Does erythrocyte infusion improve 3.2-km run performance at high altitude?

The effects of autologous erythrocyte infusion on improving exercise performance at high altitude have not previously been studied. The effects of erythrocyte infusion on 3.2-km (2-mile) run performance were evaluated during 3 days (HA3) and 14 days (HA14) exposure to high altitude (4300 m) in erythrocyte-infused (ER) and control (CON) subjects that were initially matched (P>0.05; n = 8 in each group) for age, body size and aerobic fitness. After sea-level runs (SL; 50 m), unacclimated-male subjects received either 700 ml of saline and autologous erythrocytes (42% hematocrit; ER) or saline alone (CON). The 3.2-km run times (min:s) did not differ (P>0.05) between groups at SL [mean (SEM) ER, 13:14 (00:19); CON, 13:39 (00:32)] or during HA3 [ER, 19:02 (00:18); CON, 19:44 (00:43)] and HA14 [ER, 17:44 (00:27); CON, 18:45 (00:55)] but times were slower (P<0.05) when comparing HA3 or HA14 to SL. Heart rates (HR) did not differ between groups at SL [ER, 188 (3) beats x min(-1); CON, 191 (3) beats x min(-1)], or during HA3 [ER, 170 (4) beats x min(-1); CON, 178 (4) beats x min(-1)] and HA14 [ER, 162 (6) beats x min(-1); CON, 169 (5) beats x min(-1)], but HR were lower (P<0.05) when comparing HA3 or HA14 to SL. Ratings of perceived exertion (local, central, and overall ratings) did not differ between groups at SL, HA3 or HA14, but local ratings were higher (P<0.05) at HA3 and HA14 compared to SL, and overall ratings were higher for HA3 than SL. Analysis of covariance (adjusted for SL group run times) revealed (min:s) 00:14 (HA3) and 00:28 (HA14) mean improvement tendencies (P>0.05) for ER compared to CON. Thus, no significant improvements in 3.2-km run performance were associated with erythrocyte infusion, although the ER group showed a tendency to run slightly faster at high altitude.     

Human thermoregulatory responses during serial cold-water immersions

This studyexamined whether serial cold-water immersions over a 10-h period wouldlead to fatigue of shivering and vasoconstriction. Eight men wereimmersed (2 h) in 20°C water three times (0700, 1100, and 1500) in1 day (Repeat). This trial was compared with single immersions(Control) conducted at the same times of day. Before Repeat exposuresat 1100 and 1500, rewarming was employed to standardize initial rectaltemperature. The following observations were made in the Repeatrelative to the Control trial: 1)rectal temperature was lower and heat debt was higher(P < 0.05) at 1100; 2) metabolic heat production waslower (P < 0.05) at 1100 and 1500;3) subjects perceived the Repeattrial as warmer at 1100. These data suggest that repeated coldexposures may impair the ability to maintain normal body temperaturebecause of a blunting of metabolic heat production, perhaps reflectinga fatigue mechanism. An alternative explanation is that shiveringhabituation develops rapidly during serially repeated cold exposures.

     

Hypohydration and thermoregulation in cold air

O'Brien, Catherine, Andrew J. Young, and Michael N. Sawka.Hypohydration and thermoregulation in cold air.J. Appl. Physiol. 84(1): 185-189, 1998.This study examined the effects of hypohydration onthermoregulation during cold exposure. In addition, the independentinfluences of hypohydration-associated hypertonicity and hypovolemiawere investigated. Nine male volunteers were monitored for 30 min at25°C, then for 120 min at 7°C, under three counterbalancedconditions: euhydration (Eu), hypertonic hypohydration (HH), andisotonic hypohydration (IH). Hypohydration was achieved 12 h beforecold exposure by inducing sweating (HH) or by ingestion of furosemide(IH). Body weight decrease (4.1 ± 0.2%) caused by hypohydrationwas similar for HH and IH, but differences(P < 0.05) were found between HH andIH in plasma osmolality (292 ± 1 vs. 284 ± 1 mosmol/kgH₂O) andplasma volume reduction (8 ± 2 vs. 18 ± 3%).Heat debt (349 ± 14 among) did not differ(P > 0.05) among trials. Mean skintemperature decreased throughout cold exposure during Eu but plateauedafter 90 min during HH and IH. Forearm-fingertemperature gradient tended (P = 0.06)to be greater during Eu (10.0 ± 0.7°C) than during HH or IH(8.9 ± 0.7°C). This suggests weaker vasoconstrictor tone duringhypohydration than during Eu. Final mean skin temperature was higherfor HH than for Eu or IH (23.5 ± 0.3, 22.6 ± 0.4, and 22.9 ± 0.3°C, respectively), and insulation was lower on HH than onIH (0.13 ± 0.01 vs. 0.15 ± 0.01°C · W¹ · m²,respectively), but not with Eu (0.14 ± 0.01°C · W¹ · m²).This provides some evidence that hypertonicity impairs the vasoconstrictor response to cold. Although mild hypohydration did notaffect body heat balance during 2-h whole body exposure to moderatecold, hypohydration-associated hypertonicity may have subtle effects onvasoconstriction that could become important during a more severe coldexposure.

