Spinal cord injury‐induced cardiomyocyte atrophy and impaired cardiac function are severity dependent

Abstract

What is the central question of this study? How does the severity of spinal cord injury affect left ventricular mechanics, function and the underlying cardiomyocyte morphology? What is the main finding and its importance? Here, we show that severe, but not moderate, spinal cord injury causes cardiomyocyte atrophy, altered left ventricular mechanics and impaired cardiac function. The principal aim of the present study was to assess how the severity of spinal cord injury (SCI) affects left ventricular (LV) mechanics, function and underlying cardiomyocyte morphology. Here, we used different severities of T3 spinal cord contusions (MODERATE, 200 kdyn contusion; SEVERE, 400 kdyn contusion; SHAM) and combined standard echocardiography with speckle tracking analyses to investigate in vivo cardiac function and deformation (contractility) after experimental SCI in the Wistar rat. In addition, we investigated changes in the intrinsic structure of cardiac myocytes ex vivo. We demonstrate that SEVERE SCI induces a characteristic decline in LV chamber size and a reduction in in vivo LV deformation (i.e. radial strain) throughout the entire systolic portion of the cardiac cycle [25.6 ± 3.0 versus 44.5 ± 8.1% (Pre-injury); P = 0.0029]. SEVERE SCI also caused structural changes in cardiomyocytes, including decreased length [115.6 ± 7.63 versus 125.8 ± 6.75 μm (SHAM); P = 0.0458], decreased width [7.78 ± 0.71 versus 10.78 ± 1.08 μm (SHAM); P = 0.0015] and an increase in the length/width ratio [14.88 ± 0.66 versus 11.74 ± 0.89 (SHAM); P = 0.0018], which was significantly correlated with LV flow-generating capacity after SCI (i.e. stroke volume, R = 0.659; P = 0.0013). Rats with MODERATE SCI exhibited no changes in any metric versus SHAM. This is the first study to demonstrate that the severity of SCI determines the course of changes in the intrinsic structure of cardiomyocytes, which are directly related to contractile function of the LV.

A Long-Term Pilot Study on Sex and Spinal Cord Injury Shows Sexual Dimorphism in Functional Recovery and Cardio-Metabolic Responses

“…www.nature.com/scientificreports www.nature.com/scientificreports/ For cardiac function, it is well established that male rats with SCI exhibit alterations in cardiac structure and function largely consistent with the results of our study, albeit using different injury models and a shorter timeline of analysis[29][30][31][32][33] . In comparing the sexes, the results here show males exhibited a slight increase in LVID while females exhibited a reduction(Fig.…”

Effects of early exercise training on the severity of autonomic dysreflexia following incomplete spinal cord injury in rodents

“…Equally, it has been shown that some individuals with neurologically motor incomplete injuries (i.e., AIS C-D) still exhibit CV and hemodynamic instability, though anecdotally this appears less common West, Wong, et al, 2014). Our present results do not refute these clinically observations, but rather lend support to the notion that relatively little spinal cord sparing (i.e., enough to produce a BBB score of 6-11 but not more) can partially mitigate or improve overt CV and hemodynamic dysfunction (Squair et al, 2016(Squair et al, , 2018.…”

Chronic, complete cervical6–7cord transection: distinct autonomic and cardiac deficits

“…The remaining T1 segment is responsible for Ͻ10% of postganglionic cardiac innervation (70). Thus, high-thoracic models produce relevant cardiac and hemodynamic function that closely mimics that of cervical injuries, including left ventricular atrophy and reduced contractile function (17,69).…”