bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men
Authors: Brown Gregory A. , Vukovich Matthew D. , Sharp Rick L. , Reifenrath Tracy A. , Parsons Kerry A. , King Douglas S.
Published: December 2017

This study examined the effects of acute dehydroepiandrosterone (DHEA) ingestion on serum steroid hormones and the effect of chronic DHEA intake on the adaptations to resistance training. In 10 young men (23 ± 4 yr old), ingestion of 50 mg of DHEA increased serum androstenedione concentrations 150% within 60 min ( P < 0.05) but did not affect serum testosterone and estrogen concentrations. An additional 19 men (23 ± 1 yr old) participated in an 8-wk whole body resistance-training program and ingested DHEA (150 mg/day, n = 9) or placebo ( n = 10) during weeks 1, 2, 4, 5, 7, and 8. Serum androstenedione concentrations were significantly ( P < 0.05) increased in the DHEA-treated group after 2 and 5 wk. Serum concentrations of free and total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases were unaffected by supplementation and training, while strength and lean body mass increased significantly and similarly ( P < 0.05) in the men treated with placebo and DHEA. These results suggest that DHEA ingestion does not enhance serum testosterone concentrations or adaptations associated with resistance training in young men.
Effect of carbohydrate supplementation on postexercise GLUT-4 protein expression in skeletal muscle
Authors: Kuo Chia-Hua , Hunt Desmond G. , Ding Zhenping , Ivy John L.
Published: December 2017

The effect of carbohydrate supplementation on skeletal muscle glucose transporter GLUT-4 protein expression was studied in fast-twitch red and white gastrocnemius muscle of Sprague-Dawley rats before and after glycogen depletion by swimming. Exercise significantly reduced fast-twitch red muscle glycogen by 50%. During a 16-h exercise recovery period, muscle glycogen returned to control levels (25.0 ± 1.4 μmol/g) in exercise-fasted rats (24.2 ± 0.3 μmol/g). However, when carbohydrate supplementation was provided during and immediately postexercise by intubation, muscle glycogen increased 77% above control (44.4 ± 2.1 μmol/g). Exercise-fasting resulted in an 80% increase in fast-twitch red muscle GLUT-4 mRNA but only a 43% increase in GLUT-4 protein concentration. Conversely, exercise plus carbohydrate supplementation elevated fast-twitch red muscle GLUT-4 protein concentration by 88% above control, whereas GLUT-4 mRNA was increased by only 40%. Neither a 16-h fast nor carbohydrate supplementation had an effect on fast-twitch red muscle GLUT-4 protein concentration or on GLUT-4 mRNA in sedentary rats, although carbohydrate supplementation increased muscle glycogen concentration by 40% (35.0 ± 0.9 μmol/g). GLUT-4 protein in fast-twitch white muscle followed a pattern similar to fast-twitch red muscle. These results indicate that carbohydrate supplementation, provided with exercise, will enhance GLUT-4 protein expression by increasing translational efficiency. Conversely, postexercise fasting appears to upregulate GLUT-4 mRNA, possibly to amplify GLUT-4 protein expression on an increase in glucose availability. These regulatory mechanisms may help control muscle glucose uptake in accordance with glucose availability and protect against postexercise hypoglycemia.
Effects of intratracheal instillation of TNF-α on surfactant metabolism
Authors: Salome Ronald G. , McCoy Diann M. , Ryan Alan J. , Mallampalli Rama K.
Published: December 2017

Tumor necrosis factor-α (TNF-α) has been shown to play an integral role in the pathogenesis of the acute respiratory distress syndrome. This disorder is characterized by a deficiency of alveolar surfactant, a surface-active material that is composed of key hydrophobic proteins and the major lipid disaturated phosphatidylcholine (DSPC). We investigated how TNF-α might alter DSPC content in rat lungs by instilling the cytokine (2.5 μg) intratracheally for 10 min and then assaying parameters of DSPC synthesis and degradation in alveolar type II epithelial cells, which produce surfactant. Cells isolated from rats given TNF-α had 26% lower levels of phosphatidylcholine compared with control. TNF-α treatment also decreased the ability of these cells to incorporate [3H]choline into DSPC by 45% compared with control isolates. There were no significant differences in the levels of choline substrate or choline transport between the groups. However, TNF-α produced a 64% decrease in the activity of cytidylyltransferase, the rate-regulatory enzyme required for DSPC synthesis. TNF-α administration in vivo also tended to stimulate phospholipase A2activity, but it did not alter other parameters for DSPC degradation such as activities for phosphatidylcholine-specific phospholipase C or phospholipase D. These observations indicate that TNF-α decreases the levels of surfactant lipid by decreasing the activity of a key enzyme involved in surfactant lipid synthesis. The results do not exclude stimulatory effects of the cytokine on phosphatidylcholine breakdown.
Involvement of substance P in neutral endopeptidase modulation of carotid body sensory responses to hypoxia
Authors: Kumar Ganesh K. , Kou Yu Ru , Overholt Jeffrey L. , Prabhakar Nanduri R.
Published: December 2017

