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.

Keywords: Cardiac; Echocardiography; Spinal cord injury.

Fig. 1

Cardiac function of T2 25 g-cm spinal cord injured (SCI) female SD rats and age matched uninjured controls (CON) followed for six weeks post-SCI. A, stroke volume (SV). B, heart rate (HR). C, cardiac output (CO). D, ejection fraction (EF). E, end diastolic volume (EDV). F, end systolic volume (ESV). Data are represented as means ± standard deviations. * P ≤ 0.05 SCI vs. CON.

Fig. 2

(A–F) Responses to increasing doses of Dobutamine pre-SCI and at one and six weeks post-SCI. A, stroke volume (SV). B, heart rate (HR). C, cardiac output (CO). D, ejection fraction (EF). E, end diastolic volume (EDV). F, end systolic volume (ESV).G, correlation of locomotor function with CO six weeks post-SCI (Pearson correlation R = 0.02575). There was a significant main effect for dose and time in all outcome measures (P < 0.05). There was a significant interaction effect for time and dose in all outcome measures (P < 0.05). Data are represented as means ± standard deviations. * P < 0.05 pre-SCI 0 µg vs. all other doses, ^ P < 0.051week post-SCI0 µg vs. all other doses, † P < 0.05 6week SCI 0 µg vs. all other doses, # P < 0.05 pre-SCI vs. 1 week post-SCI, ‡ P < 0.05 pre-SCI vs. 6 weeks post-SCI, σ P < 0.05 1 week post-SCI vs. 6 weeks post-SCI.

Fig. 3

The BBB scores of the SCI group followed for six weeks after SCI and the histological comparisons of SCI groups to the CON group. A, Locomotor recovery from injury to six-weeks post-SCI. B&C, Representative images of white matter spared at the injury epicenter from and SCI and CON animal, respectively. Scale bar is 500 µm. E&F, Representative images of collagen in the left ventricle free wall of CON and SCI animals, respectively. Scale bar is 50 µm.