Correlation Between Cardiovascular Remodeling and Cardiovascular Deficits Following Chronic Spinal Cord Injury

After spinal cord injury (SCI), cardiovascular remodeling occurs at multiple levels. Despite the high prevalence of cardiovascular disease following SCI, there are few studies that attempt to illustrate the interplay between cardiac structure and function following injury. This study aims to assess cardiovascular remodeling and its relationship to cardiovascular dysfunction following chronic cervical (C8) midline spinal contusion. Nineteen Sprague-Dawley rats either received C8 midline contusion (cSCI, n = 10; Infinite Horizon Impact Device; 250 kilodynes; 0 s dwell time) or laminectomy (LAM, n = 9) as sham control. Fifteen weeks post-surgery, echocardiography was performed to assess cardiac function and morphology. At week 16, rats were anesthetized by urethane and a blood pressure catheter was placed into the aortic arch via the left common carotid artery. Orthostatic stress testing was introduced to evaluate the cardiovascular responses during 3-minute 90 degrees head-up tilting, followed by pharmacological stress testing via norepinephrine (NE) infusion (i.v.) at low (1 µg/kg/min) and high (4 µg/kg/min) doses. After tissue collection, collagen content (Masson trichrome stain), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation (IC 100 stain), and sympathetic innervation (tyrosine hydroxylase stain) were next investigated in the cardiovascular tissues. Correlation analyses were also performed between cardiovascular structural and functional measures. Results demonstrated that cSCI rats became hypotensive at rest and 70% of cSCI rats experienced significant orthostatic hypotension with an inability to maintain heart rate (HR) during head-up tilting. HR and mean arterial pressure reactivity in response to high-dose NE infusion were also significantly decreased in cSCI rats ( p <0.05) compared to LAM rats. Echocardiographic results showed reduced left ventricular (LV) diameter and volume ( p <0.01). Additionally, histological results revealed increased LV collagen content ( p <0.001), number of ASC specks (p<0.05), and increased sympathetic nerve density and quantity, especially within the LV posterior wall ( p <0.01 and p <0.05, respectively). Moreover, a strong linear relationship between histopathological and cardiovascular functional measures was observed. Overall, this study demonstrates that cardiovascular dysfunction is strongly correlated with cardiac atrophy, myocardial fibrosis, cardiac inflammation that is in part mediated by the inflammasome in the form of ASC specks, and enhanced cardiac sympathetic activity following chronic C8 midline contusion. This study was supported by: NIH (R01 NS131493) and Florida Department of Health (COPBC). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.