Previously, we showed that carotid bodies express neutral endopeptidase (NEP)-like enzyme activity and that phosphoramidon, a potent inhibitor of NEP, potentiates the chemosensory response of the carotid body to hypoxia in vivo. NEP has been shown to hydrolyze methionine enkephalin (Met-Enk) and substance P (SP) in neuronal tissues. The purpose of the present study is to determine whether NEP hydrolyzes Met-Enk and SP in the carotid body and if so whether these peptides contribute to phosphoramidon-induced potentiation of the sensory response to hypoxia. Experiments were performed on carotid bodies excised from anesthetized adult cats ( n = 72 carotid bodies). The hydrolysis of Met-Enk and SP was analyzed by HPLC. The results showed that both SP and Met-Enk were hydrolyzed by the carotid body, but the rate of Met-Enk hydrolysis was approximately fourfold higher than that of SP. Phosphoramidon (400 μM) markedly inhibited SP hydrolysis (∼90%) but had only a marginal effect on Met-Enk hydrolysis (∼15% inhibition). Hypoxia (Po 2, 68 ± 6 Torr) as well as exogenous administration of SP (10 and 20 nmol) increased the sensory discharge of the carotid body in vitro. Sensory responses to hypoxia and SP (10 nmol) were potentiated by ∼80 and ∼275%, respectively ( P < 0.01), in the presence of phosphoramidon. SP-receptor antagonists Spantide (peptidyl) and CP-96345 (nonpeptidyl) either abolished or markedly attenuated the phosphoramidon-induced potentiation of the sensory response of the carotid body to hypoxia as well as to SP. These results demonstrate that SP is a preferred substrate for NEP in the carotid body and that SP is involved in the potentiation of the hypoxic response of the carotid body by phosphoramidon.
Cocaine and exercise: α-1 receptor blockade does not alter muscle glycogenolysis or blood lactacidosis
Authors: Conlee Robert K. , Kelly K. Patrick , Ojuka Edward O. , Hammer Roger L.
Published: December 2017

In our previous work, we routinely observed that a combined cocaine-exercise challenge results in an abnormally rapid muscle glycogen depletion and excessive blood lactacidosis. These phenomena occur simultaneously with a rapid rise in norepinephrine and in the absence of any rise in epinephrine. We postulated that norepinephrine may cause vasoconstriction of the muscle vasculature through activation of α-1 receptors during cocaine-exercise, thus inducing hypoxia and a concomitant rise in glycogenolysis and lactate accumulation. To test this hypothesis, rats were pretreated with the selective α-1-receptor antagonist prazosin (P) (0.1 mg/kg iv) or saline (S). Ten minutes later, the animals were treated with cocaine (-C) (5 mg/kg iv) or saline (-S) and run for 4 or 15 min at 22 m/min at 10% grade. In the S-S group, glycogen content of the white vastus lateralis muscle was unaffected by exercise at both time intervals, whereas in S-C rats glycogen was reduced by 47%. This effect of cocaine-exercise challenge was not attenuated by P. Similarly, blood lactate concentration in S-C rats was threefold higher than that of S-S after exercise, a response also not altered by pretreatment with P. On the basis of these observations, we conclude that the excessive glycogenolysis and lactacidosis observed during cocaine-exercise challenge is not the result of vasoconstriction secondary to norepinephrine activation of α-1 receptors.
Substrate profile in rat soleus muscle fibers after hindlimb unloading and fatigue
Authors: Grichko Varvara P. , Heywood-Cooksey Anne , Kidd Kameha R. , Fitts Robert H.
Published: December 2017

Limb muscles from rats flown in space and after hindlimb unloading (HU) show an increased fatigability, and spaceflight has been shown to result in a reduced ability to oxidize fatty acids. The purpose of this investigation was to determine the effects of HU on the substrate content in fast- and slow-twitch fibers and to assess the substrate utilization patterns in single slow type I fibers isolated from control and HU animals. A second objective was to assess whether HU altered the ability of the heart or limb muscle to oxidize pyruvate or palmitate. After 2 wk of HU, single fibers were isolated from the freeze-dried soleus and gastrocnemius muscles. HU increased the glycogen content in all fiber types, and it increased lactate, ATP, and phosphocreatine in the slow type I fiber. After HU, the type I fiber substrate profile was shifted toward that observed in fast fibers. For example, fiber glycogen increased from 179 ± 16 to 285 ± 25 mmol/kg dry wt, which approached the 308 ± 23 mmol/kg dry wt content observed in the post-HU type IIa fiber. With contractile activity, the type I fiber from the HU animal showed a greater utilization of glycogen and accumulation of lactate compared with the control type I fiber. HU had no effect on the ability of crude homogenate or mitochondria fractions from the soleus or gastrocnemius to oxidize pyruvate or palmitate. The increased fatigability after HU may have resulted from an elevated glycolysis producing an increased cell lactate and a decreased pH.
NaHCO3 and KHCO3 ingestion rapidly increases renal electrolyte excretion in humans
Authors: Lindinger Michael I. , Franklin Thomas W. , Lands Larry C. , Pedersen Preben K. , Welsh Donald G. , Heigenhauser George J. F.
Published: December 2017

This paper describes and quantifies acute responses of the kidneys in correcting plasma volume, acid-base, and ion disturbances resulting from NaHCO3 and KHCO3 ingestion. Renal excretion of ions and water was studied in five men after ingestion of 3.57 mmol/kg body mass of sodium bicarbonate (NaHCO3) and, in a separate trial, potassium bicarbonate (KHCO3). Subjects had a Foley catheter inserted into the bladder and indwelling catheters placed into an antecubital vein and a brachial artery. Blood and urine were sampled in the 30-min period before, the 60-min period during, and the 210-min period after ingestion of the solutions. NaHCO3 ingestion resulted in a rapid, transient diuresis and natriuresis. Cumulative urine output was 44 ± 11% of ingested volume, resulting in a 555 ± 119 ml increase in total body water at the end of the experiment. The cumulative increase (above basal levels) in renal Na+ excretion accounted for 24 ± 2% of ingested Na+. In the KHCO3 trial, arterial plasma K+ concentration rapidly increased from 4.25 ± 0.10 to a peak of 7.17 ± 0.13 meq/l 140 min after the beginning of ingestion. This increase resulted in a pronounced, transient diuresis, with cumulative urine output at 270 min similar to the volume ingested, natriuresis, and a pronounced kaliuresis that was maintained until the end of the experiment. Cumulative (above basal) renal K+ excretion at 270 min accounted for 26 ± 5% of ingested K+. The kidneys were important in mediating rapid corrections of substantial portions of the fluid and electrolyte disturbances resulting from ingestion of KHCO3 and NaHCO3 solutions.
Ventilatory and arousal responses of sleeping lambs to respiratory challenges: effect of prenatal maternal anemia
Authors: Moss Timothy J. , Harding Richard
Published: December 2017

