Compartmental chest wall volume changes during volitional hyperpnoea with constant tidal volume in healthy individuals

Prolonged high-intensity ventilation is associated with the development of rapid shallow breathing with decreased end-inspiratory volumes of all chest wall compartments. During respiratory muscle endurance training using normocapnic hyperpnoea, tidal volume (V_T) is normally kept constant. The aim of this study was to investigate possible changes in muscle recruitment during constant-V_T hyperpnoea, to assess potential mechanisms related to rapid shallow breathing. Ten healthy subjects performed 1 h of normocapnic hyperpnoea at 70% of maximal voluntary ventilation. Chest wall volume changes were assessed by optoelectronic plethysmography. End-inspiratory (1.08 ± 0.18 versus 0.96 ± 0.27 l, p = 0.017) and end-expiratory volumes (−0.13 ± 0.15 versus −0.31 ± 0.19 l, p = 0.007) of the pulmonary ribcage decreased significantly and lung function and respiratory muscle strength were reduced (all p < 0.05). Since with forced, constant V_T only the inspiratory rib cage muscles were unable to sustain end-inspiratory volume of their compartment, inspiratory rib cage muscles are the most likely candidate responsible for the development of rapid shallow breathing.     

Effect of acetazolamide on respiratory muscle fatigue in humans

Previous studies have demonstrated that carbonic anhydrase inhibition with acetazolamide reduces exercise capacity. The mechanism responsible for this early fatigue is unclear, but may be partly mediated by impaired respiratory muscle function. Inspiratory muscle strength and endurance were assessed in seven healthy men (age 28 ± 5 yrs, ±SD) by measuring maximal inspiratory pressure (MIP) and time to task failure during a constant-load breathing test (CLBT), respectively, under control (CON) and acetazolamide (ACZ; 500 mg/8 h po for 3 days) conditions that were separated by two weeks and randomized between subjects. In addition, MIP was measured before and after moderate-intensity cycling exercise to fatigue while pulmonary gas exchange, plasma pH, and ventilation were measured during exercise. ACZ did not alter pulmonary function (FVC, FEV1, MVV) or MIP measured at rest (CON, −157 ± 47 vs. ACZ, −154 ± 45 cmH₂O, p > 0.05), but decreased time to task failure during the CLBT (CON, 1340 ± 820 vs. ACZ, 698 ± 434 s; p = 0.01). Exercise duration during cycling exercise was reduced (p = 0.003) with ACZ (1090 ± 254 s) compared to CON (1944 ± 532 s) in the presence of a significantly lower plasma pH and higher ventilation compared to control (p < 0.05). Compared to resting values, MIP was reduced (p = 0.03) in ACZ but not CON at exhaustion. In conclusion, carbonic anhydrase inhibition with ACZ is associated with impaired respiratory muscle function at rest and following constant load cycling which may contribute to reduced exercise tolerance with carbonic anhydrase inhibition.     

Mitochondrial function in physically active elders with sarcopenia

Physical activity is reported to protect against sarcopenia and preserve mitochondrial function. Healthy normal lean (NL: n = 15) and sarcopenic (SS: n = 9) participants were recruited based on body composition (DXA, Lunar DPX™), age, and physical activity. Gastrocnemius mitochondrial function was assessed by ³¹P MRS using steady-state exercise in a 4 T Bruker Biospin. Total work (429.3 ± 160.2 J vs. 851.0 ± 211.7 J, p < 0.001) and muscle volume (p = 0.006) were lower in SS, although these variables were not correlated (NL r = −0.31, p = 0.33, SS r = (0.03, p = 0.93). In the SS resting ATP/ADP was lower (p = 0.03) and ATP hydrolysis higher (p = 0.02) at rest. Free energy ATP hydrolysis was greater at the end of exercise (p = 0.02) and [ADP] relative to total work output was higher in SS (ANCOVA, p = 0.005). [PCr] recovery kinetics were not different between the groups. Adjusting these parameters for differences in total work output and muscle volume did not explain these findings. These data suggest that aerobic metabolism in physically active older adults with sarcopenia is mildly impaired at rest and during modest levels of exercise where acidosis was avoided. Muscle energetics is coordinated at multiple cellular levels and further studies are needed to determine the loci/locus of energy instability in sarcopenia.     

