IR and Microvascular Blood Flow in SCI

Study 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 iontop

Primary Outcome

Iontophoresis with insulin will be performed in the arm and leg of individuals with spinal cord injury and able-bodied control subjects. The respective responses of the cutaneous microvascular beds to iontophoresis with insulin will be determined with considerations for the effects of sympathetic nervous system dysfunction as a result of spinal cord injury and systemic insulin sensitivity (as measured by an intravenous glucose tolerance test).

Interventions

• DRUG Insulin iontophoresis
• DRUG Placebo Iontophoresis
• DRUG Acetylcholine Iontophoresis
• OTHER Heat application