Abstract
Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the β-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.
Highlights
Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility
At 4 h post-injury there was a slight but significant increase to LV filling volume (i.e. EDV; Fig. 1e); there were no significant alterations to LV stroke volume (SV, Fig. 1f), ejection fraction (EF, Fig. 1g), cardiac output measured with thermodilution (QTD, Fig. 1h), or heart rate (Supplementary Table 1) within the 4 h following T2 SCI
We observed that LV load-independent systolic function assessed as Ees (Fig. 2a, b), preload-recruitable stroke work (Fig. 2d) and maximal rates of pressure generation for a given filling volume (Fig. 2e) were all reduced by 1 h post-SCI and remained depressed until 4 h post-SCI (Supplementary Table 2)
Summary
Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Hemodynamic management is one of the only neuroprotective strategies available to clinicians, and current guidelines suggest that mean arterial pressure (MAP) be maintained between 85 and 90 mmHg with intravenous fluids and vasopressors such as norepinephrine (NE), with the aim of offsetting systemic hypotension and maintaining adequate spinal cord perfusion[2] Though this “one-size-fits-all” strategy can improve spinal cord blood flow (SCBF), vasopressor management with NE has been shown to produce potentially harmful SCBF profiles in some acute SCI patients[3] and has been shown by multiple investigators to exacerbate intraparenchymal hemorrhage[4,5,6]. In experiment 2, we conducted a randomized intervention trial in the same porcine model to compare the efficacy of using the cardiac β-agonist DOB versus NE (i.e., current clinical standard) in augmenting SCO2 and SCBF acutely following T2 SCI. We further establish the potential long-term benefits of cardio-centric hemodynamic management by experimentally demonstrating that DOB treatment, but not NE, preserves cardiac function and normalizes blood pressure in a chronic model of T2 SCI
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