We have examined the effects of exposure to chronic maternal anemia, throughout the final one-third of gestation, on postnatal ventilatory and arousal responses to hypoxia, hypercapnia, and combined hypoxia-hypercapnia in sleeping lambs. While resting quietly awake, lambs from anemic ewes had higher arterial [Formula: see text] levels than control animals during the first 2–3 postnatal wk, but pH, arterial [Formula: see text], and arterial O2 saturation were not different. During active and quiet sleep lambs from anemic ewes had higher end-tidal CO2levels than control animals when breathing room air and at the time of spontaneous arousal or when aroused by progressive hypercapnia or by combined hypoxia-hypercapnia. Ventilation and arterial O2saturation during uninterrupted sleep and ventilatory responsiveness to hypoxia (inspiratory O2 fraction, 10%), progressive hypercapnia, and combined hypoxia/hypercapnia were not significantly affected by exposure to maternal anemia. Our findings show that maternal anemia results in elevated[Formula: see text] levels in the offspring. This effect may be due, at least in part, to altered pulmonary function.
Ventilation heterogeneity does not change following pulmonary microembolism
Authors: Tsang John Y. C. , Frazer David , Hlastala Michael P.
Published: December 2017

By using the multiple-breath helium washout technique, ventilation heterogeneity (V˙H) after embolic injury in the lung can be quantitatively partitioned into the conductive and acinar components. Total V˙H, represented by the normalized slope of the phase III alveolar plateau, SnIII (total), was studied for 120 min in three groups of anesthetized and paralyzed mongrel dogs. Group 1 ( n = 3) received only normal saline and served as controls. Group 2 ( n = 4) received repeated infusions of polystyrene beads (250 μm) into the right atrium at 10, 40, 80, and 120 min. Group 3 ( n = 3) was similarly treated, except that the embolic beads used were 1,000 μm in diameter. The data show that, despite repeated embolic injury by polystyrene beads of different diameters, there was no significant increase in total V˙H. The acinar component of SnIII, which represents V˙H in the distal airways, accounts for over 90% of the totalV˙H. The conductive component of SnIII, which represents V˙H between larger conductive airways, remains relatively constant and a minor component. We conclude that pulmonary microembolism does not result in significant redistribution of ventilation.
Iron supplementation improves endurance after training in iron-depleted, nonanemic women
Authors: Hinton Pamela S. , Giordano Christina , Brownlie Thomas , Haas Jere D.
Published: December 2017

Our objective was to investigate the effects of iron depletion on adaptation to aerobic exercise, assessed by time to complete a 15-km cycle ergometer test. Forty-two iron-depleted (serum ferritin <16 μg/l), nonanemic (Hb >12 g/dl) women (18–33 yr old) received 100 mg of ferrous sulfate (S) or placebo (P) per day for 6 wk in a randomized, double-blind trial. Subjects trained for 30 min/day, 5 days/wk at 75–85% of maximum heart rate for the final 4 wk of the study. There were no group differences in baseline iron status or in 15-km time. Iron supplementation increased serum ferritin and decreased transferrin receptors in the S compared with the P group. The S and P groups decreased 15-km time and respiratory exchange ratio and increased work rate during the 15-km time trial after training. The decrease in 15-km time was greater in the S than in the P group ( P = 0.04) and could be partially attributed to increases in serum ferritin and Hb. These results indicate that iron deficiency without anemia impairs favorable adaptation to aerobic exercise.
Tyrosine kinase inhibitors modulate agonist-induced vasodilation in the hamster cheek pouch
Authors: Ikezaki Hiroyuki , Akhter Syed R. , Hong Dennis , Suzuki Hideyuki , Gao Xiao-Pei , Rubinstein Israel
Published: December 2017

The purpose of this study was to determine whether inhibitors of tyrosine kinase attenuate vasodilation elicited by endogenously elaborated and exogenously applied nitric oxide in the in situ peripheral microcirculation. Using intravital microscopy, we found that pretreatment with genistein (1.0 μM) and tyrphostin 25 (10.0 μM), two structurally unrelated tyrosine kinase inhibitors, significantly attenuated acetylcholine-, bradykinin- and nitroglycerin-induced dilation of second-order arterioles (51 ± 1 μm) in the in situ hamster cheek pouch ( P < 0.05). Both inhibitors nearly abrogated acetylcholine-induced responses but only partially blocked bradykinin- and nitroglycerin-induced vasodilation. Genistein and tyrphostin 25 alone had no significant effects on resting arteriolar diameter and on adenosine-induced vasodilation in the cheek pouch. On balance, these data indicate that tyrosine kinase inhibitors attenuate endogenously elaborated and exogenously applied nitric oxide-induced vasodilation in the in situ hamster cheek pouch. However, the extent of tyrosine kinase inhibitor-sensitive pathway involvement in this response appears to be agonist dependent.
Influence of positive airway pressure on the pressure gradient for venous return in humans
Authors: Jellinek H. , Krenn H. , Oczenski W. , Veit F. , Schwarz S. , Fitzgerald R. D.
Published: December 2017

