Spinal cord injury: optimising clinical outcomes by harnessing the heart

By Alex Williams, @AlexM_Williams and Christopher West, @DrCRWest, International Collaboration On Repair Discoveries (ICORD) and Department of Cellular and Physiological Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, Canada

While traumatic spinal cord injury (SCI) is widely recognized as a condition that leads to life-altering paralysis, SCI can also have devastating autonomic and cardiovascular consequences that critically impact long-term health outcomes and quality of life.

When traumatic SCI occurs at or above the mid-back (i.e. the fifth thoracic level, T5), there is a partial if not complete loss of descending sympathetic input to the vasculature and the heart.

Consequently, individuals with high-level SCI experience notable dysregulation of the heart and blood pressure, resulting in persistent bouts of low blood pressure (orthostatic hypotension) and uncontrolled hypertension (autonomic dysreflexia).

These drastic fluctuations in blood pressure are a chronic burden, to the point that patients often rank the recovery of autonomic function above the recovery of motor function (1).

Of particular concern, cardiovascular disease (CVD) has emerged as a leading cause of death in SCI, where SCI is associated with three- to four-fold increased odds of heart disease and stroke, respectively (2).

Accordingly, an improved understanding of the cardiovascular consequences of SCI is essential for optimizing the management of those patients.

Acutely following a traumatic SCI, neurogenic shock — a hemodynamic triad of peripheral vasodilation, hypotension and bradycardia — places the injured spinal cord at an even greater risk for perfusion-induced ischemia and exacerbated secondary damage.

Presently, one of the only neuroprotective approaches available to clinicians for the treatment of acute SCI is hemodynamic management, which aims to restore spinal cord perfusion and oxygenation, reduce secondary damage, and ultimately improve neurological recovery in SCI patients (3).

Vasopressors such as norepinephrine are most commonly used for hemodynamic management, with a “one-size-fits-all” approach of targeting a mean arterial pressure (MAP) to 85 mm Hg or higher (4).

While this may seem straight-forward, achieving the target MAP with vasopressors can be quite difficult, as blood pressure often drops in injured patients below that target despite being treated on experienced clinical SCI units (5,6).

What’s more, recent data suggest that this generalized approach does not always improve neurological outcomes in patients with acute SCI and may in fact produce dangerous perfusion profiles with exacerbated hemorrhage in the injured spinal cord (7, 8).

Until now, the clinical world has largely overlooked the cardiac consequences of SCI. In high-level SCI, a loss of descending sympathetic input to the heart would be expected to impair the heart’s intrinsic contractile function.

However, no study nor guideline has yet considered that such acute cardiac dysfunction may contribute to the poor spinal cord perfusion immediately after injury. This raises the important question of whether an approach to hemodynamic management that specifically targets the heart may be more appropriate for optimizing spinal cord hemodynamics in acute SCI.

To address those questions, we have recently examined the acute (i.e. initial hours post-injury) impacts of high-thoracic SCI on the heart, and further whether cardio-centric hemodynamic management is more effective than vasopressor therapy in optimizing spinal cord oxygenation and hemodynamics (9).

For this work, we utilized a novel large animal (pig) model of T2 SCI, developed by our team with Dr. Brian Kwon (University of British Columbia, Vancouver, Canada), to assess the cardiovascular consequences of SCI (10).

The pig model is especially advantageous in that its cardiovascular and spinal cord anatomies are very similar to those in humans, and the spinal cord is of large enough calibre that we can invasively measure intraparenchymal oxygenation, blood flow, pressure and metabolism.

By performing left ventricular (LV) catheterization in the porcine model of acute T2 SCI, we have found that LV contractility is immediately impaired within the first hour following injury.

Then, when treating the acute reductions in contractile function with sufficient doses of dobutamine (cardiac inotrope), spinal cord oxygenation, blood flow profiles and metabolism are improved more effectively than in animals treated with norepinephrine.

Dobutamine treatment also appears to partially mitigate the exacerbated hemorrhaging observed with norepinephrine treatment. As such, these recent findings support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy in acute traumatic SCI.

In the chronic setting of SCI, a recent meta-analysis of echocardiographic data from human participants demonstrates that individuals with SCI have reduced LV size, volumes and mass, as well as alterations to both systolic and diastolic function when compared to able-bodied individuals (11).

Whether such changes represent adaptation versus dysfunction remains a topic of debate; however, there is clear evidence from animal models that LV load-independent contractile function is chronically reduced in high-level SCI (12) due to a loss of descending sympathetic input to the heart.

Individuals with high-level SCI also have impaired cardiac responses physiological stressors such as orthostatic stress and dynamic exercise (13), which further compromises the effectiveness of exercise as a means to offset the development of cardio-metabolic disease.

As such, several studies have attempted to develop interventions that either activate the sympathetic nervous system (e.g. transcutaneous stimulation, epidural stimulation, or boosting) or “mechanically” mobilize the blood that has pooled in the abdomen and legs (lower-limb cycling, abdominal binders) (14-17).

These approaches seek to either improve the sympathetic activation of the heart and blood vessels or increase venous return to boost stroke volume and cardiac output.

Though these studies are still in their infancy, early results suggest both types of interventions may hold promise to offset, delay or reverse the changes in the heart induced by SCI.

Please note that all views expressed on The Physiological Society’s blog reflect those of the author(s) and not of The Society. 

References

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