Applied Physiology

PROBLEM: An acute bout of resistance exercise may have a negative effect on vascular function. METHODS: Ten young, healthy, resistance-trained individuals (8 males, 2 females; aged 23±3 yrs) volunteered. One-repetition maximum (1RM) was assessed on the squat (144±32kg), bench press (109±33kg), and deadlift (160±40kg). Forearm blood flow (FBF) was assessed by strain gauge plethysmography at rest and followed by 5 minutes of circulatory occlusion (220 mmHg) to induce reactive hyperemia (RH) and to measure vasodilatory capacity before and 25 minutes after an acute bout of resistance exercise. Each participant also completed a quiet control session of the same duration. Area under the curve for FBF-RH was also utilized to determine differences in blood flow. Data were analyzed by an ANOVA to examine the effects of condition (acute resistance exercise, control) by time (rest, recovery). RESULTS: Area under the curve for FBF-RH significantly (p≤0.05) increased after the acute bout of free...

In order to investigate the tracheal pressures for different percentages of stenotic constriction, flow simulations are performed on a realistic geometry based on CT-scans of a patient for sedentary breathing (15 l/min) and normal breathing (30 l/min) conditions using a Reynolds Averaged Navier Stokes approach for unstructured hexahedral meshes. Turbulence modeling is based on low Reynolds number Yang-Shih kε model. The realistic airway model in itself is highly irregular and the presence of stenosis adds to its geometrical complexity, resulting in very complex flow patterns with flow separations and skewed velocity profiles. Detailed analysis of these flows is presented for 0%, 49%, 75%, 84% and 91% stenotic constrictions. The pressure drop shows modest increases with the degree of narrowing up to 75% constriction, beyond which it steeply rises. Such a pattern agrees with the appearance of breathing symptoms only when patients already show a very marked stenosis. In order to temporarily ease work of breathing, a decrease of the pressure drop is sometimes induced by having the patient inhale heliox. An additional flow analysis is performed with heliox as the working fluid.

O besity is now well-known as an important risk factor for developing several respiratory diseases. Whether it is associated with respiratory muscle strength (RMS) impairment is unsettled. We aimed to investigate the infl uence of obesity on the RMS in Thai women aged between 20-60 years old. Sixteen obese (body mass index, BMI > 25 kg/m 2 ) and 16 normal-weight women (BMI > 18.5 to 22.9 kg/m 2 ) matched for age were studied. RMS including PImaxRV, PImaxFRC, Pnsn and PEmax were measured using a MICRORPM ® , Medical, UK. A pneumotach airfl ow transducer (medium fl ow), BIOPAC Systems (USA) was used to measure tidal volume (VT), respiratory rate (RR) and total expired ventilation (V °E). BMI were 32.9±4.5 and 20.1±1.1 kg/m 2 whereas ages were 32.0±8.6 and 32.2±8.7 yrs in obese and lean groups, respectively. Absolute PImaxRV, PImaxFRC, Pnsn, PEmax and RMS in obese women were signifi cantly higher than in normal-weight women (p<0.001). VT but not RR or V °E in obese women was signifi cantly higher (p<0.01) than that of normal-weight peers. This study indicates that obese women studied have greater respiratory muscle strength than normal-weight peers. This could be due to deep breathing constantly loaded to the respiratory muscles and adaptation of muscle fi bers.

In ferrets, we investigated the presence of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and markers for nitric oxide synthase (NOS) in preganglionic parasympathetic neurons innervating extrathoracic trachea and intrapulmonary airways. Cholera toxin β-subunit, a retrograde axonal transganglionic tracer, was used to identify airway-related vagal preganglionic neurons. Double-labeling immunohistochemistry and confocal microscopy were employed to characterize the chemical nature of identified airway-related vagal preganglionic neurons at a single cell level. Physiological experiments were performed to determine whether activation of the VIP and ChAT coexpressing vagal preganglionic neurons plays a role in relaxation of precontracted airway smooth muscle tone after muscarinic receptor blockade. The results showed that 1) all identified vagal preganglionic neurons innervating extrathoracic and intrapulmonary airways are acetylcholine-producing cells, 2) choliner...

Background. Oliceridine, an investigational IV opioid, is a first-in-class G-protein selective agonist at the μ-opioid receptor. The G-protein selectivity results in potent analgesia with less recruitment of β-arrestin, a signaling pathway associated with opioid-related adverse events (ORAEs). In randomized controlled studies in both hard and soft tissue models yielding surgical pain, oliceridine provided effective analgesia with a potential for an improved safety and tolerability profile at equianalgesic doses to morphine. The phase 3, open-label, single-arm, multicenter ATHENA trial demonstrated the safety, tolerability, and effectiveness of oliceridine in moderate to severe acute pain in a broad range of patients undergoing surgery or with painful medical conditions warranting use of an IV opioid. This retrospective, observational chart review study compared respiratory depression events associated with oliceridine administration as found in the ATHENA trial to a control cohort t...

Lack of sarcolemma-localized neuronal nitric oxide synthase mu (nNOSμ) contributes to muscle damage and fatigue in dystrophic muscle. In this study, we examined the effects of compensating for lack of nNOSμ with a phosphodiesterase type 5 (PDE5) inhibitor in mdx mice following downhill running and endurance training. Dystrophic mice ( mdx) were treated with sildenafil citrate and compared with untreated mdx and wild-type mice after an acute bout of downhill running and during a progressive low-intensity treadmill running program (5 days/wk, 4 wk). Magnetic resonance imaging (MRI) and spectroscopy (MRS) transverse relaxation time constant (T2) of hindlimb and forelimb muscles were measured as a marker of muscle damage after downhill running and throughout training. The MRI blood oxygenation level dependence (BOLD) response and 31phosphorus MRS (31P-MRS) data were acquired after stimulated muscle contractions. After downhill running, the increase in T2 was attenuated ( P &lt; 0.05) in...

