Implications of a patent foramen ovale for environmental physiology and pathophysiology: do we know the 'hole' story?

The foramen ovale is an essential component of the fetal circulation contributing to oxygenation and carbon dioxide elimination that remains patent under certain circumstances in ∼30% of the healthy adult population, without major negative sequelae in most. Adults with a patent foramen ovale (PFO) have a greater tendency to develop symptoms of acute mountain sickness and high-altitude pulmonary oedema upon ascent to high altitude, and PFO presence is associated with worse cardiopulmonary function in chronic mountain sickness. This increase in altitude illness prevalence may be related to dysregulated cerebral blood flow associated with altered respiratory chemoreflex sensitivity; however, the mechanisms remain to be elucidated. Interestingly, men with a PFO appear to have a shift in thermoregulatory control to higher internal temperatures, both at rest and during exercise, and they have blunted thermal hyperpnoea. The teleological 'reason' for this thermoregulatory shift is unclear, but the shift of ∼0.5°C in core body temperature does not appear to be sufficient to have any significant negative consequences in terms of risk of heat illness. Further work in this area is needed, particularly in women, to evaluate mechanisms of heat storage and dissipation in these individuals compared to people without a PFO. Consequences of a PFO in SCUBA divers include a greater incidence of unprovoked decompression sickness, but whether PFO is beneficial or detrimental to breath hold diving remains unexplored. Whether PFO presence will explain interindividual variability in responses to, and consequences from, other environmental stressors such as spaceflight remain entirely unknown.

Effect of 8 days of exercise-heat acclimation on aerobic exercise performance of men in hypobaric hypoxia.

Exercise-heat acclimation (EHA) induces adaptations that improve tolerance to heat exposure. Whether adaptations from EHA can also alter responses to hypobaric hypoxia (HH) conditions remains unclear. This study assessed whether EHA can alter time-trial performance and/or incidence of acute mountain sickness (AMS) during HH exposure. Thirteen sea-level (SL) resident men [SL peak oxygen consumption (V̇o2peak) 3.19 ± 0.43 L/min] completed steady-state exercise, followed by a 15-min cycle time trial and assessment of AMS before (HH1; 3,500 m) and after (HH2) an 8-day EHA protocol [120 min; 5 km/h; 2% incline; 40°C and 40% relative humidity (RH)]. EHA induced lower heart rate (HR) and core temperature and plasma volume expansion. Time-trial performance was not different between HH1 and HH2 after 2 h (106.3 ± 23.8 vs. 101.4 ± 23.0 kJ, P = 0.71) or 24 h (107.3 ± 23.4 vs. 106.3 ± 20.8 kJ, P > 0.9). From HH1 to HH2, HR and oxygen saturation, at the end of steady-state exercise and time-trial tests at 2 h and 24 h, were not different (P > 0.05). Three of 13 volunteers developed AMS during HH1 but not during HH2, whereas a fourth volunteer only developed AMS during HH2. Heat shock protein 70 was not different from HH1 to HH2 at SL [1.9 ± 0.7 vs. 1.8 ± 0.6 normalized integrated intensities (NII), P = 0.97] or after 23 h (1.8 ± 0.4 vs. 1.7 ± 0.5 NII, P = 0.78) at HH. Our results indicate that this EHA protocol had little to no effect-neither beneficial nor detrimental-on exercise performance in HH. EHA may reduce AMS in those who initially developed AMS; however, studies at higher elevations, having higher incidence rates, are needed to confirm our findings.

Influences of hypobaric hypoxia on skin blood flow and sweating responses during exercise in neutral and hot environments.

