Dehydration, Muscle Damage, and Exercise in the Heat: Impacts on Renal Stress, Thermoregulation, and Muscular Damage Recovery

Purpose: The purpose was to identify the combined influence of dehydration, muscle damage, and exertional hyperthermia on biological markers of acute kidney injury and renal function. We also investigated the effects of performing muscle damaging exercise during mild hypohydration on muscle damage biomarkers and muscular strength recovery. Methods: Eighteen recreationally-active males (age 24 ± 5 y, body fat 17.3 ± 6.2%) completed a familiarization visit and two experimental trials separated by ≥28 days. The two experimental conditions consisted of either euhydration (EU; maintaining hydration, -1.2 ± 0.8%) or hypohydration (HY; restricting fluid consumption for 24 hours prior to and during the trial, -4.4 ± 1.9%). Participants completed a unilateral eccentric knee flexion muscle damaging protocol, 60-minute treadmill exercise in the heat, 30-minute passive recovery, and a rehydrated 24-h follow-up visit, respectively. Results: Strength was reduced across time independent of trial for isometric strength at 70° (P\u3c0.001), isometric strength at 90° (P=0.001), and isokinetic strength at 60°·sec-1 (P=0.001). Serum creatine kinase increased regardless of trial (P\u3c0.001), with the 24-h follow-up greater (grand mean; 58.7 ± 25.1 U/L) than at baseline (grand mean; 35.7 ± 23.1 U/L, P\u3c0.001) and post-exercise (grand mean; 51.6 ± 23.2 U/L, P=0.009). Percent change in plasma neutrophil gelatinous associated lipocalin was greater in the HY trial post-exercise (EU 28.0 ± 15.2%, HY 41.8 ± 17.5%, P\u3c0.001), but not at 24-h follow-up (P=0.39). Serum creatinine was increased in the HY trial regardless of time (EU 0.97 ± 0.14, HY 1.04 ± 0.15, mg/dL, P=0.025). Urine NGAL and urine creatinine were also elevated in the HY trial pre-exercise and post-exercise (all, P\u3c0.05) but were returned to EU levels by 24-h follow-up (all, P\u3e0.05). Conclusions: We demonstrated no significant impact of hydration status when performing muscle damaging exercise, followed by exercise in the heat, on indices of muscle damage recovery. Exercise in the heat with muscle damage increased physiological and renal strain when HY, but the rehydration protocol ameliorated differences between trials by the 24-h follow-up. These findings highlight the importance of proper fluid intake following exercise to mitigate renal stress

The Effect of Type II Diabetes Mellitus on Oxygen Uptake Kinetics during Heavy Exercise

The kinetics of oxygen uptake (Vo2) during the rest to exercise transition are thought to be modulated by intracellular metabolic processes. Diabetes has been shown to slow Vo2 kinetics, likely due to the impact of diabetes upon microvascular oxygen exchange (Padilla et al, 2007). However, to date, recovery from exercise has yet to be studied in these patients. Thus, the purpose of this study was to test the hypothesis that the existence of diabetes would hamper Vo2 kinetics during transitions to and from heavy leg cycling (H: Supra-LT). Nine subjects (4 control, 5 diabetic) completed three separate H exercise bouts. Vo2 was measured continuously at the mouth during exercise and recovery for each bout. During the on-transient, the total amplitude was decreased (Atot: Control 2.16±0.29 vs Diabetic 1.33±0.42 L/min, p=0.01). In an attempt to correct for differences in Atot, the rate of change in Vo2 (A1/T1 ) was calculated. This variable was significant reduced in diabetics during both the on-(A1/T1: Control 0.059±0.03 vs Diabetic 0.016±0.01, p=0.02), and off-transients (Control -0.10±0.10 vs Diabetic 0.035±0.012, p=0.09). In addition, the time constant during the on-transition was greatly slowed in diabetes (Tau: Control 24.07±8.39 vs Diabetic 76.76±37.94 sec, p=0.03). These findings suggest strongly that diabetes and it’s sequelae lead to impairments in oxidative metabolism during both exercise and recovery, which would serve to cause a faster rate of fatigue and a longer temporal course of recovery

Carotid Baroreflex Control of Heart Rate is Enhanced during Whole-body Heat Stress