The present study was designed to determine the effects of physical training on the development of cancer induced by the injection of Ehrlich tumor cells in mice. Male Swiss mice were subjected to a swim training protocol (5 days/wk for 6 wk, 1 h at 50% of maximal capacity-trained groups) or remained sedentary in their cages (sedentary groups). The inoculation of Ehrlich tumor cells was performed at the end of the fourth week, and animals were killed after 6 wk of training. Heart and solid tumor weights were recorded, and tumor volumes were calculated. Portions of the tumors were used for the evaluation of macrophages and neutrophil accumulation or fixed in neutral 10% buffered formalin for histological analysis. The tumor volume and weight were, respectively, ∼270% and 280% greater in sedentary mice than in trained mice. Macrophage infiltration in the tumor tissue was significantly lower in trained mice (0.65 ± 0.16 vs. 1.78 ± 0.43 macrophages × 103in the sedentary group). Moreover...

Our laboratory has previously demonstrated that maximal bronchoconstriction produces a greater degree of airway narrowing in immature than in mature rabbit lungs (33). To determine whether these maturational differences could be related to airway structure, we compared the fraction of the airway wall occupied by airway smooth muscle (ASM) and cartilage, the proportion of wall area internal to ASM, and the number of alveolar attachments to the airways, from mature and immature (6-mo- and 4-wk-old, respectively) rabbit lungs that were formalin fixed at total lung capacity. The results demonstrate that the airway walls of immature rabbits had a greater percentage of smooth muscle, a lower percentage of cartilage, and fewer alveolar attachments compared with mature rabbit airways; however, we did not find maturational differences in the airway wall thickness relative to airway size. We conclude that structural differences in the airway wall may contribute to the greater airway narrowing...

Exercise-induced bronchoconstriction displays refractoriness manifested as a decreased response to repeated exercise challenge within hours. The refractoriness may be attenuated by inhibition of the biosynthesis of prostaglandins (PG). The aim of the study was to determine which PGs and other lipid mediators are excreted during the refractory period. First, 16 subjects with mild stable asthma performed two repeated 4-min challenges with eucapnic voluntary hyperpnea (EVH) 1 and 3 h apart. There was a similar degree of refractoriness in both protocols (ϳ15% protection). The 1-h interval was too short to study mediator excretion because the urinary levels did not return to baseline before the second challenge. With the 3-h protocol, there was increased urinary excretion of cysteinyl-leukotrienes and metabolites of the mast cell product PGD 2 after both challenges. Next, another eight subjects performed two 6-min challenges with EVH 3 h apart, which produced a greater bronchoconstrictor response than the 4-min protocol (30.0 Ϯ 5.4 vs. 17.7 Ϯ 1.5%; P ϭ 0.0029) and a greater degree of refractoriness (ϳ30%). Analysis by ultra-performance liquid chromatography triple quadrupole mass spectrometry confirmed excretion of the bronchoconstrictor cysteinyl-leukotrienes and PGD2 during both challenges. In addition, there was increased excretion of the bronchoprotective PGE2, and also of the main metabolite of PGI2. This is the first report of excretion of PGE2 and PGI2 during the refractory period to EVH challenge, suggesting that they may mediate the refractoriness. Maintained excretion of PGD2 and leukotriene E4 following the repeat challenge argues against mast cell mediator depletion as the mechanism of refractoriness.

Although short-term disuse does not result in measurable muscle atrophy, studies suggest that molecular changes associated with protein degradation may be initiated within days of the onset of a disuse stimulus. We examined the global gene expression patterns in sedentary men ( n = 7, mean age ± SD = 22.1 ± 3.7 yr) following 48 h unloading (UL) via unilateral lower limb suspension and 24 h reloading (RL). Biopsy samples of the left vastus lateralis muscle were collected at baseline, 48 h UL, and 24 h RL. Expression changes were measured by microarray and gene clustering; identification of enriched functions and canonical pathways were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). Four genes were validated with quantitative RT-PCR (qRT-PCR), and protein levels were measured with Western blot. Of the upregulated genes after UL, the most enriched functional group and highest ranked canonical pathway wer...

To test the hypothesis that muscle O2 uptake (V˙o 2) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined theV˙o 2 on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles ( n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60–70% peakV˙o 2). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q˙), at a level measured at steady state during contractions in preliminary trials with spontaneous Q˙. Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q˙. Q˙ was measured continuously, arterial and popliteal venous O2 concentration...

and other authors have proposed that central motor command (CMC) and, consequently, exercise performance in hypoxia is determined by the following. 1) By simple negative feedback (1, 2) or complex feedback/ feedforward (4) subconscious homeostatic control systems that, based on afferent information from central and peripheral chemoreceptors, limit skeletal muscle recruitment to avoid dangerous brain deoxygenation (4), respiratory failure (2), or excessive locomotor muscle fatigue and pain (1), or 2) by the direct negative effects of severe brain hypoxia on maximal voluntary CMC and/or motivation to exercise (1, 6). However, these authors have overlooked a third possibility, which, in our opinion, is simpler and biologically more plausible. Indeed, it is well established that the sensation of respiratory effort increases when ventilation is reflexly stimulated by hypoxia. According to our psychobiological model of exercise performance based on Brehm's motivational intensity theory (3), this perceptual effect of hypoxia can increase overall perceived exertion and cause subjects to disengage from a task (which, in physiological terms, means a sudden reduction in CMC and exhaustion) earlier than in normoxic conditions even assuming no effect of hypoxia on motivation to exercise. During time trials, subjects are able to compensate for the increased sensation of respiratory effort by voluntarily reduce power output. This behavioral strategy maintains overall perception exertion within normal limits to ensure successful completion of the time trial despite hypoxia. Future studies need to control for rival hypotheses and establish experimentally which of the above three models is the most valid explanation for reduced CMC and exercise performance in hypoxia.

