bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter- and intraregional ventilation inhomogeneity in hypergravity and after pressurization of an anti-G suit
Authors: Grönkvist Mikael , Bergsten Eddie , Eiken Ola , Gustafsson Per M.
Published: March 2015

This study assessed the effects of increased gravity in the head-to-foot direction (+Gz) and anti-G suit (AGS) pressurization on functional residual capacity (FRC), the volume of trapped gas (VTG), and ventilation distribution by using inert- gas washout. Normalized phase III slope ( SnIII) analysis was used to determine the effects on inter- and intraregional ventilation inhomogeneity. Twelve men performed multiple-breath washouts of SF6 and He in a human centrifuge at +1 to +3 Gzwearing an AGS pressurized to 0, 6, or 12 kPa. Hypergravity produced moderately increased FRC, VTG, and overall and inter- and intraregional inhomogeneities. In normogravity, AGS pressurization resulted in reduced FRC and increased VTG, overall, and inter- and intraregional inhomogeneities. Inflation of the AGS to 12 kPa at +3 Gz reduced FRC markedly and caused marked gas trapping and intraregional inhomogeneity, whereas interregional inhomogeneity decreased. In conclusion, increased +Gzimpairs ventilation distribution not only between widely separated lung regions, but also within small lung units. Pressurizing an AGS in hypergravity causes extensive gas trapping accompanied by reduced interregional inhomogeneity and, apparently, results in greater intraregional inhomogeneity.
Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children
Authors: Waters Karen A. , McBrien Fergus , Stewart Penny , Hinder Murray , Wharton Sally
Published: March 2015

To assess effects of anesthesia and opioids, we studied 13 children with obstructive sleep apnea (OSA, age 4.0 ± 2.2 yr, mean ± SD) and 24 age-matched control subjects (5.8 ± 4.0 yr). Apnea indexes of children with OSA were 29.4 ± 18 h−1, median 30 h−1. Under inhalational anesthetic, closing pressure at the mask was 2.2 ± 6.9 vs. −14.7 ± 7.8 cmH2O, OSA vs. control ( P < 0.001). After intubation, spontaneous ventilation was 115.5 ± 56.9 vs. 158.7 ± 81.6 ml · kg−1 · min−1, OSA vs. control ( P = 0.02), despite elevated Pco 2 (49.3 vs. 42.1 Torr, OSA vs. control, P < 0.001). Minute ventilation fell after fentanyl (0.5 μg/kg iv), with central apnea in 6 of 13 OSA cases vs. 1 of 23 control subjects ( P < 0.001). Consistent with the finding of reduced spontaneous ventilation, apnea was most likely when end-tidal CO2 exceeded 50 Torr during spontaneous breathing under anesthetic. Thus children with OSA had depressed spontaneous ventilation under anesthesia, and opioids precipitated apnea in almost 50% of children with OSA who were intubated but breathing spontaneously under inhalational anesthesia.
Effects of oral contraceptives on peak exercise capacity
Authors: Casazza Gretchen A. , Suh Sang-Hoon , Miller Benjamin F. , Navazio Franco M. , Brooks George A.
Published: March 2015

We examined the effects of menstrual cycle phase and oral contraceptive (OC) use on peak oxygen consumption (V˙o 2 peak). Six moderately active, eumenorrheic women (25.5 ± 1.5 yr) were studied before and after 4 mo of OC. Subjects were tested during the follicular and luteal phases before OC and the inactive and high-dose phases after OC. Before OC, there were no significant differences between the follicular and luteal phases in any of the variables studied. There were also no differences between the inactive and high-dose phases. Dietary composition, exercise patterns, and peak heart rate, minute ventilation, and respiratory exchange ratio did not change with OC use. However, OC use significantly ( P ≤ 0.05) increased body weight (59.6 ± 2.3 to 61.2 ± 2.6 kg) and fat mass (13.3 ± 1.3 to 14.5 ± 1.3 kg) and decreased V˙o 2 peak(−11%, 2.53 ± 0.21 to 2.25 ± 0.18 l/min). In conclusion, 1) endogenous ovarian steroids have little effect onV˙o 2 peak, but 2) the exogenous ovarian steroids in OC decrease peak exercise capacity in moderately physically active young women.
Effects of l-tyrosine and carbohydrate ingestion on endurance exercise performance
Authors: Chinevere Troy D. , Sawyer Robert D. , Creer Andrew R. , Conlee Robert K. , Parcell Allen C.
Published: March 2015

