Endothelial Dysfunction After SCI: Mechanism and Therapeutic Target for SCI-related Cardiovascular Disease
Craig Hospital
Summary
This study plans to learn how endothelial cells, single cell lining of blood vessels may be dysfunctional after a spinal cord injury. Endothelial dysfunction will be measured by the capacity of blood vessels to vasodilate (increase in size) and alter blood flow is lower in adults with a spinal cord injury in comparison to adults without a spinal cord injury. The mechanisms which may alter this function may be critical in reducing the risk of heart attacks and strokes in people with spinal cord injuries.
Description
Vascular endothelial dysfunction is prevalent after spinal cord injury (SCI) which predispose individuals with SCI to accelerated, atherosclerotic cardiovascular disease (ASCVD) and future myocardial infarctions and ischemic strokes. The central objective of this study is to determine whether adults with SCI exhibit impaired endothelial function. Specifically, if endothelium-dependent vasodilation is impaired and if endothelial cell derived microvesicles (EMVs) are elevated and dysfunctional in adults with paraplegia. Endothelium-dependent vasodilation will be assessed by pharmacologically man…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- Yes
SCI Inclusion Criteria * Over age 18 years * Chronic (\>12 months) SCI * Motor complete (AIS A/B) SCI * Paraplegia (neurological level of injury \[NLI\] at T2 or below) Non-injured Inclusion Criteria • Over age 18 years Exclusion Criteria (Both SCI and Non-injured) * Overt chronic diseases as assessed by: a) clinically documented medical history; b) physical examination; c) blood pressure and ECG at rest; and d) complete blood chemistries and hematological evaluation. * Active infection * Recent (\< 3 months) surgery * Current smoking history (within past 12 months) * Report more than low…
Interventions
- ProcedureIntra-arterial Infusion of Vasoactive Agents
A catheter is placed in the brachial artery of the non-dominant arm, and small doses of vasoactive drugs \[acetylcholine (Ach), isoproterenol (ISO), sodium nitroprusside (SNP)\] are infused. Forearm blood flow (FBF) is measured using venous occlusion plethysmography. The purpose of this procedure is to assess endothelium-dependent and independent vasodilation by stimulating different vascular pathways. The Ach infusion is to test muscarinic receptor, nitro oxide (NO) dependent, endothelium-dependent vasodilation. ISO infusion is to evaluate β-adrenergic, NO-dependent endothelium-dependent vasodilation. SNP infusion is to assess endothelium-independent vasodilation.
- ProcedureIntra-arterial Vitamin C Infusion
Vitamin C, a potent antioxidant, will be infused into the arm and forearm blood flow (FBF) will be re-evaluated to determine whether oxidative stress contributes to endothelial dysfunction.
- ProcedureBlood Sampling
Blood will be sampled from the antecubital vein (\~50 mL) for biomarker analysis. This is to assess circulating biochemical and molecular indicators of vascular health and inflammation including levels of endothelial cell derived microvesicles (EMVs)
Location
- Craig HospitalEnglewood, Colorado