This study investigated the effects of acute creatine kinase (CK) inhibition (CKi) on contractile performance, cytosolic Ca2+concentration ([Ca2+]c), and intracellular Po2(Pi[Formula: see text]) in Xenopus laevis isolated myocytes during a 2-min bout of isometric tetanic contractions (0.33-Hz frequency). Peak tension was similar between trials during the first contraction but was significantly ( P &lt; 0.05) attenuated for all subsequent contractions in CKivs. control (Con). The fall in Pi[Formula: see text](ΔPi[Formula: see text]) from resting values was significantly greater in Con (26.0 ± 2.2 Torr) compared with CKi(17.8 ± 1.8 Torr). However, the ratios of Con to CKiend-peak tension (1.53 ± 0.11) and ΔPi[Formula: see text](1.49 ± 0.11) were similar, suggesting an unaltered aerobic cost of contractions. Additionally, the mean response time (MRT) of ΔPi[Formula: see text]was significantly faster in CKivs. Con during both the onset (31.8 ± 5.5 vs. 49.3 ± 5.7 s; P &lt; 0.05) and cess...

Central" and "peripheral" limitations to oxidative metabolism during exercise were evaluated in 10 young males following a 35-day horizontal bed rest (BR). Incremental exercise (IE) and moderate-and heavy-intensity constant-load exercises (CLE) were carried out on a cycloergometer before and 1-2 days after BR. Pulmonary gas exchange, cardiac output (Q ˙; by impedance cardiography), skeletal muscle (vastus lateralis), and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined. After BR, "peak" (values at exhaustion during IE) workload, peak O2 uptake (V ˙O2peak), peak stroke volume, Q ˙peak, and peak skeletal muscle O2 extraction were decreased (Ϫ18, Ϫ18, Ϫ22, Ϫ19, and Ϫ33%, respectively). The gas exchange threshold was ϳ60% of V ˙O2peak both before and after BR. At the highest workloads, brain oxygenation data suggest an increased O2 extraction, which was unaffected by BR. V ˙O2 kinetics during CLE (same percentage of peak workload before and after BR) were slower (time constant of the "fundamental" component: 31.1 Ϯ 2.0 s before vs. 40.0 Ϯ 2.2 s after BR); the amplitude of the "slow component" was unaffected by BR, thus it would be greater, after BR, at the same absolute workload. A more pronounced "overshoot" of skeletal muscle O2 extraction during CLE was observed after BR, suggesting an impaired adjustment of skeletal muscle O2 delivery. The role of skeletal muscles in the impairment of oxidative metabolism during submaximal and maximal exercise after BR was identified. The reduced capacity of peak cardiovascular O2 delivery did not determine a "competition" for the available O2 between skeletal muscles and brain.

At the onset of muscular exercise, the kinetics of pulmonary O2uptake (V̇o2P) reflect the integrated dynamic responses of the ventilatory, circulatory, and neuromuscular systems for O2transport and utilization. Muscle O2uptake (V̇o2m) kinetics, however, are dissociated from V̇o2Pkinetics by intervening O2capacitances and the dynamics of the circulation and ventilation. We developed a multicompartment computational model (MCM) to investigate these dynamic interactions and optimized and validated the MCM using previously published, simultaneously measured V̇o2m, alveolar O2uptake (V̇o2A), and muscle blood flow (Q̇m) in healthy young men during cycle ergometry. The model was used to show that 1) the kinetics of V̇o2Aduring exercise transients are very sensitive to preexercise blood flow distribution and the absolute value of Q̇m, 2) a low preexercise Q̇mexaggerates the magnitude of the transient fall in venous O2concentration for any given V̇o2mkinetics, necessitating a tighter couplin...

earlier, Edwards (10) in his initial study showed that subjects who had not been at high altitude long enough for good acclimatization had higher maximum blood lactate levels than well-acclimatized subjects. The data in Fig. predict that there would be no rise in blood lactate concentration on maximal exercise above the resting level at altitudes above ϳ7,600 m and indeed the highest data point (6) seems to confirm this. It is very extraordinary that under these conditions of extreme tissue hypoxia, blood lactate levels are so different from those seen in acute hypoxic exposure. Irrespective of whether this strange state of affairs does not occur in everybody (although the data in Fig. are from a large number of subjects including both acclimatized lowlanders and high-altitude residents), and there may be some recovery of blood lactate levels with increased time spent at high altitude, this extreme reduction in blood lactate is certainly intriguing.

Previous studies have suggested that a reduction in cerebral oxygen delivery may limit motor drive, particularly in hypoxic conditions, where oxygen transport is impaired. We hypothesized that raising end-tidal Pco2 (PetCO2) during incremental exercise would increase cerebral blood flow (CBF) and oxygen delivery, thereby improving peak power output (Wpeak). Amateur cyclists performed two ramped exercise tests (25 W/min) in a counterbalanced order to compare the normal, poikilocapnic response against a clamped condition, in which PetCO2 was held at 50 Torr throughout exercise. Tests were performed in normoxia (barometric pressure = 630 mmHg, 1,650 m) and hypoxia (barometric pressure = 425 mmHg, 4,875 m) in a hypobaric chamber. An additional trial in hypoxia investigated effects of clamping at a lower PetCO2 (40 Torr) from ∼75 to 100% Wpeak to reduce potential influences of respiratory acidosis and muscle fatigue imposed by clamping PetCO2 at 50 Torr. Metabolic gases, ventilation, mid...

