bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo studies of cellular energy state, pH, and sodium in rat liver after thermal injury
Authors: Xia Z. F. , Horton J. W. , Zhao P. Y. , Bansal N. , Babcock E. E. , Sherry A. D. , Malloy C. R.
Published: December 2017

In vivo 31P- and 23Na-magnetic resonance spectroscopy was used to measure phosphorus metabolites, intracellular pH, cytosolic free Mg2+, and intracellular Na+ in the liver of rats 24 h after 40% total body surface area full-thickness burn injury. Studies were performed during infusion of thulium (III) 1,4,7,10-tetraazacyclododecane N,N′,N″,N″′-tetra(methylenephosphonate), which served as the Na+ shift agent. Compared with the sham-burn group, there was a significant increase in hepatic intracellular Na+ along with a decrease in intracellular pH and free Mg2+. The ratio of intra- to extra-cellular Na+ increased, indicating a decreased Na+ gradient that may determine the hepatic transmembrane potential difference. Hepatic beta-ATP/P(i) also significantly decreased, which suggests that either ATP utilization is significantly accelerated or ATP synthesis is inhibited after the thermal injury. Of the cations measured (Na+, Mg2+, H+), the change in intracellular Na+ was most dramatic. This study demonstrates that major burn injury may cause profound changes in hepatic bioenergetics and ionic metabolism 24 h after injury and that intracellular Na+ may be a sensitive indicator of hepatic dysfunction 24 h after injury. Because these animals tolerated the shift reagent, thuliumIII) 1,4,7,10-tetraazacyclododecane N,N′,N″,N″′-tetra(methylenephosphonate), nuclear magnetic resonance spectroscopy may prove valuable in monitoring intracellular cations in the liver after major injury.
Acetylcholine and carotid body excitation during hypoxia in the cat
Authors: Fitzgerald R. S. , Shirahata M.
Published: December 2017

The purpose of this study was to test the hypothesis that acetylcholine (ACh) is an excitatory neurotransmitter during the hypoxic stimulation of the carotid body. Cats were anesthetized, paralyzed, and artificially ventilated. The common carotid artery was fitted with a loop containing a stopcock for selectively perfusing the carotid body. Neural activity was recorded from the whole carotid sinus nerve. After the cats had been ventilated on 10% O2 for 3 min with the carotid body being normally perfused with its own hypoxic arterial blood, the stopcock was turned, and either equally hypoxic Krebs-Ringer bicarbonate solution (KRB) containing alpha-bungarotoxin, mecamylamine, and atropine or hypoxic blocker-free KRB perfused the carotid body for 2 min. The stopcock was returned to its original position, allowing blocker-free hypoxic blood to perfuse the carotid body once again. With this protocol we found 1) the cholinergic blockers reduced the carotid body response to hypoxic KRB in a dose-dependent manner; 2) carotid baroreceptor activity was not reduced by the blockers, suggesting that the action of the blockers was not nonspecific (whereas lidocaine rapidly reduced both chemoreceptor and baroreceptor activity); 3) inclusion of the blockers in perfused hypoxic blood also reduced neural output from the carotid body; and 4) the blockers reduced the carotid body's neural response to hypoxic KRB containing substance P (20 micrograms/100 ml), suggesting that substance P may be linked to ACh in the carotid body. We conclude that these data provide good evidence supportive of an excitatory role for ACh in carotid body hypoxic excitation.
Effect of FLAP antagonist MK-0591 on leukotriene production and ozone-induced airway responses in dogs
Authors: Stevens W. H. , Lane C. G. , Woolley M. J. , Ellis R. , Tagari P. , Black C. , Ford-Hutchinson A. , O′Byrne P. M.
Published: December 2017

