Chronic Cervical Midline Contusion in Rats Disrupts Multiple Facets of Cardiovascular Function

Abstract

Cardiovascular dysfunction is the leading cause of morbidity and mortality following spinal cord injury (SCI). There are a limited number of studies assessing cardiovascular deficits after cervical SCI. This study aimed to assess disrupted cardiovascular function following a chronic severe incomplete C8 SCI in rats, via damaging descending sympathetic projections to the spinal sympathetic preganglionic neurons. Rats were first trained on the isometric pull task before receiving a C8 midline contusion (Infinite Horizon Impact Device; 250 kilodynes; 0 s dwell time) or laminectomy and were tested one day per week from weeks 7-13 following surgery. Isometric forelimb strength and correlates of muscle endurance were monitored during pull task sessions. Cardiovascular function was evaluated 16 weeks post-surgery. Tilt table testing was used to induce an orthostatic challenge by tilting rats 90 degrees head-up from a supine position and 90 degrees head-down from supine position as a control. Following tilt table testing, dobutamine (DOB; 2 μg/kg/min and 10 μg/kg/min) and norepinephrine (NE; 1 μg/kg/min and 4 μg/kg/min) were infused into the femoral vein separately to assess cardiovascular responses to a pharmacological challenge. We monitored cardiovascular physiology during all terminal testing. A blood pressure catheter was inserted into the left common carotid artery and advanced to the aortic arch to monitor interatrial blood pressure, 2 pairs of impedance cardiography (ICG) electrodes were placed on the left side of the thorax to evaluate inotropic correlates of cardiac function, and 2 photoplethysmography (PPG) sensors were affxed over the forelimbs flexor muscles to examine peripheral hemodynamics. To verify the accuracy of ICG-derived cardiac function, rats were examined by echocardiography at week 15. Spinal cords were collected for lesion analysis and were also stained for tyrosine hydroxylase. Our preliminary results demonstrate that chronic severe incomplete C8 SCI resulted in a significant and sustained hypotension during the 3-minute period of 90 degrees head-up tilting (systolic blood pressure = ~ -22 mmHg; diastolic blood pressure = ~ -19 mmHg) compared to laminectomy. There were also significant differences in left ventricular ejection time, heart rate, and stroke volume across groups, whereas forelimb hemodynamics did not differ across groups. Additionally, correlates of forelimb muscle endurance significantly decreased in SCI rats, despite similar isometric forelimb strength across groups. Intravenous infusion of DOB and NE demonstrated significant and dose-dependent effects on cardiovascular parameters. Overall, our data demonstrate that chronic severe C8 SCI in rats leads to orthostatic hypotension and also impairs multiple additional aspects of function. This study was supported by: NIH (R01 NS131493) and Florida Department of Health (COPBC). This is the full abstract presented at the American Physiology Summit 2024 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.