Ligament heals in a synchronized and complex series of events. The remodeling process may last months or years. Experimental evidence suggests the damaged ligament does not recover its normal functional properties. Specific mechanisms to prevent scar formation and to regenerate the original mechanical function remain elusive but likely involve regulation of creeping substitution. Creeping substitution creates a larger hypercellular, hypervascular, and disorganized granulation tissue mass that results in an inefficient and nonregenerative wound healing process for the ligament. Control of creeping substitution may limit the extent of this tissue compromise and reduce the time necessary for healing. The objective of this study is to better understand the mechanism behind scar formation by identifying the extracellular matrix factors and other unique genes of interest differentially expressed during rat ligament healing via microarray. For this study, rat medial collateral ligaments we...

The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3–4 to 24 mo old) is 45–25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury ...

Subjective nasal obstruction is common among users of continuous positive airway pressure (CPAP). The aim of this study was to measure the acute effect of CPAP on nasal resistance and nasal symptoms in awake normal subjects. Twenty-four healthy CPAP-naive adults [8 men, 16 women; mean age 30 yr (SD 14)] underwent a randomized controlled crossover study comparing nasal CPAP (8 cmH2O) for 6 h on one occasion and the control condition (nasal mask without CPAP) on the other. Nasal resistance measurements (posterior active rhinometry) before and after the test exposure were similar on both test days. Nasal resistance during CPAP exposure [2.04 cmH2O·l−1·s (SD 0.72)] was significantly lower than that of the control [2.67 cmH2O·l−1·s (SD 1.07)]: mean difference 0.66 cmH2O·l−1·s, 95% confidence interval 0.19–1.13 cmH2O·l−1·s. The gradient in pressure from CPAP mask to posterior naris during CPAP exposure varied from 1.6 to 2 cmH2O but was not significantly different between time points. Sub...

Three different levels of hyperchloremia were induced in healthy Friesian calves to study the effects of chloride on blood oxygen transport. By infusion, the calves received either 5 ml/kg of 0.9% NaCl (low-level hyperchloremia; group A), 5 ml/kg of 7.5% NaCl (moderate hyperchloremia; group B), or 7.5 ml/kg of 7.5% NaCl (high-level hyperchloremia; group C). Blood was sampled from the jugular vein and the brachial artery. Chloride concentration, hemoglobin content, arterial and venous pH, [Formula: see text], and[Formula: see text] were determined. At each time point (0, 15, 30, 60, and 120 min), the whole blood oxygen equilibrium curve (OEC) was measured under standard conditions. In groups B and C, hyperchloremia was accompanied by a sustained rightward shift of the OEC, as indicated by the significant increase in the standard [Formula: see text] at 50% hemoglobin saturation. Infusion of hypertonic saline also induced relative acidosis. The arterial and venous OEC were calculated, ...

Gustin, P., B. Detry, A. Robert, M. L. Cao, F. Lessire, C. Cambier, V. Katz, M. Ansay, A. Frans, and T. Clerbaux.Influence of age and breed on the binding of oxygen to red blood cells of bovine calves. J. Appl. Physiol. 82(3): 784–790, 1997.—The influence of somatic growth and genetic selection on the whole blood oxygen equilibrium curve (OEC) was measured under standard conditions in double-muscled and dairy calves during their first 3 mo of life. Crossbreed animals were also investigated. Hemoglobin, 2,3-diphosphoglycerate (DPG), Cl, and Piconcentrations were also measured. The percentage of fetal hemoglobin (HbF) was determined. The influence of exogenous Cl, Pi, and pH on the OEC was also assessed. The[Formula: see text] at 50% hemoglobin saturation (P50) increased during somatic growth, probably because of the increase in DPG recorded in double-muscled neonates and to the progressive disappearance of HbF in both breeds. The oxygen exchange fraction (OEF%) was used to assess the...

Autonomic dysreflexia (AD) can occur during penile vibratory stimulation in men with spinal cord injury, but this is variable, and the association with lesion level is unclear. The purpose of this study was to characterize the cardiovascular responses to penile vibratory stimulation in men with spinal cord injury. We hypothesized that those with cervical injuries would demonstrate a greater degree of AD compared with men with thoracic injuries. We also questioned whether the rise in blood pressure could be attenuated by sildenafil citrate. Participants were classified as having cervical ( n = 8) or thoracic ( n = 5) injuries. While in a supine position, subjects were instrumented with an ECG, and arterial blood pressure was determined beat by beat. Subjects reported to the laboratory twice and received an oral dose of sildenafil citrate (25–100 mg) or no medication. Penile vibratory stimulation was performed using a handheld vibrator to the point of ejaculation. At ejaculation durin...

Upright hyperventilation occurs in ~25% of our patients with postural tachycardia syndrome (POTS). Poikilocapnic hyperventilation alone causes tachycardia. Here, we examined changes in respiration and hemodynamics comprising cardiac output (CO), systemic vascular resistance (SVR), and blood pressure (BP) measured during head-up tilt (HUT) in three groups: patients with POTS and hyperventilation (POTS-HV), patients with panic disorder who hyperventilate (Panic), and healthy controls performing voluntary upright hyperpnea (Voluntary-HV). Though all were comparably tachycardic during hyperventilation, POTS-HV manifested hyperpnea, decreased CO, increased SVR, and increased BP during HUT; Panic patients showed both hyperpnea and tachypnea, increased CO, and increased SVR as BP increased during HUT; and Voluntary-HV were hyperpneic by design and had increased CO, decreased SVR, and decreased BP during upright hyperventilation. Mechanisms of hyperventilation and hemodynamic changes differ...

