Role of Vascular Endothelial Function After Spinal Cord Injury Related Cardiovascular Disease Risk
Craig Hospital
Summary
Individuals with spinal cord injury have heart attacks and strokes more frequently, and much earlier in life. People with spinal cord injuries develop plaque in vessels much faster, and the reasons why are unclear. Doctors generally attributed the increased risk with weight gain and developing diabetes, but many studies have shown that even without these common factors, plaque in vessels is developing more often and faster. Endothelial cells are a single layer of cells that line all vessels in the body and plays an important role in vessel health. Damage to endothelial cells is known to lead to heart attacks and strokes. Past studies on endothelial cells of people with spinal cord injury have been unclear. The investigators have new data that these cells are unhealthy after spinal cord injury a measurement. This includes measuring endothelial health by directly altering its function using a catheter in the arm and measuring small particles in blood called endothelial microvesicles. If the project is successful, the investigators will learn important information on the health of endothelial cells after spinal cord injury. The investigators will also be able to use these markers of endothelial cell function to create treatments to improve vessel health and prevent heart attacks and strokes later in life in people with spinal cord injury.
Description
Adults with spinal cord injury (SCI) demonstrate accelerated atherosclerotic cardiovascular disease (ASCVD) occurring \~4 fold more often, and decades earlier in life. Importantly, atherosclerosis has been detected in people with SCI independent of traditional risk factors, much earlier in life, and appear recalcitrant to conventional risk mitigating inventions such as exercise and diet. Also, as disease is silent, many individuals are not screened for this atherosclerotic burden and only aware after the major vascular event of a myocardial infarction or stroke. The mechanisms which drive earl…
Eligibility
- Age range
- 18–89 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Men and women of all races, ethnic backgrounds\>18 years of age * Traumatic spinal cord injury (Sports, Assault, Transport, Fall, Other Traumatic Causes) * Time since injury (\> 12 months) * Paraplegia Motor Complete Injury (neurological level of injury at T2 or below, ASIA Impairment Scale A or B Exclusion Criteria: * History of high blood pressure * History cardiovascular disease (coronary artery disease, congestive heart failure, myocardial infarction, cerebrovascular accident). * History high cholesterol * History of Diabetes Type I or Type II * History of Obstruct…
Interventions
- ProcedureBrachial intra-arterial infusion of vasoactive and antioxidant drugs (acetylcholine, nitroprusside, ascorbic acid)
The brachial artery in the non-dominant arm will be catheterized to infuse endothelium-dependent vasodilator acetylcholine, endothelium-independent vasodilator nitroprusside, and antioxidant ascorbic acid at concentrations to have isolated effect in the forearm.
- Procedurevenous occlusion plethysmography
Whole forearm blood flow will be measured by mercury-strain gauge while venous occlusion is applied to the forearm and hand by rapid-cuff inflation to sub-arterial pressures. Changes in whole forearm blood flow with be measured at baseline, endothelial agonists, and removal of oxidative stress via acorbic acid.
- DrugAcetylcholine
Endothelium-dependent vasodilation will then be assessed by changes in FBF in response to intra-arterial infusions of the endothelial agonist acetylcholine infused at rates of 4.0, 8.0, 16.0 μg/100 mL of forearm tissue/min to generate a dose-response curve.
- DrugSodium Nitroprusside
Endothelium-independent vasodilation will be assessed by changes in forearm blood flow in response to intra-arterial infusions of sodium nitroprusside at 1.0, 2.0, 4.0 μg/100 mL forearm tissue/min.
Location
- Craig HospitalEnglewood, Colorado