Human limb muscle and skin perfusion alters with changes in tissue temperature evoked by heating or cooling and these processes may involve temperature sensitive regulatory mechanisms. We have previously shown that passive heating and exercise increase limb tissue blood flow in humans in association with the increases in muscle temperature and plasma adenosine 5'-triphosphate concentration [ATP] (1,2). Reduced haemoglobin O2 saturation is thought to be the main stimulus for erythrocyte ATP release in the muscle microcirculation (3,4). Recent evidence, however, suggests that temperature is another potent stimulus. Here we tested the hypothesis that the release of the vasodilator mediator ATP from human erythrocytes is sensitive to physiological reductions and increases in blood temperature independently of oxygenation induced ATP release in the human forearm circulation. To accomplish this aim, we measured forearm blood flow (FBF; Doppler ultrasound), deep venous blood temperature (Tb), retrograde venous plasma [ATP], blood gas parameters and calculated forearm vascular conductance (FVC) in the experimental and the control contralateral forearm in 7 males (19 ± 2 years) during 1 hour of passive heating using a water perfused cuff and 1 hour of passive cooling using ice with 1 hour of rest in between. All data are mean ± SEM and were compared with ANOVA and Pearson correlation (SPSS). With heating Tb increased from 34.0 ± 0.5 to 36.8 ± 0.1°C (p<0.05) while with cooling Tb decreased from 34.4 ± 0.4 to 29.1 ± 0.7°C (p<0.05). Plasma [ATP] doubled with heating from 0.21 ± 0.03 to 0.43 ± 0.05 µmol.l-1 (p<0.05) but did not change with cooling remaining at 0.23 ± 0.03 µmol.l-1 similar to values in the control forearm. FBF progressively and significantly increased with heating from 124 ± 11 to 418 ± 10 ml.min-1 (p<0.05) and decreased with cooling from 121 ± 11 to 90 ± 14 ml.min-1 (p<0.05). Similar significant responses were observed with FVC, indicating that flow changes with heating and cooling were due to vasodilatation and vasoconstriction, respectively. In contrast, control forearm values for Tb, [ATP], FBF and FVC were unchanged throughout the study. During heating and cooling, FBF and FVC were exponentially correlated to Tb (R2 = 0.86 and 0.87, respectively; p<0.01) and [ATP] (both R2= 0.85; p<0.01). Contrary to the reported involvement of the O2 saturation pathway, plasma [ATP] remained unchanged during cooling despite decreasing O2 saturation from 62 ± 4 to 35 ± 4% (p<0.05) but increased with heating when O2 saturation was elevated from 59 ± 6 to 82 ± 4% (p<0.05). These findings suggest that ATP from erythrocytes may be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature. Furthermore, it seems that temperature works through a distinct pathway to that sensitive to blood oxygenation.
|Publication status||Published - Jul 2013|