Role of Endothelial Function in SCI CVD Risk

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.

Conditions

• Spinal Cord Injuries
• Cardiovascular Diseases
• Endothelial Dysfunction

Interventions

PROCEDURE

Brachial 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.

PROCEDURE

venous 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.

DRUG

Acetylcholine

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.

DRUG

Sodium 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.

DRUG

Ascorbic acid

Ascorbic acid will be infused at a constant rate (12 mg/100 mL tissue/min) and maintained at the same rate while the acetylcholine and sodium nitroprusside dose-response curves are repeated.

PROCEDURE

venous phlebotomy

Venous blood samples will be collected to measure baseline cardiometabolic characteristics and isolate endothelial cell microvesicles for characterizations and in vitro experiments.

Sponsors & Collaborators

• University of Colorado, Boulder

  collaborator OTHER

• Craig Hospital

  lead OTHER

Principal Investigators

• Andrew Park, MD · Craig Hospital

Eligibility

Min Age

18 Years

Max Age

89 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-09-01

Primary Completion

2027-03-30

Completion

2027-03-30

Countries

• United States

Study Locations