We used the 5-lipoxygenase-activating protein (FLAP) antagonist MK-0591 to investigate the importance of leukotrienes (LT) in causing ozone-induced bronchoconstriction, airway inflammation, and airway hyperresponsiveness in dogs. Six random source dogs were studied. On one day, dogs were treated with MK-0591 (2 mg/kg iv) followed by a continuous intravenous infusion of 8 micrograms.kg-1.min-1. On the other day, the diluent was infused. Acetylcholine airway responsiveness was measured before and 1 h after ozone inhalation (3 ppm for 30 min). On each day, whole blood and bronchoalveolar lavage (BAL) cells were challenged with calcium ionophore to stimulate LTB4 production. Urinary LTE4 levels were measured before and after ozone. MK-0591 inhibited LTB4 production in whole blood by 96% (P = 0.001) and that from BAL cells by 91% (P = 0.001). By contrast, MK-0591 had no effect on ozone-induced bronchoconstriction, airway hyperresponsiveness, or influx of neutrophils into BAL. The mean log difference of the pre- to post-acetylcholine provocative concentration was 0.64 +/- 0.40 during MK-0591 treatment and 0.68 +/- 0.40 during diluent treatment (P = 0.71). These results indicate that peptidoleukotrienes are produced during ozone inhalation and that MK-0591 inhibits LT production in dogs. However, LTs do not play a role in ozone-induced bronchoconstriction, airway inflammation, or airway hyperresponsiveness in dogs.
Responses to pressure and vasoactive agents by isolated pulmonary arteries from monocrotaline-treated rats
Authors: Madden J. A. , Keller P. A. , Effros R. M. , Seavitte C. , Choy J. S. , Hacker A. D.
Published: December 2017

Intralobar and side branch pulmonary arteries removed from rats 7, 14, and 21 days after injection with monocrotaline (MCT) were cannulated and pressurized, and their responses to potassium chloride, norepinephrine, acetylcholine, and angiotensin II were measured. Static pressure-diameter curves were also performed, and arterial distensibility was calculated. Arteries from all three MCT-treated groups showed reduced responses to potassium chloride and angiotensin II compared with control arteries (P < 0.05). The norepinephrine response was significantly reduced in arteries from the 14- and 21-day groups (P < 0.05). Dilations in response to acetylcholine were similar in arteries from the control and 7-day groups but were reduced compared with those in control vessels from the 14- and 21-day groups (P < 0.05). Compared with control values, the slopes of the pressure-diameter curves and the arterial distensibility decreased significantly with time after MCT treatment (P < 0.05). Values for arterial distensibilities obtained in the isolated pulmonary arteries support the theory that structural changes that occur as a result of MCT administration contribute to vessel stiffness. The acetylcholine-induced dilation of vessels from MCT-treated rats indicates that endothelium-derived factors are still produced, but diminished vasodilation coupled with decreased distensibilities after MCT suggest that abnormal vascular remodeling rather than a change in agonist sensitivity may be responsible for the reduced responsiveness seen in these arteries.
Effect of resistance training on muscle use during exercise
Authors: Ploutz L. L. , Tesch P. A. , Biro R. L. , Dudley G. A.
Published: December 2017

This study examined the effect of resistance training on exercise-induced contrast shift in magnetic resonance (MR) images. It was hypothesized that a given load could be lifted after training with less muscle showing contrast shift, thereby suggesting less muscle was used to perform the exercise. Nine males trained the left quadriceps femoris (QF) muscle 2 days/wk for 9 wk using 3–6 sets of 12 knee extensions each day. The right QF served as a “control.” Exercise-induced contrast shifts in MR images evoked by each of three bouts of exercise (5 sets of 10 knee extensions with a load equal to 50, 75, and 100% of the maximum pretraining load that could be lifted for 5 sets of 10 repetitions) were quantified pre- and posttraining. MR image contrast shift was quantified by determining QF cross-sectional area (CSA) showing increased spin-spin relaxation time. One repetition maximum increased 14% in the left trained QF and 7% in the right untrained QF. Left QF CSA increased 5%, with no change in right QF CSA. Left QF CSA showing contrast shift was less after each bout of the exercise test posttraining. This was also true, to a lesser extent, for the right QF at the higher two loads. The results suggest that short-term resistance training reduces MR image contrast shift evoked by a given effort, thereby reflecting the use of less muscle to lift the load. Because this response was evident in both trained and contralateral untrained muscle, neural factors are suggested to be responsible.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of sprint training on human skeletal muscle purine nucleotide metabolism
Authors: Stathis C. G. , Febbraio M. A. , Carey M. F. , Snow R. J.
Published: December 2017

