Cutaneous microvascular perfusion responses to insulin iontophoresis are differentially affected by insulin resistance after spinal cord injury.

NEW FINDINGS: What is the central question of this study? What impact does insulin resistance have on cutaneous perfusion responses to insulin iontophoresis in vascular beds with markedly reduced or functionally ablated sympathetic nervous system vasomotor function resulting from spinal cord injury? What is the main finding and its importance? Persons with spinal cord injury have sublesional microvascular endothelial dysfunction, as indicated by a blunted cutaneous perfusion response to acetylcholine iontophoresis, and the presence of insulin resistance has a further confounding effect on endothelium-mediated changes to cutaneous perfusion in the lower extremities. Endothelium-mediated mechanisms that regulate skin blood flow might play an integral role in optimizing skin perfusion in vascular beds with sympathetic nervous system vasomotor impairment, such as in spinal cord injury (SCI). Insulin is a vasoactive hormone and second messenger of nitric oxide that facilitates endothelium-mediated dilatation. The effects of insulin resistance (IR) on sublesional cutaneous perfusion responses to insulin provocation have yet to be described in persons with SCI. Persons with SCI and an able-bodied (AB) cohort were divided into subgroups based upon fasting plasma insulin concentration cut-offs for IR (≥13.13 mIU ml-1 ) or insulin sensitivity (IS; <13.13 mIU ml-1 ), as follows: AB, IS (ABIS, n = 21); SCI, IS (SCIS, n = 21); AB, IR (ABIR, n = 9); and SCI, IR (SCIR, n = 11). Laser Doppler flowmetry characterized peak blood perfusion unit (BPU) responses (percentage change from baseline) to insulin, acetylcholine or placebo iontophoresis in the lower extremities; BPU responses were log10 transformed to facilitate comparisons, and the net insulin response (NetIns) BPU response was calculated (insulin minus placebo BPU response). The NetIns was significantly greater in both IS groups compared with their corresponding IR group. The acetylcholine-mediated BPU responses in the SCI subgroups were significantly lower than those in the ABIS group. The proportional BPU responses of NetIns to acetylcholine in the IS cohorts (i.e. ABIS and SCIS) were significantly greater (P < 0.05) than that of each IR subgroup. The presence of IR has a confounding effect on sublesional microvascular endothelium-mediated cutaneous perfusion responses to provocation. Preservation of endothelial sensitivity to its agonists appears to be an important modifiable risk factor to optimize cutaneous perfusion in the lower extremities of persons with SCI.

Self-reported effects of cold temperature exposure in persons with tetraplegia.

OBJECTIVE: Cervical spinal cord injury (tetraplegia) is known to interrupt sympathetic vasculature control, thereby preventing shunting of blood from the periphery to central organs when exposed to cold temperatures. As a result, persons with tetraplegia are at risk to develop hypothermia. However, information regarding the discomfort experienced during the cooler months (late fall, winter, early spring) is overwhelmingly anecdotal. It is not known, with any certainty, how those with tetraplegia perceive cold and if discomfort in colder environments restricts them from performing activities that they routinely would perform. DESIGN: Prospective, two-group, self-report surveys. SETTING: VA Medical Center and Kessler Institute for Rehabilitation. PARTICIPANTS: Forty-four subjects with tetraplegia; 41 matched non-SCI controls. OUTCOME MEASURES: Tetraplegic and control groups responded "yes" or "no" when asked whether cold seasonal temperatures allowed comfort or negatively affected participation in routine activities. RESULTS: Percentage of responses of tetraplegia compared to controls was different as to whether they felt cold when others in the same room were comfortable (82 vs. 24%; χ2 = 28.2, P < 0.0001), felt comfortable outdoors (17 vs. 43%; χ2 = 6.8, P = 0.009), or whether cold negatively affected bathing routines (55 vs. 15%; χ2 = 14.8, P = 0.0001), keeping physician appointments (46 vs. 12%; χ2 = 11.3, P = 0.0008), thinking clearly (41 vs. 7%; χ2 = 12.9, P = 0.0003), and completing usual work duties (46 vs. 10%; χ2 = 13.3, P = 0.0003). CONCLUSION: Cold seasonal temperatures have a reported greater negative impact on personal comfort and ability to perform vital activities in persons with tetraplegia than that of non-SCI controls. These findings highlight the need to address thermoregulatory impairment in persons with tetraplegia.

Orthostatic responses to anticholinesterase inhibition in spinal cord injury.

INTRODUCTION: Acetylcholine (Ach) is the pre-synaptic neurotransmitter of the sympathetic nervous system. Increased pre-synaptic Ach may augment post-synaptic release of norepinephrine, thereby increasing systemic blood pressure (BP). OBJECTIVES: The primary objective of this investigation was to determine the hemodynamic effect of pyridostigmine bromide (PYRIDO: 60 mg), an Ach inhibitor (AchI), compared to no-drug (NO-D) during head-up tilt (HUT) in individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effects of PYRIDO compared to NO-D on symptoms of orthostatic intolerance (OI) and adverse event reporting (AE). METHODS: Ten individuals with SCI (C4-C7) were studied on two occasions: visit (1) NO-D and visit (2) PYRIDO. On each visit subjects underwent a progressive HUT maneuver to 15°, 25°, 35° for 5 min at each angle and 45 min at 45°. Supine and orthostatic heart rate (HR), systolic and diastolic BP (SBP and DBP), as well as monitored and symptoms of OI and AE were monitored and recorded. RESULTS: Supine hemodynamics did not differ between the trials. The significant fall in SBP during the NO-D trial was diminished with PYRIDO, and five subjects had an increased DBP during HUT with PYRIDO compared to the NO-D trial. Individuals that responded to PYRIDO with an increase in orthostatic BP had significantly lower resting HR than non-responders (p < 0.01), which suggests increased levels of pre-synaptic Ach. Subjective symptoms of OI and AE reporting did not differ between the two trials. CONCLUSIONS: These preliminary data suggest that PYRIDO is safe and may be effective at ameliorating the orthostatic fall in BP in select individuals with SCI.