To study the effect of positive airway pressure (Paw) on the pressure gradient for venous return [the difference between mean systemic filling pressure (Pms) and right atrial pressure (Pra)], we investigated 10 patients during general anesthesia for implantation of defibrillator devices. Paw was varied under apnea from 0 to 15 cmH2O, which increased Pra from 7.3 ± 3.1 to 10.0 ± 2.3 mmHg and decreased left ventricular stroke volume by 23 ± 22%. Episodes of ventricular fibrillation, induced for defibrillator testing, were performed during 0- and 15-cmH2O Paw to measure Pms (value of Pra 7.5 s after onset of circulatory arrest). Positive Paw increased Pms from 10.2 ± 3.5 to 12.7 ± 3.2 mmHg, and thus the pressure gradient for venous return (Pms − Pra) remained unchanged. Echocardiography did not reveal signs of vascular collapse of the inferior and superior vena cava due to lung expansion. In conclusion, we demonstrated that positive Paw equally increases Pra and Pms in humans and alters venous return without changes in the pressure gradient (Pms − Pra).
A new method for measurement of blood pressure, heart rate, and activity in the mouse by radiotelemetry
Authors: Mills Perry A. , Huetteman Daniel A. , Brockway Brian P. , Zwiers Lynn M. , Gelsema A. J. Mick , Schwartz Robert S. , Kramer Klaas
Published: December 2017

A simple and reliable means for accurate, chronic measurement of pulsatile blood pressure (BP) from conscious, freely moving laboratory mice was developed and validated. The newly developed device consists of a small (1.9 ml, 3.4 g), fully implantable radiotelemetry transmitter. Initial frequency response tests showed an adequate dynamic response; the average −3-dB point found in five transmitters was 145 ± 14 (SD) Hz. BP, heart rate, and locomotor activity were recorded from 16 chronically (30–150 days) implanted mice. Mean arterial and pulse pressure, checked at regular intervals, ranged from 90–140 mmHg and from 30–50 mmHg, respectively, throughout the study. Transmitter BP measurements were validated against a Millar 1.4-Fr. transducer-tipped catheter. The mean error of the transmitters for diastolic pressures was +1.1 ± 6.9 mmHg ( n = 7). The error for systolic pressures was, on average, 2.7 ± 3.9 mmHg larger. This new device accurately monitors BP, heart rate, and locomotor activity in conscious, untethered, freely moving mice living in their home cages for periods of at least 150 days.
Possible mechanisms of muscle cramp from temporal and spatial surface EMG characteristics
Authors: Roeleveld K. , van Engelen B. G. M. , Stegeman D. F.
Published: December 2017

In this study, the initiation and development of muscle cramp are investigated. For this, we used a 64-channel surface electromyogram (EMG) to study the triceps surae muscle during both cramp and maximal voluntary contraction (MVC) in four cramp-prone subjects and during cramp only in another four cramp-prone subjects. The results show that cramp presents itself as a contraction of a slowly moving fraction of muscle fibers, indicating that either the spatial arrangement of the motoneurons and muscle fibers is highly related or that cramp spreads at a level close to the muscle. Spectral analyses of the EMG and peak-triggered average potentials show the presence of extremely short potentials during cramp compared with during MVC. These results can also be interpreted in two ways. Either the motoneurons fire with enlarged synchronization during MVC compared with cramp, or smaller units than motor units are active, indicating that cramp is initiated close to or even at the muscle fiber level. Further research is needed to draw final conclusions.
Myogenic and scalp signals evoked by midinspiratory airway occlusion
Authors: Garden A. L.
Published: December 2017

A somatosensory potential that is evoked by transient added inspiratory load has previously been described (Davenport PW, Friedman WA, Thompson FJ, and Franzen O. J Appl Physiol60: 1843–1848, 1986). This evoked potential is novel because it arises in response to a stimulus that also evokes a muscle response, and so this potential could contain myogenic components. The present study was undertaken to define the relationship between the scalp response and other physiological responses that are evoked by airway occlusion. Evoked signals were recorded from the scalp, scalenus anterior, masseter, and electrooculogram. Responses to a 200-ms midinspiratory occlusion were recorded in 12 healthy volunteers. Evoked responses were reliably recorded at C3-CZ and C4-CZ and from the skin overlying the scalenus anterior in 11 of these subjects. The onset latencies were 15.7 ± 3.1 at C3-CZ, 15.9 ± 2.1 at C4-CZ, and 17.6 ± 5.5 ms at scalenus anterior. In nine subjects, the masseter response appeared to coincide with the mouth pressure trace, and this was interpreted as movement artifact. No consistent electrooculogram or frontal electroencephalogram response was recorded. Because of the similarity in onset latency at C3-CZ, C4-CZ, and scalenus anterior, it was concluded that the myogenic signal may contribute to the scalp response and should be viewed as a potential source of artifact in experiments of this nature.
Analysis of ultrasonically extracted interstitial fluid as a predictor of blood glucose levels
Authors: Mitragotri Samir , Coleman Matthew , Kost Joseph , Langer Robert
Published: December 2017

