A Study of Blood Pressure and Blood Supply to the Brain in Persons With a Spinal Cord Injury.

Study Overview
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Brief Summary
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The purpose of this study is to determine how blood pressure and blood flow are controlled during head-up tilt in a semi-upright position. In this investigation we are studying blood pressure and blood flow to the brain, with and without a medication which lowers blood pressure (Vasotec). We will determine how persons with a spinal cord injury are able to maintain blood flow to the brain (not get dizzy) as they assume a more upright position and their blood pressure decreases.

Detailed Description
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Individuals with tetraplegia lack normal sympathetic nervous system regulation of blood pressure and, therefore, relative hypotension is a common occurrence. This hypotension may be more pronounced with postural stress. Loss in mental acuity and sometimes even consciousness is an associated symptom of postural hypotension in individuals with tetraplegia. There is some evidence to suggest that although mean arterial blood pressure (MAP) is relatively low in these individuals, middle cerebral arterial blood flow (CBF) may be maintained. Consequently, individuals with chronic tetraplegia often compensate and are stable in the seated upright position. Autoregulation of CBF has been defined as the stability of cerebral blood flow throughout a range of systemic blood pressures (MAP). This proposal will examine systemic hemodynamics and middle cerebral artery blood flow during HUT with and without Vasotec, an angiotensin II inhibitor. By partially or completely ablating the renin-angiotensin system, which is postulated to play a major role in blood pressure regulation, the potential dissociation between systemic blood pressure and middle cerebral artery blood flow, in individuals with tetraplegia, may be demonstrated. The aim is to determine whether persons with chronic tetraplegia are able to maintain similar CBF, or similar CBF changes, as able-bodied controls despite a greater decrease in MAP to the same hypotensive challenge. The relationship between MAP and CBF has not been defined in this population. Understanding this relationship may lead to improved screening and treatment for prevention of postural hypotension in persons with tetraplegia.

Official Title
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Systemic Hemodynamics and Cerebral Blood Flow in Persons With Tetraplegia

Conditions
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Orthostatic Hypotension, Spinal Cord Injuries

Intervention / Treatment
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* Drug: 1.25 mg enalaprilat IV
* Other: Head up tilt (HUT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Duration of spinal cord injury (SCI) at least 1 year Level of SCI C4-8 and T6 and below matched non-SCI subjects Chronological age between 18-65 years Euhydration: Subjects will be instructed to avoid caffeine and alcohol and to maintain normal salt and water intake for several days prior to study. Exclusion Criteria: Known heart and/or blood vessel disease Dehydration High blood pressure Kidney disease Diabetes mellitus Prescribed ACE inhibitors Acute Infection Smoking Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: ARM 1<br>Head-up tilt maneuver without drug in subjects with spinal cord injury | Other: Head up tilt (HUT)<br>* 45 degree head-up tilt to lower blood pressure and measure cerebral blood flow.<br>|
| Placebo Comparator: ARM 3<br>Head-up tilt maneuver without drug in able-bodied controls | Other: Head up tilt (HUT)<br>* 45 degree head-up tilt to lower blood pressure and measure cerebral blood flow.<br>|
| Active Comparator: ARM 2<br>Head-up tilt maneuver with an angiotensin converting enzyme inhibitor (1.25 mg enalaprilat) in subjects with spinal cord injury | Drug: 1.25 mg enalaprilat IV<br>* an angiotensin converting enzyme (ACE) inhibitor given to lower blood pressure (BP) and measure cerebral blood flow (CBF)<br>Other: Head up tilt (HUT)<br>* 45 degree head-up tilt to lower blood pressure and measure cerebral blood flow.<br>|
| Active Comparator: ARM 4<br>Head-up tilt maneuver with an angiotensin converting enzyme inhibitor (1.25 mg enalaprilat) in able-bodied controls. | Drug: 1.25 mg enalaprilat IV<br>* an angiotensin converting enzyme (ACE) inhibitor given to lower blood pressure (BP) and measure cerebral blood flow (CBF)<br>Other: Head up tilt (HUT)<br>* 45 degree head-up tilt to lower blood pressure and measure cerebral blood flow.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure | Systolic blood pressure during head-up tilt in subjects with spinal cord injury without drug intervention | acute testing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Blood Flow | Measurement of middle cerebral artery blood flow velocity supine and during head-up tilt | acute testing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Pressure, Low, Hypotension, Postural, Injuries, Spinal Cord, Spinal Cord Transection, Spinal Cord Trauma