To examine the effect of sprint training on human skeletal muscle purine nucleotide metabolism, eight active untrained subjects completed a maximal 30-s sprint bout on a cycle ergometer before and after 7 wk of sprint training. Resting muscle ATP and total adenine nucleotide content were reduced (P < 0.05) by 19 and 18%, respectively, after training. Training resulted in a 52% attenuation (P < 0.05) in the magnitude of ATP depletion after exercise and a similar reduction (P < 0.05) in the accumulation of inosine 5′-monophosphate and ammonia. During recovery, muscle inosine 5′-monophosphate (P < 0.05) and inosine (P < 0.01) content were reduced after training, as was the accumulation of inosine (P < 0.05). Plasma ammonia was higher (P < 0.05) after training early in recovery; in contrast, plasma hypoxanthine concentrations were reduced (P < 0.05) during the latter stages of recovery. The attenuated resting ATP and total adenine nucleotide contents after training probably result from the acute effects of prior training sessions. The reduction in the magnitude of ATP depletion during a 30-s sprint bout after training must reflect an improved balance between ATP hydrolysis and resynthesis. It is unclear which mechanism(s) is responsible for the reduction in the magnitude of ATP degradation after training.
Epithelium acts as a modulator and a diffusion barrier in the responses of canine airway smooth muscle
Authors: Gao Y. , Vanhoutte P. M.
Published: December 2017

The present study was designed to determine the role of the respiratory epithelium as a diffusion barrier and a modulator of the responsiveness of airway smooth muscle to bronchoactive agents. Segments of canine bronchi, with or without epithelium, were suspended in organ chambers and perfused intraluminally. The isometric tension was recorded. Acetylcholine, given intraluminally, induced significantly smaller contractions in bronchi with than in bronchi without epithelium. When this agonist was given extraluminally, no difference in contractions was noted between the tissues. In the presence of acetylcholine and phentolamine, norepinephrine, given either intra- or extraluminally, induced significantly larger relaxations in bronchi with than in bronchi without epithelium. High potassium given intraluminally induced contractions only in bronchi without epithelium; however, in the presence of ouabain, both tissues contracted similarly. When high potassium was given extraluminally, no difference in contraction between tissues with and without epithelium was noted. When [3H]acetylcholine and [3H]norepinephrine were perfused intraluminally, the accumulation of 3H radioactivity in the extraluminal solutions was significantly less in bronchi with than in bronchi without epithelium. These observations suggest that the epithelium acts as both a diffusion barrier and a modulator of the responses of canine airways to bronchoactive agents.
Thyroid hormone changes in a cold air environment after local cold acclimation
Authors: Savourey G. , Caravel J. P. , Barnavol B. , Bittel J. H.
Published: December 2017

Serum thyroid hormones (TH) and internal temperatures were investigated in 8 euthyroid men during a general standard cold air test (SCAT) (dry bulb temperature = 1 degree C, 2 h, nude, at rest) performed both before and after a local cold acclimation. Serum total thyroxin (TT4), total triiodothyronine (TT3), free thyroxin (FT4), free triiodothyronine (FT3), and thyrotropin (TSH) were studied during the SCT. The TH values were corrected following the plasmatic volume reduction (delta PV) calculated with Dill and Costill's formula. During SCAT, delta PV reached -9 to -11% (P < 0.05) without any effect of local cold acclimation. Slight TH changes were observed according to delta PV: TT4, TT3, and TSH increased during SCAT (P < 0.05) only before correction. FT4 and FT3 did not vary before correction but increased after correction (P < 0.05). After acclimation, a slightly decreased TT3 was observed both before and after correction (-18% and -11.7%, respectively; P < 0.05). Decreased internal temperatures after local cold acclimation suggested a hypothermic general cold adaptation. It was concluded that TH changes during SCAT differed if correction due to delta PV was applied and that the slight decrease in TT3 observed after local cold acclimation could suggest the presence of a “T3 polar syndrome.”
Bactericidal/permeability-increasing protein ameliorates acute lung injury in porcine endotoxemia
Authors: Vandermeer T. J. , Menconi M. J. , O′Sullivan B. P. , Larkin V. A. , Wang H. , Kradin R. L. , Fink M. P.
Published: December 2017