After chronic, low-frequency stimulation, a rapid decline in Ca2+pump activity is observed during the early stages of skeletal muscle transformation. However, this variation in enzymatic activity does not coincide with a drastic reduction in the amount of sarcoplasmic reticulum Ca2+-ATPases. To investigate whether changes in subunit interactions within Ca2+pump complexes contribute to this phenomena, we performed a chemical cross-linking analysis of 4 days continuously, and 4 days discontinuously, electrostimulated fast muscle fibers. The abundance of the slow and fast Ca2+-ATPase isoforms sarco(endo)plasmic reticulum Ca2+- ATPase types 1 and 2 was affected during the fast-to-slow transition process, demonstrating that, even after short-term stimulation, distinct changes in the isoform expression pattern of muscle proteins occur. However, the oligomeric status of both ion pump species did not change. Hence, chemical modifications of critical enzyme domains must be responsible for th...

Cardiovascular fitness is essential for both improving athletic performance and preserving general health. Engaging in physical activity helps the body increase its supply of oxygen more efficiently by increasing the effectiveness of the heart, lungs, and blood vessels. Better energy use, faster recovery, and less tiredness are all supported by increasing cardiovascular endurance and are essential for successful sports performance. It also reduces the chance of developing lifestyle-related illnesses like diabetes mellitus, heart disease, and high blood pressure. Strong cardiovascular fitness benefits athletes by enhancing and sustaining performance. Overall, it is the cornerstone of both a healthy lifestyle and athletic excellence. Talking about cardiovascular fitness, maximum oxygen uptake or VO 2 Max, is commonly considered the golden standard for assessing an individual's aerobic capability. As a clear measure of cardio-respiratory fitness, it represents the maximum rate at which the body can take in and use oxygen during vigorous activity. Greater endurance and effective oxygen transport by the respiratory and circulatory systems are indicated by a higher VO 2 Max [3]. It is a crucial metric in evaluations of athletic performance since it is impacted by several variabilities, such as age, sex, training intensity, and heredity. Conversely, Resting Heart Rate (RHR) is a readily available and non-invasive indicator of cardiovascular efficiency. A well-conditioned heart that pumps more blood with fewer beats is frequently associated with a lower RHR. Consistent aerobic training, which increases stroke volume and develops heart muscles, usually causes this adaptation [12]. Training progress, recovery state, and even early indicators of overtraining or cardiovascular A B S T R A C T Cardiovascular fitness, measured through Resting Heart Rate (RHR) and Maximal Oxygen Uptake (VO2 Max), is critical for optimizing athletic performance. High-Intensity Interval Training (HIIT) and Fast Continuous Training (FCT) are two aerobic conditioning modalities widely used to improve cardiovascular efficiency, but their comparative effects remain insufficiently studied in adult competitive athletes. This study aimed to compare the effects of an 8-week HIIT and FCT program on RHR and VO2 Max in adult athletes, thereby evaluating the efficacy of each training modality in enhancing aerobic performance. A randomized controlled trial design was employed involving 90 adult athletes (45 males and 45 females, aged 21-26), randomly located into three groups: HIIT (n=30), FCT (n=30), and Control (n=30). RHR and VO2 Max were assessed during pre-and post-intervention using Polar H10 monitors and Vmax Encore Metabolic Cart, respectively. Data were analysed using ANCOVA (Analysis of Covariance) to control for pre-test differences, followed by Tukey's post-hoc comparison. Post-intervention results revealed statistically significant improvements in both RHR and VO2 Max across the training groups (p < 0.05). The HIIT group exhibited the most significant reduction in RHR (62.72 bpm) and the highest increase in VO2 Max (52.12 ml/kg/min), outperforming both FCT (RHR = 65.06 bpm; VO2 Max = 49.40 ml/kg/min) and the Control group (RHR = 70.32 bpm; VO2 Max = 41.28 ml/kg/min). Effect sizes were large for both RHR (η² = 0.950) and VO2 Max (η² = 0.982), indicating robust model fit. The findings confirm that both HIIT and FCT are effective in improving cardiovascular parameters among adult athletes, with HIIT demonstrating superior efficacy in a shorter duration. These results support the strategic incorporation of HIIT in training regimens aimed at maximizing aerobic performance and cardiovascular health.

Leukocytosis following exercise is a well-described phenomenon of stress/inflammatory activation in healthy humans. We hypothesized that, despite this increase in circulating inflammatory cells, exercise would paradoxically induce expression of both pro-and anti-inflammatory cytokines and growth factors within these cells. To test this hypothesis, 11 healthy adult men, 18 -30 yr old, performed a 30-min bout of heavy cycling exercise; blood sampling was at baseline, end-exercise, and 60 min into recovery. The percentage of leukocytes positive for intracellular cytokines and growth factors and mean fluorescence intensity was obtained by flow cytometry. Proinflammatory cytokines (IL-1␣, IL-2, IFN-␥, and TNF-␣), a pleiotropic cytokine (IL-6), and anti-inflammatory cytokines and growth factors [IL-4, IL-10, growth hormone (GH), and IGF-I] were examined. Median fluorescence intensity was not affected by exercise; however, we found a number of significant changes (P Ͻ 0.05 by mixed linear model and modified t-test) in the numbers of circulating cells positive for particular mediators. The pattern of expression reflected both pro-and anti-inflammatory functions. In T-helper lymphocytes, TNF-␣, but also IL-6, and IL-4 were significantly increased. In monocytes, both IFN-␥ and IL-4 increased. B-lymphocytes positive for GH and IGF-I increased significantly. GH-positive granulocytes also significantly increased. Collectively, these observations indicate that exercise primes an array of pro-and anti-inflammatory and growth factor expression within circulating leukocytes, perhaps preparing the organism to effectively respond to a variety of stressors imposed by exercise. immunology; interleukin-6; growth hormone; intracellular MANY OF THE HEALTH EFFECTS of exercise are influenced by the balance of stress/inflammatory-related cytokines and growth factors that are known to be altered by physical activity. For example, in elderly humans, higher levels of the circulating cytokine IL-6 are inversely correlated with levels of physical activity, with muscle mass, and with the anabolic mediator . Brief bouts of heavy exercise also lead to increased numbers of circulating stress/inflammatory cells, such as lymphocytes [T, B, and natural killer (NK) cells], monocytes, and neutrophils, all of which can secrete a variety

