Spinal Cord Injury Causes Systolic Dysfunction and Cardiomyocyte Atrophy

Squair, Jordan W.; DeVeau, Kathryn M.; Harman, Kathryn A.; Poormasjedi‐Meibod, Malihe‐Sadat; Hayes, Brian; Liu, Jie; Magnuson, David S.K.; Krassioukov, Andrei V.; West, Christopher R.

doi:10.1089/neu.2017.4984

Cited by 30 publications

(45 citation statements)

References 41 publications

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“…Interestingly, our previous work in rodent models of complete transection SCI at the T2 level resulted in a reduction in blood pressure of approximately 20 mmHg from baseline (Squair et al . ). Interestingly the pattern of tissue damage at the epicentre and degree of tissue sparing following our contusion injury in the pig were very similar to those we have previously reported in our rodent model of high‐thoracic contusion injury (Squair et al .…”

Section: Discussionmentioning

confidence: 97%

A porcine model for studying the cardiovascular consequences of high‐thoracic spinal cord injury

West

Poormasjedi‐Meibod

Manouchehri

et al. 2020

The Journal of Physiology

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Key points We have developed a novel porcine model of high‐thoracic midline contusion spinal cord injury (SCI) at the T2 spinal level. We describe this model and the ensuing cardiovascular and neurohormonal responses, and demonstrate the model is efficacious for studying clinically relevant cardiovascular dysfunction post‐SCI. We demonstrate that the high‐thoracic SCI model, but not a low‐thoracic SCI model, induces persistent hypotension along with a gradual reduction in plasma noradrenaline and increases in plasma aldosterone and angiotensin II. We additionally conducted a proof‐of‐concept long‐term (12 weeks) survival study in animals with T2 contusion SCI demonstrating the potential utility of this model for not only acute experimentation but also long‐term drug studies prior to translation to the clinic. Abstract Cardiovascular disease is a leading cause of morbidity and mortality in the spinal cord injury (SCI) population, especially in those with high‐thoracic or cervical SCI. With this in mind, we aimed to develop a large animal (porcine) model of high‐thoracic (T2 level) contusion SCI and compare the haemodynamic and neurohormonal responses of this injury against a low‐thoracic (T10 level) model. Ten Yorkshire pigs were randomly subjected to 20 cm weight drop contusion SCI at either the T2 or the T10 spinal level. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were continuously monitored until 4 h post‐SCI. Plasma noradrenaline (NA), aldosterone and angiotensin II (ANGII) were measured pre‐SCI and at 30, 60, 120 and 240 min post‐SCI. Additionally, two Yucatan pigs were subjected to T2‐SCI and survived up to 12 weeks post‐injury to demonstrate the efficacy of this model for long‐term survival studies. Immediately after T2‐SCI, SBP, MAP and HR increased (P < 0.0001). Between decompression (5 min post‐SCI) and 30 min post‐decompression in T2‐SCI, SBP and MAP were lower than pre‐SCI (P < 0.038). At 3 and 4 h after T2‐SCI, SBP remained lower than pre‐SCI (P = 0.048). After T10‐SCI, haemodynamic indices remained largely unaffected. Plasma NA was lower in T2‐ vs. T10‐SCI post‐SCI, whilst aldosterone and ANGII were higher. Both chronically injured pigs demonstrated a vast reduction in SBP at 12 weeks post‐SCI. Our model of T2‐SCI causes a rapid and sustained alteration in neurohormonal control and cardiovascular function, which does not occur in the T10 model.

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Section: Discussionmentioning

confidence: 97%

A porcine model for studying the cardiovascular consequences of high‐thoracic spinal cord injury

West

Poormasjedi‐Meibod

Manouchehri

et al. 2020

The Journal of Physiology

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“…Spinal cord contusions were conducted as we have previously described (Squair et al . , b). Animals were started on a prophylactic dose of enrofloxacin [10 mg kg −1 , s.c. ; Baytril; Associated Veterinary Purchasing (AVP), Langley, BC, Canada] 3 days before surgery.…”

Section: Methodsmentioning

confidence: 99%

“…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 . ). In contrast, when descending sympatho‐excitatory input to the upper thoracic spinal cord is intact after SCI (T5 SCI), there is an increased density of tyrosine hydroxylase‐positive terminals in the heart and enlargement of stellate soma, suggesting increased cardiac sympathetic nerve activity (Lujan et al .…”

Section: Introductionmentioning

confidence: 97%

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

Squair

Liu

Tetzlaff

et al. 2018

Experimental Physiology

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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.

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“…Neuroanatomical overview of the impacts of SCI on cardiovascular pathophysiology (adapted from Squair et al 3). The cardiovascular consequences of SCI are level-dependent: in injuries below T6, descending sympathetic input to the heart remains intact; in injuries between T1 and T6, there is partial or complete loss of descending sympathetic input to the heart; in cervical injuries, there is complete loss of all descending sympathetic input to the heart.…”

Section: Introductionmentioning

confidence: 99%

Cardiac consequences of spinal cord injury: systematic review and meta-analysis

Williams

Gee

Voss

et al. 2018

Heart

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ObjectiveConduct a meta-analysis to determine the impact of traumatic spinal cord injury (SCI) on echocardiographic measurements of left ventricular (LV) structure and function.MethodsMEDLINE and Embase were used for primary searches of studies reporting LV echocardiographic data in individuals with SCI. Of 378 unique citations, 36 relevant full-text articles were retrieved, and data from 27 studies were extracted for meta-analyses. Literature searches, article screening and data extraction were completed by two independent reviewers and compared for agreement. Primary analyses compared echocardiographic indices between individuals with SCI and able-bodied individuals, using a random effects model.ResultsData are reported as pooled effect estimates (95% CI). Data from 22 articles (474 participants) were included in the primary meta-analysis. Compared with able-bodied individuals, individuals with SCI had reductions to LV stroke volume of 11.8 mL (95% CI −17.8 to −5.9, p<0.001), end-diastolic volume of 19.6 mL (95% CI −27.2 to −11.9, p<0.001) and LV massindex of −7.7 g/m2 (95% CI −11.6 to −3.8, p<0.001), but ejection fraction was not different between the groups (95% CI −2.6% to 0.6%, p=0.236). Individuals with SCI also had altered indices of diastolic function, specifically a lowered ratio of early-to-late filling velocities (p=0.039), and augmented ratio of early diastolic flow-to-tissue velocities (p=0.021).ConclusionsIndividuals with SCI have smaller LV volumes and mass, and altered systolic and diastolic function. While this meta-analysis demonstrates important alterations to echocardiographic measures of cardiac structure and function at rest, future work should consider the impacts of SCI on the heart’s capacity or ‘reserve’ to respond to physiological challenges.PROSPERO registration numberCRD42017072333.

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Spinal Cord Injury Causes Systolic Dysfunction and Cardiomyocyte Atrophy

Cited by 30 publications

References 41 publications

A porcine model for studying the cardiovascular consequences of high‐thoracic spinal cord injury

A porcine model for studying the cardiovascular consequences of high‐thoracic spinal cord injury

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

Cardiac consequences of spinal cord injury: systematic review and meta-analysis

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