Matthew M. Mallette

Spectral analysis of reflex cutaneous vasodilatation during passive heat stress

Previous work has demonstrated that spectral analysis is a useful tool to non-invasively ascertain the mechanisms of control of the cutaneous circulation. The majority of work using spectral analysis has focused on local control mechanisms, with none examining reflex control. Skin blood flow was analysed using spectral analysis on the dorsal aspect of the forearm of 7 males and 7 females during passive heat stress, with mean forearm and local temperature at the site of measurement maintained at thermoneutral (33°C) to minimize the effect of local control mechanisms. Participants were passively heated to ~1.2±0.1°C above baseline rectal temperature (d=4.0, P<0.001) using a water-perfused, tube lined suit, with skin blood flow assessed using a laser-Doppler probe with an integrated temperature monitor. Spectral analysis was performed using a Morlet wavelet on the entire data set, with median power extracted during 20min of data during baseline (normothermia) and hyperthermia. Passive heat stress significantly increased laser-Doppler flux above baseline (d=4.7, P<0.001). Spectral power of the endothelial nitric oxide-independent (0.005-0.01Hz; d=1.1, P=0.004), neurogenic (0.2-0.05Hz; d=0.6, P=0.025), myogenic (0.05-0.15Hz; d=1.5, P=0.002), respiratory (0.15-0.4Hz; d=1.4 P=0.002), and cardiac (0.4-2.0Hz; d=1.1, P=0.012) frequency intervals increased with passive heat stress. In contrast, the endothelial nitric oxide-dependent frequency interval did not change (0.01-0.02Hz; d=0.3, P=0.09) with passive heat stress. These data suggest that cutaneous reflex vasodilatation is neurogenic in origin and not mediated by endothelial-nitric oxide synthase, and are congruent with invasive examinations of reflex cutaneous vasodilatation.

Effect of age on cutaneous vasomotor responses during local skin heating

This study examined the effect of ageing on the low-frequency oscillations (vasomotion) of skin blood flow in response to local heating (LH). Skin blood flow was assessed by laser-Doppler flowmetry on the forearm at rest (33°C) and in response to LH of the skin to both 42°C and 44°C in 14 young (24±1years) and 14 older (64±1years) participants. Vasomotion was analyzed using a wavelet transform to investigate power of the frequency intervals associated with endothelial, neural, myogenic, respiratory, and cardiac activities of the laser-Doppler signal. Laser-Doppler flux increased in both groups with LH (both d>1.8, p<0.001). Endothelial activity increased in both groups following LH to 42°C (young d=1.4, p<0.001; older d=1.2, p=0.005) and 44°C (young d=1.4, p=0.001; older d=1.5, p=0.005). Endothelial activity was higher in the young compared to older group during LH to 42°C (d=1.4, p=0.017) and 44°C (d=1.5, p=0.004). In response to LH to 42°C and 44°C, neural activity in both groups was decreased (both groups and conditions: d>1.2, p<0.001). Myogenic activity increased in the younger group following LH to 44°C (d=1, p=0.042), while in the older group, myogenic activity increased following LH to 42°C (d=1.2, p=0.041) and 44°C (d=1.1, p=0.041). Respiratory and cardiac activities increased in both groups during LH to 42°C and 44°C (All: d>0.9, p<0.017). There were no differences in wavelet amplitude between younger and older in the neural (d=0.1, p>0.7), myogenic (d=0.3, p>0.7), respiratory (d=0.4, p>0.6), and cardiac (d=0.1, p>0.7) frequency intervals. These data indicate that LH increases cutaneous endothelial and myogenic activity, while decreasing neural activity. Furthermore, ageing reduces the increase in cutaneous endothelial activity in response to LH.

Effect of sympathetic nerve blockade on low-frequency oscillations of forearm and leg skin blood flow in healthy humans

To Examine the effect of inhibiting sympathetic function on cutaneous vasomotion in the forearm and leg.