Transdermal extraction of clinically relevant analytes offers a potentially noninvasive method of diagnostics. However, development of such a method is limited by the low permeability of skin. In this paper, we present a potential method for noninvasive diagnostics based on ultrasonic skin permeabilization and subsequent extraction of interstitial fluid (ISF) across the skin using vacuum. ISF extracted by this method was collected and analyzed for glucose and other analytes. Glucose concentration in the extracted fluid correlates well with blood glucose concentration over a range of 50–250 mg/dl. A mathematical model describing vacuum-induced transport of ISF through ultrasonically permeabilized skin is presented as well. The model accounts for convective, as well as diffusive, transport processes across blood capillaries, epidermis, and the stratum corneum. The overall predictions of the model compare favorably with the experimental observations.
Effects of aortic nerve on hemodynamic response to obstructive apnea in sedated pigs
Authors: Chen Ling , Scharf Steven M.
Published: December 2017

In this study we test the hypothesis that aortic nerve traffic is responsible for the pressor response to periodic apneas. In nine intubated, sedated chronically instrumented pigs, periodic obstructive apneas were caused by occlusion of the endotracheal tube for 30 s, followed by spontaneous breathing for 30 s. This was done under control (C) conditions, after section of the aortic nerve (ANS), and after bilateral cervical vagotomy (Vagot). Blood-gas tensions and airway pressure changed similarly under all conditions: Po 2 decreased to 50–60 Torr, Pco 2 increased to ∼55 Torr, and airway pressure decreased by 40–50 mmHg during apnea. With C, mean arterial pressure (MAP) increased from 111 ± 4 mmHg at baseline to 120 ± 5 mmHg at late apnea ( P < 0.01). After ANS and Vagot, there was no change in MAP with apneas compared with baseline. Relative to baseline, cardiac output and stroke volume decreased with C but not with ANS or Vagot during apneas. Increased MAP was due to increased systemic vascular resistance. Heart rate behaved similarly with C and ANS, being greater at early interapnea than late apnea. With Vagot, heart rate increased throughout the apnea-interapnea cycle relative to baseline. We conclude that, in sedated pigs, aortic nerve traffic mediates the increase in MAP and systemic vascular resistance observed during periodic apneas. Increase in MAP is responsible for decreased cardiac output and stroke volume. Additional vagal reflexes, most likely parasympathetic efferents, are responsible for interacting with sympathetic excitatory influences in modulating heart rate.
Sequential V˙a/Q˙ distributions in the normal rabbit by micropore membrane inlet mass spectrometry
Authors: Baumgardner James E. , Choi In-Cheol , Vonk-Noordegraaf Anton , Frasch H. Frederick , Neufeld Gordon R. , Marshall Bryan E.
Published: December 2017

We developed micropore membrane inlet mass spectrometer (MMIMS) probes to rapidly measure inert-gas partial pressures in small blood samples. The mass spectrometer output was linearly related to inert-gas partial pressure ( r 2 of 0.996–1.000) and was nearly independent of large variations in inert-gas solubility in liquid samples. We infused six inert gases into five pentobarbital-anesthetized New Zealand rabbits and used the MMIMS system to measure inert-gas partial pressures in systemic and pulmonary arterial blood and in mixed expired gas samples. The retention and excretion data were transformed into distributions of ventilation-to-perfusion ratios (V˙a/Q˙) with the use of linear regression techniques. Distributions ofV˙a/Q˙ were unimodal and broad, consistent with prior reports in the normal rabbit. Total blood sample volume for eachV˙a/Q˙ distribution was 4 ml, and analysis time was 8 min. MMIMS provides a convenient method to perform the multiple inert-gas elimination technique rapidly and with small blood sample volumes.
Role of positive airway pressure on pulmonary acinar perfusion heterogeneity
Authors: Tanabe Nobuhiro , Todoran Thomas M. , Zenk Gerald M. , Aono Jun , Wagner Wiltz W. , Presson Robert G.
Published: December 2017

Perfusion of the pulmonary acinus has been shown to be generally homogeneous, but there is a significant component that is heterogeneous. To investigate the contribution of the alveolar septal capillary network to acinar perfusion heterogeneity, the passage of fluorescent dye boluses through the subpleural microcirculation of isolated dog lung lobes was videotaped using fluorescence microscopy. As the videotapes were replayed, dye-dilution curves were recorded from each of the tributary branches of Y-shaped venules that drained single acini. For each Y-shaped venule, the mean appearance time difference between the pair of tributary branches was calculated from the dye curves. When the complex septal capillary networks were derecruited by high positive airway pressure, venular perfusion became proportionally more homogeneous. This result shows that septal capillary resistance and pathlength differences are important contributors to intra-acinar perfusion heterogeneity.
Dynamic exercise attenuates sympathetic responsiveness of canine vascular smooth muscle
Authors: Ruble Stephen B. , Valic Zoran , Buckwalter John B. , Clifford Philip S.
Published: December 2017

The phenomenon of reduced responsiveness of the skeletal muscle arterial vasculature to sympathetic activation during exercise (sympatholysis) remains controversial. The purpose of this study was to examine the vascular effects of sympathoactivation in dynamically exercising skeletal muscle. Mongrel dogs (19–24 kg) were instrumented chronically with transit-time ultrasonic flow probes on the external iliac arteries. After pretreatment with atropine (0.2 mg/kg), an intravenous bolus (4 μg/kg) of a nicotinic ganglion stimulant [1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)] was given at rest and during treadmill exercise at graded intensities. Administration of DMPP was associated with prompt reductions in iliac blood flow and increases in arterial pressure under all conditions. There were significant reductions ( P < 0.05) in iliac vascular conductance of 58 ± 4 (SE), 48 ± 3, 36 ± 5, and 16 ± 3% at rest, 3 miles/h and 0% grade, 6 miles/h and 0% grade, and 6 miles/h and 15% grade, respectively. These data demonstrate that activation of postganglionic sympathetic nerves with DMPP caused vasoconstriction in the skeletal muscle vasculature at rest and during exercise. Additionally, the magnitude of vasoconstriction was inversely related to exercise intensity. These results support the concept of exercise sympatholysis.
Prolonged fasting significantly changes nutrient oxidation and glucose tolerance after a normal mixed meal
Authors: Horton Tracy J. , Hill James O.
Published: December 2017

