Impaired Cardiac Function Following Experimental Spinal Cord Injury Occurs Due to the Loss of Descending Sympathetic Control and Precedes Structural Remodeling

Introduction Chronic high-level spinal cord injury (SCI) impairs cardiac function and cardiomyocyte morphology. However, the temporal progression of these changes post-SCI remain undetermined as do the contributing pathways. Aims To (1) characterize the temporal effects of SCI on the heart and (2) to determine the contribution of descending sympathetic control to cardiac function in rodents with SCI. Hypotheses We hypothesize that a reduction in cardiac function will precede structural changes, and that a disruption in sympathetic control will be the primary cause of cardiac functional decline after SCI. Aim 1 - Methods & Results Cardiac functional and structural outcomes were characterized using in vivo echocardiography, invasive in vivo left-ventricular (LV) catheterization and ex vivo histology. Male Wistar rats were assessed at multiple time-points along the acute-to-chronic continuum following complete transection SCI at the 3rd thoracic segment (T3) and were compared to controls (SHAM) (n=6-10 per group). End-systolic elastance (contractility) and maximal rate of pressure generation (dP/dtmax) were reduced within 1 day post-SCI (both P<0.001 versus SHAM), which preceded a reduction in both end-diastolic volume and cardiomyocyte size. Aim 2 - Methods & Results LV function was assessed using invasive in vivo LV catheterization in male rats with various lesions on the brainstem-sympathetic axis. First, we compared rats with complete transection SCI at T3 versus at the 2nd lumbar segment (L2) (reduced versus intact sympathetic control; n=6-7 per group). Second, we compared T3 severely contused rats treated with neuroprotective agent minocycline versus vehicle (n=5-6 per group). Lastly, we compared rats which either underwent a T3 complete transection SCI or a ganglionic blockade with hexamethonium (HEX; n=4-5 per group). Contractility was lower in vehicle-treated rats versus those treated with minocycline (P=0.022), and tended to be lower in rats with T3-SCI versus those with L2-SCI (P=0.059). dP/dtmax was lower in rats with T3-SCI versus those with L2-SCI (P<0.001), and was equally reduced by both SCI or HEX (main effect for time, P<0.001). Conclusion Our findings suggest that a rapid reduction in LV function occurs prior to changes in LV volumes or cardiomyocyte dimensions after SCI, and that this functional decline is primarily caused by the loss of descending sympathetic control over the cardiovascular system.