Investigating the roles of core and local temperature on forearm skin blood flow

We sought to isolate the contributions of core and local temperature on forearm skin blood flow (SkBF), and to examine the interaction between local- and reflexive-mechanisms of SkBF control. Forearm SkBF was assessed using laser-Doppler flowmetry in eight males and eight females during normothermia and hyperthermia (+1.2°C rectal temperature). Mean experimental forearm temperature was manipulated in four, 5min blocks between neutral (A: 33.0°C) and warm (B: 38.5°C) in an A-B-A-B fashion during normothermia, and B-A-B-A during hyperthermia. Mean control forearm skin temperature was maintained at ~33°C. Finally, local heating to 44°C was performed on both forearms to elicit maximal SkBF. Data are presented as a percentage of maximal cutaneous vascular conductance (CVC), calculated as laser-Doppler flux divided by mean arterial pressure. No sex differences were observed in any CVC measures (P>0.05). During normothermia, increasing experimental forearm temperature to 38.5°C elevated CVC by 42±8%max (d=3.1, P<0.001). Subsequently decreasing experimental forearm temperature back down to 33.0°C reduced CVC by 36±7%max (d=2.5, P<0.001). Finally, the second increase in experimental forearm temperature to 38.5°C increased CVC by 25±6%max (d=1.9, P<0.0001). During hyperthermia, decreasing experimental forearm temperature to 33.0°C reduced CVC by 6±1%max (d=0.5, P<0.001). Increasing experimental forearm temperature to 38.5°C increased CVC by 4±2%max (d=0.4, P<0.001). Finally, decreasing experimental forearm temperature to 33.0°C reduced CVC by 8±2%max (d=0.7, P<0.001). Compared to normothermia, CVC responses to local temperature changes during hyperthermia were almost abolished (normothermia: d=1.9-3.1; hyperthermia: d=0.4-0.7). These data indicate that local temperature drives SkBF during normothermia, while reflexive mechanisms regulate SkBF during hyperthermia.

The contribution of sensory nerves to the onset threshold for cutaneous vasodilatation during gradual local skin heating of the forearm and leg.

During local skin heating, the temporal onset of vasodilatation is delayed in the leg compared to the forearm, and sensory nerve blockade abolishes these differences. However, previous work using rapid skin heating did not allow for determination of sensory nerve influences on temperature thresholds for vasodilatation. Two sites were examined on both the forearm and leg, one control (CTRL), and one treated for sensory nerve blockade (EMLA). Skin blood flux was monitored using laser-Doppler probes, with heaters controlling local skin temperature (Tloc). Tloc was increased from 32-44 °C (+1 °C·10 min(-1)). Stimulus-response curves were constructed by fitting a four-parameter logistic function. EMLA significantly increased Tloc onset in the forearm (CTRL=35.3 ± 0.4 °C; EMLA=36.8 ± 0.7 °C) and leg (CTRL=36.5 ± 0.4 °C; EMLA=38.4 ± 0.5 °C; both P<0.05). At both CTRL and EMLA, Tloc onset was higher in the leg compared to the forearm (both P<0.05). In the forearm, median effective temperature to elicit 50% vasodilatation (ET50) was similar between sites (CTRL=39.7 ± 0.3 °C; EMLA=40.2 ± 0.4 °C; P=0.09); however, in the leg, EMLA significantly increased ET50 (CTRL=40.2 ± 0.3 °C; EMLA=41.0 ± 0.3 °C)(P<0.05). At CTRL sites, no limb difference was observed for ET50 (P=0.06); however, with EMLA, ET50 was significantly higher in the leg (P<0.05). EMLA significantly increased the gain of the slope at the forearm, (CTRL=0.31 ± 0.01%CVCmax·°C(-1); EMLA=0.45 ± 0.07%CVCmax·°C(-1)), and leg (CTRL=0.37 ± 0.05%CVCmax·°C(-1); EMLA=0.54 ± 0.04%CVCmax·°C(-1))(both P<0.05). At CTRL sites, the gain was significantly higher in the leg (P<0.05); however, for EMLA, no significant limb difference existed (P=0.10). These data indicate that the onset of vasodilatation occurs at a lower temperature in the forearm than the legs, and sensory nerves play an important role in both limbs.