Impact of laparoscopic surgery on thoracoabdominal mechanics and inspiratory muscular activity

Objective

To evaluate the effect of laparoscopic surgery on pulmonary volume distributions and inspiratory muscles activity. Respiratory consequences associated with postoperative pain were also evaluated.

Methods

This study enrolled 20 patients without lung disease performed spirometry and chest wall kinematic analyses (i.e., chest wall, upper and lower ribcage and abdominal volumes), and measured the activity of inspiratory muscular before and 2 days after laparoscopic surgery. Pain was also assessed.

Results

After laparoscopy, the patients demonstrated decreased volumes in all three thoracoabdominal compartments: abdomen (ABD), upper and lower rib cage (URC and LRC, respectively) compared with the pre-operative measurements: ABD = 0.38 ± 0.20 L vs. 0.55 ± 0.25 L; URC = 0.45 ± 0.18 L vs. 0.55 ± 0.21 L; and LRC = 0.31 ± 0.18 L vs. 0.41 ± 0.23 L; p < 0.05. A reduction in the inspiratory muscular activity after surgery was also observed (sternocleidomastoid: 10.6 ± 5.1 × 10⁻³ mV vs. 12.8 ± 6.3 × 10⁻³ mV; intercostals: 16.8 ± 12.4 × 10⁻³ mV vs. 25.1 ± 21.3 × 10⁻³ mV; p < 0.05). In addition, lower volumes during deep breathing were observed in patients who reported significant pain than those who did not (0.51 ± 0.17 L vs. 0.79 ± 0.29 L; p < 0.05, respectively).

Conclusion

Laparoscopic surgery reduces chest wall ventilation and inspiratory muscular activity during deep breathing. The effects appear to depend on the patient's reported pain level.     

Midkine-deficient mice delayed degeneration and regeneration after skeletal muscle injury

Midkine (MK), a heparin-binding growth factor, was previously found to be expressed in the rat myotube-forming stage. We investigated MK gene-deficient (Mdk^−/−) mice in terms of skeletal muscle degeneration and regeneration after injury by bupivacaine injection into the tibialis anterior muscle. Injured muscles showed intense inflammatory cell infiltration. Myotubes, myofibers with centrally located nuclei in their cytoplasm, were significantly smaller in Mdk^−/− mice than in wild type (Mdk^+/+) mice 7 days after injury (p = 0.02). The distribution of myotube sizes showed quantitative differences between the two groups at 5 and 7 days, but not at 14 days. Many small myotubes were found in the regenerative area of Mdk^−/− mice compared with that of Mdk^+/+mice 5 and 7 days after injury. The expression of Iba1, a macrophage marker, was significantly lower in Mdk^−/− mice 3 days after injury (p = 0.01). The number of desmin-positive cells like myoblasts in Mdk^−/− mice was significantly fewer than that in Mdk^+/+ mice 3 days after injury. Our results suggested that deletion of MK results in a delay in regeneration, preceded by decelerated migration of macrophages to the damaged area, and that MK has a role in cell differentiation and maturation after skeletal muscle injury.     