The aim of this study was to establish the experimental paradigm of fasting, followed by refeeding, to investigate individual differences in nutrient partitioning. Eight nonobese men were fed a normal meal (25% of daily energy requirements) on two occasions, after an overnight (13-h) fast and after a prolonged (72-h) fast. During the entire fasting period, subjects were resident in a whole room indirect calorimeter, and blood samples were drawn periodically. Because no other food was consumed over the 12 h after either meal, negative energy balance was observed after the overnight and prolonged fast. Postprandial carbohydrate oxidation was significantly reduced after the 72- vs. 13-h fast ( P < 0.0001), whereas fat oxidation was significantly increased ( P < 0.0001). Interestingly, carbohydrate balance was positive after the prolonged fast but negative after the overnight fast (24 ± 17 vs. −57 ± 16 g/12 h, respectively; P < 0.001), whereas fat balance was negative under both conditions (−78 ± 7 vs. −47 ± 8 g/12 h, respectively; P < 0.002). With 72 h of fasting, the glucose and insulin excursions in response to the mixed meal were significantly greater compared with the 13-h fast ( P < 0.001). In conclusion, prolonged fasting resulted in a significant decrease in carbohydrate oxidation and an increase in fat oxidation, after a normal mixed meal, in healthy men. This was associated with a significant decrease in glucose tolerance. Because circulating free fatty acids were greatly elevated at all times after the prolonged fast, these may be mediating some of the changes in postprandial metabolism.
Electrical and mechanical Hmax-to-Mmaxratio in power- and endurance-trained athletes
Authors: Maffiuletti Nicola A. , Martin Alain , Babault Nicolas , Pensini Manuela , Lucas Brigitte , Schieppati Marco
Published: December 2017

The aim of this study was to compare the mechanical and electromyographic (EMG) characteristics of soleus motor units activated during maximal H reflex and direct M response among subjects with different histories of physical activity. Power-trained athletes produced stronger twitches, with a higher rate of twitch tension buildup and relaxation, than their endurance counterparts for both maximal H-reflex and maximal M-wave responses. The maximal H-reflex-to-maximal M-wave ratios for both force output (twitch) and EMG wave amplitude were significantly lower in power-trained than endurance-trained athletes. However, power-trained athletes exhibited a significantly greater twitch-to-EMG ratio for the reflexly activated motor units with respect to the entire motor pool, whereas endurance-trained athletes had comparable twitch-to-EMG ratios for both reflexly and directly activated units. Power training increases the force output of the whole ensemble of the motor units, thereby compensating for the lower efficacy of the reflex transmission between Ia spindle afferent input and soleus α-motoneuron. On the other hand, the lower level of force evoked by the reflexly activated units in endurance-trained athletes is associated with a greater motor pool reflex excitability. Therefore, endurance-trained athletes produce the necessary force by recruitment of more slow-twitch units than do other subjects for comparable levels of force and type of task.
Age, sex, race, initial fitness, and response to training: the HERITAGE Family Study
Authors: Skinner James S. , Jaskólski Artur , Jaskólska Anna , Krasnoff Joanne , Gagnon Jacques , Leon Arthur S. , Rao D. C. , Wilmore Jack H. , Bouchard Claude
Published: December 2017

Effects of age, sex, race, and initial fitness on training responses of maximal O2 uptake (V˙o 2 max) are unclear. Data were available on 435 whites and 198 blacks (287 men and 346 women), aged 17–65 yr, before and after standardized cycle ergometer training. Individual responses varied widely, butV˙o 2 max increased significantly for all groups. Responses by men and women and by blacks and whites of all ages varied widely. There was no sex difference for change (Δ) inV˙o 2 max(ml · kg−1 · min−1); women had lower initial values and greater relative (%) increases. Blacks began with lower values but had similar responses. Older subjects had a lower Δ but a similar percent change. BaselineV˙o 2 max correlated nonsignificantly with ΔV˙o 2 max but significantly with percent change. There were high, medium, and low responders in all age groups, both sexes, both races, and all levels of initial fitness. Age, sex, race, and initial fitness have little influence onV˙o 2 max response to standardized training in a large heterogeneous sample of sedentary black and white men and women.
Genomic scan for genes affecting body composition before and after training in Caucasians from HERITAGE
Authors: Chagnon Yvon C. , Rice Treva , Pérusse Louis , Borecki Ingrid B. , Ho-Kim My-Anh , Lacaille Michel , Paré Chantal , Bouchard Luigi , Gagnon Jacques , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Rao D. C. , Bouchard Claude
Published: December 2017

An autosomal genomewide search for genes related to body composition and its changes after a 20-wk endurance-exercise training program has been completed in the HERITAGE Family Study. Phenotypes included body mass index (BMI), sum of eight skinfold thicknesses, fat mass (FM), fat-free mass, percent body fat (%Fat), and plasma leptin levels. A maximum of 364 sib-pairs from 99 Caucasian families was studied with the use of 344 markers with single-point and multipoint linkage analyses. Evidence of significant linkage was observed for changes in fat-free mass with the S100A and the insulin-like growth factor I genes ( P = 0.0001). Suggestive evidence (2.0 ≤ Lod < 3.0; 0.0001 < P ≤ 0.001) was also observed for the changes in FM and %Fat at 1q31 and 18q21-q23, in %Fat with the uncoupling protein 2 and 3 genes, and in BMI at 5q14-q21. At baseline, suggestive evidence was observed for BMI at 8q23-q24, 10p15, and 14q11; for FM at 14q11; and for plasma leptin levels with the low-density lipoprotein receptor gene. This is the first genomic scan on genes involved in exercise-training-induced changes in body composition that could provide information on the determinants of weight loss.
Midlatency respiratory-related somatosensory activity and perception of oral pressure pulses in normal humans
Authors: Daubenspeck J. Andrew , Manning Harold L. , Baird John C.
Published: December 2017

