Preserved Cardio‐Inotropic Baroreflex Function Following Optimized Hemodynamic Management in High‐Thoracic Spinal Cord Injury

Abstract

. Chronic high-level spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, notably impairments to cardiac contractile function and baroreflex control of blood pressure. Recently, our group has demonstrated that hemodynamic management targeting the heart (i.e. dobutamine, DOB), rather than standard vasopressor treatment (i.e. norepinephrine, NE) improves cord oxygenation and mitigates hemorrhage in a porcine model of acute T2 SCI. Yet, the potential long-term cardiovascular benefits of acute cardio-centric hemodynamic management remain elusive.Assess the chronic changes in hemodynamics and baroreflex function associated with acute DOB administration in animals with T2 SCI.17 Yucatan mini-pigs received a T2 weight-drop contusion SCI, with either DOB (2.5 ug/kg/min, n=6), NE (4.25 ug/kg/min, n=6) or no treatment (CON, n=5) starting at 30 mins until 6 hrs post-SCI. Animals were subsequently recovered and housed for 12 weeks post-SCI. During terminal experiments, animals were instrumented with left ventricular (LV), pulmonary artery and femoral artery catheters to assess LV function, cardiac output (Q) and blood pressure, respectively. Linear regression analyses were used to estimate cardiovagal baroreflex (V-BRx) gain from the relationship of pulse interval vs. systolic blood pressure, and "cardio-inotropic" baroreflex (I-BRx) gain from the relationship of LV contractile function (rate of pressure rise for a given end-diastolic volume) vs. diastolic blood pressure during modified Oxford tests.Data are presented as means±SD. At 12 weeks post-SCI, DOB animals had preserved cardiac output (∆Q=+531±471ml/min) and mean arterial pressure (MAP=81±9mmHg), whereas both Q and MAP were lower in CON animals (∆Q=-385±720ml/min, p=0.44; MAP=65±3mmHg, p<0.0037). In contrast, NE-treated animals had uncharacteristic hypertension as indicated by elevations to MAP (NE=88±11 vs. CON=65±3mmHg, p=0.0029), arterial elastance (NE=3.7±0.4 vs. CON=2.7±0.1mmHg/ml, p=0.016) and total peripheral resistance (NE=50.3±4.3 vs. CON:35.7±10.3mmHg/ml/min, p=0.074). I-BRx function also appeared to be improved in DOB (slope=-0.56±0.33ml/s) vs. CON (slope=-0.04±0.05ml/s, p=0.044), while V-BRx gain did not differ between groups.Cardio-centric management appears to optimize cardiovascular hemodynamics more effectively than vasopressor therapy in chronic high-thoracic SCI. Reduced secondary spinal cord damage with DOB therapy may preserve descending sympathetic pathways to the heart, ultimately improving baroreflex control of blood pressure.