Experimental high-thoracic spinal cord injury reduces splanchnic sympathetic nerve activity and is associated with persistent hypotension
Authors: West Christopher , Ahmadian Mehdi , Erskine Erin , Wainman Liisa , Duffy Jennifer , Stewart Liam , Wearing Oliver , Taki Alissa , Perim Raphael , Shoemaker Kevin , Foster Glen , Mueller Patrick 
Published: May 2023

Objective: High-thoracic spinal cord injury (SCI) is associated with blood pressure (BP) dysregulation that consists of persistent hypotension, orthostatic intolerance and autonomic dysreflexia. Whilst several mechanisms have been suggested to underlie blood pressure dysregulation post-SCI, the most common inference made is that the sub-lesional sympathetic circuitry is hypoactive due to a loss of medullary input to the sympathetic preganglionic neurons. Yet, a remarkable paucity of data exists from electrophysiological studies that have assessed sympathetic nerve activity (SNA) in the setting of SCI. Aim: Assess the changes in SNA and resting BP in rats with and without high-thoracic SCI. Methods: 24 male Wistar rats (10wks old) were randomized and counterbalanced to receive a severe contusion SCI at the T3 spinal level (n=12) or remain as naïve controls (CON). Two weeks post-SCI, rats underwent our neurovascular terminal preparation. Animals were ventilated, anesthetized with inhalant isoflurane, and underwent catheterization of the left-femoral artery (BP), as well as the right femoral artery and vein for arterial blood gas sampling and i.v. fluid/drugs, respectively. Rats were then transitioned to urethane anesthesia (~2.1g.kg-1 i.v). Next, the splanchnic nerve was isolated from a retroperitoneal approach, cut, and the proximal end was recorded using a suction electrode for the measurement of splanchnic sympathetic nerve activity (sSNA). Following 30 minutes of hemodynamic stabilization, SNA and cardiovascular hemodynamics were sampled for 10 minutes, from which a 1 min recording was selected for analyses. Animals were subsequently administered a hexamethonium bolus (30 mg.kg-1) to block ganglionic transmission and the euthanized with chloral hydrate. Results: SCI animals exhibited lower systolic, diastolic and mean arterial BP (all p<0.007), but heart rate was not different between groups. SCI animals also exhibited lower total sSNA (1.9 ± 0.7 vs. 3.2 ± 1.9 mv.s-1, p=0.038) as well reduced burst height (2.2 ± 1.5 vs. 3.7 ± 0.8 v.s-1, p=0.033), but the number of sSNA spikes.s-1 was higher in SCI vs. CON (182 ± 65 vs. 155 ± 33, p=0.043). Blood gases were stable and similar between groups. Conclusions: Our findings show that persistent hypotension in SCI animals is associated with lower total sub-lesional sSNA. While SCI resulted in more spontaneous sSNA spikes, these spikes fail to coordinate into equally-sized sSNA bursts. International Spinal Research Trust and Natural Sciences and Engineering Research Council of Canada (NSERC). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.