IR and Microvascular Blood Flow in SCI

Summary

Persons with spinal cord injury (SCI) are at an increased risk for metabolic disorders, including that of insulin resistance. As a result of neurological injury, they often have impaired mechanisms that regulate blood vessel function below the level of injury. Insulin, which facilitates the transport of glucose into muscle cells, is also capable of regulating skin blood flow, with insulin resistance reducing perfusion. Although beyond the scope of this proposal, the possibility exists that impaired microvascular skin blood flow responses due to insulin may further predispose to ischemia of the skin at pressure points of bony prominence. This perturbed cutaneous vascular response may place persons with SCI at risk for the development and poor healing of pressure ulcers due to microvascular dysfunction secondary to neurologic and metabolic disorders.

Primary Aim: To determine the association between systemic insulin sensitivity and insulin-mediated vasodilatation below the neurological level of injury.

We hypothesize that individuals with systemic insulin sensitivity compared to those with insulin resistance will have greater insulin-mediated vasodilatation and an associated proportional increase in cutaneous blood perfusion. Thus, intact and appropriate endothelial-mediated regulation by insulin will be operative despite sub-lesional neurological impairment in insulin sensitive individuals with SCI. However, because of the absence of the SNS-mediated insulin action on the microvasculature (i.e., insulin-mediated sympathetic withdrawal), it is being hypothesized that the vasodilatory response to iontophoresis with insulin in insulin sensitive subjects with SCI will be less than that observed in neurologically intact controls with insulin sensitivity.

Secondary Aim: To compare peak microvascular perfusion responses to endothelial-dependent vasodilatation by iontophoresis with acetylcholine to insulin.

We hypothesize that the peak blood perfusion responses to iontophoresis with insulin will be comparable in magnitude to that of acetylcholine in individuals with greater systemic insulin sensitivity. This will be in contrast to individuals with systemic insulin resistance who will demonstrate a diminished response to iontophoresis with insulin when compared to that of acetylcholine. Because of SNS impairment, the peak vasodilatory response observed to these interventions will be lower in the group with SCI.

Conditions

• Spinal Cord Injury
• Insulin Resistance

Interventions

DRUG

Insulin iontophoresis

For insulin iontophoresis, the cathode electrode will contain 0.2 ml of liquid insulin. For preparation and instrumentation, the arms will be uncovered below the elbow; the participant's lower extremities will be uncovered below knee for leg evaluations. The laser Doppler flowmetry (LDF) lead will be placed bilaterally, 2 inches proximal to the lateral malleolus over the peroneus longus muscle. For arm evaluations, a lead will be placed (and secured with dual-sided transparent tape) bilaterally, 2 inches distal to the lateral epicondyle over the flexor carpi ulnaris muscle along the midline with the ulnar process. Baseline and peak cutaneous blood flow responses to application of insulin iontophoresis will be determined for each LDF lead during the evaluation.

DRUG

Placebo Iontophoresis

For placebo iontophoresis, the cathode electrode will contain 0.2 ml of preservative-free normal saline; the anode electrode will contain a medical grade adhesive for skin placement and last 20 minutes. Preparation, instrumentation and data collection for this intervention are the same as the insulin iontophoresis.

DRUG

Acetylcholine Iontophoresis

For acetylcholine iontophoresis, the anode electrode will contain 0.2 ml of 1% acetylcholine chloride; the cathode electrode will contain a medical grade adhesive for skin placement and last 20 minutes. Preparation, instrumentation and data collection for this intervention are the same as the insulin iontophoresis.

OTHER

Heat application

For the provocation with heat, an insulated thermal heat pack (\~106°F) will be applied to the exposed arm or leg for 18 minutes. The thermal heat pack is comparable to what is routinely used as a heat therapy in conventional rehabilitation settings. LDF leads and temperature sensors will be placed in the previously specified locations to evaluate the changes.

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center

  lead FED

Principal Investigators

• William A Bauman, MD · James J. Peters VA Medical Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

69 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-12-31

Primary Completion

2015-12-31

Completion

2016-12-31

Countries

• United States

Study Locations