A direct relationship exists within subjects between midlatency features (<100 ms poststimulus) of respiratory-related evoked potentials and the perceived magnitude of applied oral pressure pulse stimuli. We evaluated perception in 18 normal subjects using cross-modality matching of applied pressure pulses via grip force and estimated mechanoafferent activity in these subjects by computing the global field power (GFP) from respiratory-related evoked potentials recorded over the right side of the scalp. We compared across subjects 1) the predicted magnitude production for a standard pressure pulse and 2) the slope (β) and 3) the intercept (INT) of the Stevens power law to the summed GFP over 20–100 ms poststimulus. Both the magnitude production for a standard pressure pulse and the β showed an inverse relationship with the summed GFP over 20–100 ms poststimulus, although there was no relationship between INT and the summed GFP. This may partially reflect characteristics of the mechanosensors and surely includes aspects of cognitive judgment, because we found and corrected for a high correlation between, respectively, β (and INT) for pressure pulses and β (and INT) for estimation of line lengths, a nonrespiratory modality. The relatively shallow, even inverse GFP-to-perception relationship suggests that, despite marked differences in the magnitude of afferent traffic, normal subjects seem to perceive things similarly.
Muscle-specific atrophy of the quadriceps femoris with aging
Authors: Trappe T. A. , Lindquist D. M. , Carrithers J. A.
Published: December 2017

We examined the size of the four muscles of the quadriceps femoris in young and old men and women to assess whether the vastus lateralis is an appropriate surrogate for the quadriceps femoris in human studies of aging skeletal muscle. Ten young (24 ± 2 yr) and ten old (79 ± 7 yr) sedentary individuals underwent magnetic resonance imaging of the quadriceps femoris after 60 min of supine rest. Volume (cm3) and average cross-sectional area (CSA, cm2) of the rectus femoris (RF), vastus lateralis (VL), vastus intermedius (VI), vastus medialis (VM), and the total quadriceps femoris were decreased ( P < 0.05) in older compared with younger women and men. However, percentage of the total quadriceps femoris taken up by each muscle was similar ( P > 0.05) between young and old (RF: 10 ± 0.3 vs. 11 ± 0.4; VL: 33 ± 1 vs. 33 ± 1; VI: 31 ± 1 vs. 31 ± 0.4; VM: 26 ± 1 vs. 25 ± 1%). These results suggest that each of the four muscles of the quadriceps femoris atrophy similarly in aging men and women. Our data support the use of vastus lateralis tissue to represent the quadriceps femoris muscle in aging research.
On-line detection of sleep-wake states and application to produce intermittent hypoxia only in sleep in rats
Authors: Hamrahi Hedieh , Chan Beverley , Horner Richard L.
Published: December 2017

Sleep-disordered breathing is associated with adverse clinical consequences such as daytime sleepiness and hypertension. The mechanisms behind these associations have been studied in animal models, especially rats, but intermittent stimuli such as hypoxia have been applied without reference to sleep-wake states. To determine mechanisms underlying the adverse physiological consequences of stimuli associated with sleep-disordered breathing requires criteria for detection of sleep-wake states on-line to trigger stimuli only in sleep. This study aimed to develop such a system for freely behaving rats. Twelve rats with implanted electroencephalogram and neck electromyogram electrodes were studied in the light and dark phases. Electroencephalogram frequencies in the high (20–30 Hz) and low (2–4 Hz) frequency bands distinguished non-rapid eye movement (REM) sleep, whereas neck electromyogram distinguished REM. Using these parameters in a simple algorithm led to detection accuracies of 94.5 ± 1.0 (SE) % for wakefulness, 96.2 ± 0.8% for non-REM sleep, and 92.3 ± 1.6% for REM compared with blinded human judgment. The algorithm was then used to trigger hypoxic stimuli only in sleep. Because frequency and amplitude analysis is readily performed using a variety of commercial systems, incorporation of these parameters into such an algorithm will facilitate studies investigating mechanisms underlying the physiological consequences of sleep-related respiratory stimuli in a fashion that more effectively models clinical disorders.
Variance of ventilation during exercise
Authors: Beck Kenneth C. , Wilson Theodore A.
Published: December 2017

Expired gas concentrations were measured during a multibreath washin of He in one female and seven male subjects at rest (seated) and during cycle exercise at work rates of 70–210 W. In a computational model, the ventilation distribution was represented as a log-normal distribution with standard deviation (ςV˙); values of ςV˙ were obtained by fitting the output of the model to the data. At rest, ςV˙ was 0.89 ± 0.18; during exercise, ςV˙ was 0.60 ± 0.13, independent of the level of exercise. These values for the width of the functional ventilation distribution at the scale of the acinus are approximately two times larger than those obtained from anatomic measurements in animals at a scale of 1 cm3. The values for ςV˙, together with data from the literature on the width of the functional ventilation-perfusion distribution, show that ventilation and perfusion are highly correlated at rest, in agreement with anatomic data. The structural sources of nonuniform ventilation and perfusion and of the correlation between them are unknown.
An automated flinch detecting system for use in the formalin nociceptive bioassay
Authors: Yaksh Tony L. , Ozaki George , McCumber Damon , Rathbun Michael , Svensson Camilla , Malkmus Shelle , Yaksh Michael C.
Published: December 2017