Core and skin temperature influences on the surface electromyographic responses to an isometric force and position task

The large body of work demonstrating hyperthermic impairment of neuromuscular function has utilized maximal isometric contractions, but extrapolating these findings to whole-body exercise and submaximal, dynamic contractions may be problematic. We isolated and compared core and skin temperature influences on an isometric force task versus a position task requiring dynamic maintenance of joint angle. Surface electromyography (sEMG) was measured on the flexor carpi radialis at 60% of baseline maximal voluntary contraction while either pushing against a rigid restraint (force task) or while maintaining a constant wrist angle and supporting an equivalent inertial load (position task). Twenty participants performed each task at 0.5°C rectal temperature (Tre) intervals while being passively heated from 37.1±0.3°C to ≥1.5°C Tre and then cooled to 37.8±0.3°C, permitting separate analyses of core versus skin temperature influences. During a 3-s contraction, trend analysis revealed a quadratic trend that peaked during hyperthermia for root-mean-square (RMS) amplitude during the force task. In contrast, RMS amplitude during the position task remained stable with passive heating, then rapidly increased with the initial decrease in skin temperature at the onset of passive cooling (p = 0.010). Combined hot core and hot skin elicited shifts toward higher frequencies in the sEMG signal during the force task (p = 0.003), whereas inconsistent changes in the frequency spectra occurred for the position task. Based on the patterns of RMS amplitude in response to thermal stress, we conclude that core temperature was the primary thermal afferent influencing neuromuscular response during a submaximal force task, with minimal input from skin temperature. However, skin temperature was the primary thermal afferent during a position task with minimal core temperature influence. Therefore, temperature has a task-dependent impact on neuromuscular responses.

Ischemia-reperfusion injury alters skin microvascular responses to local heating of the index finger

BACKGROUND Ischemia-reperfusion (IR) injury impairs microcirculatory function by reducing nitric oxide (NO) bioavailability and increasing sympathetic tone. This study non-invasively examined the effects of acute upper limb IR injury on local thermal hyperemia (LTH) in glabrous and non-glabrous finger skin. MATERIALS AND METHODS In ten healthy males, LTH was examined twice (~7-10 d apart) for each skin type on the index finger using laser-Doppler flowmetry in a counterbalanced design with either 1) 20 min ischemia, followed by reperfusion (ISCH) or 2) time-matched control (SHAM). LTH tests were performed using a standard heating protocol (33-42 °C at 1 °C·20 s-1 + 20 min at 44 °C) and baseline, initial peak, nadir, delayed plateau and maximal heating phases were identified as well as vasodilatory onset time and time to initial peak. Cutaneous vasomotion was evaluated using spectral analysis and comparing absolute and normalized wavelet amplitudes between conditions for both skin types at baseline and during LTH. RESULTS In non-glabrous skin, IR injury delayed the vasodilatory onset of local heating by 27.4 [11.3, 43.4] s (p = 0.004) and attenuated cutaneous vasodilation during the initial peak and sustained heating by -44.5 [-73.0, -15.9] PU (p = 0.003) and -34.4 [-62.9, -5.8] PU (p = 0.020), respectively. Analysis of normalized wavelet amplitudes in non-glabrous skin identified impaired microvascular function at baseline via NO-dependent mechanisms (-3.64 [-7.22, -0.05] %, p = 0.047), and during LTH via respiratory influences (-2.83 [-5.39, -0.21] %, p = 0.031). In glabrous skin, IR injury delayed vasodilatory onset time by 24.9 [1.1, 67.6] s (p = 0.042). The vasodilatory response to sustained local skin heating in glabrous skin was increased following IR injury (+56.3 [15.1, 116.5], p = 0.012), however, this was not evident when accounting for differences in blood pressure between conditions. Additionally, no other differences in vasodilatory or vasomotor functions were observed in this skin type between conditions (all, p > 0.05). CONCLUSIONS The current IR model elicits impaired cutaneous vasodilatory responses to local heating in young males, primarily in non-glabrous skin, and may be useful for exploring mechanisms of IR-injury and for testing potential countermeasures in otherwise healthy humans.

The contribution of sensory nerves to cutaneous vasodilatation of the forearm and leg to local skin warming

Purpose The initial cutaneous vasodilatory response to local skin heating is larger in the forearm than the leg. While the initial vasodilatation of the forearm to local heating is primarily dependent on sensory nerves, their role in the leg is unknown. We compared the contribution of sensory nerves in driving the cutaneous vasodilatory response of the forearm and leg to local heating using local anaesthetic (EMLA) cream.