The effects of acute intermittent hypoxia on cardiovascular function in a murine model of spinal cord injury

Purpose: Spinal cord injury (SCI) reduces resting blood pressure (BP), orthostatic tolerance (OT) and cardiac function due to disrupted descending spinal sympathetic control of the heart and vasculature and contributes to early development of cardiovascular disease. Acute intermittent hypoxia (AIH; exposure to brief periods of breathing low oxygen) improves somatic motor and respiratory function in incomplete SCI, with greater improvements seen after daily exposure. We sought to describe the effects of a single bout, or repeated daily exposure to AIH on cardiovascular function at rest and during orthostatic challenge in SCI. Methods: Chapter 4; We sought to develop a model of SCI appropriate to test the effects of neurotherapeutic agents on the cardiovascular system. Chapter 5; We described the cardiovascular recovery and spinal cord characteristics to determine the most appropriate timepoint for the application of AIH. Chapter 6; We tested the effect of a single bout of AIH on cardiovascular function at rest and during challenge in SCI rats compared to naïve rats. Chapter 7; We tested if AIH impacts cardiovascular function at rest and during challenge in rats with T3 transection. Chapter 8; We assessed the impact of daily repeated exposure to AIH on cardiovascular function in incomplete SCI. Results and conclusions: Findings from chapter 4 confirm that the T3 300 Kdyn SCI model is appropriate to test neurotherapeutic strategies with sufficient spinal cord sparing at the injury site and decreased cardiovascular metrics. Chapter 5 found that there was no difference in cardiovascular function between rats recovered for 2 and 4 weeks from the T3 300 Kdyn SCI and both are lower than naïve rats, despite differences in spinal cord characteristics. Chapter 6 found that AIH exposure increases OT in incomplete SCI and naïve rats. Chapter 7 found that increases in OT can be achieved in rats with complete transection at the T3 level without changes in resting BP. Finally, chapter 8 found that 2-weeks of daily exposure to AIH in rats with chronic incomplete SCI imparts higher resting cardiac function, BP, and OT. In conclusion, AIH imparts beneficial effects on cardiovascular function following single and repeated exposure.