The biphasic display of paw-flinch behavior in the rat after injection of formalin into the dorsum of the hind paw is used for the screening of anti-hyperalgesic agents. Described and characterized here is a less labor-intensive system for counting flinch activity by detecting movement of a small metal band placed on the formalin-injected paw. A signal is generated as the band breaks the electromagnetic field of a loop antenna located under the rat and processed through an algorithm that determines flinch activity using 1) amplitude, 2) zero-voltage crossing, and 3) signal duration. Flinches are summed and stored over a selected collection interval throughout the assay for later analysis. Studies have validated the measures with respect to 1) system stability over time; 2) system-to-“practiced observer” correlation on flinch detection, r2= 0.94; 3) system variables including time of day, sex, age, and body weight; and 4) 50% effective dose values similar to those previously reported for intrathecal morphine and the NMDA antagonist MK-801.
Validity of inspiratory and expiratory methods of measuring gas exchange with a computerized system
Authors: Bassett David R. , Howley Edward T. , Thompson Dixie L. , King George A. , Strath Scott J. , McLaughlin James E. , Parr Brian B.
Published: December 2017

The accuracy of a computerized metabolic system, using inspiratory and expiratory methods of measuring ventilation, was assessed in eight male subjects. Gas exchange was measured at rest and during five stages on a cycle ergometer. Pneumotachometers were placed on the inspired and expired side to measure inspired (V˙i) and expired ventilation (V˙e). The devices were connected to two systems sampling expired O2and CO2from a single mixing chamber. Simultaneously, the criterion (Douglas bag, or DB) method assessed V˙e and fractions of O2and CO2in expired gas (FeO2and FeCO2) for subsequent calculation of O2uptake (V˙o2), CO2production (V˙co2), and respiratory exchange ratio. Both systems accurately measured metabolic variables over a wide range of intensities. Though differences were found between the DB and computerized systems for FeO2(both inspired and expired systems), FeCO2(expired system only), andV˙o2(inspired system only), the differences were extremely small (FeO2= 0.0004, FeCO2= −0.0003,V˙o2= −0.018 l/min). Thus a computerized system, using inspiratory or expiratory configurations, permits extremely precise measurements to be made in a less time-consuming manner than the DB technique.
Effect of REM sleep on retroglossal cross-sectional area and compliance in normal subjects
Authors: Rowley James A. , Sanders Carrie S. , Zahn Brian R. , Badr M. Safwan
Published: December 2017

It has been proposed that the upper airway compliance should be highest during rapid eye movement (REM) sleep. Evidence suggests that the increased compliance is secondary to an increased retroglossal compliance. To test this hypothesis, we examined the effect of sleep stage on the relationship of retroglossal cross-sectional area (CSA; visualized with a fiber-optic scope) to pharyngeal pressure measured at the level of the oropharynx during eupneic breathing in subjects without significant sleep-disordered breathing. Breaths during REM sleep were divided into phasic (associated with eye movement, PREM) and tonic (not associated with eye movements, TREM). Retroglossal CSA decreased with non-REM (NREM) sleep and decreased further in PREM [wake 156.8 ± 48.6 mm2, NREM 104.6 ± 65.0 mm2( P < 0.05 wake vs. NREM), TREM 83.1 ± 46.4 mm2 ( P = not significant NREM vs. TREM), PREM 73.9 + 39.2 mm2 ( P < 0.05 TREM vs. PREM)]. Retroglossal compliance, defined as the slope of the regression CSA vs. pharyngeal pressure, was the same between all four conditions (wake −0.7 + 2.1 mm2/cmH2O, NREM 0.6 ± 3.0 mm2/cmH2O, TREM −0.2 ± 3.3 mm2/cmH2O, PREM −0.6 ± 5.1 mm2/cmH2O, P = not significant). We conclude that the intrinsic properties of the airway wall determine retroglossal compliance independent of changes in the neuromuscular activity associated with changes in sleep state.
Ultrasound measurements of fetal breathing movements in the rat
Authors: Kobayashi Koichi , Lemke Robert P. , Greer John J.
Published: December 2017

The goal of this study was to determine when fetal breathing movements (FBMs) commence in the rat and to characterize age-dependent changes of FBMs in utero. These data provide a frame of reference for parallel in vitro studies of the cellular, synaptic, and network properties of the perinatal rat respiratory system. Ultrasound recordings were made from unanesthetized Sprague-Dawley rats from embryonic (E) day 15 (E15) to E20. Furthermore, the effects of respiratory stimulants (doxapram and aminophylline) and hypoxia on FBMs were studied. Single FBMs, occurring at a very low frequency (∼8 FBMs/h), commenced at E16. The incidence of single FBMs increased to ∼80 FBMs/h by E20. Episodes of clustered rhythmic FBMs were first observed at E18 (∼40 FBMs/h). The incidence of episodic clustered FBMs increased to ∼300 FMBs/h by E20, with the duration of each episode ranging from ∼40 to 180 s. Doxapram, presumably acting to stimulate carotid body receptors, did not increase FBMs until E20, when the incidence of episodic clustered FBMs increased twofold. Aminophylline, a central-acting stimulant, caused an increase in episodic clustered FBMs after E17, reaching significance at E20 (3-fold increase). Exposing the dam to 10% O2 caused a rapid, marked suppression of FBMs (5-fold decrease) that was readily reversed on exposure to room air.