This study aimed to understand the screen time activities of toddlers and their parents, the relationship between toddlers' screen time and socioeconomic status (SES), the relationship between toddlers' screen time and language skills, and the screen time restrictions set by their families. Methods: The participants comprised 33 typically developing toddlers aged 12-24 months and their parents. Informed consent was obtained from the parents of all participants who passed the screening. Children's and their parents' screen time activities and other leisure activities, the family's SES, and receptive and expressive language scores were assessed. Results: A total of 96.9% of children had a mean screen time of 750 minutes per week, equivalent to 1.8 hours per day, which is significantly higher than the recommended guidelines. Children were mostly exposed to smartphones and televisions. Nine children did not meet ageappropriate language scores, and all other children had age-appropriate language scores despite having excess screen time. No significant correlation was found between language scores and screen time in children and parents. A positive correlation was found between parents' screen time and SES, but not between children's screen time and SES. Discussion: This study highlights the significance of co-viewing and interactive screen time in supporting the development of language skills. It also highlights the need to revise guidelines on screen time restrictions in young children. Guidelines should include recommendations in choosing high-quality, age-appropriate strategies to encourage co-viewing to enhance parentchild interaction. The paper also emphasizes the significance of restricting parents' screen time as it may interfere with qualitative interactions with the child leading to language delay.

Cardiovascular fitness, measured through Resting Heart Rate (RHR) and Maximal Oxygen Uptake (VO2 Max), is critical for optimizing athletic performance. High-Intensity Interval Training (HIIT) and Fast Continuous Training (FCT) are two aerobic conditioning modalities widely used to improve cardiovascular efficiency, but their comparative effects remain insufficiently studied in adult competitive athletes. This study aimed to compare the effects of an 8-week HIIT and FCT program on RHR and VO2 Max in adult athletes, thereby evaluating the efficacy of each training modality in enhancing aerobic performance. A randomized controlled trial design was employed involving 90 adult athletes (45 males and 45 females, aged 21-26), randomly located into three groups: HIIT (n=30), FCT (n=30), and Control (n=30). RHR and VO2 Max were assessed during pre- and post-intervention using Polar H10 monitors and Vmax Encore Metabolic Cart, respectively. Data were analysed using ANCOVA (Analysis of Covariance) to control for pre-test differences, followed by Tukey’s post-hoc comparison. Post-intervention results revealed statistically significant improvements in both RHR and VO2 Max across the training groups (p < 0.05). The HIIT group exhibited the most significant reduction in RHR (62.72 bpm) and the highest increase in VO2 Max (52.12 ml/kg/min), outperforming both FCT (RHR = 65.06 bpm; VO2 Max = 49.40 ml/kg/min) and the Control group (RHR = 70.32 bpm; VO2 Max = 41.28 ml/kg/min). Effect sizes were large for both RHR (η² = 0.950) and VO2 Max (η² = 0.982), indicating robust model fit. The findings confirm that both HIIT and FCT are effective in improving cardiovascular parameters among adult athletes, with HIIT demonstrating superior efficacy in a shorter duration. These results support the strategic incorporation of HIIT in training regimens aimed at maximizing aerobic performance and cardiovascular health.

Hypergravity disrupts the circadian regulation of temperature (Temp) and locomotor activity (Act) mediated through the vestibular otolithic system in mice. In contrast, we do not know whether the anatomical structures associated with vestibular input are crucial for circadian rhythm regulation at 1 G on Earth. In the present study we observed the effects of bilateral vestibular loss (BVL) on the daily rhythms of Temp and Act in semipigmented rats. Our model of vestibular lesion allowed for selective peripheral hair cell degeneration without any other damage. Rats with BVL exhibited a disruption in their daily rhythms (Temp and Act), which were replaced by a main ultradian period (τ &lt;20 h) for 115.8 ± 68.6 h after vestibular lesion compared with rats in the control group. Daily rhythms of Temp and Act in rats with BVL recovered within 1 wk, probably counterbalanced by photic and other nonphotic time cues. No correlation was found between Temp and Act daily rhythms after vestibular...

Excessive liquid in airways and/or in distal lung tissue may underpin the respiratory morbidity associated with transient tachypnea of the newborn (TTN). However, its effects on lung aeration and respiratory function following birth are unknown. We investigated the effect of elevated airway liquid volumes on newborn respiratory function. Near term rabbit kittens (30 days gestation; term ~32 days) were delivered, had lung liquid drained and either had no liquid replaced (Control, n=7) or 30 mL/kg of liquid was re-added to the airways (liquid added; LA, n=7). Kittens were mechanically ventilated in a plethysmograph. Measures of chest and lung parameters, uniformity of lung aeration and airway size were analysed using phase contrast X-ray imaging. The maximum peak inflation pressure required to recruit a tidal volume of 8 mL/kg was significantly greater in LA compared to Control kittens (35.0±0.7 vs 26.8±0.4 cmH2O; P&lt;0.001). LA kittens required greater time to achieve lung aeration ...