Effect of specific inspiratory muscle warm-up on intense intermittent run to exhaustion

The effects of inspiratory muscle (IM) warm-up on the maximum dynamic IM function and the maximum repetitions of 20-m shuttle run (Ex) in the Yo-Yo intermittent recovery test were examined. Ten men were recruited to perform identical IM function test and exercise test in three different trials randomly. The control trial was without IM warm-up while the placebo and experimental trials were with IM warm-up by performing two sets of 30 breaths with inspiratory pressure-threshold load equivalent to 15% (IMW_P) and 40% (IMW) maximum inspiratory mouth pressure, respectively. In IMW, maximum dynamic IM functions including the maximal inspiratory pressure at zero flow (P ₀) and maximal rate of P ₀ development (MRPD) were increased compared with control values (P<0.05). The Ex was also augmented [mean (SD)] [19.5% (12.6)] while the slope of the linear relationship of the increase in rating of perceived breathlessness for every 4th exercise interval (RPB/4i) was reduced (P<0.05). In IMW_P, although increase in Ex and reduction in RPB/4i were occurred concomitantly in some subjects, the differences in Ex, RPB/4i and dynamic IM functions between control and IMW_P trials were not statistically significant. For the changes (Δ) in parameters in IMW and IMW_P (n=20), negative correlations were found between Δ RPB/4i and Δ Ex (r=−0.92), ΔP ₀ and Δ RPB/4i (r=−0.48), and Δ MRPD and Δ RPB/4i (r=−0.54). Such findings suggested that the specific IM warm-up in IMW may entail reduction in breathlessness sensation, partly attributable to the enhancement of dynamic IM functions, in subsequent exhaustive intermittent run and, in turn, improve the exercise tolerance.     

Regulatory role of 1, 25-dihydroxyvitamin D3 and vitamin D receptor gene variants on intracellular granzyme A expression in pulmonary tuberculosis

Vitamin D receptor (VDR) genotypes have been shown to be associated with differential susceptibility or resistance to tuberculosis. The influence of FokI, BsmI, ApaI and TaqI variants of VDR gene on 1, 25(OH)₂ D₃ modulated granzyme A expression of cytotoxic lymphocytes induced by culture filtrate antigen (CFA) of Mycobacterium tuberculosis was studied in 40 pulmonary tuberculosis (PTB) patients and 49 normal healthy subjects (NHS) by flow cytometry. In both the study groups, addition of 1, 25(OH)₂ D₃ (10^− 7M) significantly reduced the percentage of granzyme A positive cells in both unstimulated (NHS, p < 0.0001; PTB, p = 0.02) and stimulated culture conditions (CFA, NHS, p < 0.0001; PTB, p = 0.0001) which correlated positively with the IFN-γ levels (unstimulated, p = 0.01; CFA stimulated, p = 0.004) in NHS. The ApaI aa genotype and bbaaTT extended genotype were associated with a significantly decreased percentage of granzyme A positive cells in NHS (p < 0.05). Our results suggest that 1, 25(OH)₂ D₃ suppresses granzyme A probably by down-regulating Th1 cytokine response. Moreover, the VDR gene variants might regulate cytotoxic T-cell response via 1, 25(OH)₂ D₃ mediated suppression of granzyme A expression in tuberculosis.     

Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE.

Results

A total of 15 studies involving 1956 SLE cases and 2347 controls were included in the meta-analysis. The meta-analysis showed an association between SLE and the IL1A −889 T allele in the overall population and Europeans (OR = 0.858, 95% CI = 0.737–0.986, p = 0.032; OR = 0.827, 95% CI = 0.687–0.994, p = 0.043). Meta-analysis of the IL1RN polymorphism revealed an association with SLE in all study subjects (OR for IL1RN^∗2 = 1.539, 95% CI = 1.266–1.871, p = 1.5 × 10⁻²) and in Europeans and Asians (OR = 1.483, 95% CI = 1.187–1.852, p = 0.001; OR = 1.787, 95% CI = 1.167–2.736, p = 0.008). No associations were found between SLE and the IL1B −511 C/T, 3953 C/T, and IL1A +4845 G/T polymorphisms.

Conclusions

This meta-analysis suggests IL1A −889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN^∗2 allele is associated with susceptibility to SLE in Europeans and Asians.     

