Acute cardio-centric haemodynamic management preserves chronic cardiovascular function in pigs with high-thoracic spinal cord injury.

Chronic high-level spinal cord injury (SCI) leads to a complex phenotype of long-term cardio-autonomic dysregulation. In the initial hours post-injury, cardio-centric management with dobutamine (DOB) can optimize cardiovascular haemodynamics and mitigate secondary injury compared with standard vasopressor-based management (i.e. norepinephrine, NE) in a porcine model of T2 SCI; however, any potential long-term benefits remain to be determined. We therefore sought to assess whether acute DOB treatment could mitigate cardiovascular dysfunction in the chronic setting of high-level SCI. Seventeen Yucatan minipigs with T2 SCI received acute management with DOB (2.5 µg kg-1 min-1, n = 6), NE (4.25 µg kg-1 min-1, n = 6) or no management (CON, n = 5) from 30 min until 6 h post-SCI, then were recovered and housed for 12 weeks. Outcome assessments were performed at 12 weeks post-SCI, including left ventricular (LV), Swan-Ganz and arterial catheterization to characterize cardiac and peripheral haemodynamics. Resting mean arterial pressure (MAP) was higher in both treatment groups (DOB:80 ± 9 mmHg, NE:88 ± 11 mmHg vs. CON:65 ± 3 mmHg; P = 0.0147 for DOB, P = 0.00679 for NE), and DOB-treated animals had greater stroke volume (33 ± 4 ml vs. NE:25 ± 5 ml, P = 0.0269), while NE-treated animals had elevated total peripheral resistance (41 ± 11 mmHg l-1 min-1 vs. CON:24 ± 4 mmHg l-1 min-1, P = 0.0345) and arterial elastance (3.60 ± 0.95 mmHg ml-1 vs. CON:2.08 ± 0.34 mmHg ml-1, P = 0.0258 vs. CON). Dynamic LV function was also preserved in DOB-treated animals, with greater contractile responses during the DOB stress test (end-systolic elastance; +8.96 mmHg ml-1 vs. CON:+1.28 mmHg ml-1, P = 0.036) and modified Oxford challenges (preload-adjusted maximal rate of pressure development (dp/dtmax-EDV) vs. MAP; -0.56 ± 0.33 ml s-1 vs. CON:0.04 ± 0.05 mls-1, P = 0.044). Collectively, these findings demonstrate that acute cardio-centric management with DOB provides a viable alternative for haemodynamic management following high-thoracic SCI. KEY POINTS: Spinal cord injuries (SCIs) at or above the mid-thoracic level lead to long-term heart and circulatory complications. This research primarily sought to understand whether a heart-focused treatment (dobutamine, DOB) could support long-term cardiovascular benefits when compared with current standard treatments (norepinephrine, NE) in a pig model with a high-thoracic SCI. Treatments were administered from 30 min to 6 h post-injury, and after 12 weeks' survival both DOB and NE animals had improved blood pressure. However, the DOB group additionally had preserved reflexive heart function when compared with control animals. Animals treated with DOB also exhibited more white matter sparing at study termination compared with animals treated with NE, implying superior neuroprotection.