Regulation of cerebral and systemic blood flow in humans with high level spinal cord injury: the infleunce of alpha1-agonist midodrine hydrochloride

• Main Author: Phillips, Aaron
• Language: English
• Published: University of British Columbia 2013
• Online Access: http://hdl.handle.net/2429/44956

RATIONALE: Spinal cord injury (SCI) is a devastating condition, often resulting in severe autonomic dysfunction. Secondary to autonomic dysfunction, many individuals with SCI have low blood pressure, which likely challenges the brain’s capacity to maintain suitable perfusion. Individuals with SCI suffer from a myriad of conditions that may be associated with dysfunctional regulation of cerebral blood flow (CBF), including cognitive dysfunction, orthostatic intolerance and stroke risk. Current knowledge regarding CBF regulation in SCI is limited. AIMS: To comprehensively examine cerebrovascular control in those with SCI, including: 1) the CBF response to cognition, 2) the acute CBF response to tilt, 3) the relationship between baroreflex sensitivity and CBF regulation, 4) the role arterial stiffening plays in baroreflex sensitivity, and 5) to examine the influence of increasing blood pressure through oral administration of 10 mg midodrine (alpha1-agonist). The first investigation found that the CBF response to cognition is absent in those with SCI when compared with able-bodied individuals. When restoring blood pressure to normal levels with midodrine, the CBF response to cognition was improved by 70% which was reflected in a 13% improvement in cognitive function. The second investigation showed that midodrine improved orthostatic tolerance 59% in SCI, and mitigated the reduction of CBF during tilt. The CBF response to tilt was well-maintained in SCI. The third investigation assessed the relationship between common carotid artery stiffness and baroreflex sensitivity in those with SCI. Elevated arterial stiffness (+12%) in those with SCI were negatively related to reduced in baroreflex sensitivity (R2 =0.45; p<0.05). Administration of midodrine did not influence baroreflex sensitivity or arterial stiffness. SUMMARY: Studies one and two provide evidence that the CBF response to metabolic stimuli (i.e., cognition) is reduced in SCI, while CBF is effectively maintained in response to alterations in blood pressure. Furthermore, study three shows that reduced baroreflex sensitivity in SCI is closely related to increased arterial stiffness in the SCI population. It is concluded that CBF regulation is altered in those with SCI, and may be related to clinical outcomes such as cognitive decline and orthostatic intolerance. === Medicine, Faculty of === Medicine, Department of === Experimental Medicine, Division of === Graduate