Expression of cancer stem cell markers in basal and penta-negative breast carcinomas – A study of a series of triple-negative tumors

Purpose

Breast cancer is a heterogeneous disease. Immunohistochemistry has given rise to triple-negative carcinoma (TNC). Concomitantly, biological origins of neoplasia and its heterogeneity has been strongly debated in cancer stem cells (CSC) theme. This study investigates the prevalence of basal (BCC) and penta-negative carcinomas (5NC) in TNC and establishes associations with CSC (CD44CD24).

Materials and methods

94 TNC were tested for CK5/6, HER1, CD44 and CD24, evaluated by a simple immunohistochemistry score and correlated with clinicopathological and survival data.

Results

BCC had higher tumor grades than 5NC (p = 0.004). CD44 negativity (p = 0.007) and CD44⁻CD24⁺ phenotype (p = 0.013) were associated with less vascular invasion amongst TNC. CD44 expression was associated with BCC (p = 0.007). CD44⁻CD24^−/low phenotype was associated with 5NC. None of the variables were associated with clinical outcome.

Conclusion

BCC and 5NC are closely related tumor subtypes. CD44⁻CD24^−/low phenotype was associated with 5NC and CD44⁻CD24⁺ phenotype was associated with vascular invasion. These results require histogenetic confirmation in larger studies.     

“Ventilatory alternans”: A left–right alternation of inspiratory airflow in humans

In a study visualizing ventilation with hyperpolarized ³He magnetic resonance imaging (MRI) in elite breath hold divers, the dynamic MRI images in one subject exhibited an apparent alternation of the image intensity between left and right lung. We hypothesized that the alternation resulted from alternating variations in inspiratory flow rate to left and right lungs. Analysis showed that the alternation was not due to random uncorrelated temporal fluctuations of intensity (p < 0.001). The frequency of alternation was approximately 56 min⁻¹, suggesting a cardiac origin. Similar alternation of ventilation was confirmed retrospectively in 4 of 6 additional subjects. These observations are consistent with previous studies showing cardiogenic mixing of gas in the lung. We speculate that cardiogenic pendelluft, possibly from ballistic lateral motion of the beating heart, could cause alternating variations of inspiratory flow to the lungs.     

Daytime modulation of cortical spreading depression according to blood glucose levels

The plantar surface of the foot senses local pressures during stance and locomotion. These foot loading characteristics may be affected by long distance running. Little is known about the physiological effects of sports-related loading on plantar sensitivity and their relationship with plantar foot loading. The purpose of this study was to investigate the acute effects of long distance running on plantar sensitivity to touch and their relationship with foot loading characteristics. It was hypothesized that plantar sensation would decrease after long distance running and may be related to foot loading characteristics. In 15 middle-aged runners, sensory detection thresholds to light touch and plantar pressures were measured before and after a 10 km run. After the run, no significant changes in sensory perception thresholds were observed so that correlations between foot sensitivity and foot loading could not be calculated. A significant decrease of force-time integrals and maximum forces was demonstrated in the whole foot (−6.2%, p = 0.003; −3.9%, p = 0.001) and the heel (−10.5%, p = 0.003; −8.5%, p = 0.002). Furthermore, maximum force was significantly reduced in the lateral midfoot (−6.4%, p = 0.002). In conclusion, a sub-maximal 10 km running exercise appears to have no significant acute effects on plantar sensitivity, plantar pressure distribution and peak forces.     

Change in the peripheral CO2 chemoreflex from rest to exercise

A single-breath CO₂ test of peripheral chemosensitivity has recently been described, and elaborated based on model simulations. This study was designed to measure the peripheral CO₂ chemoreflex at rest and during heavy exercise to see if carotid chemosensitivity to CO₂ increased. Ten healthy, adult males performed an incremental exercise test to determine their ventilatory anaerobic threshold (VAT), and 20 minutes of steady-state exercise at a pre-determined power output above VAT. Arterialized venous blood was obtained during each minute of incremental exercise to verify development of metabolic acidosis. Carotid chemosensitivity was tested repeatedly at rest and in steady-state exercise by the ventilatory response to a single breath of 13% CO₂ in air. The peripheral chemoreflex for CO₂ for the group of subjects doubled from rest to exercise (mean 0.0961 · s^–1 · kPa^–1) with all subjects showing an increase. We conclude that the gain of the carotid CO₂ chemoreflex increases from rest to exercise at work above the VAT.     

