Challenging cardiac function post-spinal cord injury with dobutamine

Abstract

There is general consensus that spinal cord injuries (SCI) above T6 result in altered sympathetic control of the heart, which negatively influences cardiac structure and function. To by-pass disrupted circuitry and investigate cardiac responses under enhanced sympathetic activity we utilized dobutamine (DOB) stress echocardiography. Animals were divided into a T2, 25g-cm contusive SCI (SCI) or an uninjured control (CON) group. Echocardiography was performed pre-SCI and at 1, 2 and 6weeks post-SCI. Increasing doses of DOB (5, 10 & 20μg/min/kg) were infused intravenously pre-SCI and at 1 and 6weeks post-SCI. Parasternal-short axis images were used to compare group differences in systolic function and track changes in response to SCI and DOB over time. One week post-SCI, stroke volume (SV), end diastolic volume (EDV), cardiac output (CO) and ejection fraction (EF) were all reduced compared to CON and these deficits persisted to 6weeks. We also found an increase in collagen deposition at 6weeks post SCI. Pre-SCI, DOB elicited a decrease in EDV and increases in CO, EF and HR but not SV. At 6weeks following SCI, in addition to increases in CO, EF and HR, DOB also induced increases in SV. This is the first report, to our knowledge, of DOB responses in a contusive SCI model with persistent cardiac impairments. The return of CO to pre-SCI levels and the substantial increase in SV at low DOB dosages shows that impaired descending control of the heart is directly contributing to reduced resting SV after SCI.

Temporal analysis of cardiovascular control and function following incomplete T3 and T10 spinal cord injury in rodents

“…; DeVeau et al. ). If rodents, even those with incomplete injuries, experience improvements after that time point, it could have profound implications for individuals living with SCI, especially if the improvements correspond to changes in locomotor behavior or capacity.…”

“…Dobutamine is a sympathomimetric drug and has been used previously following SCI to increase the chronotrophy and inotrophy of the heart (DeVeau et al. , ; Squair et al. ).…”

“…Week 10 finding is important, as most preclinical studies investigating cardiac structure and function post-SCI conduct "terminal assessments" around the five or 6 week time point (West et al 2014;DeVeau et al 2018). If rodents, even those with incomplete injuries, experience improvements after that time point, it could have profound implications for individuals living with SCI, especially if the improvements correspond to changes in locomotor behavior or capacity.…”

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

“…We have additionally identified a reduction to LV contractile reserve acutely after the injury, which may be attributable to a rapid loss of ‘baseline’ contractility and tonic neuro-hormonal activation of the myocardium that occurs following high-level SCI. Though our group has previously reported that systolic reserve is relatively intact in chronically-injured rats with T2 SCI 13,14 , those observations may reflect chronic hyper-responsiveness of cardiac β-adrenergic receptors 15,16 , which would not have occurred in the acute setting of the current study.…”

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

“…SCI 13,14 , those observations may result from chronic hyperresponsiveness of cardiac β-adrenergic receptors 15,16 , which would not have occurred in the acute setting of the current study. Finally, we found that heart rate was essentially unaltered up to 4 h post-SCI, mirroring data recently reported by our group in Yorkshire pigs 9 .…”