Nicholas A. Strom

Skin blood flow and nitric oxide during body heating in type 2 diabetes mellitus

Individuals with type 2 diabetes mellitus (T2DM) often exhibit microvascular dysfunction that may contribute to impaired thermoregulation, but potential mechanisms remain unclear. Our goals were to quantify skin blood flow responses and nitric oxide-mediated vasodilation during body heating in individuals with T2DM compared with nondiabetic control subjects of similar age. We measured skin blood flow (laser-Doppler flowmetry) in conjunction with intradermal microdialysis of N(G)-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase inhibitor) or vehicle during 45-60 min of whole body heating (WBH) in 10 individuals with T2DM and 14 control subjects. In six individuals from each group, we also measured forearm blood flow (FBF) by venous occlusion plethysmography on the contralateral forearm. FBF responses showed diminished absolute cutaneous vasodilation during WBH in the T2DM group (P(ANOVA) < 0.01; peak FBF in control 13.1 +/- 1.7 vs. T2DM 9.0 +/- 1.6 ml.100 ml(-1).min(-1)). However, the relative contribution of nitric oxide to the cutaneous vasodilator response (expressed as % of maximal cutaneous vascular conductance) was not different between groups (P > 0.05). We conclude that cutaneous vasodilator responses to WBH are decreased in individuals with T2DM, but the contribution of nitric oxide to this smaller vasodilation is similar between T2DM and control individuals. This decrease in cutaneous vasodilation is likely an important contributor to impaired thermoregulation in T2DM.

Cutaneous sympathetic neural responses to body cooling in type 2 diabetes mellitus.

In humans, sympathetic vasoconstrictor nerves in the skin contribute to resting vascular tone and mediate reflex vasoconstrictor responses to body cooling. Although it is well recognized that type 2 diabetes mellitus (T2DM) is associated with peripheral neurovascular changes, it is unclear to what extent the thermal responsiveness of the cutaneous vasoconstrictor system is altered in individuals with relatively uncomplicated T2DM. We tested the hypothesis that skin sympathetic nerve activity (SSNA) is decreased at baseline and during body cooling in individuals with T2DM compared to healthy controls (C) of similar age and body size. We measured SSNA (microneurography) and skin blood flow (laser-Doppler flowmetry) in the innervated area in 8 T2DM and 12 C subjects at baseline and during 3-4min of rapid whole body cooling via a water-perfused suit. SSNA (total integrated activity) increased, and cutaneous vascular conductance decreased in both groups during body cooling (P<0.01 for both). However, SSNA was not different between groups during either baseline or body cooling conditions (P=NS). The deltas in SSNA between baseline and body cooling were similar between groups: T2DM: 55±27 and C: 57±12 units (P=NS). We conclude that reflex cutaneous sympathetic and vascular responses to rapid whole body cooling are preserved in relatively healthy individuals with T2DM.

Influence of Rapid Fluid Loading on Airway Structure and Function in Healthy Humans

BACKGROUND The present study examined the influence of rapid intravenous fluid loading (RFL) on airway structure and pulmonary vascular volumes using computed tomography imaging and the subsequent impact on pulmonary function in healthy adults (n = 16). METHODS AND RESULTS Total lung capacity (DeltaTLC = -6%), forced vital capacity (DeltaFVC = -14%), and peak expiratory flow (DeltaPEF = -19%) decreased, and residual volume (DeltaRV = +38%) increased post-RFL (P < .05). Airway luminal cross-sectional area (CSA) decreased at the trachea, and at airway generation 3 (P < .05), wall thickness changed minimally with a tendency for increasing in generation five (P = .13). Baseline pulmonary function was positively associated with airway luminal CSA; however, this relationship deteriorated after RFL. Lung tissue volume and pulmonary vascular volumes increased 28% (P < .001) post-RFL, but did not fully account for the decline in TLC. CONCLUSIONS These data suggest that RFL results in obstructive/restrictive PF changes that are most likely related to structural changes in smaller airways or changes in extrapulmonary vascular beds.

Exercise-related change in airway blood flow in humans: Relationship to changes in cardiac output and ventilation

This study examined the relationship between airway blood flow (Q(aw)), ventilation (V(E)) and cardiac output (Q(tot)) during exercise in healthy humans (n=12, mean age 34+/-11 yr). Q(aw) was estimated from the uptake of the soluble gas dimethyl ether while V(E) and Q(tot) were measured using open circuit spirometry. Measurements were made prior to and during exercise at 34+/-5 W (Load 1) and 68+/-10 W (Load 2) and following the cessation of exercise (recovery). Q(aw) increased in a stepwise fashion (P<0.05) from rest (52.8+/-19.5 microl min(-1) ml(-1)) to exercise at Load 1 (67.0+/-20.3 microl min(-1) ml(-1)) and Load 2 (84.0+/-22.9 microl min(-1) ml(-1)) before returning to pre-exercise levels in recovery (51.7+/-13.2 microl min(-1) ml(-1)). Q(aw) was positively correlated with both Q(tot) (r=0.58, P<0.01) and V(E) (r=0.50, P<0.01). These results demonstrate that the increase in Q(aw) is linked to an exercise related increase in both Q(tot) and V(E) and may be necessary to prevent excessive airway cooling and drying.