Autonomic function and change in insulin for exercising postmenopausal women

Purpose

Obesity, physical inactivity and altered estrogen metabolism play an integrated role contributing to the disease risk profiles of postmenopausal women. These same risk factors also affect modulation of the autonomic nervous system (ANS).

Methods

We examined 332 postmenopausal, overweight, previously sedentary women (mean ± SD; age, 57.6 ± 6.3 years; weight, 84.3 ± 11.9 kg; BMI, 31.7 ± 3.7 kg/m²) participating in a 6-month, moderate intensity, aerobic exercise training intervention to determine the relationship between heart rate variability (HRV) derived autonomic function and fasting insulin. We analyzed quartiles of change in time and frequency domain indices of ANS activity and changes in insulin for between and within group differences using ANCOVA and Tukey post hoc tests adjusted for age, ethnicity, randomization group, change in fitness, and change in weight.

Results

We observed at baseline that insulin was positively correlated with body anthropometry (body weight, r² = 0.34; BMI, r² = 0.39; waist circumference, r² = 0.29; all, P < 0.001), and inversely associated with rMSSD (r² = −0.12) and SDNN (r² = −0.18; all, P < 0.01). After the intervention, changes in rMSSD (r² = −0.21, P < 0.002) and SDNN r² −0.19, P < 0.0001) were inversely correlated to insulin change. Further ANCOVA analysis revealed that rMSSD and SDNN were both significant (P < 0.0001); however, only rMSSD exhibited a step-wise pattern of improvement when quartiles of rMSSD were compared to corresponding insulin reductions: Q1 (referent group, 8.41 ± 3.2 uIU/ml), Q2 (−3.30 ± −3.2 uIU/ml), Q3 (−5.66 ± −3.2 uIU/ml; P < 0.02), and Q4 (−9.60 ± −3.2 uIU/ml; P < 0.006).

Conclusion

Our study shows that changes in autonomic function are associated with changes in insulin and that exercise training may influence this relationship in postmenopausal women.     

CD45RA expression on HCMV-specific effector memory CD8+ T cells is associated with the duration and intensity of HCMV replication after transplantation

In this cross-sectional study on 42 solid organ transplant recipients, the association of kinetics of human cytomegalovirus (HCMV) replication and EMRA HCMV-specific CD8+ T cells was investigated. Correlation was observed between the duration of HCMV replication after transplantation and CD45RA+CD27− (r = 0.609; p = 0.004), CD45RA+ CD28− (r = 0.579; p = 0.008) or CD45RA+CCR7− (r = 0.488; p = 0.029) HCMV-specific CD8+ T cells percentages. In the multivariate regression analyses, CD45RA+CD27−, CD45RA+CD28− or CD45RA+CCR7− HCMV-specific CD8+ T cells percentages increased 5.58% (p = 0.001), 5.35% (p = 0.001) or 4.49% (p = 0.012), respectively, with every 10-day increase in the duration of HCMV replication. Moreover, CD45RA+CD27− or CD45RA+CD28− frequencies increased 4.16% (p = 0.024) or 3.58% (p = 0.049), respectively, with every unity increase in log₁₀ genomes/mL. These observations support the major association between the frequency of EMRA HCMV-specific CD8+ T cells and the duration of post-transplant HCMV replication episodes in solid organ transplantation recipients.     