Whole-body heat stress (WBH) reduces orthostatic tolerance. While impaired carotid baroreflex (CBR) function during WBH has been reported, study design considerations may limit interpretation of previous findings. We sought to test the hypothesis that CBR function is unaltered during WBH. CBR function was assessed in ten subjects using 5-sec trials of neck pressure (45, 30 and 15 Torr) and neck suction (-20, -40, -60 and - 80 Torr) during normothermia (NT) and passive WBH (Δ core temp ~1 °C). Analysis of stimulus response curves (4-parameter logistic model) for CBR control of heart rate (CBR-HR) and mean arterial pressure (CBR-MAP), as well as separate 2-way ANOVA of the hypo- and hypertensive stimuli (factor 1: thermal condition, factor 2: chamber pressure) were performed. For CBR-HR, maximal gain was increased during WBH (-0.73±0.37) compared to NT (-0.39±0.11, p=0.03). In addition, the CBR-HR responding range was increased during WBH (32±15) compared to NT (18±8 bpm, p=0.03). Separate analysis of hypertensive stimulation revealed enhanced HR responses during WBH at -40, -60 and -80 Torr (condition*chamber pressure interaction, p=0.049) compared to NT. For CBR-MAP, both logistic analysis and separate 2-way ANOVA revealed no differences during WBH. Therefore, despite marked orthostatic intolerance observed during WBH, CBR control of heart rate (enhanced) and arterial pressure (no change) is well-preserved

The Impact of Physiologic Reductions In Blood Pressure Upon Oxygen Uptake During Moderate Intensity Leg Cycling

INTRODUCTION: Control of oxygen uptake (VO2) during the rest-to-exercise transition is thought to be dominated by intracellular processes rather than oxygen delivery. However, large changes in arterial pressure (i.e., supraphysiologic) have been shown to alter VO2 and its kinetics. Importantly, no studies have investigated the consequence of physiologic alterations in blood pressure on VO2 and its kinetics during exercise in humans. PURPOSE: The aim of this preliminary study was to assess the effect of modest reductions in MAP achieved via neck suction upon Vo2 across the rest-exercise transition, to test the hypothesis that physiologic reductions in arterial pressure during moderate intensity, steady-state exercise will not alter VO2. METHODS: Five subjects completed four exercise trials of 6 minute leg cycling at the workloads 50% of VO2max. Each workload was completed with and without carotid baroreceptor loading (i.e., Neck Suction: blood pressure lowering stimulation) with a 20 minute resting period between trials. Heart rate, mean arterial pressure (MAP), and VO2 at the mouth, were continuously measured while upper arm blood pressure was taken every minute. RESULTS: MAP tended to be reduced during the Neck Suction condition (delta MAP: Control 13.0±8.7 vs Neck Suction 6.3±6.3 mm Hg, P=0.079). However, there was no main effect for exercise condition on VO2 (Control 13.25±1.70 vs Neck Suction 13.17±1.72 ml/kg/min, P=0.61). In addition, the on-transient mean response time was not different between groups (Control 46.7±27.2 vs Neck Suction 40.9±16.2 s). CONCLUSIONS: These preliminary findings indicate that oxygen uptake or its kinetics during moderate intensity leg cycling are not affected by modest reductions in blood pressure

Gastrointestinal Cell Injury and Percieved Symptoms after Running the Boston Marathon

Gastrointestinal (GI) disturbances are a prevalent cause of marathon related complaints, and in extreme cases can promote life-threatening conditions such as exertional heat stroke. PURPOSE: Our aim was to study intestinal cell injury (via intestinal fatty acid binding protein [I-FABP]) and perceived GI distress symptoms among marathon runners. Potential risk factors (e.g., inadequate sleep) that could exacerbate GI disturbances in healthy, trained endurance runners were also examined. METHODS: A parallel mixed-methods study design was utilized. 2019 Boston Marathon participants were recruited via email. Before the race subjects completed surveys describing demographics and training history. Immediately pre-race, post-race, and 24-hours post-race participants completed a GI questionnaire to assess presence and severity of symptoms, a survey regarding risk factors (e.g., recent illness, medications) that could promote GI disturbances, and provided a urine sample. Due to weather, blood samples were only collected immediately and 24-hours post-race. RESULTS: A total of 40 runners (males: n = 19, age = 44.9 ± 10.8 years; females: n = 21, age = 44.8 ± 10.6 years) completed this study. I-FABP significantly decreased from post-race (3367.5 ± 2633.5 pg/ml) to 24-hours post-race (1657.3 ± 950.7 pg/ml, t(39) = -4.228, p \u3c .001, d = -.669). A significant difference in overall GI symptom scores across the three time points occurred (F(2, 39) = 41.37, p \u3c .001). Compared to pre-race (.09 ± .12) and 24-hour post-race (.44 ± .28), the highest average score occurred post-race (.84 ± .68). Post-race I-FABP (r = .31, p = .048) and post-race urine specific gravity (r = .33, p = .041) were significantly correlated with post-race GI symptom scores. CONCLUSION: Our study further supports the individualized presentation of GI disturbances, with participants experiencing a wide range of risk factors that can influence the extent of GI damage and perceived symptoms during and after exercise