To test the effects of tyrosine ingestion with or without carbohydrate supplementation on endurance performance, nine competitive cyclists cycled at 70% peak oxygen uptake for 90 min under four different feeding conditions followed immediately by a time trial. At 30-min intervals, beginning 60 min before exercise, each subject consumed either 5 ml/kg body wt of water sweetened with aspartame [placebo (Pla)], polydextrose (70 g/l) (CHO), l-tyrosine (25 mg/kg body wt) (Tyr), or polydextrose (70 g/l) and l-tyrosine (25 mg/kg body wt) (CHO+Tyr). The experimental trials were given in random order and were carried out by using a counterbalanced double-blind design. No differences were found between treatments for oxygen uptake, heart rate, or rating of perceived exertion at any time during the 90-min ride. Plasma tyrosine rose significantly from 60 min before exercise to test termination (TT) in Tyr (means ± SE) (480 ± 26 μmol) and CHO+Tyr (463 ± 34 μmol) and was significantly higher in these groups from 30 min before exercise to TT vs. CHO (90 ± 3 μmol) and Pla (111 ± 7 μmol) ( P < 0.05). Plasma free tryptophan was higher after 90 min of exercise, 15 min into the endurance time trial, and at TT in Tyr (10.1 ± 0.9, 10.4 ± 0.8, and 12.0 ± 0.9 μmol, respectively) and Pla (9.7 ± 0.5, 10.0 ± 0.3, and 11.7 ± 0.5 μmol, respectively) vs. CHO (7.8 ± 0.5, 8.6 ± 0.5, and 9.3 ± 0.6 μmol, respectively) and CHO+Tyr (7.8 ± 0.5, 8.5 ± 0.5, 9.4 ± 0.5 μmol, respectively) ( P < 0.05). The plasma tyrosine-to-free tryptophan ratio was significantly higher in Tyr and CHO+Tyr vs. CHO and Pla from 30 min before exercise to TT ( P < 0.05). CHO (27.1 ± 0.9 min) and CHO+Tyr (26.1 ± 1.1 min) treatments resulted in a reduced time to complete the endurance time trial compared with Pla (34.4 ± 2.9 min) and Tyr (32.6 ± 3.0 min) ( P < 0.05). These findings demonstrate that tyrosine ingestion did not enhance performance during a cycling time trial after 90 min of steady-state exercise.
Effect of hyperbaric oxygen on apoptosis in neonatal hypoxia-ischemia rat model
Authors: Calvert John W. , Zhou Changman , Nanda Anil , Zhang John H.
Published: March 2015

We have previously demonstrated that a transient exposure to hyperbaric oxygen (HBO) attenuated the neuronal injury after neonatal hypoxia-ischemia. This study was undertaken to determine whether HBO offers this neuroprotection by reducing apoptosis in injured brain tissue. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% oxygen). Apoptotic cell death was examined in the injured cortex and hippocampus tissue. Caspase-3 expression and activity increased at 18 and 24 h after the hypoxia-ischemia insult. At 18-48 h, poly(ADP-ribose) polymerase (PARP) cleavage occurred, which reduced the band at 116 kDa and enhanced the band at 85 kDa. There was a time-dependent increase in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive cells. A single HBO treatment (100% oxygen, 3 ATA for 1 h) 1 h after hypoxia reduced the enhanced caspase-3 expression and activity, attenuated the PARP cleavage, and decreased the number of TUNEL-positive cells observed in the cortex and hippocampus. These results suggest that the neuroprotective effect of HBO is at least partially mediated by the reduction of apoptosis.
Temporal dynamics of recurrent airway symptoms and cellular random walk
Authors: Suki Béla , Frey Urs
Published: March 2015

Asthma is a complex chronic inflammatory disease of the small airways that has dramatically increased in prevalence in industrialized countries during the last decades. Risk factors for adult asthma have been related to the complex array of gene-environment interactions and exposure of the immune system to allergens in early childhood. In genetically predisposed subjects, continuous exposure to environmental agents such as allergens or infections can lead to recurrent airway symptoms characterized by recurrent episodes of airway inflammation and bronchoconstriction with clinical symptoms of cough, dyspnea, or wheezing. In this study, we report that the longterm temporal dynamics of recurrent airway symptoms in a population of unselected infants display a complex intermittent pattern and that the distribution of interepisode intervals follows a power law. We interpret the data by using a model of the dynamics of attack episodes in which an attack is triggered by an avalanche of airway constrictions. We map the dynamics of this model to the known problem of a random walk in the presence of an absorbing boundary in which the walker corresponds to the fluctuations in contractile state of airway smooth muscle cells. These findings may provide new insight into the mechanisms of otherwise unexplained symptom episodes.
Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting
Authors: Schrage William G. , Woodman Christopher R. , Laughlin M. Harold
Published: March 2015

The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (∼300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 μM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N ω-nitro-l-arginine (l-NNA; 300 μM) reduced flow-induced dilation by 65–70% in Con and HLU 1As. In contrast, l-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with l-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of l-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10−9-10−4 M) in soleus 2As.l-NNA reduced ACh-induced dilation by ∼40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment withl-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.
Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats
Authors: Allen Matthew R. , Bloomfield Susan A.
Published: March 2015

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (−49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (−4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.
Partitioning of inhaled ventilation between the nasal and oral routes during sleep in normal subjects
Authors: Fitzpatrick Michael F. , Driver Helen S. , Chatha Neela , Voduc Nha , Girard Alison M.
Published: March 2015