TO THE EDITOR: Fatigue during exercise is a complex phenomenon and has historically been assigned to peripheral mechanisms. Recently more attention is paid to the "central" origin of fatigue, where failure of the motor cortex, changing neurotransmitter concentrations, decreased blood flow, etc., are put forward as underlying mechanisms (3). Both hypotheses (peripheral and central) contain the same "mistake" when isolating the head from the body and vice versa. In their Viewpoint, Robertson and Marino (4) link the prefrontal cortex (PFC) with exercise tolerance and possible fatigue. The PFC could play a role as switchboard during exhaustive exercise, taking part in "decision" making on exercise cessation (4). A declined EEG response to exercise was found in the PFC when exercise intensity increased (5), which confirms previous results with exhaustive exercise in the heat (2). This might indicate that electrocortical activity is diminished at exercise cessation or that other brain areas become more "active" (1). The important message of the recent paper ( ) is that the authors clearly try to explain that the brain integrates several signals and emotions. However, the question remains if the brain really "thinks" and "makes decisions" to avoid catastrophe. It might also be that during exercise the disturbance of peripheral and central homeostasis are integrated and that several neurotransmitter systems influencing frontal and other brain regions overshoot or even become depleted at exhaustion (3). Also, temporary depletion of brain substrates (glucose, glycogen, lactate) could be involved. At this stage we probably don't have the right tools (methods) available to confirm or reject this hypothesis.

One of the most important but least studied environmental factors playing a major role in bone physiology is gravity. While the knowledge of deleterious effects of microgravity on the skeleton is expanding, little is known about hypergravity and its osteogenic potential. Centrifugation was used to assess effects of 21-d continuous 2g or 3g acceleration on femur and L2-vertebra of 7 week-old male C57BL/6 mice. Under 3g, body mass growth slowed down, and deleterious skeletal effects were found (p&lt;0.05 compared to control): cortical thinning, osteoclasts surface increase (+41% in femur; +20% in vertebra), and bone formation rate decrease (-34% in femur; -38% in vertebra). A 2g centrifugation did not reduce body mass, and improved trabecular volume (+18% in femur; +13% in vertebra) and microarchitecture (+32% connectivity density in femur; +9% trabecular thickness in vertebra, p&lt;0.05 compared to control). 2g also decreased osteoclast surfaces (-36% in femur; -16% in vertebra) and ...

We demonstrated the relationship between the change rates of muscular outputs and horizontal perturbation under stable and unstable conditions in dynamic bench press movement. Twenty-seven male collegiate athletes attended the study. We used a tri-axis accelerometer attached to the barbell shaft to obtain the acceleration data in the bench press and computed peak force output, rate of force development (RFD), and horizontal acceleration trajectory length for 0.2 seconds after the initiation. Significant reduction was found in the peak force output and RFD under stable and unstable conditions, but not in the horizontal acceleration trajectory length. Significant correlation was found between the change rate of RFD and the horizontal acceleration trajectory length under stable and unstable conditions (r=0.55, P<0.01).

The purpose of this study was to determine the separate and combined effects of exercise and insulin on the activation of phosphatidylinositol 3-kinase (PI3-kinase) and glycogen synthase in human skeletal muscle in vivo. Seven healthy men performed three trials in random order. The trials included 1) ingestion of 2 g/kg body wt carbohydrate in a 10% solution (CHO); 2) 75 min of semirecumbent cycling exercise at 75% of peak O2 consumption; followed by 5 × 1-min maximal sprints (Ex); and 3) Ex, immediately followed by ingestion of the carbohydrate solution (ExCHO). Plasma glucose and insulin were increased ( P &lt; 0.05) at 15 and 30 (Post-15 and Post-30) min after the trial during CHO and ExCHO, although insulin was lower for ExCHO. Hyperinsulinemia during recovery in CHO and ExCHO led to an increase ( P &lt; 0.001) in PI3-kinase activity at Post-30 compared with basal, although the increase was lower ( P &lt; 0.004) for ExCHO. Furthermore, PI3-kinase activity was suppressed ( P &lt;...

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 ± 1 yr, body mass index 33.2 ± 1.4 kg/m2) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (V̇o2max)] with either normal caloric intake (eucaloric group, 1,901 ± 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 ± 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (V̇o2max), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) i...

There is increasing evidence that upregulation of arginase contributes to impaired endothelial function in aging. In this study, we demonstrate that arginase upregulation leads to endothelial nitric oxide synthase (eNOS) uncoupling and that in vivo chronic inhibition of arginase restores nitroso-redox balance, improves endothelial function, and increases vascular compliance in old rats. Arginase activity in old rats was significantly increased compared with that shown in young rats. Old rats had significantly lower nitric oxide (NO) and higher superoxide (O2−) production than young. Acute inhibition of both NOS, with NG-nitro-l-arginine methyl ester, and arginase, with 2( S)-amino- 6-boronohexanoic acid (ABH), significantly reduced O2− production in old rats but not in young. In addition, the ratio of eNOS dimer to monomer in old rats was significantly decreased compared with that shown in young rats. These results suggest that eNOS was uncoupled in old rats. Although the expression...

