Cardiac Consequences of Autonomic Dysreflexia in Spinal Cord Injury

Abstract

Abstract-Autonomic dysreflexia (AD), which describes episodic hypertension, is highly prevalent in people with spinal cord injury (SCI). In non-SCI, primary hypertension depresses cardiac contractile reserve via β-adrenergic mechanisms.In this study, we investigated whether AD contributes to the impairment in cardiac contractile function that accompanies SCI. We induced SCI in rodents and stratified them into sham, SCI, or SCI plus repetitive induction of AD. At 6-week post-SCI, we assessed cardiac function using in vivo (speckle-tracking echocardiography), ex vivo (working heart), and molecular approaches (Western blot). We also provide unique translational insight by comparing the relationship between the number of daily AD events and cardiac function in 14 individuals with cervical SCI. We found SCI and SCI plus repetitive induction of AD exhibited a reduction in left ventricular dimensions at 6-week post-SCI versus preinjury (P<0.049). Compared with sham, SCI exhibited a reduction in peak radial strain along with a down and rightward shift in the Starling curve (P<0.037), both of which were further depressed in SCI plus repetitive induction of AD (P<0.042). In response to β-adrenergic stimulation, SCI plus repetitive induction of AD exhibited an attenuated increase in contractile indices (P<0.001), despite no differences in β-receptor expression within the left ventricle. Our clinical data confirm our experimental findings by demonstrating significant associations between the number of daily AD events and markers of systolic and diastolic function along with left ventricular mechanics. Here, we provide the first evidence from a translational perspective that AD exerts insidious effects on cardiac function in rodents and humans with SCI.

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

“…) and maximal pressure‐generating capacity is impaired (West et al . ; Squair et al . ) points to the potential long‐term consequences of reduced venous return.…”

“…We completed echocardiography using a commercially available imaging system (Vivid 7; GE Healthcare, Horten, Norway) and specialized transducer specifically designed for use in rodents (GE Healthcare i13L; 5.6–14.1 MHz), as we have previously described (West et al . , ; Squair et al . ).…”

“…), all of which are perpetuated by chronic exposure to autonomic dysreflexia (West et al . ). Furthermore, we have shown more recently that load‐independent LV function is impaired after T3 SCI and is accompanied by atrophy of cardiomyocytes (Squair et al .…”

“…When sympathetic preganglionic neurons to the upper thoracic spinal cord are devoid of supraspinal control, our group showed that SCI (T3) induces a reduction in global left ventricular (LV) dimensions (West et al . , ; Squair et al . ) and LV mechanics (West et al .…”

“…A recent surge in the number of preclinical rodent experiments has enhanced our understanding of cardiac dysfunction in this population. When sympathetic preganglionic neurons to the upper thoracic spinal cord are devoid of supraspinal control, our group showed that SCI (T3) induces a reduction in global left ventricular (LV) dimensions (West et al 2014(West et al , 2016Squair et al 2017a) and LV mechanics (West et al 2016) and impairs LV contractility (West et al 2014;Squair et al 2017a), all of which are perpetuated by chronic exposure to autonomic dysreflexia (West et al 2016). Furthermore, we have shown more recently that load-independent LV function is impaired after T3 SCI and is accompanied by atrophy of cardiomyocytes (Squair et al 2017a).…”