Kimberly A. Hubing

Effects of heat stress on dynamic cerebral autoregulation during large fluctuations in arterial blood pressure

Impaired cerebral autoregulation during marked reductions in arterial blood pressure may contribute to heat stress-induced orthostatic intolerance. This study tested the hypothesis that passive heat stress attenuates dynamic cerebral autoregulation during pronounced swings in arterial blood pressure. Mean arterial blood pressure (MAP) and middle cerebral artery blood velocity were continuously recorded for approximately 6 min during normothermia and heat stress (core body temperature = 36.9 +/- 0.1 degrees C and 38.0 +/- 0.1 degrees C, respectively, P < 0.001) in nine healthy individuals. Swings in MAP were induced by 70-mmHg oscillatory lower body negative pressure (OLBNP) during normothermia and at a sufficient lower body negative pressure to cause similar swings in MAP during heat stress. OLBNP was applied at a very low frequency ( approximately 0.03 Hz, i.e., 15 s on-15 s off) and a low frequency ( approximately 0.1 Hz, i.e., 5 s on-5 s off). For each thermal condition, transfer gain, phase, and coherence function were calculated at both frequencies of OLBNP. During very low-frequency OLBNP, transfer function gain was reduced by heat stress (0.55 +/- 0.20 and 0.31 +/- 0.07 cm x s(-1) x mmHg(-1) during normothermia and heat stress, respectively, P = 0.02), which is reflective of improved cerebrovascular autoregulation. During low-frequency OLBNP, transfer function gain was similar between thermal conditions (1.19 +/- 0.53 and 1.01 +/- 0.20 cm x s(-1) x mmHg(-1) during normothermia and heat stress, respectively, P = 0.32). Estimates of phase and coherence were similar between thermal conditions at both frequencies of OLBNP. Contrary to our hypothesis, dynamic cerebral autoregulation during large swings in arterial blood pressure during very low-frequency (i.e., 0.03 Hz) OLBNP is improved during heat stress, but it is unchanged during low-frequency (i.e., 0.1 Hz) OLBNP.

End-tidal carbon dioxide tension reflects arterial carbon dioxide tension in the heat-stressed human with and without simulated hemorrhage

End-tidal carbon dioxide tension (Pet(CO(2))) is reduced during an orthostatic challenge, during heat stress, and during a combination of these two conditions. The importance of these changes is dependent on Pet(CO(2)) being an accurate surrogate for arterial carbon dioxide tension (Pa(CO(2))), the latter being the physiologically relevant variable. This study tested the hypothesis that Pet(CO(2)) provides an accurate assessment of Pa(CO(2)) during the aforementioned conditions. Comparisons between these measures were made: 1) after two levels of heat stress (N = 11); 2) during combined heat stress and simulated hemorrhage [via lower-body negative pressure (LBNP), N = 8]; and 3) during an end-tidal clamping protocol to attenuate heat stress-induced reductions in Pet(CO(2)) (N = 7). Pet(CO(2)) and Pa(CO(2)) decreased during heat stress (P < 0.001); however, there was no group difference between Pa(CO(2)) and Pet(CO(2)) (P = 0.36) nor was there a significant interaction between thermal condition and measurement technique (P = 0.06). To verify that this nonsignificant trend for the interaction was not due to a type II error, Pet(CO(2)) and Pa(CO(2)) at three distinct thermal conditions were also compared using paired t-tests, revealing no difference between Pa(CO(2)) and Pet(CO(2)) while normothermic (P = 0.14) and following a 1.0 ± 0.2°C (P = 0.21) and 1.4 ± 0.2°C (P = 0.28) increase in internal temperature. During LBNP while heat stressed, measures of Pet(CO(2)) and Pa(CO(2)) were similar (P = 0.61). Likewise, during the end-tidal carbon dioxide clamping protocol, the increases in Pet(CO(2)) (7.5 ± 2.8 mmHg) and Pa(CO(2)) (6.6 ± 3.4 mmHg) were similar (P = 0.31). These data indicate that mean Pet(CO(2)) reflects mean Pa(CO(2)) during the evaluated conditions.