It is unclear whether accumulation of lactate in skeletal muscle during exercise contributes to muscle fatigue. The purpose of the present study was to examine the effect of lactate infusion on muscle fatigue during prolonged indirect stimulation in situ. For this purpose, the plantaris muscle was electrically stimulated (50 Hz, for 200 ms, every 2.7 s, 5 V) in situ through the sciatic nerve to perform concentric contractions for 60 min while either saline or lactate was infused intravenously (8 rats/group). Lactate infusion (lactate concentration ∼12 mM) attenuated the reduction in submaximal dynamic force (-49 vs. -68% in rats infused with saline; P &lt; 0.05). Maximum dynamic and isometric forces at the end of the period of stimulation were also higher ( P &lt; 0.05) in rats infused with lactate (3.8 ± 0.3 and 4.4 ± 0.3 N) compared with saline (3.1 ± 0.2 and 3.6 ± 0.2 N). The beneficial effect of lactate infusion on muscle force during prolonged stimulation was associated with a ...

For quite some time the debate between free weights and machines has caused some significant controversy. Everyone loves to champion squats, deadlifts, and bench presses, but machines are fairly often undermined. Both free weights and machines have directly led to increase in lean muscle mass and proven to improve strength vigorously. Yet functional strength is more than being able to move 3 plates, it's about training in a way thats safe, controlled, and transferable into one's real life movements.

The objectives of the present study were to evaluate the impact of a single bout of high-intensity aerobic exercise on 1) long-term potentiation (LTP)-like neuroplasticity via response to paired associative stimulation (PAS) and 2) the temporal and spatial components of sequence-specific implicit motor learning. Additionally, relationships between exercise-induced increases in systemic brain-derived neurotrophic factor (BDNF) and response to PAS and motor learning were evaluated. Sixteen young healthy participants completed six experimental sessions, including the following: 1) rest followed by PAS; 2) aerobic exercise followed by PAS; 3) rest followed by practice of a continuous tracking (CT) task and 4) a no-exercise 24-h retention test; and 5) aerobic exercise followed by CT task practice and 6) a no-exercise 24-h retention test. The CT task included an embedded repeated sequence allowing for evaluation of sequence-specific implicit learning. Slope of motor-evoked potential recru...

Our purpose was to determine the effects of gender and exercise training on endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) protein content of porcine skeletal muscle arteries and to evaluate the role of 17beta-estradiol (E2) in these effects. We measured eNOS and SOD content with immunoblots and immunohistochemistry in femoral and brachial arteries of trained and sedentary male and female pigs and measured estrogen receptor (ER) mRNA and alpha-ER and beta-ER protein in aortas of male and female pigs. Results indicate that female arteries contain more eNOS than male arteries and that exercise training increases eNOS content independent of gender. Male and female pigs expressed similar levels of alpha-ER mRNA and protein and similar amounts beta-ER protein in their arteries. E2 concentrations as measured by RIA were 180 +/- 34 pg/ml in male sera and approximately 5 pg/ml in female sera, and neither was changed by training. However, bioassay indicated that biol...

Ischemic preconditioning (IPC) before sustained ischemia decreases myocardial infarct size mediated in part via protection of cardiac mitochondria. Reversible blockade of electron transport at complex I immediately before sustained ischemia also preserves mitochondrial respiration and decreases infarct size. We proposed that IPC would attenuate electron transport from complex I as a potential effector mechanism of cardioprotection. Isolated, Langendorff-perfused rat hearts underwent IPC (3 cycles of 5-min 37°C global ischemia and 5-min reperfusion) or were perfused for 40 min without ischemia as controls. Subsarcolemmal (SSM) and interfibrillar (IFM) populations of mitochondria were isolated. IPC did not decrease ADP-stimulated respiration measured in intact mitochondria using substrates that donate reducing equivalents to complex I. Maximally expressed complex I activity measured as rotenone-sensitive NADH:ubiquinone oxidoreductase in detergent-solubilized mitochondria was also una...

Metaboreflex is a reflex triggered during exercise or postexercise muscle ischemia (PEMI) by metaboreceptor stimulation. Typical features of metaboreflex are increased cardiac output (CO) and blood pressure. Patients suffering from metabolic syndrome display hemodynamic abnormalities, with an exaggerated systemic vascular resistance (SVR) and reduced CO response during PEMI-induced metaboreflex. Whether patients with type 2 diabetes mellitus (DM2) have similar hemodynamic abnormalities is unknown. Here we contrast the hemodynamic response to PEMI in 14 patients suffering from DM2 (age 62.7 ± 8.3 yr) and in 15 age-matched controls (CTLs). All participants underwent a control exercise recovery reference test and a PEMI test to obtain the metaboreflex response. Central hemodynamics were evaluated by unbiased operator-independent impedance cardiography. Although the blood pressure response to PEMI was not significantly different between the groups, we found that the SVR and CO responses...

We examined the initial effect of sleeping at a simulated moderate altitude of 2,650 m on the frequency of apneas and hypopneas, as well as on the heart rate and blood oxygen saturation from pulse oximetry (SpO2) during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep of 17 trained cyclists. Pulse oximetry revealed that sleeping at simulated altitude significantly increased heart rate (3 +/- 1 beats/min; means +/- SE) and decreased SpO2 (-6 +/- 1%) compared with baseline data collected near sea level. In response to simulated altitude, 15 of the 17 subjects increased the combined frequency of apneas plus hypopneas from baseline levels. On exposure to simulated altitude, the increase in apnea was significant from baseline for both sleep states (2.0 +/- 1.3 events/h for REM, 9.9 +/- 6.2 events/h for NREM), but the difference between the two states was not significantly different. Hypopnea frequency was significantly elevated from baseline to simulated altitude exposure...