Fatigue during high-intensity endurance exercise: the interaction between metabolic factors and thermal stress.

The purpose of this study was to examine the effects of hot (37° C) and cool (10° C) environments on cycling time to exhaustion (TTE), pH, lactate, and core temperature (Tc). Eleven endurance-trained subjects completed 4 TTE trials: Hot 80% VO2max (H80), Cool 80% (C80), Hot 100% (H100), and Cool 100% VO2max (C100). Esophageal temperature and blood was sampled before, every 5 minutes, at exhaustion, and 3 minutes after exercise and analyzed for lactate, pH, and HCO3-. Multifactorial analysis of variance with repeated measures was used to determine differences between mean values (± SD). Time to exhaustion was shorter in H100 and C100 vs. H80 and C80 (5.64 ± 1.49 minutes, 5.83 ± 1.03 minutes, 12.82 ± 2.0 minutes, and 24.85 ± 6.0 minutes, respectively) and shorter in H80 vs. C80 (p < 0.01). The pH at exhaustion was different among all conditions (7.17 ± 0.06, 7.15 ± 0.07, 7.21 ± 0.04, and 7.24 ± 0.06 units for H100, C100, H80, and C80, respectively, p = 0.02). The Tc at exhaustion was lower in H100 and C100 (37.93 ± 0.67 and 37.62 ± 0.58° C) vs. H80 and C80 (38.54 ± 0.51° C and 38.53 ± 0.38° C) (p < 0.01). In H80 and C80, the higher Tc likely played a greater role in the termination of exercise, whereas, in H100 and C100, pH and metabolic changes may have been more important. Despite these differences, neither an upper limit for Tc nor a lower limit for pH was identified; thus, fatigue based entirely on peripheral factors was not supported, and a combination of peripheral and central processes must be considered. The practical implications of these findings are that aerobic exercise at or near VO2max may be impacted more by metabolic factors, whereas lower intensities (∼80% VO2max) may be affected more by heat stress; these differences should be considered when training for events of this type.

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.

Exercise-associated hyponatremia: the influence of pre-exercise carbohydrate status combined with high volume fluid intake on sodium concentrations and fluid balance.

To evaluate the effect of hydration and carbohydrate (CHO) status on plasma sodium, fluid balance, and regulatory factors (IL-6 & ADH) during and after exercise; 10 males completed the following conditions: low CHO, euhydrated (fluid intake = sweat loss) (LCEH); low CHO, dehydrated (no fluid) (LCDH); high CHO, euhydrated (HCEH); and high CHO, dehydrated (HCDH). Each trial consisted of 90-min cycling at 60% VO(2) max in a 35°C environment followed by 3-h rehydration (RH). During RH, subjects received either 150% of sweat loss (LCDH & HCDH) or an additional 50% of sweat loss (LCEH and HCEH). Blood was analyzed for glucose, IL-6, ADH, and Na(+). Post-exercise Na(+) was greater (p < 0.001) for LCDH and HCDH (141.7 + 0.72 and 141.6 + 0.4 mM) versus LCEH and HCEH (136.4 + 0.6 and 135.9 + 0.3 mM). Post-exercise IL-6 was similar in all conditions, and post-exercise ADH was greater (p = 0.01) in dehydrated versus euhydrated conditions. The rate of urine production was greater in HCEH (7.59 + 3.0 mL/min) compared to all other conditions (3.86 + 2.2, 5.29 + 3.1, and 2.96 + 1.1 mL/min for LCDH, LCEH, and HCDH, respectively). Despite CHO and hydration manipulations, no regulatory effects of IL-6 and ADH on plasma [Na(+)] were observed. With euhydration during exercise and additional fluid consumed during recovery, a high-CHO status increased urinary output during recovery, and it decreased the frequency of hyponatremia (Na(+) < 135 mM). Therefore, a high-CHO status may provide some protection against exercise-associated hyponatremia.

Influence of commonly employed resistance exercise protocols on circulating IL-6 and indices of insulin sensitivity.