Methodological assessment of skin and limb blood flows in the human forearm during thermal and baroreceptor provocations

Skin blood flow responses in the human forearm, assessed by three commonly used technologies-single-point laser-Doppler flowmetry, integrated laser-Doppler flowmetry, and laser-Doppler imaging-were compared in eight subjects during normothermic baseline, acute skin-surface cooling, and whole body heat stress (Δ internal temperature=1.0±0.2 degrees C; P<0.001). In addition, while normothermic and heat stressed, subjects were exposed to 30-mmHg lower-body negative pressure (LBNP). Skin blood flow was normalized to the maximum value obtained at each site during local heating to 42 degrees C for at least 30 min. Furthermore, comparisons of forearm blood flow (FBF) measures obtained using venous occlusion plethysmography and Doppler ultrasound were made during the aforementioned perturbations. Relative to normothermic baseline, skin blood flow decreased during normothermia+LBNP (P<0.05) and skin-surface cooling (P<0.01) and increased during whole body heating (P<0.001). Subsequent LBNP during whole body heating significantly decreased skin blood flow relative to control heat stress (P<0.05). Importantly, for each of the aforementioned conditions, skin blood flow was similar between the three measurement devices (main effect of device: P>0.05 for all conditions). Similarly, no differences were identified across all perturbations between FBF measures using plethysmography and Doppler ultrasound (P>0.05 for all perturbations). These data indicate that when normalized to maximum, assessment of skin blood flow in response to vasoconstrictor and dilator perturbations are similar regardless of methodology. Likewise, FBF responses to these perturbations are similar between two commonly used methodologies of limb blood flow assessment.

Effect of whole body heat stress on peripheral vasoconstriction during leg dependency

The venoarteriolar response (VAR) increases vascular resistance upon increases in venous transmural pressure in cutaneous, subcutaneous, and muscle vascular beds. During orthostasis, it has been proposed that up to 45% of the increase in systemic vascular tone is due to VAR-related local mechanism(s). The objective of this project was to test the hypothesis that heat stress attenuates VAR-mediated cutaneous and whole leg vasoconstriction. During normothermic conditions, measurements of cutaneous blood flow (laser-Doppler flowmetry) and femoral artery blood flow (Doppler ultrasound) were obtained from both legs during supine and leg-dependent conditions. These measurements were repeated following a whole body heat stress (increase in internal temperature of 1.4 +/- 0.2 degrees C). Before leg dependency, cutaneous (CVC) and femoral vascular conductances (FVC) were significantly elevated in both legs during heat stress relative to normothermia (P < 0.001). During leg dependency the absolute decrease in CVC was attenuated during heat stress (P < 0.01) while the absolute decrease in FVC was unaffected (P = 0.90). When CVC and FVC data were analyzed as a relative change from their respective baseline values, heat stress significantly attenuated the magnitude of vasoconstriction due to leg dependency in the cutaneous and femoral circulations (P < 0.001 for both variables). These data suggest that an attenuated local vasoconstriction, evoked via the venoarteriolar response, may contribute to reduced blood pressure control and thus reduced orthostatic tolerance that occurs in heat-stressed individuals.

Nitric oxide synthase inhibition attenuates cutaneous vasodilation during postmenopausal hot flash episodes

Objective: The purpose of this study was to test the hypothesis that local inhibition of nitric oxide and prostaglandin synthesis attenuates cutaneous vasodilator responses during postmenopausal hot flash episodes. Methods: Four microdialysis membranes were inserted into the forearm skin (dorsal surface) of eight postmenopausal women (mean ± SD age, 51 ± 7 y). Ringer solution (control), 10 mM ketorolac (Keto) to inhibit prostaglandin synthesis, 10 mM NG-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase, and a combination of 10 mM Keto + 10 mM l-NAME were each infused at the separate sites. Skin blood flow at each site was indexed using laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial blood pressure and was expressed as a percentage of the maximal calculated CVC (CVCmax) obtained after infusion of 50 mM sodium nitroprusside at all sites at the end of the study. Data from 13 hot flash episodes were analyzed. Results: At the control site, the mean ± SD peak increase in CVC was 15.5% ± 6% CVCmax units. This value was not different relative to the peak increase in CVC at the Keto site (13.0% ± 5% CVCmax units; P = 0.09). However, the peak increase in CVC during hot flash episodes were attenuated at the l-NAME and l-NAME + Keto sites (7.4% ± 4% and 8.7% ± 7% CVCmax units, respectively) relative to both the control and the Keto sites (P < 0.05 for both comparisons). There were no significant differences in the peak increases in sweat rate between any of the sites (P = 0.24). Conclusions: These data demonstrate that the mechanism for cutaneous vasodilation during hot flash episodes has a nitric oxide component. Increases in CVC despite the inhibition of prostaglandin synthesis suggest that prostaglandins do not contribute to cutaneous vasodilation during hot flash episodes.