Abstract 285: The Hemodynamic Actions of Insulin Are Blunted in the Sublesion Microvasculature of Healthy Persons with Spinal Cord Injury

Abstract

Background: The hemodynamic actions of insulin (HAI) involve endothelial-mediated and sympathetic nervous system (SNS)-facilitated vasodilatation of the microvasculature. Spinal cord injury (SCI) is characterized by interruption of supraspinal SNS control of sub-lesion vasomotor tone, and a high prevalence of disordered carbohydrate metabolism, cardiovascular-related morbidity and pressure ulcers, are well appreciated. Objective: To gain a better understanding of the HAI on sub-lesion microcirculation in SCI. Procedures: Insulin iontophoresis (InsI; FDA IND #110886) was performed in an otherwise healthy cohort of persons with SCI and an age- and gender-matched cohort of neurologically intact control subjects. Laser Doppler flowmetry characterized peak blood perfusion unit (BPU) responses (%change from baseline) to InsI or placebo iontophoresis (PlacI) above and below the neurological level of injury. Parametric statistics were employed to test for statistical differences within and between condition (InsI, PlacI), location (arm, leg), and group (SCI, control). An a priori level of significance was set at p≤0.05. Results: Demographics (SCI: n=10, age 39 ± 12, 8 males: control: n=10, age 37 ± 10, 8 males), fasting plasma glucose (SCI: 5.2 ± 0.5; control 5.3±0.2 mmol/l) and fasting plasma insulin (SCI: 12.4 ± 7.8; control 13.1 ± 5.8 μIU/ml) concentrations did not differ between groups. PlacI did not result in any significant BPU changes in the arm or leg of either group. In the arm, insulin iontophoresis resulted in a 20% average BPU increase (p<0.05) in controls and a 9% increase in the SCI group (p=0.14). In the legs, InsI resulted in an 81% (p<0.01) and 29% (p<0.001) average BPU increase in the control and SCI groups, respectively, a change that was significant between groups (p<0.05). InsI of the leg resulted in a 19% (p<0.05) and 61% (p<0.05) greater BPU increase than the arm in the SCI and control groups, respectively. Conclusion: The HAI are blunted in the sub-lesion microvasculature of persons with SCI. Our findings could have implications for the prevalence and genesis of skin breakdown, the initiation of pressure ulcers and/or cardiovascular disease and peripheral insulin insensitivity due to reduced tissue perfusion in persons with SCI.