated. Thyroid glands, superior cervical ganglia, and intracranial parts of vagal nerve sections obtained from our tissue archives were reexamined with routine/immunohistochemical methods. Thyroid hormone levels, hormone-filled total follicle volumes (TFVs) per cubic millimeter, degenerated neuron density (DND) of vagal nuclei and neuron density of superior cervical ganglia were measured and statistically compared. Results: The mean neuron density of both superior cervical ganglia was estimated as 8230±983/ mm3 in study group animals with severe thyroiditis, 7496±787/mm3 in the sham group and 6416±510/mm3 in animals with normal thyroid glands. In control group (group I), T3 was 107±11 μg/dL, T4: 1,43±0.32 μg/dL and TSH <0.5, while mean TFV was 43%/mm3 and DND of vagal nuclei was 3±1/mm3. In sham group (group II), T3 was 96±11 μg/dL, T4: 1.21±0.9 μg/ dL and TSH>0.5 while TFV was 38%/mm3 and DND of vagal nuclei was 13±4. In study group, T3 was 54±8 μg/dL, T4: 1,07±0.3 μg/dL and TSH >0.5, while TFV was 27%/mm3 and DND of vagal nuclei was 42±9/mm3. Conclusion: Sympathovagal imbalance characterized by relative sympathetic hyperactivity based on vagal insufficiency should be considered as a new causative agent for hypothyroidism.

Reperfusion Arrhythmias Increase after Superior Cervical Ganglionectomy Due to Conduction Disorders and Changes in Repolarization

Pharmacological concentrations of melatonin reduce reperfusion arrhythmias, but less is known about the antiarrhythmic protection of the physiological circadian rhythm of melatonin. Bilateral surgical removal of the superior cervical ganglia irreversibly suppresses melatonin rhythmicity. This study aimed to analyze the cardiac electrophysiological effects of the loss of melatonin circadian oscillation and the role played by myocardial melatonin membrane receptors, SERCA2A, TNFα, nitrotyrosine, TGFβ, KATP channels, and connexin 43. Three weeks after bilateral removal of the superior cervical ganglia or sham surgery, the hearts were isolated and submitted to ten minutes of regional ischemia followed by ten minutes of reperfusion. Arrhythmias, mainly ventricular tachycardia, increased during reperfusion in the ganglionectomy group. These hearts also suffered an epicardial electrical activation delay that increased during ischemia, action potential alternants, triggered activity, and dispersion of action potential duration. Hearts from ganglionectomized rats showed a reduction of the cardioprotective MT2 receptors, the MT1 receptors, and SERCA2A. Markers of nitroxidative stress (nitrotyrosine), inflammation (TNFα), and fibrosis (TGFβ and vimentin) did not change between groups. Connexin 43 lateralization and the pore-forming subunit (Kir6.1) of KATP channels increased in the experimental group. We conclude that the loss of the circadian rhythm of melatonin predisposes the heart to suffer cardiac arrhythmias, mainly ventricular tachycardia, due to conduction disorders and changes in repolarization.