Exposure to hot environments augments cutaneous vasodilation and sweating during exercise compared with these responses in cooler environments. The effects of hypobaric hypoxia on these responses are less clear, as are the effects of heat and simulated altitude combined. We evaluated the individual and potential additive effects of environmental heat and hypobaric hypoxia on skin blood flow and sweating responses during exercise. Thirteen volunteers (11 M, 2 F; age 25.3 ± 6.1 yr; height 177 ± 9 cm; weight 81.2 ± 16.8 kg) completed 30 min of steady-state (SS) exercise on a cycle ergometer at 50% V̇o2peak during four separate conditions: 1) sea level thermoneutral (SLTN; 250 m, 20°C, 30-50% RH), 2) sea level hot (SLH; 250 m, 35°C, 30% RH), 3) simulated altitude thermoneutral (ATN; 3,000 m, 20°C, 30-50% RH), and 4) simulated altitude hot (AH; 3,000 m, 35°C, 30% RH). Skin blood flow and local sweating rate (LSR) were recorded on the ventral forearm. During exercise, SS cutaneous vascular conductance in AH (63 ± 31% peak) and SLH (52 ± 19% peak) were significantly higher than both SLTN (20 ± 9% peak, P < 0.001) and ATN (25 ± 12% peak, P < 0.05) but were not different from each other (P > 0.05). SS LSR was similarly increased in the hot environments but unaffected by simulated altitude. We propose that multiple antagonistic mechanisms during exposure to 3,000-m simulated altitude result in no net effect on skin blood flow or sweating responses during exercise in thermoneutral or hot environments.

Sympathetic neural and hemodynamic responses to head-up tilt during isoosmotic and hyperosmotic hypovolemia.

We hypothesized that muscle sympathetic nerve activity (MSNA) during head-up tilt (HUT) would be augmented during exercise-induced (hyperosmotic) dehydration but not isoosmotic dehydration via an oral diuretic. We studied 26 young healthy subjects (7 female, 19 male) divided into three groups: euhydrated (EUH, n = 7), previously exercised in 40°C while maintaining hydration; dehydrated (DEH, n = 10), previously exercised in 40°C during which ~3% of body weight was lost via sweat loss; and diuretic (DIUR, n = 9), a group that did not exercise but lost ~3% of body weight via diuresis (furosemide, 80 mg by mouth). We measured MSNA, heart rate (HR), and blood pressure (BP) during supine rest and 30° and 45° HUT. Plasma volume (PV) decreased similarly in DEH (-8.5 ± 3.3%) and DIUR (-11.4 ± 5.7%) (P > 0.05). Plasma osmolality was similar between DIUR and EUH (288 ± 4 vs. 284 ± 5 mmol/kg, respectively) but was significantly higher in DEH (299 ± 5 mmol/kg) (P < 0.05). Mixed-model ANOVA was used with repeated measures on position (HUT) and between-group analysis on condition. HR and MSNA increased in all subjects during HUT (main effect of position; P < 0.05). There was also a significant main effect of group, such that MSNA and HR were higher in DEH compared with DIUR (P < 0.05). Changes in HR with HUT were larger in both hypovolemic groups compared with EUH (P < 0.05). The differential HUT response "strategies" in each group suggest a greater role for hypovolemia per se in controlling HR responses during dehydration, and a stronger role for osmolality in control of SNA.NEW & NOTEWORTHY Interactions of volume regulation with control of vascular sympathetic nerve activity (SNA) have important implications for blood pressure regulation. Here, we demonstrate that SNA and heart rate (HR) during hyperosmotic hypovolemia (exercise-induced) were augmented during supine and tilt compared with isoosmotic hypovolemia (diuretic), which primarily augmented the HR response. Our data suggest that hypovolemia per se had a larger role in controlling HR responses, whereas osmolality had a stronger role in control of SNA.

The Effectiveness of a Standardized Ice-Sheet Cooling Method Following Exertional Hyperthermia.