The oral and nasal contributions to inhaled ventilation were simultaneously quantified during sleep in 10 healthy subjects (5 men, 5 women) aged 43 ± 5 yr, with normal nasal resistance (mean 2.0 ± 0.3 cmH2O · l−1 · s−1) by use of a divided oral and nasal mask. Minute ventilation awake (5.9 ± 0.3 l/min) was higher than that during sleep (5.2 ± 0.3 l/min; P < 0.0001), but there was no significant difference in minute ventilation between different sleep stages ( P = 0.44): stage 2 5.3 ± 0.3, slow-wave 5.2 ± 0.2, and rapid-eye-movement sleep 5.2 ± 0.2 l/min. The oral fraction of inhaled ventilation during wakefulness (7.6 ± 4%) was not significantly different from that during sleep (4.3 ± 2%; mean difference 3.3%, 95% confidence interval −2.1–8.8%, P = 0.19), and no significant difference ( P = 0.14) in oral fraction was observed between different sleep stages: stage two 5.1 ± 2.8, slow-wave 4.2 ± 1.8, rapid-eye-movement 3.1 ± 1.7%. Thus the inhaled oral fraction in normal subjects is small and does not change significantly with sleep stage.
Ca2+-activated Cl− channels in corpus cavernosum smooth muscle: a novel mechanism for control of penile erection
Authors: Karkanis Tom , DeYoung Ling , Brock Gerald B. , Sims Stephen M.
Published: March 2015

Little is known of the excitatory mechanisms that contribute to the tonic contraction of the corpus cavernosum smooth muscle in the flaccid state. We used patch-clamp electrophysiology to investigate a previously unidentified inward current in freshly isolated rat and human corporal myocytes. Phenylephrine (PE) contracted cells and activated whole cell currents. Outward current was identified as large-conductance Ca2+-activated K+ current. The inward current elicited by PE was dependent on the Cl− gradient and was inhibited by niflumic acid, indicative of a Ca2+-activated Cl− (ClCa) current. Furthermore, spontaneous transient outward and inward currents (STOCs and STICs, respectively) were identified in both rat and human corporal myocytes and derived from large-conductance Ca2+-activated K+ and ClCa channel activity. STICs and STOCs were inhibited by PE and A-23187, and combined 8-bromoadenosine cAMP and 8-bromoadenosine cGMP decreased their frequency. When studied in vivo, chloride channel blockers transiently increased intracavernosal pressure and prolonged nerve-evoked erections. This report reveals for the first time ClCa current in rat and human corpus cavernosum smooth muscle cells and demonstrates its key functional role in the regulation of penile erection.
Role of nitric oxide in heparin-induced attenuation of hypoxic pulmonary vascular remodeling
Authors: Horstman Damian J. , Fischer Lars G. , Kouretas Peter C. , Hannan Robert L. , Rich George F.
Published: March 2015

Heparin and nitric oxide (NO) attenuate changes to the pulmonary vasculature caused by prolonged hypoxia. Heparin may increase NO; therefore, we hypothesized that heparin may attenuate hypoxia-induced pulmonary vascular remodeling via a NO-mediated mechanism. In vivo, rats were exposed to normoxia (N) or hypoxia (H; 10% O2) with or without heparin (1,200 U · kg−1 · day−1) and/or the NO synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester (l-NAME; 20 mg · kg−1 · day−1) for 3 days or 3 wk. Heparin attenuated increases in pulmonary arterial pressure, the percentage of muscular pulmonary vessels, and their medial thickness induced by 3 wk of H. Importantly, althoughl-NAME alone had no effect, it prevented these effects of heparin on vascular remodeling. In H lungs, heparin increased NOS activity and cGMP levels at 3 days and 3 wk and endothelial NOS protein expression at 3 days but not at 3 wk. In vitro, heparin (10 and 100 U · kg−1 · ml−1) increased cGMP levels after 10 min and 24 h in N and anoxic (0% O2) endothelial cell-smooth muscle cell (SMC) coculture. SMC proliferation, assessed by 5-bromo-2′-deoxyuridine incorporation during a 3-h incubation period, was decreased by heparin under N, but not anoxic, conditions. The antiproliferative effects of heparin were not altered byl-NAME. In conclusion, the in vivo results suggest that attenuation of hypoxia-induced pulmonary vascular remodeling by heparin is NO mediated. Heparin increases cGMP in vitro; however, the heparin-induced decrease in SMC proliferation in the coculture model appears to be NO independent.
Enhanced myocyte-based biosensing of the blood-borne signals regulating chronotropy
Authors: Edelberg Jay M. , Jacobson Jason T. , Gidseg David S. , Tang Lilong , Christini David J.
Published: March 2015

Biosensors play a critical role in the real-time determination of relevant functional physiological needs. However, typical in vivo biosensors only approximate endogenous function via the measurement of surrogate signals and, therefore, may often lack a high degree of dynamic fidelity with physiological requirements. To overcome this limitation, we have developed an excitable tissue-based implantable biosensor approach, which exploits the inherent electropotential input-output relationship of cardiac myocytes to measure the physiological regulatory inputs of chronotropic demand via the detection of blood-borne signals. In this study, we report the improvement of this application through the modulation of host-biosensor communication via the enhancement of vascularization of chronotropic complexes in mice. Moreover, in an effort to further improve translational applicability as well as molecular plasticity, we have advanced this approach by employing stem cell-derived cardiac myocyte aggregates in place of whole cardiac tissue. Overall, these studies demonstrate the potential of biologically based biosensors to predict endogenous physiological dynamics and may facilitate the translation of this approach for in vivo monitoring.
Early changes of type 2B fibers after denervation of rat EDL skeletal muscle
Authors: Germinario Elena , Esposito Alessandra , Megighian Aram , Midrio Menotti , Biral Donatella , Betto Romeo , Danieli-Betto Daniela
Published: March 2015

