In 1927, Norris described individuals with low blood pressure (BP) as persons who lacked stamina, tired easily, complained of cold extremities and showed an inability to do prolonged mental or physical work; he was quoted as saying; they are not exactly ill; yet they are rarely well. 1 However, several more recent papers have challenged the notion that low BP is a health concern, and even suggest that hypotension is the ideal normal BP.2, 3 Individuals with spinal cord injury (SCI) above T5 are reported to struggle with chronic hypotension,4-11 episodic orthostatic hypotension (OH) 12-16 and post-prandial hypotension.17 In fact, we recently reported that, over the course of a typical 24-hour day, the incidence of hypotension was as high as 70% in those with cervical lesions.18 In addition our unpublished data suggest that the incidence of hypotension is 2.5 fold increased in veterans with SCI compared to age-matched veterans without SCI. However, chronic hypotension is often not clinically addressed because the vast majority of hypotensive individuals remain asymptomatic. That said there evidence in the general medical literature supporting associations between asymptomatic hypotension, cognitive deficits, adverse changes in mood and quality of life (QOL). Compared to normotensive age-matched controls, otherwise healthy subjects with chronic asymptomatic hypotension are reported to have slowed cognitive speed, 19 fewer word recall, 20 decreased accuracy of response,21 limited attention,20 prolonged reaction times,19, 21, 22 and reduced memory and concentration capacity. 21, 22 In addition, several papers have reported findings suggesting significant associations between chronic hypotension and increased incidence of depression,23-30 anxiety,25, 26 unexplained tiredness,24, 31 and poor perception of well being.32 Although many hypotensive individuals with chronic SCI remain asymptomatic and do not raise clinical suspicion warranting intervention, we believe, and have demonstrated that asymptomatic chronic hypotension has adverse cognitive consequences.33-35 It must be appreciated that the superimposition of cognitive impairment on the physical, social and emotional limitations already experienced by many individuals with SCI may severely impact autonomy and social independence thereby diminishing QOL.36, 37 There is compelling evidence in the general medical literature suggesting that elevation in systemic BP, following midodrine hydrochloride administration, increases resting cerebral blood flow (CBF) and improves CBF responses to cognitive testing resulting in better test performance in healthy individuals with chronic hypotension. 38, 39 Because it is believed that the etiology of hypotension in the SCI population is the result of adrenergic insufficiency, midodrine, an alpha-adrenergic agonist, is considered a first line treatment, 40-42 and we have demonstrated significant increases in systemic BP in hypotensive individuals with SCI.43, 44 However, in general, data describing the BP effect of midodrine have been collected in small samples of hypotensive subjects with SCI during laboratory observations,44, 45 the benefit of sustained elevation in systemic BP on CBF, cognitive function, mood and QOL has not been rigorously studied in the SCI population. Data generated in this pilot project will be used to power a large-scale clinical trial to determine the clinical benefit of sustained increases in BP on CBF, cognitive function, mood and QOL in persons with SCI.

Public Health Relevance

We have found that the incidence of hypotension is increased 2.5-fold in veterans with spinal cord injury (SCI) compared to age-matched veterans without SCI. Although many chronically hypotensive individuals with SCI remain overtly asymptomatic, we have reported evidence of impaired memory and reduced attention and processing speed in a hypotensive SCI cohort compared to a normotensive SCI cohort. Increase in systemic blood pressure (BP), secondary to administration of an anti-hypotensive agent (midodrine), has been shown to increase cerebral blood flow (CBF) at rest and in response to cognitive testing, which was associated with improved test performance in hypotensive controls. In a relatively small group of hypotensive individuals with SCI we have demonstrated that midodrine significantly increases BP and CBF, which may improve cognitive function. Therefore, we aim to determine the long term benefit of sustained elevation in BP following midodrine administration on CBF, cognitive performance, mood and quality of life in persons with SCI.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (I21)
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Special Emphasis Panel (RRDS)
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James J Peters VA Medical Center
United States
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