INTRODUCTION: Exertional heat illnesses remain a major threat to military service members in the United States and around the world. Exertional heat stroke (EHS) is the most severe heat illness, characterized by core hyperthermia and central nervous system dysfunction. Per current Army regulations, iced-sheet cooling (ISC) is the recommended immediate treatment for heat casualties in the field, but concerns have been raised regarding the efficacy of this approach. Thus, the purpose of this study was to quantify the cooling rate of ISC following exertional hyperthermia. MATERIALS AND METHODS: We utilized a randomized crossover design with 2 experimental trials. In both trials, exertional hyperthermia was induced by walking (3.5 mph at 5% grade) on a treadmill in an environmental chamber (40 °C, 30% RH) for up to 3 hours or until core body temperature reached 39.2 °C. After the walking portion, individuals either received ISC (experimental trial) or cooling and rested supine in the same environmental conditions for 30 minutes with no ISC (control trial). For ISC, bed sheets soaked in ice water were applied (per Army guidance) at the neck, chest, and groin with another sheet covering the body. Sheets were rotated and resoaked every 3 minutes until core temperature decreased to <38.0 °C. RESULTS: By design, participants finished exercise with increased core temperature (38.8 ± 0.39 °C vs. 38.90 ± 0.34 °C, ISC and control trials, P = 1.00). The ISC trial provided significantly (P = .023) greater cooling rates, 0.068 °C/min 95% confidence interval [CI; 0.053, 0.086], compared to the control trial, 0.047 °C/min 95% CI [0.038, 0.056]. Additionally, the time to decrease to less than 38.0 °C was significantly (P = .018) faster in the ISC trial (median = 9.3 minutes) compared to the control trial (median = 26.6 minutes). CONCLUSION: ISC increases the cooling rate of those recovering from exertional hyperthermia. With the observed cooling rate, we can extrapolate that ISC would reduce core temperature by ∼2 °C within 30 minutes during a case of EHS. We conclude that ISC provides a safe and effective alternative for the field where cold water immersion resources may not be readily available.

Heat Acclimation Improves Heat Tolerance Test Specificity in a Criteria-dependent Manner.

PURPOSE: This study aimed to characterize HTT specificity and to determine any effect of HA on the outcome. METHODS: Thirteen unacclimatized, healthy men (V˙O2peak, 43.0 ± 4.8 mL·kg-1⋅min-1) with no previous history of heat illness completed 8 d of HA using the HTT protocol (40°C/40% RH; 120 min; 5 km·h-1 and 2% grade). Heart rate (HR) and core temperature (Tcore) recorded every 5 min during exercise and at the end of 120 min (terminal value) were compared between days 1 and 8. Test specificity (given no previous history of heat illness, the probability of being heat tolerant) was calculated on days 1 and 8. RESULTS: There was a significant reduction in HR and Tcore between days 1 and 8, indicating successful HA. All volunteers successfully completed 120 min of walking on all days. HTT specificity ranged between 54% and 85% on day 1 and between 77% and 92% on day 8, depending on the HTT criteria used. CONCLUSION: Young healthy men without any previous heat illness experienced a 15% to 46% false-positive fail rate for the HTT without HA. After HA, the false-positive fail rate decreased to between 8% and 13%. Outcomes of the HTT are significantly affected by the criteria used and by HA status. The use of HTT for RTA decisions should be done with the recognition of these effects.

Effects of carbohydrate supplementation on aerobic exercise performance during acute high altitude exposure and after 22 days of acclimatization and energy deficit.

BACKGROUND: The ergogenic effects of supplemental carbohydrate on aerobic exercise performance at high altitude (HA) may be modulated by acclimatization status. Longitudinal evaluation of potential performance benefits of carbohydrate supplementation in the same volunteers before and after acclimatization to HA have not been reported. PURPOSE: This study examined how consuming carbohydrate affected 2-mile time trial performance in lowlanders at HA (4300 m) before and after acclimatization. METHODS: Fourteen unacclimatized men performed 80 min of metabolically-matched (~ 1.7 L/min) treadmill walking at sea level (SL), after ~ 5 h of acute HA exposure, and after 22 days of HA acclimatization and concomitant 40% energy deficit (chronic HA). Before, and every 20 min during walking, participants consumed either carbohydrate (CHO, n = 8; 65.25 g fructose + 79.75 g glucose, 1.8 g carbohydrate/min) or flavor-matched placebo (PLA, n = 6) beverages. A self-paced 2-mile treadmill time trial was performed immediately after completing the 80-min walk. RESULTS: There were no differences (P > 0.05) in time trial duration between CHO and PLA at SL, acute HA, or chronic HA. Time trial duration was longer (P < 0.05) at acute HA (mean ± SD; 27.3 ± 6.3 min) compared to chronic HA (23.6 ± 4.5 min) and SL (17.6 ± 3.6 min); however, time trial duration at chronic HA was still longer than SL (P < 0.05). CONCLUSION: These data suggest that carbohydrate supplementation does not enhance aerobic exercise performance in lowlanders acutely exposed or acclimatized to HA. TRIAL REGISTRATION: NCT, NCT02731066, Registered March 292,016.

