Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Thermoregulation and fluid balance during a 30-km march in 60-versus 80-year-old subjects

The presence of impaired thermoregulatory and fluid balance responses to exercise in older individuals is well established. To improve our understanding on thermoregulation and fluid balance during exercise in older individuals, we compared thermoregulatory and fluid balance responses between sexagenarians and octogenarians during prolonged exercise. Forty sexagenarians (60 ± 1 year) and 36 octogenarians (81 ± 2 year) volunteered to participate in a 30-km march at a self-selected pace. Intestinal temperature (T in) and heart rate were recorded every 5 km. Subjects reported fluid intake, while urine output was measured and sweat rate was calculated. Octogenarians demonstrated a lower baseline T in and a larger exercise-induced increase in T in compared to sexagenarians (1.2 ± 0.5 °C versus 0.7 ± 0.4 °C, p  0.05). These results suggest that thermoregulatory responses deteriorate with advancing age, while fluid balance is regulated appropriately during a 30-km walking march under moderate ambient conditions

Effects of aging and type 2 diabetes on resting and post occlusive hyperemia of the forearm; the impact of rosiglitazone

BACKGROUND: Both Diabetes and ageing are associated with reduced vascular endothelial function. The exact relationship between the 2 and any improvements from the insulin sensitizer rosiglitazone have not been explored. METHODS: Thirty controls and sixteen subjects with type 2 diabetes participated in a series of experiments to examine the interrelationships between age, diabetes and endothelial cell function. In subjects with diabetes, the insulin sensitizer rosiglitazone (RSG), a drug also known to improve vascular function, was administered for 3 months to see how it altered these relationships. Resting forearm flows (RF) and blood flows after 4 min of vascular occlusion (PF) were measured as an index of endothelial cell function. RESULTS: RF, measured by venous occlusion plethysmography, was negatively correlated to both age and diabetes. Administration of RSG for 3 months was associated with an increase in the blood flow response to venous occlusion so that it was not significantly different than that of age matched controls. Total PF in control subjects, compared to subjects with diabetes, averaged 56.58 +/- 12.57 and 13.6 +/- 8.01 cc/100 cc tissue per min respectively, and were significantly different (p < 0.01). After 3 months on RSG, differences between PF in the two groups were no longer evident. CONCLUSION: These studies suggest a different mechanism causing a reduction in vascular reactivity with aging and diabetes

Effects of supervised exercise training on lower-limb cutaneous microvascular reactivity in adults with venous ulcers

Purpose: To investigate the effects of a 12-week supervised exercise programme on lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Methods: Thirty-eight adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm2) were randomly allocated to exercise or control groups. Exercise participants (n=18) were invited to attend thrice weekly sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg). Results: Thirty-seven participants completed follow-up assessments. Median class attendance was 36 (range 2 to 36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at 3 months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504 to 1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028 to 1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at 3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274 to 1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95% CI -0.377 to 1.161). Conclusion: Supervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration. Keywords Randomized controlled trial; Exercise; Ulceration; Vascular function; Laser Doppler fluxmetry; Iontophoresi

Oxidative Stress and Vascular Function: Implications for Pharmacologic Treatments

Production of considerable amounts of reactive oxygen species (ROS) eventually leads to oxidative stress. A key role of oxidative stress is evident in the pathologic mechanisms of endothelial dysfunction and associated cardiovascular diseases. Vascular enzymes such as NADPH oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide synthase are involved in the production of ROS. The question remains whether pharmacologic approaches can effectively combat the excessive ROS production in the vasculature. Interestingly, existing registered cardiovascular drugs can directly or indirectly act as antioxidants, thereby preventing the damaging effects of ROS. Moreover, new compounds targeting NADPH oxidases have been developed. Finally, food-derived compounds appear to be effective inhibitors of oxidative stress and preserve vascular function

Assessing the evidence: exploring the effects of exercise on diabetic microcirculation

Diabetes mellitus (DM) is associated with cardiovascular complications. Impairment of glycemic control induces noxious glycations, an increase in oxydative stress and dearangement of various metabolic pathways. DM leads to dysfunction of micro and macrovessels, connected to metabolic, endothelial and autonomic nervous system. Thus, assessing vascular reactivity might be one of the clinical tools to evaluate the impact of harmful effects of DM and potential benefit of treatment; skin and skeletal muscle microcirculation have usually been tested. Physical exercise improves vascular dysfunction through various mechanisms, and is regarded as an additional effective treatment strategy of DM as it positively impacts gylcemic control, improves insulin sensitivity and glusose uptake in the target tissues, thus affecting glucose and lipid metabolism, and increases the endothelium dependent vasodilation. Yet, not all patients respond in the same way so titrating the exercise type individualy would be desired. Resistance training has, apart from aerobic one, been shown to positively correlate to glycemic control, and improve vascular reactivity. It has been prescribed in various forms or in combination with aerobic training. This review would assess the impact of different modes of exercise, the mechanisms involved, and its potential positive and negative effects on treating patients with Type I and Type II DM, focusing on the recent literature. Keywords: Diabetes, exercise, aerobic training, resistance training, high intensity interval training, microcirculation, laser Doppler fluxmetr

Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography

Previous studies showed strong correlations between low fingertip temperature rebound measured by digital thermal monitoring (DTM) during a 5 min arm-cuff induced reactive hyperemia and both the Framingham Risk Score (FRS), and coronary artery calcification (CAC) in asymptomatic populations. This study evaluates the correlation between DTM and coronary artery disease (CAD) measured by CT angiography (CTA) in symptomatic patients. It also investigates the correlation between CTA and a new index of neurovascular reactivity measured by DTM. 129 patients, age 63 ± 9 years, 68% male, underwent DTM, CAC and CTA. Adjusted DTM indices in the occluded arm were calculated: temperature rebound: aTR and area under the temperature curve aTMP-AUC. DTM neurovascular reactivity (NVR) index was measured based on increased fingertip temperature in the non-occluded arm. Obstructive CAD was defined as ≥50% luminal stenosis, and normal as no stenosis and CAC = 0. Baseline fingertip temperature was not different across the groups. However, all DTM indices of vascular and neurovascular reactivity significantly decreased from normal to non-obstructive to obstructive CAD [(aTR 1.77 ± 1.18 to 1.24 ± 1.14 to 0.94 ± 0.92) (P = 0.009), (aTMP-AUC: 355.6 ± 242.4 to 277.4 ± 182.4 to 184.4 ± 171.2) (P = 0.001), (NVR: 161.5 ± 147.4 to 77.6 ± 88.2 to 48.8 ± 63.8) (P = 0.015)]. After adjusting for risk factors, the odds ratio for obstructive CAD compared to normal in the lowest versus two upper tertiles of FRS, aTR, aTMP-AUC, and NVR were 2.41 (1.02–5.93), P = 0.05, 8.67 (2.6–9.4), P = 0.001, 11.62 (5.1–28.7), P = 0.001, and 3.58 (1.09–11.69), P = 0.01, respectively. DTM indices and FRS combined resulted in a ROC curve area of 0.88 for the prediction of obstructive CAD. In patients suspected of CAD, low fingertip temperature rebound measured by DTM significantly predicted CTA-diagnosed obstructive disease