Skeletal muscle type 2B fibers normally receive a moderate level of motoneuron discharge. As a consequence, we hypothesize that type 2B fiber properties should be less sensitive to the absence of the nerve. Therefore, we have investigated the response of sarcoplasmic reticulum and myofibrillar proteins of type 2B fibers isolated from rat extensor digitorum longus muscle after denervation (2 and 7 days). Single fibers were identified by SDS-PAGE of myosin heavy chain isoforms. Electrophysiological and isometric contractile properties of the whole muscle were also analyzed. The pCa-tension relationship of type 2B single fibers was shifted to the left at 2 days and to right at 7 days after denervation, with significant differences in the Hill coefficients and pCa threshold values in 2- vs. 7-day-denervated fibers. The sarcoplasmic reticulum Ca2+uptake capacity and rate significantly decreased after 2 days of denervation, whereas both increased at 7 days. Caffeine sensitivity of sarcoplasmic reticulum Ca2+release was transitory and markedly increased in 2-day-denervated fibers. Our results indicate that type 2B fiber functional properties are highly sensitive to the interruption of nerve supply. Moreover, most of 2-day-denervated changes were reverted at 7 days.
Hypohydration effect on finger skin temperature and blood flow during cold-water finger immersion
Authors: O'Brien Catherine , Montain Scott J.
Published: March 2015

This study was conducted to determine whether hypohydration (Hy) alters blood flow, skin temperature, or cold-induced vasodilation (CIVD) during peripheral cooling. Fourteen subjects sat in a thermoneutral environment (27°C) during 15-min warm-water (42°C) and 30-min cold-water (4°C) finger immersion (FI) while euhydrated (Eu) and, again, during Hy. Hy (−4% body weight) was induced before FI by exercise-heat exposure (38°C, 30% relative humidity) with no fluid replacement, whereas during Eu, fluid intake maintained body weight. Finger pad blood flow [as measured by laser-Doppler flux (LDF)] and nail bed (Tnb), pad (Tpad), and core (Tc) temperatures were measured. LDF decreased similarly during Eu and Hy (32 ± 10 and 33 ± 13% of peak during warm-water immersion). Mean Tnb and Tpad were similar between Eu (7.1 ± 1.0 and 11.5 ± 1.6°C) and Hy (7.4 ± 1.3 and 12.6 ± 2.1°C). CIVD parameters (e.g., nadir, onset time, apex) were similar between trials, except Tpad nadir was higher during Hy (10.4 ± 3.8°C) than during Eu (7.9 ± 1.6°C), which was attributed to higher Tc in six subjects during Hy (37.5 ± 0.2°C), compared with during Eu (37.1 ± 0.1°C). The results of this study provide no evidence that Hy alters finger blood flow, skin temperature, or CIVD during peripheral cooling.
Relaxation of guinea pig trachealis during electrical field stimulation increases with age
Authors: Chitano Pasquale , Cox Carrie M. , Murphy Thomas M.
Published: March 2015

Our laboratory has previously shown that maturation of airway smooth muscle (ASM) contractility may play a role in the airway hyperresponsiveness displayed by juveniles of many species, including humans (Chitano P, Wang J, Cox CM, Stephens NL, and Murphy TM. J Appl Physiol 88: 1338–1345, 2000). ASM relaxation, which could also contribute to airway hyperresponsiveness, has neither been described nor quantified during maturation. Therefore, we studied ASM relaxation during and after electrical field stimulation (EFS) in tracheal strips from 1-wk-old, 3-wk-old, and 3-mo-old guinea pigs. Strips were stimulated (60 Hz, 18 V) at their optimal length for 15, 20, and 25 s, with and without the cyclooxygenase inhibitor indomethacin. To evaluate the role of the epithelium, deepithelialized strips from adult animals were also studied. New indexes were developed to quantify relaxation during EFS. We measured the time course of tension relaxation and its maximum rate (RTR) during the EFS, as well as the residual tension at the end of the EFS (TCTend). After EFS, we measured the maximum RTR and the time needed to reduce to half the TCTend. Relaxation during the EFS significantly increased with age. Indomethacin reduced this age difference by increasing relaxation in strips from younger animals. By contrast, removal of the epithelium in adult strips decreased relaxation. Relaxation after EFS decreased with age and was not affected by indomethacin. In adult strips, it was further reduced by epithelium removal. Our results show that during EFS 1) airway smooth muscle relaxation increases with age, 2) cyclooxygenase metabolites oppose relaxation in younger animals, and 3) epithelium removal inhibits relaxation. We suggest that a reduced ASM relaxing ability during stimulation may be involved in juvenile airway hyperresponsiveness.
CT-based assessment of regional pulmonary microvascular blood flow parameters
Authors: Won Chulho , Chon Deokiee , Tajik Jehangir , Tran Binh Q. , Robinswood G. Blake , Beck Kenneth C. , Hoffman Eric A.
Published: March 2015