Distribution of Killer cell immunoglobulin like receptor genes in end stage renal disease among North Indian population

Introduction

NK cell function is regulated by cell surface inhibitory and activating receptors including the C-type lectin receptors and Killer Immunoglobulin-like receptors (KIR). The effect of immune modulating cytokines produced by NK cells in the pathogenesis of end stage renal disease (ESRD) remained intriguing. In this regard the present study assesses the combinatorial association of KIR gene content and KIR receptor–HLA ligand in the North Indian ESRD patients.

Material and methods

KIR gene polymorphism as a susceptible marker in ESRD among 512 patients and 512 ethnically matched controls was analyzed. PCR-SSP based genotyping for KIR gene content and HLA-A, B, C typing was carried out.

Results

Significant difference in frequencies of KIR2DS1–HLA-C2 (p ? 0.0001, OR = 1.98, CI = 1.50–2.61), KIR2DS2–HLAC1 (p ? 0.0001, OR = 1.87, CI = 1.42–2.46), KIR3DS1–HLA-Bw4 (p = 0.0038, OR = 1.46, CI = 1.13–1.88) combinations for ESRD was found. In the combinatorial analysis Bw4⁺/3DL1⁻/3DS1⁺ (p ? 0.0001, OR = 4.90, CI = 2.75–8.71) and C1⁺/2DL2⁻/2DL3⁻/2DS2⁺/2DS3⁺ (p = 0.0037, OR = 2.50, CI = 1.35–4.63) showed risk association. KIR3DS1 was observed to be susceptible for all four primary kidney disease groups.

Conclusion

NK cell de-regulation due to HLA ligand binding KIR receptors may be involved in the patho-physiology of ESRD. Upon analyzing the data in this context it was found that C2/C2 donor might improve the clinical outcome of patients having C2 ligands.     

Cardio-respiratory fitness,habitual physical activity and serum brain derived neurotrophic factor (BDNF) in men and women

Short episodes of high intensity exercise transiently increase serum levels of BDNF in humans, but serum levels of BDNF at rest appear to be lower in more physically active humans with greater levels of energy expenditure. The relationship between serum BDNF concentration, cardio-respiratory fitness (Åstrand–Rhyming test estimated VO₂ max) and volume of long-term, regular exercise and sporting activity (Baecke Habitual Physical Activity Index) was investigated in 44 men and women between the age range of 18–57 years. In this group an inverse relationship between resting serum BDNF concentration and measures of both estimated VO₂ max (r = −0.352; P < 0.05) and long-term sporting activity (r = −0.428, P < 0.01) was found. These results indicate that increased levels of cardio-respiratory fitness and habitual exercise are associated with lower resting levels of serum BDNF in healthy humans. This is the first study to demonstrate an inverse relationship between a physiological estimate of cardio-respiratory fitness and serum BDNF.     

Increased cutaneous NGF and CGRP-labelled trkA-positive intra-epidermal nerve fibres in rat diabetic skin

In this study we have determined the amount of Nerve Growth Factor (NGF) and the innervation density of the glabrous hindpaw skin of diabetic rats (n = 4) and controls (n = 3). The proportion of intra-epidermal nerve fibres (IENF) expressing the high affinity NGF receptor (trkA) and calcitonin gene-related peptide (CGRP) were also determined. Four weeks after induction of diabetes by intraperitoneal streptozotocin injection skin was analyzed for: (i) NGF content using ELISA and (ii) the innervation density of peptidergic afferents that also expressed trkA using immunocytochemistry. NGF levels were approximately three-fold higher in diabetic skin compared to controls (diabetic: 134.7 ± 24.0 (SD) pg ml⁻¹, control: 42.7 ± 21.5 pg ml⁻¹, p = 0.002). As expected there was a significant reduction in IENF density in diabetic skin (2.7 ± 1.3 fibres mm⁻¹) compared to controls (6.9 ± 1.5 fibres mm⁻¹; p = 0.01). In diabetic rats there was no significant difference in the proportion of trkA-labelled IENF (diabetic 74 ± 21%; control 83 ± 15%, p = 0.6), but significantly more trkA-positive IENF were also labelled by CGRP antibodies in diabetic skin compared to controls (diabetic 89 ± 22%; control 38 ± 2%, p = 0.03). These data suggest that in diabetes the upregulation of cutaneous NGF may ‘over-troph’ the surviving axons, increasing CGRP labelling, which may be important in the aetiology of painful diabetic neuropathy.     