Bactericidal/permeability-increasing protein (BPI), a cationic protein isolated from human neutrophils, binds lipopolysaccharide (LPS), kills gram-negative bacteria, and neutralizes many of the effects of LPS in vitro and in vivo. We hypothesized that a recombinant 23-kDa NH2-terminal fragment of BPI (BPI23) would reduce acute lung injury in endotoxemic pigs. At -18 h, pigs received an intravenous priming dose of LPS (20 micrograms/kg). Anesthetized ventilated swine were randomized to receive 1) no further treatment (n = 4); 2) LPS (250 micrograms/kg over 50 min) and BPI23 (3-mg/kg bolus and 3 mg/kg over 60 min) (n = 6); or 3) LPS and thaumatin, a cationic protein devoid of LPS neutralizing activity that has a molecular mass and isoelectric point that are similar to that of BPI23 (n = 7). BPI23 treatment significantly ameliorated LPS-induced hypoxemia, functional upregulation of opsonin receptors on circulating phagocytes, and alveolitis but had no effect on the elaboration of tumor necrosis factor-alpha or thromboxane A2. The salutory effects of BPI23 on acute lung injury in endotoxemic pigs may be mediated, at least in part, by inhibition of direct activation of phagocytes by LPS.
Application of an air-filled tube for measuring intraesophageal pressure
Authors: Shiraishi K. , Yaekashiwa M. , Nakagawa J. , Isawa T. , Motomiya M.
Published: December 2017

We devised a new method for measuring esophageal pressure (Pes) with use of a flexible tube without a balloon at a constant rate of airflow through the tube into the esophagus (balloonless method). A study with 133Xe showed that the air that accumulated in the esophagus did not interfere with the measurement of Pes. We measured dynamic compliance (Cdyn) and pulmonary resistance (RL) with the balloonless method in 19 subjects and obtained a static deflation pressure-volume curve (P-V curve) in 10 other subjects. Cdyn was 0.243 +/- 0.099 l/cmH2O and RL was 1.52 +/- 0.42 cmH2O.l-1.s. In 6 of the 10 subjects, a P-V curve was also obtained with the balloon tube (balloon method). K, the index of compliance in the exponential function V = V0(1-e-KP) where V0 is volume at infinite pressure, was 0.136 +/- 0.040 cmH2O-1 with the balloonless method and 0.153 +/- 0.023 cmH2O-1 with the balloon method. No statistically significant difference was found between these two values. In conclusion, Cdyn, RL, and the P-V curve can be obtained precisely with the balloonless method.
Pulmonary airway area by the two-microphone acoustic reflection method
Authors: Louis B. , Glass G. M. , Fredberg J. J.
Published: December 2017

We noninvasively assessed airway dimensions from acoustic reflection data measured at the mouth. We recently described a two-transducer system for measurement of the nasal airway. Here we apply this approach to the measurement of the upper airway and trachea. We describe the theoretical implications of breathing on this kind of measurement and propose a new procedure that, unlike single- and dual-transducer systems used currently, does not require the use of He-O2 for inference of geometry of subglottic airways.
Balance of carbohydrate and lipid utilization during exercise: the "crossover" concept
Authors: Brooks G. A. , Mercier J.
Published: December 2017

The “crossover” concept represents a theoretical means by which one can understand the effects of exercise intensity and prior endurance training on the balance of carbohydrate (CHO) and lipid metabolism during sustained exercise. According to the crossover concept, endurance training results in muscular biochemical adaptations that enhance lipid oxidation as well as decrease the sympathetic nervous system responses to given submaximal exercise stresses. These adaptations promote lipid oxidation during mild- to moderate-intensity exercise. In contrast, increases in exercise intensity are conceived to increase contraction-induced muscle glycogenolysis, alter the pattern of fiber type recruitment, and increase sympathetic nervous system activity. Therefore the pattern of substrate utilization in an individual at any point in time depends on the interaction between exercise intensity-induced responses (which increase CHO utilization) and endurance training-induced responses (which promote lipid oxidation). The crossover point is the power output at which energy from CHO-derived fuels predominates over energy from lipids, with further increases in power eliciting a relative increment in CHO utilization and a decrement in lipid oxidation. The contemporary literature contains data indicating that, after endurance training, exercise at low intensities (< or = 45% maximal O2 uptake) is accomplished with lipid as the main substrate. In contrast, the literature also contains reports that are interpreted to indicate that during hard-intensity exercise (approximately 75% maximal O2 uptake) CHO is the predominant substrate. Seen within the context of the crossover concept these apparently divergent results are, in fact, consistent.(ABSTRACT TRUNCATED AT 250 WORDS)
Cricothyroid muscle activity during sleep in normal adult humans
Authors: Kuna S. T. , Smickley J. S. , Vanoye C. R. , McMillan T. H.
Published: December 2017

