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UBC Theses and Dissertations

Characterizing the temporal development of cardiovascular dysfunction and examining morphology and function of resistance mesenteric vasculature in a T3 experimental spinal cord injury rodent model Popok, David


Spinal cord injury (SCI) disrupts autonomic pathways and perturbs cardiovascular homeostasis. High thoracic or cervical SCI may result in a variety of dire cardiovascular consequences such as persistent hypotension, impaired hemodynamic diurnal rhythmicity and autonomic dysreflexia (AD). If left untreated, AD may lead to myocardial infarction, stroke and even death. One of the primary causes underlying impaired arterial blood pressure (ABP) control may be disrupted sympathetic control of the splanchnic resistance circulation. Thus the goal of the thesis is to (1) characterize the temporal development of cardiovascular dysfunction post SCI and (2) to investigate the time course of structural and functional changes in splanchnic resistance vasculature in a T3 SCI experimental rodent model. First, male Wistar rats were implanted with telemetry devices, and subjected to a T3 complete transection surgery. Beat by beat ABP, heart rate and core body temperature was continuously monitored and development of AD was assessed using the in-house AD detection algorithm. Second, primary mesenteric arteries were assessed in our SCI rodent model for structure and function ex-vivo using pressure myography. Vasoconstrictive properties were assessed using α1-adrenoceptor agonists: phenylephrine (PE) and methoxamine (MET). Results suggest that AD is present in acute SCI and there is a significant reduction in AD events between days 6 and 10 post SCI followed by a substantial increase in AD event frequency and severity at day 14 post SCI. Nocturnal dip in blood pressure and core body temperature was absent up to 14 days post SCI and partially restored after 21 days post SCI. There was a significant reduction in PMA wall to lumen ratio in the 1 month-SCI group compared to the 1 week SCI and control group. In addition, there was an increased sensitivity (reduced EC₅₀) to PE in the 1 week SCI group compared to all groups (p<0.05), without significant changes in sensitivity to MET. This is the first study to show that experimental SCI exerts maladaptive hypotrophic remodelling and dysfunction at the level of the splanchnic resistance vasculature, which may underlie the primary cause of chronic ABP dysregulation in SCI individuals.

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