Fitness alters fluid regulatory but not behavioural responses to hypohydrated exercise

Dehydration is typical during prolonged exercise. Because training stimulates numerous adaptations, some involving fluid regulation, it is conceivable that training involves adaptations to dehydration. This study tested the hypothesis that trained individuals have altered fluid regulatory, but not behavioural or perceptual responses to exercise when hypohydrated. Six trained (V.O_{2 peak}: 65 ± 8 mL kg^− 1 min^− 1) and six untrained (V.O_{2 peak}: 45 ± 4 mL kg⁻¹ min⁻¹) males cycled for 40 min at 70%V.O_{2 peak}, once whilst euhydrated (EUH) and once whilst hypohydrated by ~ 2% body mass (HYPO), before a 40-min performance trial with euhydration (in EUH) or ad libitum drinking (in HYPO), in temperate conditions (24.3 °C, 50% rh). Baseline hydration was achieved by complete or partial rehydration from exercise + heat stress on the previous evening. Body mass was reduced (− 1.8 ± 0.1%) and plasma osmolality was increased (5 ± 1 mosmol kg^− 1) similarly between fitness groups in HYPO compared to EUH (P < 0.05). During exercise, plasma [AVP] rose more in HYPO than EUH; the elevation was greater in the Untrained (4.1 ± 1.7 vs. 2.0 ± 0.8 pmol L^− 1, P < 0.01) than Trained (1.4 ± 0.6 vs. 1.1 ± 0.5 pmol L^− 1, P < 0.01; P = 0.02). Increases in plasma [AVP] relative to osmolality were higher in Untrained than Trained (0.47 ± 0.06 vs. 0.025 ± 0.05 pmol mosmol^− 1, P = 0.03). Fitness groups had equivalent thirst ratings during fixed exercise but Trained were thirstier than Untrained when self regulating in HYPO (4.0 ± 1.5 vs. 2.7 ± 1.2; P = 0.05); thus Trained tended to consume more fluid (1.20 ± 0.16 vs. 0.88 ± 0.16 L; P = 0.19), but maintained similar hypohydration consistent with their greater sweat rate during HYPO. In conclusion, aerobic fitness attenuates the neuroendocrine ([AVP]) response to hypohydrated exercise, but not perceptual (thirst) or behavioural (ad libitum drinking) responses.     

Diaphragm motor unit recruitment in rats

We hypothesized that considerable force reserve exists for the diaphragm muscle (DIAm) to generate transdiaphragmatic pressures (Pdi) necessary to sustain ventilation. In rats, we measured Pdi and DIAm EMG activity during different ventilatory (eupnea and hypoxia (10% O₂)–hypercapnia (5% CO₂)) and non-ventilatory (airway occlusion and sneezing induced by intranasal capsaicin) behaviors. Compared to maximum Pdi (Pdi_max generated by bilateral phrenic nerve stimulation), the Pdi generated during eupnea (21 ± 2%) and hypoxia–hypercapnia (28 ± 4%) were significantly less (p < 0.0001) than that generated during airway occlusion (63 ± 4%) and sneezing (94 ± 5%). The Pdi generated during spontaneous sighs was 62 ± 5% of Pdi_max. Relative DIAm EMG activity (root mean square [RMS] amplitude) paralleled the changes in Pdi during different ventilatory and non-ventilatory behaviors (r² = 0.78; p < 0.0001). These results support our hypothesis of a considerable force reserve for the DIAm to accomplish ventilatory behaviors. A model for DIAm motor unit recruitment predicted that ventilatory behaviors would require activation of only fatigue resistant units.