Previous investigators reported that cricothyroid (CT) muscle usually exhibits phasic inspiratory activity in normal adult humans during wakefulness. The purpose of this study was to determine respiratory-related CT activity in normal adult humans during sleep. Nighttime polysomnograms were performed in 16 subjects. Hooked-wire electrodes were percutaneously implanted in CT with 21-gauge needle-catheter unit that allowed artifact-free monopolar recordings during electrode placement. During wakefulness, CT was usually phasically active on inspiration, with tonic activity throughout the respiratory cycle. Phasic inspiratory activity was present throughout sleep in all subjects, even those without respiratory-related CT activity during wakefulness. Compared with non-rapid-eye-movement (NREM) sleep, phasic CT activity uniformly increased in rapid-eye-movement (REM) sleep. No differences were apparent in height of phasic CT activity between phasic and tonic REM sleep. Application of nasal continuous positive pressure in stage 3/4 NREM sleep was associated with a decrease in phasic CT activity. Passively induced hypocapnia with positive-pressure ventilation via a nose mask in stage 3/4 NREM sleep was associated with a disappearance of phasic CT activity. Cessation of positive-pressure ventilation under hypocapnic conditions frequently resulted in apnea. Phasic CT activity remained absent during apnea but reappeared coincident with or soon after resumption of spontaneous respiration. In summary, CT′s phasic inspiratory activity and respiratory-related response to various stimuli during sleep were very similar to those of posterior cricoarytenoid muscle, the principal vocal cord abductor.
Comparison of static and dynamic measurements of intrinsic PEEP in anesthetized cats
Authors: Hernandez P. , Navalesi P. , Maltais F. , Gursahaney A. , Gottfried S. B.
Published: December 2017

Dynamic measurements of intrinsic positive end-expiratory pressure (PEEPi,dyn) considerably underestimate values obtained under static conditions (PEEPi,stat) in patients with severe airway obstruction. This may be related to regional differences in respiratory system mechanical properties and/or viscoelastic behavior. To evaluate this concept, PEEPi,stat and PEEPi,dyn were compared in six anesthetized paralyzed cats during dynamic hyperinflation produced by inverse ratio ventilation (IRV) and aerosolized methacholine (MCh). PEEPi,stat did not differ between IRV and MCh, averaging 2.70 +/- 0.33 (SE) and 2.70 +/- 0.25 cmH2O, respectively. PEEPi,dyn was significantly less with MCh (0.25 +/- 0.05 cmH2O) than IRV (2.05 +/- 0.28 cmH2O) (P < 0.0001), resulting in a lower PEEPi,dyn/PEEPi,stat ratio for MCh (0.10 +/- 0.02) than for IRV (0.76 +/- 0.03) (P < 0.0001). Compared with control values (33.5 +/- 3.7 cmH2O.l-1.s), maximum resistance (Rmax) was unchanged during IRV (29.1 +/- 2.1 cmH2O.l-1.s) but increased considerably with MCh (288.8 +/- 18.4 cmH2O.l-1.s) (P < 0.0001). Similar changes in minimum resistance (Rmin) and delta R (Rmax-Rmin) were noted. There was a strong inverse relationship between delta P, an index of time constant inequalities and viscoelastic pressure losses and PEEPi,dyn/PEEPi,stat ratio. No correlation was found between this ratio and Rmax, Rmin, delta R, or compliance. In conclusion, PEEPi,dyn considerably underestimates PEEPi,stat in acute nonhomogeneous airway obstruction with MCh in contrast to IRV, where the magnitude and distribution of mechanical properties remain unaltered. These findings support the concept that the difference between PEEPi,dyn and PEEPi,stat is related to regional time constant inequalities and/or increased viscoelastic pressure losses.
Distinguishing between aerobic and anaerobic appearance of dissolved CO2 in intestine during low flow
Authors: Schlichtig R. , Bowles S. A.
Published: December 2017

