(560.5) Acute Intermittent Hypoxia Improves Orthostatic Tolerance in Chronic but not Acute Spinal Cord Injured Rats

Poster Board Number: E161

Liisa Wainman (University of British Columbia, University of British Columbia, University of British Columbia), Mehdi Ahmadian (University of British Columbia), Glen Foster (University of British Columbia Okanagan), Philip Ainslie (University of British Columbia Okanagan), Raphael Rodrigues Perim (University of Texas Health Science Centre), Gordon Mitchell (University of Floria), Christopher West (University of British Columbia, University of British Columbia)

Spinal cord injury (SCI) causes hypotension and orthostatic intolerance due to disrupted sympathetic input to the heart and vasculature following injury1. A neuro-therapeutic strategy shown to increase somatic motor function below the injury is acute intermittent hypoxia (AIH). While AIH is known to improve control over respiratory and non-respiratory motor systems with incomplete cervical SCI2,3, cardio-autonomic responses to AIH after SCI are unknown. In able-bodied individuals, AIH increases blood pressure (BP), improves orthostatic tolerance (OT), and heightens sympathetic activity4. In incomplete SCI, intact neural pathways regulating sympathetic nerve activity suggest the potential for AIH to increase sub-lesional sympathetic activity, thus improving cardiovascular function. Previous work has demonstrated that the response to AIH is greatest in rats at least 4 weeks post-injury due to reestablishment of serotonergic pathways2, therefore the purpose of this project is to investigate whether AIH improves OT in rats following acute (2 weeks) and/or chronic (4 weeks) high-thoracic SCI. We believe AIH will improve OT more in chronically versus acutely injured rats.

12 Wistar rats underwent T3 300 kdyn SCI. At 14 (n=6) or 28 (n=6) days post-SCI rats were tracheotomized, ventilated and arterial catheterization was performed to assess BP. Rats were subjected to lower body negative pressure (LBNP; recorded with manometer) to decrease mean arterial pressure (MAP) by 5 and 10 mmHg for 1 min. Rats were exposed to isocapnic AIH (10 x 1-min FIO2=0.10 separated by 2 min of FIO2=1.00; targeting a PaCO2 of 40 mmHg). LBNP was repeated 90 minutes post-AIH, the expected peak response. Blood gases were measured pre- and post-AIH. A mixed-design ANOVA was performed to examine effects of time post-SCI (group) and AIH (treatment) on change in box pressure required to decrease MAP by -5 and -10 mmHg.

There was a significant group*treatment interaction for the -5 mmHg (p=0.011) and -10 mmHg LBNP stage (p=0.017). Post hoc comparisons demonstrate that in chronic SCI the box pressure required to drop MAP by -5 and -10mmHg was increased by 41±16% (p=0.009) and 46±22% (p=0.079) versus pre-AIH, respectively, implying improved OT (Fig 1).  

We demonstrate that AIH has the capacity to improve OT in a rodent model of SCI in a chronic, but not acute setting.

References:

1.        DeVeau et al. Autonomic Neuroscience (2018)

2.        Golder amp; Mitchell Journal of Neuroscience (2005)

3.        Prosser-Loose et al. Journal of Neurotrauma (2015)

4.        Stuckless et al. Journal of Physiology (2020)

This project was supported by a seed grant from the Blusson Integrated Cures Partnership.



Fig 1: AIH in chronic spinal cord injury (SCI) (B) augmented the lower body negative pressure required to decrease mean afterial pressure (MAP) by 5 and 10 mmHg by 41±16% (p=0.009) and 46±22% (p=0.079), respectively. There was no change in orthostatic tolerance in acutely injured rats (A). Data are presented as means±standard deviation.