Acetazolamide does not alter endurance exercise performance at 3,500-m altitude.

Acetazolamide (AZ) is a medication commonly used to prevent acute mountain sickness (AMS) during rapid ascent to high altitude. However, it is unclear whether AZ use impairs exercise performance; previous literature regarding this topic is equivocal. The purpose of this study was to evaluate the impact of AZ on time-trial (TT) performance during a 30-h exposure to hypobaric hypoxia equivalent to 3,500-m altitude. Ten men [sea-level peak oxygen consumption (VO2peak): 50.8 ± 6.5 mL·kg-1·min-1; body fat %: 20.6 ± 5.2%] completed 2 30-h exposures at 3,500 m. In a crossover study design, subjects were given 500 mg/day of either AZ or a placebo. Exercise testing was completed 2 h and 24 h after ascent and consisted of 15-min steady-state treadmill walking at 40%-45% sea-level VO2peak, followed by a 2-mile self-paced treadmill TT. AMS was assessed after ~12 h and 22 h at 3,500 m. The incidence of AMS decreased from 40% with placebo to 0% with AZ. Oxygen saturation was higher (P < 0.05) in AZ versus placebo trials at the end of the TT after 2 h (85 ± 3% vs. 79 ± 3%) and 24 h (86 ± 3% vs. 81 ± 4%). There was no difference in time to complete 2 miles between AZ and PL after 2 h (20.7 ± 3.2 vs. 22.7 ± 5.0 min, P > 0.05) or 24 h (21.5 ± 3.4 vs. 21.1 ± 2.9 min, P > 0.05) of exposure to altitude. Our results suggest that AZ (500 mg/day) does not negatively impact endurance exercise performance at 3,500 m.NEW & NOTEWORTHY To our knowledge, this is the first study to examine the impact of acetazolamide (500 mg/day) versus placebo on self-paced, peak-effort exercise performance using a short-duration exercise test in a hypobaric hypoxic environment with a repeated-measures design. In the present study, acetazolamide did not impact exercise performance after 2-h or 24-h exposure to 3,500-m simulated altitude.

Influence of Acetazolamide on Hand Strength and Manual Dexterity During a 30-h Simulated High Altitude Exposure.

INTRODUCTION: High altitude missions pose significant challenges to Warfighter medical readiness and performance. Decreased circulating oxygen levels cause a decrease in exercise performance and can cause debilitating symptoms associated with acute mountain sickness, especially with rapid ascent. Acetazolamide (AZ) is known to minimize symptoms of acute mountain sickness, but it is unknown whether this medication alters hand strength and manual dexterity during altitude exposure. MATERIALS AND METHODS: Ten male volunteers (22 ± 4 yr, 75.9 ± 13.7 kg, 174.9 ± 9.3 cm) participated in two separate 30 h simulated altitude exposures (496 mmHg, equivalent to 3,500 m, 20°C, 20% RH) in a hypobaric chamber. Participants were given either a placebo or 250 mg of AZ twice daily for 3.5 d (2 sea-level [SL] days + the 30 h altitude exposure) in a randomized, single-blind, crossover design. During SL and both altitude (ALT) exposures, hand function tests were performed, including hand grip and finger pinch strength tests, as well as the Purdue Pegboard (PP) and magazine loading tests to assess manual dexterity. Paired T tests and two-way repeated measure analysis of variance were used as appropriate to evaluate the effects of AZ and ALT. The value of p < 0.05 was accepted for statistical significance. RESULTS: There were no influences of acute ALT exposure or AZ treatment on hand strength (eg, grip strength; SL: 39.2 ± 5.5 kg vs. ALT: 41.5 ± 6.9 kg, p > 0.05) or dexterity (eg, PPassembly; placebo: 35.5 ± 5.3 vs. AZ: 34.3 ± 4.6, p > 0.05) in our volunteers. Two dexterity tests (PPsum and magazine loading) showed improvements over time at ALT, regardless of treatment, where scores were improved after 10 h of exposure compared to at 1 h (eg, magazine loading: 56 ± 12 vs. 48 ± 10, p < 0.001). This pattern was not seen in the PPassembly test or any strength measurements. CONCLUSIONS: Our results suggest that 500 mg/d of AZ does not influence hand strength or manual dexterity during a 30 h exposure to 3,500 m simulated ALT. Acute ALT exposure (1 h) did not influence dexterity or strength, although some measures of dexterity showed improvements as exposure time increased. We conclude that use of AZ to optimize medical readiness at ALT is unlikely to impair the Warfighter's ability to complete mission tasks that depend on hand function.