Increased intestinal mucosal PCO2 is used to detect the condition of inadequate O2 delivery, i.e., “dysoxia.” However, mucosal PCO2 (PmCO2) can arise from oxidative phosphorylation, in which case it would detect metabolism that persists as blood stagnates, and/or from HCO3- neutralization by anaerobically produced metabolic acid, in which event it could represent dysoxia. We measured portal venous PCO2 (PVCO2) directly and PmCO2 indirectly with saline-filled CO2-permeable Silastic balloon tonometers in the intestinal lumen during progressive lethal cardiac tamponade in six pentobarbital-anesthetized dogs. PVCO2 and PmCO2 were relatively constant, differing by approximately 10 Torr until an O2 delivery (DO2) of approximately 1.3 ml.kg-1.min-1 was reached, below which PVCO2 and PmCO2 diverged strikingly, achieving a final difference of 78.7 +/- 35.81 (SD) Torr. To determine whether PCO2 arose from aerobic or anaerobic metabolism, we used the Dill nomogram to predict venous oxyhemoglobin (HbO2v) saturation (%HbO2v) from PVCO2. Portal venous %HbO2 predicted by the Dill nomogram agreed well with measured portal venous %HbO2 during all but the final values, indicating primarily aerobic appearance of PCO2 in venous blood, suggesting that portions of intestine that remained perfused at very low flow produced dissolved CO2 mainly by oxidative phosphorylation. As PmCO2 increased below critical DO2, however, predicted mucosal %HbO2v became strikingly negative, achieving a final value of -192 +/- 106.1%, indicating anaerobic dissolved CO2 production in mucosa. We conclude that PCO2 measured in intestinal lumen can be used to detect dysoxia.
Role of viscoelasticity in tube model of airway reopening. I. Nonnewtonian sols
Authors: Hsu S. H. , Strohl K. P. , Jamieson A. M.
Published: December 2017

This investigation used a previously described bench-top device (Gaver et al., J. Appl. Physiol. 69: 74–85, 1990) to examine the role of nonnewtonian and viscoelastic fluids on events at reopening of a closed flexible tube. Aqueous sodium alginate solutions with and without calcium chloride and sodium dodecyl sulfate in desired concentrations provided fluids with a wide range of surface tensions, storage and loss moduli, and nonnewtonian steady shear viscosity. Dimensionless analysis, using the shear rate-dependent viscosities, was applied to reduce reopening pressure-meniscus velocity data to a master curve. With regard to fluid properties, we found that 1) fluid elasticity strongly changes the pressure-velocity relationship, causing flow instability at higher meniscus velocities; 2) decreasing surface tension gives rise to a smaller yield pressure for reopening; and 3) whereas larger tubes are easier to open, smaller tubes produce additional shear thinning of the lining fluid. These results suggest that, for both the upper (large) and lower (small) airways, nonnewtonian and viscoelastic properties of the mucosal fluid modify the time of closure and rate of reopening.
Responses of sweating and body temperature to sinusoidal exercise
Authors: Yamazaki F. , Sone R. , Ikegami H.
Published: December 2017

This study determined the phase response and amplitude response (delta) of esophageal temperature (T(es)), mean skin temperature (Tsk), and forearm sweating rate (Msw) to sinusoidal work. Six healthy male subjects exercised on a cycle ergometer with a constant load (approximately 35% maximal O2 uptake) for a 30-min period; for the next 40 min they exercised with a sinusoidal load at 25 degrees C at 35% relative humidity. The sinusoidal load varied between approximately 10 and 60% maximal O2 uptake, and three different time periods (1.3, 4, and 8 min) were selected. Each subject performed three experiments that differed only in the timing of sinusoidal work. During the 4- and 8-min periods, T(es), Tsk, and Msw changed almost sinusoidally. The phase of Msw change significantly preceded those of T(es) and Tsk changes (P < 0.05). During the 1.3-min period, the level of T(es) and Tsk remained almost constant (delta T(es) 0.01 +/- 0.00 degrees C, delta Tsk 0.03 +/- 0.01 degrees C), whereas Msw showed a clear sinusoidal pattern. We conclude that the sweating response during sinusoidal work depends on both thermal and nonthermal factors, the latter being emotional, mental, or sensory stimulation. The contribution of the nonthermal factors to the general sweating response during exercise can be separated from that of the thermal factors by using sinusoidal work during a short period (e.g., 1.3 min).
Respiratory muscle function during emesis in awake canines
Authors: Abe T. , Kieser T. M. , Tomita T. , Easton P. A.
Published: December 2017