     

Exercise-heat acclimation in humans alters baseline levels and ex vivo heat inducibility of HSP72 and HSP90 in peripheral blood mononuclear cells

The induction of cellular acquired thermal tolerance (ATT) during heat acclimation (HA) in humans is not well described. This study determined whether exercise-HA modifies the human heat shock protein (HSP)72 and HSP90 responses and whether changes are correlated with physiological adaptations to HA. Using a 10-day HA protocol comprising daily exercise (treadmill walking) in a hot environment (T(a) = 49 degrees C, 20% RH), we analyzed baseline and ex vivo heat-induced expression of HSP72 and HSP90 in peripheral blood mononuclear cells (PBMCs) isolated prior to exercise from eight subjects on day 1 and 10 of the HA protocol. Classical physiological responses to HA were observed, including significantly reduced heart rate and core body temperature, and significantly increased sweating rate. Baseline levels of HSP72 and HSP90 were significantly increased following acclimation by 17.7 +/- 6.1% and 21.1 +/- 6.5%, respectively. Ex vivo induction of HSP72 in PBMCs exposed to heat shock (43 degrees C) was blunted on day 10 compared with day 1. A correlation was identified (r(2) = 0.89) between changes in core temperature elevation and ex vivo HSP90 responses to heat shock between days 1 and 10, indicating that volunteers demonstrating the greatest physiological HA tended to exhibit the greatest blunting of ex vivo HSP induction in response to heat shock. In summary, 1) exercise-HA resulted in increased baseline levels of HSP72 and HSP90, 2) ex vivo heat inducibility of HSP72 was blunted after HA, and 3) volunteers demonstrating the greatest physiological HA tended to exhibit the greatest blunting of ex vivo HSP induction in response to heat shock. These data demonstrate that physiological adaptations in humans undergoing HA are accompanied by both increases in baseline levels and changes in regulation of cytoprotective HSPs.     

人HCN4通道的滞后现象:影响窦房结起搏的潜在决定因素(英文)

超极化活化环核苷酸门控(hyperpolarization-activated cyclic-nucleotide-gated,HCN)通道参与调制心脏跳动的节律和速率。与HCN1和HCN2有所不同,慢通道HCN4可能不存在电压依赖的滞后现象。本研究采用单细胞膜片钳方法,在稳定转染hHCN4的HEK293细胞上进行电生理记录,观察hHCN4通道是否存在滞后现象,以及cAMP对其的调制作用;同时采用实时定量RT-PCR方法检测窦房结和心房组织中HCNs的表达。电压钳实验结果显示hHCN4电流(Ih)激活随着保持电位超极化的变化而向去极化方向移动。三角电位变化钳(triangular ramp)和动作电位钳的结果也显示了hHCN4的滞后现象。cAMP增加Ih电流幅度,且使电流激活向去极化方向移动,从而改变内源性hHCN4滞后行为。RT-PCR结果显示,人窦房结组织主要表达HCN4,占75%,HCN1占21%,HCN2占3%,HCN3占0.7%。以上结果提示,人窦房结组织主要表达HCN4亚型,hHCN4的Ih存在电压依赖性的滞后现象,且受cAMP调制。由此推断,hHCN4通道的滞后现象可能在窦房结起搏活动中起到了关键作用。     

Structural basis of TRAPPIII‐mediated Rab1 activation

The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo‐EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α‐helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.     

Gastric emptying during exercise: effects of heat stress and hypohydration

To determine the effects of acute heat stress, heat acclimation and hypohydration on the gastric emptying rate of water (W) during treadmill exercise, ten physically fit men ingested 400 ml of W before each of three 15 min bouts of exercise (treadmill, approximately 50% VO2max) on five separate occasions. Stomach contents were aspirated after each exercise bout. Before heat acclimation (ACC), experiments were performed in a neutral (18 degrees C), hot (49 degrees C) and warm (35 degrees C) environment. Subjects were euhydrated for all experiments before ACC. After ACC, the subjects completed two more experiments in the warm (35 degrees C) environment; one while euhydrated and a final one while hypohydrated (-5% of body weight). The volume of ingested water emptied into the intestines at the completion of each exercise bout was inversely correlated (P less than 0.01) with the rectal temperature (r = -0.76). The following new observations were made: 1) exercise in a hot (49 degrees C) environment impairs gastric emptying rate as compared with a neutral (18 degrees C) environment, 2) exercise in a warm (35 degrees C) environment does not significantly reduce gastric emptying before or after heat acclimation, but 3) exercise in a warm environment (35 degrees C) when hypohydrated reduces gastric emptying rate and stomach secretions. Reductions in gastric emptying appear to be related to the severity of the thermal strain induced by an exercise/heat stress.