The effect of ethnicity on the vascular responses to cold exposure of the extremities

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 01/08/2014, available online: https://doi.org/10.1007/s00421-014-2962-2 The accepted version of the publication may differ from the final published version.© 2014, Springer-Verlag Berlin Heidelberg. Purpose: Cold injuries are more prevalent in individuals of African descent (AFD). Therefore, we investigated the effect of extremity cooling on skin blood flow (SkBF) and temperature (Tsk) between ethnic groups.Methods: Thirty males [10 Caucasian (CAU), 10 Asian (ASN), 10 AFD] undertook three tests in 30 °C air whilst digit Tsk and SkBF were measured: (i) vasomotor threshold (VT) test—arm immersed in 35 °C water progressively cooled to 10 °C and rewarmed to 35 °C to identify vasoconstriction and vasodilatation; (ii) cold-induced vasodilatation (CIVD) test—hand immersed in 8 °C water for 30 min followed by spontaneous warming; (iii) cold sensitivity (CS) test—foot immersed in 15 °C water for 2 min followed by spontaneous warming. Cold sensory thresholds of the forearm and finger were also assessed.Results: In the VT test, vasoconstriction and vasodilatation occurred at a warmer finger Tsk in AFD during cooling [21.2 (4.4) vs. 17.0 (3.1) °C, P = 0.034] and warming [22.0 (7.9) vs. 12.1 (4.1) °C, P = 0.002] compared with CAU. In the CIVD test, average SkBF during immersion was greater in CAU [42 (24) %] than ASN [25 (8) %, P = 0.036] and AFD [24 (13) %, P = 0.023]. Following immersion, SkBF was higher and rewarming faster in CAU [3.2 (0.4) °C min−1] compared with AFD [2.5 (0.7) °C min−1, P = 0.037], but neither group differed from ASN [3.0 (0.6) °C min−1]. Responses to the CS test and cold sensory thresholds were similar between groups.Conclusion: AFD experienced a more intense protracted finger vasoconstriction than CAU during hand immersion, whilst ASN experienced an intermediate response. This greater sensitivity to cold may explain why AFD are more susceptible to cold injuries.Published versio

Role of cyclooxygenase in the vascular response to locally delivered acetylcholine in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Elsevier in Microvascular Research on 17/01/2017, available online: https://doi.org/10.1016/j.mvr.2017.01.005 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Inc. Introduction Individuals of African descent (AFD) are more susceptible to non-freezing cold injury (NFCI) compared with Caucasian individuals (CAU). Vasodilatation to acetylcholine (ACh) is lower in AFD compared with CAU in the non-glabrous foot and finger skin sites; the reason for this is unknown. Prostanoids are responsible, in part, for the vasodilator response to ACh, however it is not known whether the contribution differs between ethnicities. Methods 12 CAU and 12 AFD males received iontophoresis of ACh (1 w/v%) on non-glabrous foot and finger skin sites following placebo and then aspirin (600 mg, single blinded). Aspirin was utilised to inhibit prostanoid production by inhibiting the cyclooxygenase (COX) enzyme. Laser Doppler flowmetry was utilised to measure changes in skin blood flow. Results Not all participants could receive iontophoresis charge due to high skin resistance; these participants were therefore excluded from the analyses. Foot: ACh elicited greater maximal vasodilatation in CAU than AFD following placebo (P = 0.003) and COX inhibition (COXib) (P < 0.001). COXib did not affect blood flow responses in AFD, but caused a reduction in the area under the curve for CAU (P = 0.031). Finger: ACh elicited a greater maximal vasodilatation in CAU than AFD following placebo (P = 0.013) and COXib (P = 0.001). COXib tended to reduce the area under the curve in AFD (P = 0.053), but did not affect CAU. Conclusions CAU have a greater endothelial reactivity than AFD in both foot and finger skin sites irrespective of COXib. It is concluded that the lower ACh-induced vasodilatation in AFD is not due to a compromised COX pathway.Published versio

ACSM Expert Consensus Statement: Injury Prevention and Exercise Performance during Cold-Weather Exercise

ABSTRACT: Cold injury can result from exercising at low temperatures and can impair exercise performance or cause lifelong debility or death. This consensus statement provides up-to-date information on the pathogenesis, nature, impacts, prevention, and treatment of the most common cold injuries

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

In pursuit of the unicorn

This short review was prompted by The Physiological Society's recent online symposium on variability. It does not deal with a specific methodology, but rather with the myth that certain environmentally-induced clinical conditions can be identified, quantified, simplified and monitored with a single methodology. Although this might be possible with some clinical conditions, others resist the prevailing reductionist approach of minimizing rather than exploring variation in pathogenesis and pathology, and will not be understood fully until the variation in cause and effect are embraced. This is likely to require comprehensive methodologies and collaboration

Role of isoleucine residues 182 and 183 in thrombin-activatable fibrinolysis inhibitor

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase that, once activated, can attenuate fibrinolysis. The active form, TAFIa, is a labile enzyme, with a half-life of a few minutes at 37 degrees C. Understanding the molecular mechanisms of TAFIa inactivation will allow the development of compounds that modulate TAFIa activity. Based on their three-dimensional model of TAFI, Barbosa Pereira et al. [J Mol Biol (2002), vol. 321, pp. 537-547] suggested that Ile182 and Ile183 were involved in the instability of TAFIa. However, these carboxypeptidases are, unlike TAFIa, stable proteases. Therefore, we constructed, expressed and characterized a TAFI mutant in which Ile182 and Ile183 were changed into the residues found in pancreas carboxypeptidase B at corresponding positions, Arg and Glu. The active form of the mutant, TAFIa-I182R-I183E, had a similar half-life as wild-type TAFIa, showing that Ile182 and Ile183 were not involved in the regulation of TAFIa stability. Remarkably, however, TAFI-I182R-I183E was activated at a lower rate by thrombin-thrombomodulin (mutant: 45 +/- 2 U L(-1) s(-1) and wild type: 103 +/- 3 U L(-1) s(-1)), thrombin (mutant: 1 +/-0.1 U L(-1) s(-1) and wild type 3 +/- 0.2 U L(-1) s(-1)) and plasmin (mutant: 0.8 +/- 0.04 U L(-1) s(-1) and wild type: 5.0 +/-0.2 U L(-1) s(-1)) compared with wild-type TAFI. Accordingly, it had a sixfold reduced antifibrinolytic potential. In conclusion, analysis of TAFI-I182R-I183E showed that I182 and I183 are not involved in TAFIa inactivation by conformational instability but that these residues may be involved in the activation of TAFI and stabilization of the fibrin clo