Emesis requires a coordinated differential recruitment of gastrointestinal smooth muscle, upper airway muscles, and several muscles involved in respiration. In seven awake intact canines we measured the electrical activity (electromyogram) and shortening of costal and crural diaphragm segments, parasternal intercostal, and transversus abdominis during emesis that was induced by instillation of apomorphine into the lower conjunctival fornix. The process of emesis was tightly coordinated with ventilation and showed four respiratory phases: baseline ventilation (Base), initial preemetic hyperventilation (Hyperv), prodromal ventilation associated with salivation and probable nausea (Prodrome), and finally retching and expulsion (Expel) of gastric contents. Ventilation was suppressed during expulsive events, but a small inspiratory airflow was interjected between expulsions. Resting electromyogram of all four muscles increased during the process of emesis, with costal and crural segments showing a marked decrease in resting length through Prodrome and Expel. To produce an expulsive maneuver, both inspiratory and expiratory muscles were activated synchronously, unlike their usual sequential activation during ventilation, with costal and crural segments and transversus abdominis showing the most shortening. The crural segment showed a biphasic length change with initial shortening and then lengthening to assist esophageal sphincter function during Expel. These results indicate a strong coordinated interaction between brain stem centers responsible for control of respiration and of emesis.
Coupling of muscle phosphorylation potential to glycolysis during work after short-term training
Authors: Cadefau J. , Green H. J. , Cusso R. , Ball-Burnett M. , Jamieson G.
Published: December 2017

To examine whether the metabolic adaptations to short-term training are expressed over a range of submaximal levels of mitochondrial respiration, seven untrained male subjects [maximal O2 uptake (VO2max) = 45.9 +/- 1.9 (SE) ml.kg-1.min-1] performed a progressive three-stage protocol of cycle exercise at 60% (20 min), 79% (20 min), and 92% (11 min) of pretraining VO2max before and after training. Training consisted of 5–6 days of cycling for 2 h/day at 65% VO2max. Muscle tissue rapidly obtained from the vastus lateralis by needle biopsy indicated that training blunted (P < 0.05) the increase in lactate observed at 60% (23.4 +/- 6.5 vs. 12.4 +/- 2.9 mmol/kg dry wt), 79% (48.9 +/- 5.1 vs. 25.6 +/- 5.2 mmol/kg dry wt), and 92% (68.3 +/- 6.4 vs. 41.5 +/- 6.5 mmol/kg dry wt) of VO2max. Training also resulted in a higher phosphocreatine and lower creatine and P(i) concentrations at both 79% (P < 0.05) and 92% (P < 0.05) of VO2max and higher muscle glycogen levels (P < 0.05). These changes were accompanied by small but significant reductions (P < 0.05) in O2 uptake at the two higher exercise intensities. Given that the lactate-to-pyruvate ratio and the calculated free ADP and AMP were also reduced (P < 0.05), it would appear that short-term training results in a tighter metabolic control over a range of mitochondrial respiratory rates.
Cardiovascular and renal function during exercise-induced blood volume expansion in men
Authors: Gillen C. M. , Nishiyasu T. , Langhans G. , Weseman C. , Mack G. W. , Nadel E. R.
Published: December 2017

To test the hypothesis that reduced baroreflex sensitivity is a direct result of exercise, we measured forearm vascular conductance (FVC) responses to graded lower body negative pressure (LBNP) 2, 20, and 44 h after intense exercise. Eight 4-min bouts of exercise at 85% of maximum oxygen uptake produced 3.5 +/- 0.7 and 3.9 +/- 1.0% blood volume (BV) expansions at 20 and 44 h of recovery, respectively. BV was unchanged from control values 2 h after exercise. The reduction in FVC was significantly less than control values during 30 and 40 mmHg of LBNP at 2 and 20 h of recovery, respectively, whereas heart rate and cardiac stroke volume responses were unchanged. Thus, a reduced FVC response to LBNP preceded BV expansion, demonstrating that exercise itself can elicit an attenuation of baroreflex function. To test the hypothesis that volume sensitivity of renal function is attenuated by intense exercise, we measured cardiovascular variables, plasma hormone concentrations, and renal output. At 20 h of recovery, resting mean arterial blood pressure and cardiac output were increased by 6 +/- 1 mmHg and 0.6 +/- 0.2 l/min, respectively, but resting plasma aldosterone and overnight Na+ excretion rate were unchanged. At 44 h of recovery, plasma aldosterone was decreased by 26 +/- 9% and overnight Na+ excretion rate was increased by 51 +/- 26%. Thus, appropriate endocrine and renal responses to increased BV were delayed until 44 h of recovery. Our findings suggest that a postexercise attenuation of baroreflex function participates in the induction of BV expansion by intense exercise.
Acute respiratory acidosis: large-dose furosemide and cerebrospinal fluid ions
Authors: Javaheri S. , Corbett W. , Adams J. M. , Davis P. J. , Gartside P. S.
Published: December 2017