To determine regional pulmonary microvascular mean transit times (MTTs), we used electrocardiogram-gated X-ray computed tomographic imaging to follow bolus radiopaque contrast material through the lungs in anesthetized animals (7 dogs and 1 pig, prone and supine). By deconvolution/reconvolution of regional time-attenuation curves obtained from parenchyma and large lobar arteries, we estimated the microvascular residue function and reconstituted the regional microvascular time-attenuation curves and, thus, regional microvascular MTTs. The mean microvascular MTTs in the supine and prone postures were 3.94 ± 1.0 and 3.40 ± 0.84 (mean ± SD), respectively. The dependent-nondependent vertical gradient of MTT was greater in the supine [slope = 0.25 ± 0.10 (SD), P < 0.001 by t-test] than in the prone (−0.03 ± 0.06 in 6 of 8 animals; 2 outliers had positive slopes) posture. In both postures, there was a trend toward faster transit times in the dorsal-basal lung region in six of the eight animals, suggesting gravity-independent higher vascular conductance dorsocaudally. We conclude that deconvolution methods, in association with electrocardiogram-gated high-speed X-ray computed tomography, can provide insights into regional heterogeneity of pulmonary microvascular MTT in vivo.
Measurement of mitochondrial DNA synthesis in vivo using a stable isotope-mass spectrometric technique
Authors: Collins Michelle L. , Eng Shannon , Hoh Rebeccah , Hellerstein Marc K.
Published: March 2015

We describe here a new stable isotope-mass spectrometric technique for measuring mitochondrial DNA (mtDNA) synthesis. Growing (2–4 mo old) and weight-stable (8–10 mo old) Sprague-Dawley rats were primed with2H2O (deuterated water) to 2.0–2.5% body water enrichment, via intraperitoneal injection, and then given 4%2H2O in drinking water for 3–11 wk. Mitochondria were isolated from cardiac and hindlimb muscle, and mtDNA was isolated and enzymatically hydrolyzed to deoxyribonucleosides. PCR confirmed the absence of nuclear DNA contamination. The isotopic enrichment of the deoxyribose moiety of deoxyadenosine was determined by GC-MS analysis, and percent new mtDNA was calculated by comparison to genomic DNA enrichments in a tissue with nearly complete turnover (bone marrow). Initial label incorporation into deoxyadenosine of mtDNA was linear, and turnover of mtDNA was observed in nongrowing adult female rats (1.1–1.3% new mtDNA per day in cardiac and skeletal muscle). Die-away curves of mtDNA after discontinuing2H2O administration gave a similar turnover rate constant. Human subjects were also given2H2O for up to 6 wk, and mitochondria from platelets were isolated. Incubation with DNase removed any contaminating genomic DNA; platelet mtDNA exhibited linear incorporation from2H2O and reached plateau values identical to those in genomic DNA from fully turned over cells (circulating monocytes). In conclusion, replication of mtDNA can be directly measured in vivo in rodents and humans without the use of radioactivity. Use of this technique may allow improved understanding of the regulation of mitochondrial biogenesis in health and disease.
Effects of oral contraceptives on glucose flux and substrate oxidation rates during rest and exercise
Authors: Suh Sang-Hoon , Casazza Gretchen A. , Horning Michael A. , Miller Benjamin F. , Brooks George A.
Published: March 2015

We examined the effects of oral contraceptives (OC) on glucose flux and whole body substrate oxidation rates during rest (90 min) and two exercise intensities [60-min leg ergometer cycling at 45 and 65% peak O2 uptake (V˙o 2 peak)]. Eight healthy, eumenorrheic women were studied during the follicular and luteal phases before OC and the inactive and high-dose phases after 4 mo of a low-dose, triphasic OC. Subjects were studied in the morning 3 h after a standardized (308 kcal) breakfast. There were significant reductions in glucose rates of appearance and disappearance during exercise of both intensities with OC but not rest. There were no phase effects on substrate oxidation during rest or exercise. These results are interpreted to mean that, in women fed several hours before study, 1) OC decreases glucose flux, but not overall carbohydrate and lipid oxidation rates during moderate-intensity exercise; and 2) synthetic ovarian hormone analogs in the doses contained in OC have greater metabolic effects on glucose metabolism during exercise than do endogenous ovarian hormones.
Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome
Authors: Henderson Luke A. , Woo Mary A. , Macey Paul M. , Macey Katherine E. , Frysinger Robert C. , Alger Jeffry R. , Yan-Go Frisca , Harper Ronald M.
Published: March 2015

The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sleep apnea (OSA) suggest dysfunction of specific neural sites that integrate afferent airway signals with autonomic and somatic outflow. We determined neural responses to the Valsalva maneuver by using functional magnetic resonance imaging. Images were collected during a baseline and three Valsalva maneuvers in 8 drug-free OSA patients and 15 controls. Multiple cortical, midbrain, pontine, and medullary regions in both groups showed intensity changes correlated to airway pressure. In OSA subjects, the left inferior parietal cortex, superior temporal gyrus, posterior insular cortex, cerebellar cortex, fastigial nucleus, and hippocampus showed attenuated signal changes compared with controls. Enhanced responses emerged in the left lateral precentral gyrus, left anterior cingulate, and superior frontal cortex of OSA patients. The anterior cingulate, cerebellar cortex, and posterior insula exhibited altered response timing patterns between control and OSA subjects. The response patterns in OSA subjects suggest deficits in particular neural pathways that normally mediate the Valsalva maneuver and compensatory actions in other structures.
Reduced activity of muscle Na+-K+-ATPase after prolonged running in rats
Authors: Fowles J. R. , Green H. J. , Schertzer J. D. , Tupling A. R.
Published: March 2015