The purpose of this project was to examine the influence of resistance exercise (RE) intensities, resulting in different total volume loads on circulating interleukin-6 (IL-6), insulin and glucose response (IGR) to a carbohydrate feeding (CHO), and whether RE-induced IL-6 was associated with postexercise IGR. Fourteen men (21.7 +/- 1.7 years, 83 +/- 14.2 kg), performed 2 RE sessions (low-intensity resulting in high volume [65% 1-repetition maximum (1RM)], LO; high intensity resulting in low volume [85% 1RM], HI); and a nonexercise control trial (CON). Resistance exercise included 3 sets (LO = 12 reps, 12 reps, and failure; HI = 8 reps, 8 reps, and failure) of 8 exercises. Blood was obtained pre- (PR) and post (PO) exercise, and 6 hours postexercise (6H). Twenty-three hours after RE or CON, participants consumed 100 g dextrose (CHO) beverage. Blood was collected before (0 minutes) and 60 minutes after CHO (n = 6, phase 1) or every 30 minutes for a 2-hour oral glucose tolerance test (n = 8; phase 2). Circulating IL-6, insulin, and glucose were analyzed via enzyme-linked immunosorbent assay, radioimmunoassay, and enzymatic methods, respectively. Total volume load was higher in LO (17,729 +/- 1,466 kg) compared with HI (13,160 +/- 1,097 kg; p < 0.001). Postexercise IL-6 was elevated (p = 0.003) in LO and HI compared with CON (7.4 +/- 1.3, 5.2 +/- 0.7, and 2.5 +/- 0.7 pg.mL, respectively), with LO IL-6 greater than HI. Areas under the curve for glucose (p = 0.081; CON: 741 +/- 46, LO: 690 +/- 28, and HI: 660 +/- 21 mM.min) and insulin (p = 0.075; CON: 6,818 +/- 1,018, LO: 5,056 +/- 869, and HI: 5,405 +/- 1,076 microIU.mL) were not different among trials (n = 8). When 0- and 60-minute values were compared (n = 14), insulin was lower at 60 minutes in LO and HI compared with CON (55 + 9.1, 83 +/- 13, 105 +/- 13 microIU.mL, respectively) with LO insulin being lower than HI (p < 0.001). No relationship was observed between PO IL-6 and IGR, but PR IL-6 was negatively related to both PR (r = -0.043, p < 0.05) and 60 minutes (r = -0.59, p < 0.01) glucose (n = 14). These results indicate that TVL contributes to RE-induced IL-6 release and that TVL may be more important than RE intensity when improvements in glucose tolerance or IS are the goal.

The effects of reduced end-tidal carbon dioxide tension on cerebral blood flow during heat stress.

Passive heat stress reduces arterial carbon dioxide partial pressure (P(aCO2)) as reflected by 3 to 5 Torr reductions in end-tidal carbon dioxide tension (P(ETCO2)). Heat stress also reduces cerebrovascular conductance (CBVC) by up to 30%. While is a strong regulator of CBVC, it is unlikely that the relatively small change in during heating is solely responsible for the reductions in CBVC. This study tested the hypothesis that P(aCO2), referenced by P(ETCO2), is not the sole mechanism for reductions in CBVC during heat stress. Mean arterial blood pressure (MAP), P(ETCO2), middle cerebral artery blood velocity (MCA V(mean)), and calculated CBVC (MCA V(mean)/MAP) were assessed in seven healthy individuals, during three separate conditions performed sequentially: (1) normothemia, (2) control passive heat stress and (3) passive heat stress with P(ETCO2) clamped at the normothermic level (using a computer-controlled sequential gas delivery breathing circuit). MAP was similar in the three thermal conditions (P = 0.55). Control heat stress increased internal temperature approximately 1.3 degrees C, which resulted in decreases in P(ETCO2), MCA V(mean) and calculated CBVC (P < 0.001 for all variables). During heat stress + clamp conditions internal temperature remained similar to that during the control heat stress condition (P = 0.31). Heat stress + clamp successfully restored to the normothermic level (P = 0.99) and increased MCA V(mean) (P = 0.002) and CBVC (P = 0.008) relative to control heat stress. Despite restoration of P(ETCO2), MCA V(mean) (P = 0.005) and CBVC (P = 0.03) remained reduced relative to normothermia. These results indicate that heat stress-induced reductions in , as referenced by P(ETCO2), contribute to the decrease in MCA V(mean) and CBVC; however, other factors (e.g. perhaps elevated sympathetic nerve activity) are also involved in mediating this response.

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.

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 N-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.

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.

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.