Title

Time-course, mechanisms and mathematical model of autonomic dysreflexia in humans

Date of Award

2010

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Chemical Engineering

Advisor(s)

Blair Calancie

Keywords

Autonomic dysreflexia, Spinal cord injury, Hypertension, Sympathetic activity

Subject Categories

Biomedical Engineering and Bioengineering

Abstract

Autonomic dysreflexia (AD) is a potentially lethal reaction in persons with spinal cord injury that is characterized by a stimulus-elicited hypertension. The time-course and mechanisms responsible for AD in humans are uncertain. However, it is thought that sensory inputs to the spinal cord caudal to the level of a lesion elicit activity in sympathetic spinal circuits that cause constriction of blood vessels and AD. The suggested mechanisms of AD mostly pertain to the origin of the spinal circuitry and neurovascular function. Herein, we developed a safe, practical test to screen persons for AD. The screening test was applied to subjects with acute (<4 weeks) and sub-acute (4 weeks ≤ 14 weeks) spinal cord injury enabling us to prospectively determine the time of AD onset in humans. Also, to better understand the role of the sympathetic spinal circuitry in AD, the screening test was applied simultaneously with direct neural recordings in subjects with chronic (≥1 year post-injury) spinal cord injury. These recordings were made from muscle fascicles of the common peroneal nerve at a site behind the knee. This enabled us to record muscle sympathetic activity, which is suspected of contributing to AD in humans. Neurovascular function was also assessed in these subjects by measuring caliber change of the anterior tibial artery with ultrasonography, in response to intraneural stimulation. The earliest manifestation of AD occurred at 6 weeks post-injury, and was more likely to occur in the weeks thereafter. These results show that the mechanisms responsible for AD in humans can be functional as soon as 6 weeks post-injury, and suggest that the sympathetic spinal circuitry thought to host AD is likely pre-existing and strengthened during the first few months post-injury. Muscle sympathetic activity was absent in the lower leg of persons with chronic spinal cord injury, despite observation of two unprovoked sessions of clinical AD. This suggests that muscle sympathetic activity in the distal lower limbs does not contribute to AD in humans and is unlikely caused by a massive sympathetic discharge. The arterial caliber of the anterior tibial artery was unaffected by stimulation. Accordingly, these results were inconclusive, and without further experimentation cannot determine if neurovascular supersensitivity contributes to AD in humans. A mathematical model was developed to simulate the baroreflex loop during the able-bodied and spinal cord injured conditions, and AD. The model that was developed is deterministic, thus the results of simulation are not amenable to statistical review. Simulation, however, aptly described the able-bodied and spinal cord injured conditions during rest, forced blood pressure increases and decreases, and autonomic dysreflexia.

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