The purpose of this study was to investigate the hypothesis that Na+-K+-ATPase activity is reduced in muscle of different fiber composition after a single session of aerobic exercise in rats. In one experiment, untrained female Sprague-Dawley rats (weight 275 ± 21 g; means ± SE; n = 30) were run (Run) on a treadmill at 21 m/min and 8% grade until fatigue, or to a maximum of 2 h, which served as control (Con), or performed an additional 45 min of low-intensity exercise at 10 m/min (Run+). In a second experiment, utilizing rats of similar characteristics (weight 258 ± 18 g; n = 32), Run was followed by passive recovery (Rec). Directly after exercise, rats were anesthetized, and tissue was extracted from Soleus (Sol), red vastus lateralis (RV), white vastus lateralis (WV), and extensor digitorum longus (EDL) and frozen for later analysis. 3- O-methylfluorescein phosphatase activity (3- O-MFPase) was determined as an indicator of Na+-K+-ATPase activity, and glycogen depletion identified recruitment of each muscle during exercise. 3- O-MFPase was decreased ( P < 0.05) at Run+ by an average of 12% from Con in all muscles ( P < 0.05). No difference was found between Con and Run. Glycogen was lower ( P < 0.05) by 65, 57, 44, and 33% (Sol, EDL, RV, and WV, respectively) at Run, and there was no further depletion during the continued low-intensity exercise period. No differences in Na+-K+-ATPase activity was observed between Con and Rec. The results of this study indicate that inactivation of Na+-K+-ATPase can be induced by aerobic exercise in a volume-dependent manner and that the inactivation that occurs is not specific to muscles of different fiber-type composition. Inactivation of Na+-K+-ATPase suggests intrinsic structural modifications by mechanisms that are unclear.
Effect of quadriceps femoris muscle length on neural activation during isometric and concentric contractions
Authors: Babault Nicolas , Pousson Michel , Michaut Anne , Van Hoecke Jacques
Published: March 2015

The effect of muscle length on neural drive (here termed “neural activation”) was investigated from electromyographic activities and activation levels (twitch interpolation). The neural activation was measured in nine men during isometric and concentric (30 and 120°/s) knee extensions for three muscle lengths (35, 55, and 75° knee flexion, i.e., shortened, intermediate, and lengthened muscles, respectively). Long (76°), medium (56°), and short (36°) ranges of motion were used to investigate the effect of the duration of concentric contraction. Neural activation was found to depend on muscle length. Reducing the duration of contraction had no effect. Neural activation was higher with short muscle length during isometric contractions and was weaker for shortened than for intermediate and lengthened muscles performing 120°/s concentric contractions. Muscle length had no effect on 30°/s concentric neural activation. Peripheral mechanisms and discharge properties of the motoneurons could partly explain the observed differences in the muscle length effect. We thus conclude that muscle length has a predominant effect on neural activation that would modulate the angular velocity dependency.
Metabolic, thermoregulatory, and perceptual responses during exercise after lower vs. whole body precooling
Authors: White Andrea T. , Davis Scott L. , Wilson Thad E.
Published: March 2015

The purpose of this investigation was to compare the thermoregulatory, metabolic, and perceptual effects of lower body (LBI) and whole body (WBI) immersion precooling techniques during submaximal exercise. Eleven healthy men completed two 30-min cycling bouts at 60% of maximal O2uptake preceded by immersion to the suprailiac crest (LBI) or clavicle (WBI) in 20°C water. WBI produced significantly lower rectal temperature (Tre) during minutes 24–30 of immersion and lower Tre, mean skin temperature, and mean body temperature for the first 24, 14, and 16 min of exercise, respectively. Body heat storage rates differed significantly for LBI and WBI during immersion and exercise, although no net differences were observed between conditions. For WBI, metabolic heat production and heart rate were significantly higher during immersion but not during exercise. Thermal sensation was significantly lower (felt colder) and thermal discomfort was significantly higher (less comfortable) for WBI during immersion and exercise. In conclusion, WBI and LBI attenuated Tre increases during submaximal exercise and produced similar net heat storage over the protocol. LBI minimized metabolic increases and negative perceptual effects associated with WBI.
Carotid body denervation eliminates apnea in response to transient hypocapnia
Authors: Nakayama Hideaki , Smith Curtis A. , Rodman Joshua R. , Skatrud James B. , Dempsey Jerome A.
Published: March 2015

We determined the effects on breathing of transient ventilatory overshoots and concomitant hypocapnia, as produced by pressure support mechanical ventilation (PSV), in intact and carotid body chemoreceptor denervated (CBX) sleeping dogs. In the intact dog, PSV-induced transient increases in tidal volume and hypocapnia caused apnea within 10–11 s, followed by repetitive two-breath clusters separated by apneas, i.e., periodic breathing (PB). After CBX, significant expiratory time prolongation did not occur until after 30 s of PSV-induced hypocapnia, and PB never occurred. Average apneas of 8.4 ± 1-s duration after a ventilatory overshoot required a decrease below eupnea of end-tidal Pco 2 5.1 ± 0.4 Torr below eupnea in the intact animal and 10.1 ± 2 Torr in the CBX dog, where the former reflected peripheral and the latter central dynamic CO2 chemoresponsiveness, as tested in the absence of peripheral chemoreceptor input. Hyperoxia when the dogs were intact shortened PSV-induced apneas and reduced PB but did not mimic the effects of CBX. We conclude that, during non-rapid eye movement sleep, carotid chemoreceptors are required to produce apneas that normally occur after a transient ventilatory overshoot and for PB.
Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta
Authors: Papadopoulos Anthony , Delp Michael D.
Published: March 2015

