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Duffy, Jennifer

University of British Columbia

Traumatic spinal cord injury (SCI) causes an initial injury followed by a protracted phase of spinal cord tissue hypoxia. This tissue hypoxia contributes to secondary injury, leading to worse motor and autonomic outcomes in the chronic setting. We have demonstrated that taking a cardio-centric approach to hemodynamic management following SCI by augmenting cardiac contractility and mean arterial pressure (MAP) with the B1-adrenoceptor agonist dobutamine (DOB), and further coupling DOB infusion with the inhalation of ethyl nitrite (ENO), an S-nitrosylating agent, is associated with improved spinal cord oxygenation in the acute phase post-SCI. Moreover, a major yet commonly over-looked outcome of chronic high-level spinal cord injury is the reduction in cardio-autonomic function due to damaged descending sympathetic tracts. As such, I aimed to determine the influence of a cardio-centric approach to hemodynamic management with added ENO inhalation following SCI on long term outcomes of blood pressure regulation. I hypothesized that treatment with DOB and ENO in the acute phase following SCI would mitigate secondary injury and improve cardiovascular outcomes in the chronic setting. To accomplish this, a total of 36 male Wistar rats underwent a T3 contusion injury (300 kdyn) and were assigned into 4 treatment groups: control (n=6), ENO (n=6), DOB (n=12), and combined DOB and ENO (n=12). At 12-weeks post-SCI, rodents were anesthetized with intravenous urethane (2.440.50 g/kg) and instrumented with a solid-state pressure transducer in the carotid artery to measure MAP. We observed a higher MAP in both DOB (113.611.4 mmHg; p=0.030) and ENO+DOB (116.714.6 mmHg; p=0.013) treated groups when compared with controls (94.6511.62 mmHg). The MAP of ENO treated animals (91.67.3 mmHg; p=0.97) was not different from controls. No difference in resting sympathetic nerve activity or -adrenergic receptor sensitivity was observed. Baroreflex sensitivity, quantified by the slope of the linear regression for % change in SNA and DBP, was greater in DOB (-0.9620.361 %/mmHg) vs. controls (-0.4330.297 %/mmHg; p=0.022) but not ENO+DOB (-0.7790.388 %/mmHg; p=0.616). Collectively, these data suggest that DOB treatment, alone or in combination with ENO, may improve systemic hemodynamics while DOB alone improves baroreflex sensitivity in the chronic high-thoracic SCI setting.

Text

2023-08-23

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/85586

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/