Separate and combined influences of heat and hypobaric hypoxia on self-paced aerobic exercise performance.

Heat and hypobaric hypoxia independently compromise exercise performance; however, their combined impact on exercise performance has yet to be quantified. This study examined the effects of heat, hypobaric hypoxia, and the combination of these environments on self-paced cycling time trial (TT) performance. Twelve subjects [2 female, 10 male; sea level (SL) peak oxygen consumption (V̇o2peak), 41.5 ± 4.4 mL·kg-1·min-1, mean ± SD] completed 30 min of steady-state cycling exercise (50% SL V̇o2peak), followed by a 15-min self-paced TT in four environmental conditions: SL thermoneutral [SLTN; 250 m, 20°C, 30-50% relative humidity (rh)], SL hot (SLH; 250 m, 35°C, 30% rh), hypobaric hypoxia thermoneutral (HTN; 3,000 m, 20°C, 30-50% rh), and hypobaric hypoxia hot (HH; 3,000 m, 35°C, 30% rh). Performance was assessed by the total work (kJ) completed. TT performance was lower (P < 0.05) in SLH, HTN, and HH relative to SLTN (-15.4 ± 9.7, -24.1 ± 16.2, and -33.1 ± 13.4 kJ, respectively). Additionally, the total work completed in HTN and HH was lower (P < 0.05) than that in SLH. In SLH, HTN, and HH, work rate was reduced versus SLTN (P < 0.05) within the first 3 min of exercise and was consistent for the remainder of the bout. No differences (P > 0.05) existed for heart rate or Ratings of Perceived Exertion at the end of exercise among conditions. The decrease in self-paced TT performance in the heat and/or hypobaric hypoxia conditions compared with SLTN conditions resulted from a nearly immediate reduction in work rate that may have been regulated by environmentally induced changes in physiological strain and perception of effort in response to TT exercise.NEW & NOTEWORTHY This is the first known study to examine the combined effects of heat and hypobaric hypoxia on short-duration self-paced cycling time trial performance. Regardless of environmental condition, subjects utilized an even work rate for the entire duration of the time trial. The presence of both environmental stressors led to a greater performance impairment than heat or hypobaric hypoxia alone, and the performance decrement stemmed from an early reduction of work rate.

Efficacy of Glucose or Amino Acid-Based Commercial Beverages in Meeting Oral Rehydration Therapy Goals After Acute Hypertonic and Isotonic Dehydration.

BACKGROUND: The efficacy of different commercial beverage compositions for meeting oral rehydration therapy (ORT) goals in the treatment of acute dehydration in healthy humans has not been systematically tested. The objective of the study was to compare fluid retention, plasma volume (PV), and interstitial fluid (ISF) volume restoration when using 1 popular glucose-based and 1 novel amino acid-based (AA) commercial ORT beverage following experimental hypertonic or isotonic dehydration. METHODS: Twenty-six healthy adults (21 males, 5 females) underwent either a controlled bout of hypertonic (n = 13) or isotonic (n = 13) dehydration (3%-4% body mass) via eccrine or renal body water and electrolyte losses induced using exercise-heat stress (EHS) or Lasix administration (LAS), respectively. Rehydration was achieved over 90 minutes by matching fluid intake to water losses (1:1) using a sports drink (SP) or AA commercial ORT beverage. Fluid retention (water and electrolytes), PV, and ISF volume changes were tracked for 180 minutes. RESULTS: AA produced significantly (P <0.05) greater fluid retention (75% vs 57%), ISF volume restoration, and tended (P = 0.06) to produce greater PV restoration in trial EHS. In trial LAS, neither beverage exceeded 65% retention, but AA replaced electrolytes and preserved ISF volume better than SP (P <0.05). CONCLUSION: The results of this study demonstrate superior rehydration when using AA compared with SP for both hypertonic and isotonic dehydration.