Previous studies have shown that hindlimb unweighting of rats, a model of microgravity, reduces evoked contractile tension of peripheral conduit arteries. It has been hypothesized that this diminished contractile tension is the result of alterations in the mechanical properties of these arteries (e.g., active and passive mechanics). Therefore, the purpose of this study was to determine whether the reduced contractile force of the abdominal aorta from 2-wk hindlimb-unweighted (HU) rats results from a mechanical function deficit resulting from structural vascular alterations or material property changes. Aortas were isolated from control (C) and HU rats, and vasoconstrictor responses to norepinephrine (10−9–10−4 M) and AVP (10−9–10−5 M) were tested in vitro. In a second series of tests, the active and passive Cauchy stress-stretch relations were determined by incrementally increasing the uniaxial displacement of the aortic rings. Maximal Cauchy stress in response to norepinephrine and AVP were less in aortic rings from HU rats. The active Cauchy stress-stretch response indicated that, although maximum stress was lower in aortas from HU rats (C, 8.1 ± 0.2 kPa; HU, 7.0 ± 0.4 kPa), it was achieved at a similar hoop stretch. There were also no differences in the passive Cauchy stress-stretch response or the gross vascular morphology (e.g., medial cross-sectional area: C, 0.30 ± 0.02 mm2; HU, 0.32 ± 0.01 mm2) between groups and no differences in resting or basal vascular tone at the displacement that elicits peak developed tension between groups (resting tension: C, 1.71 ± 0.06 g; HU, 1.78 ± 0.14 g). These results indicate that HU does not alter the functional mechanical properties of conduit arteries. However, the significantly lower active Cauchy stress of aortas from HU rats demonstrates a true contractile deficit in these arteries.
Muscle type-specific response of HSP60, HSP72, and HSC73 during recovery after elevation of muscle temperature
Authors: Oishi Yasuharu , Taniguchi Kouhachi , Matsumoto Hisahiro , Ishihara Akihiko , Ohira Yoshinobu , Roy Roland R.
Published: March 2015

An original method to induce heat stress was used to clarify the time course of changes in heat shock proteins (HSPs) in rat skeletal muscles during recovery after a single bout of heat stress. One hindlimb was inserted into a stainless steel can and directly heated by raising the air temperature inside the can via a flexible heater twisted around the steel can. Muscle temperature was increased gradually and maintained at 42°C for 60 min. Core rectal and contralateral muscle temperatures were increased <1.5°C during the heat stress. HSP60, HSP72, and heat shock cognate (HSC) 73 content in the slow soleus and fast plantaris in both limbs were determined immediately (0 h) and 2, 4 , 8, 12, 24, 36, 48, or 60 h after heat stress. Within 0–4 h, all HSPs were ∼1.5- to 2.2-fold higher in heat-stressed than contralateral soleus. Compared with the contralateral plantaris, the heat-stressed plantaris had a higher (1.5-fold) HSP60 content immediately and 2 h after heat stress and a higher (2.5- to 6.8-fold) HSP72 content between 24 and 48 h after heat stress. Plantaris HSC73 content was not affected by heat stress. This unique heat-stress method provides advantages over existing systems; muscle temperature can be controlled precisely during heating and the HSP response can be compared between muscles in heat-stressed and contralateral limbs of individual rats. Results show a differential response of HSPs in the soleus and plantaris during recovery after heat stress; soleus demonstrated a more rapid and broader HSP response to heat stress than plantaris.
Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis
Authors: Nissen Steven L. , Sharp Rick L.
Published: March 2015

The purpose of this study was to quantify which dietary supplements augment lean mass and strength gains during resistance training. Peer-reviewed studies between the years 1967 and 2001 were included in the analysis if they met a predetermined set of experimental criteria, among which were at least 3-wk duration and resistance-training 2 or more times a week. Lean mass and strength were normalized for meta-analysis by conversion to percent change per week and by calculating the effect size for each variable. Of the 250 supplements examined, only 6 had more than 2 studies that met the criteria for inclusion in the meta-analysis. Creatine and β-hydroxy-β-methylbutyrate (HMB) were found to significantly increase net lean mass gains of 0.36 and 0.28%/wk and strength gains of 1.09 and 1.40%/wk ( P < 0.05), respectively. Chromium, dehydroepiandrosterone, androstenedione, and protein did not significantly affect lean gain or strength. In conclusion, two supplements, creatine and HMB, have data supporting their use to augment lean mass and strength gains with resistance training.
Mechanical properties of the passive pharynx in Vietnamese pot-bellied pigs. II. Dynamics
Authors: Tuck Stephanie A. , Remmers John E.
Published: March 2015