Obesity, but not hypohydration, mediates changes in mental task load during passive heating in females

Background The independent effects of hypohydration and hyperthermia on cognition and mood is unclear since the two stresses often confound each other. Further, it is unknown if obese individuals have the same impairments during hyperthermia and hypohydration that is often observed in non-obese individuals. Methods The current study was designed to assess the independent and combined effects of mild hypohydration and hyperthermia on cognition, mood, and mental task load in obese and non-obese females. Twenty-one healthy females participated in two passive heating trials, wherein they were either euhydrated or hypohydrated prior to and throughout passive heating. Cognition (ImPACT), mental task load (NASA-TLX), and mood (Brunel Mood Scale; BRUMS) were measured before and after a 1.0 °C increase in core temperature (TC). Results After a 1.0 °C TC elevation, hypohydration resulted in greater (p  0.05). Hyperthermia, regardless of hydration status, impaired (∼5 A.U) measures of memory-based cognition (verbal and visual memory), and increased mental task load, while worsening mood (p  0.05). Conclusion These data indicate that hyperthermia independently impairs memory-based aspects of cognitive performance, mental task load, and leads to a negative mood state. Mild hypohydration did not exacerbate the effects of hyperthermia. However, obese individuals had increased mental task load during hyperthermia

A Multi-Component Model of the Developing Retinocollicular Pathway Incorporating Axonal and Synaptic Growth

During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP), synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway

Acute Kidney Injury Biomarkers and Hydration Outcomes at the Boston Marathon

The purpose of our field study was to investigate the effects of running the Boston Marathon on acute kidney injury (AKI) biomarkers. We hypothesized that biomarker values would be elevated immediately post-marathon but would resolve in the 24-h post-marathon. Secondarily, we sought to identify sex differences related to renal stress. Participants were 65 runners who completed the Boston Marathon (46 ± 9 years, 65.4 ± 10.8 kg). Urine samples were collected at three different time points (pre-marathon, post-marathon, and 24-h post-marathon). Blood samples were collected post-marathon and 24-h post-marathon. Urine specific gravity (USG) and AKI biomarkers were evaluated. Pre-marathon USG (1.012 ± 0.007) was significantly less than post-marathon (1.018 ± 0.008) and 24-h post-marathon (1.020 ± 0.009; P \u3c 0.001). Male USG (1.024 ± 0.009) was significantly greater 24-h post-marathon than females (1.017 ± 0.008; P = 0.019). Urinary neutrophil gelatinase-associated lipocalin values were significantly greater over time (P \u3c 0.001), and there was a main effect of sex with female urinary creatinine (UCr) greater than males at all three time points (P = 0.040). Post-marathonUCr (366.24 ± 295.16 mg/dl) was significantly greater than pre-marathon (206.65 ± 145.28.56 mg/dl; p \u3c 0.001) and 24-h post-marathon was significantly lower than other time-points (93.90 ± 125.07 mg/dl; P \u3c 0.001). FemaleUCr values were significantly greater than males 24-h post-marathon (P \u3c 0.001). There was no difference in serum cystatin C (SCys) values post- or 24-h post-marathon (P = 0.178). Serum creatinine (SCr) significantly decreased between post-marathon and 24-h post-marathon, (P \u3c 0.001). We can infer that the characteristics unique to the Boston Marathon may have attributed to prolonged elevations in AKI biomarkers. Sex differences were observed during the Boston Marathon warranting further investigation