We described the dynamic mechanical properties of the passive pharynx in Vietnamese pot-bellied pigs and the effects of caudal tracheal displacement. During general anesthesia and neuromuscular blockade, airflow through the upper airway (V˙) and pharyngeal cross-sectional area were measured during ramp decreases in pressure downstream from the pharynx (Pdown). Measurements were made with 0, 1, and 2 cm of caudal tracheal displacement. Airflow limitation and/or negative pressure dependence (NPD) were observed in all animals. Tracheal displacement (2 cm) increased maximal V˙ (V˙max) by 205.1 ± 105.1% ( P < 0.05) relative to the value with no displacement and increased the magnitude of NPD, expressed as percent decrease in V˙ from V˙max, from 22.9 ± 27.4 to 56.6 ± 37.5% ( P < 0.05). Initial decreases in Pdown narrowed all levels of the pharynx, but, once V˙max was reached, further decreases in Pdown narrowed the hypopharynx but not the nasopharynx and oropharynx. We conclude that the hypopharynx is the flow-limiting site in the pig pharynx. Tracheal displacement not only improved airflow dynamics as V˙max increased but also resulted in pronounced NPD.
Alternate muscle activity observed between knee extensor synergists during low-level sustained contractions
Authors: Kouzaki Motoki , Shinohara Minoru , Masani Kei , Kanehisa Hiroaki , Fukunaga Tetsuo
Published: March 2015

To determine quantitatively the features of alternate muscle activity between knee extensor synergists during low-level prolonged contraction, a surface electromyogram (EMG) was recorded from the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) in 11 subjects during isometric knee extension exercise at 2.5% of maximal voluntary contraction (MVC) for 60 min ( experiment 1). Furthermore, to examine the relation between alternate muscle activity and contraction levels, six of the subjects also performed sustained knee extension at 5.0, 7.5, and 10.0% of MVC ( experiment 2). Alternate muscle activity among the three muscles was assessed by quantitative analysis on the basis of the rate of integrated EMG sequences. In experiment 1, the number of alternations was significantly higher between RF and either VL or VM than between VL and VM. Moreover, the frequency of alternate muscle activity increased with time. In experiment 2, alternating muscle activity was found during contractions at 2.5 and 5.0% of MVC, although not at 7.5 and 10.0% of MVC, and the number of alternations was higher at 2.5 than at 5.0% of MVC. Thus the findings of the present study demonstrated that alternate muscle activity in the quadriceps muscle 1) appears only between biarticular RF muscle and monoarticular vasti muscles (VL and VM), and its frequency of alternations progressively increases with time, and 2) emerges under sustained contraction with force production levels ≤5.0% of MVC.
Low-volume ventilation causes peripheral airway injury and increased airway resistance in normal rabbits
Authors: D'Angelo Edgardo , Pecchiari Matteo , Baraggia Paolo , Saetta Marina , Balestro Elisabetta , Milic-Emili Joseph
Published: March 2015

Lung mechanics and morphometry of 10 normal open-chest rabbits ( group A), mechanically ventilated (MV) with physiological tidal volumes (8–12 ml/kg), at zero end-expiratory pressure (ZEEP), for 3–4 h, were compared with those of five rabbits ( group B) after 3–4 h of MV with a positive end-expiratory pressure (PEEP) of 2.3 cmH2O. Relative to initial MV on PEEP, MV on ZEEP caused a progressive increase in quasi-static elastance (+36%) and airway (Rint; +71%) and viscoelastic resistance (+29%), with no change in the viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control levels, whereas Rint remained elevated (+22%). On PEEP, MV had no effect on lung mechanics. Gas exchange on PEEP was equally preserved in groups A and B, and the lung wet-to-dry ratios were normal. Both groups had normal alveolar morphology, whereas only group A had injured respiratory and membranous bronchioles. In conclusion, prolonged MV on ZEEP induces histological evidence of peripheral airway injury with a concurrent increase in Rint, which persists after restoration of normal end-expiratory volumes. This is probably due to cyclic opening and closing of peripheral airways on ZEEP.
Estimation of lung liquid production in fetal sheep with blue dye dextran and radioiodinated serum albumin
Authors: Cassin S. , Perks A. M.
Published: March 2015

Lung liquid production and reabsorption rates and lung volumes were measured in 99 fetal sheep (119–148 days of gestation) by indicator-dilution methods with the simultaneous use of blue dye dextran (BDD) and radioiodinated serum albumin (RISA). There were no significant differences between rates of lung liquid production or reabsorption by the two methods ( n = 71 pairs; paired t-test; Wilcoxon test; ANOVA); this was equally true for rates in milliliters per hour or milliliters per kilogram body weight per hour and was independent of age. Volumes measured by both methods showed a close linear relationship ( r = 0.97; for slope P < 0.0001; n = 99), whether expressed as milliliters or milliliters per kilogram body weight. Either method could give the higher volume. Values differed by only ∼4%, independent of age or parameter (ml or ml/kg body wt; volumes regressed to original volume, or as measured in untreated control hours). However, this small difference was significant by paired t-test or Wilcoxon test when all data were combined irrespective of age; it was not significant after allowance for gestational age (two-way ANOVA). Both indicators showed the same increase in lung volume toward birth and the same fall when related to body weight (slopes significant P = 0.0003–0.0004; r = 0.93). Two-way ANOVA showed that the declines were significant ( P = 0.003). The data suggest that 1) there was no significant difference in production or reabsorption rates measured by BDD or RISA, 2) differences in volumes measured by the two indicators were only significant if gestational age was ignored and were too small to have physiological importance, and 3) although BDD and RISA each may have methodological weaknesses, for purposes of measuring lung liquid volumes both are sufficiently accurate and reproducible to obtain meaningful physiological results.