NaCl cotransport carrier is known to be involved in transepithelial fluid absorption and secretion in various tissues. Recent studies indicate that Na-K-2Cl cotransport carrier also exists in the choroid plexus cells and that inhibition of the carrier decreases cerebrospinal fluid (CSF) production. In this study, we used large-dose intravenous furosemide, an inhibitor of Na-K-2Cl carrier, to determine the effects on cisternal CSF ionic composition in acute respiratory acidosis. In pentobarbital-anesthetized mechanically ventilated dogs, renal pedicles were ligated to prevent furosemide-induced diuresis. The experimental group (group II, n = 7) received 400 mg/kg of furosemide intravenously, and group I (control group, n = 7) received the vehicle. In group II, serial serum and CSF furosemide concentrations were approximately 10(-3) and 10(-5) mol/l, respectively. During 5 h of acute respiratory acidosis in both groups, the mean arterial PCO2 increased approximately 25 Torr, with comparable changes in CSF PCO2. In both groups, CSF [HCO3-] and [H+] rose approximately 3 meq/l and 20 neq/l, respectively. Changes in CSF [Na+], [K+], [Cl-], and [Na(+)-Cl-] were also similar and were not significantly different from each other when the two groups were compared. These data show that furosemide at the dose that inhibits NaCl cotransport carrier does not significantly alter ionic composition of cisternal CSF.
Laryngeal and tracheobronchial cough in anesthetized dogs
Authors: Tatar M. , Sant′Ambrogio G. , Sant′Ambrogio F. B.
Published: December 2017

Tussigenic sensitivity of laryngeal and tracheobronchial regions to mechanical and chemical stimuli was compared in 22 urethan-alpha-chloralose-anesthetized dogs. In addition, the contribution of myelinated and unmyelinated vagal fibers in mediating laryngeal and tracheobronchial cough was investigated. The intensity of cough was evaluated from changes in esophageal pressure. Whereas all mechanical stimulations and citric acid inhalations into tracheobronchial region elicited cough, only 56.7% of mechanical stimulation and 33.3% of citric acid challenges to larynx were effective. The intensity of tracheobronchial cough was significantly higher than that of laryngeal cough. When mechanical stimulation was conducted under visual control (bronchofiberscope), cough elicitability was found to be higher from tracheal bifurcation and main stem bronchi (62.5–87.5%) than from any laryngeal structure (0–42.9%). During partial block of vagal conduction (cooling to 6 degrees C), mechanical and citric acid tracheobronchial stimulations failed to elicit cough and mechanical laryngeal stimulation was effective only in 1 of 10 dogs. Intensity of cough was strongly decreased when mechanical stimulation followed capsaicin administration into trachea (0.3 ml; 100 micrograms/ml) or intravenously (10 micrograms/kg). We conclude that, in anesthetized dogs, stimulation of tracheobronchial region is more effective and prompt in eliciting cough than stimulation of larynx, myelinated vagal afferent fibers play an important role in mediating mechanically and citric acid-induced tracheobronchial cough and mechanically induced laryngeal cough, and stimulation of tracheobronchial and pulmonary capsaicin-sensitive receptors strongly inhibits mechanically induced cough.
Passive length-force properties of senescent diaphragm: relationship with collagen characteristics
Authors: Gosselin L. E. , Martinez D. A. , Vailas A. C. , Sieck G. C.
Published: December 2017

The purpose of this study was to examine the effect of aging on collagen concentration and extent of nonreducible collagen cross-linking as well as with the passive length-force relationship of the diaphragm muscle. Midcostal diaphragm muscle strips from young (6 mo) and senescent (24 mo) Fischer 344 rats were perfused in a tissue bath containing mammalian Ringers solution (25 degrees C) aerated with 95% O2–5% CO2. The segments were lengthened and shortened from 85 to 115% of optimal length (L(o)) at a constant velocity (0.6 L(o)/s), and the passive force was measured. Hydroxyproline (HYP) and the mature nonreducible collagen cross-link, hydroxylysylpyridinoline (HP), were measured by high-pressure liquid chromatography. The resting force at Lo did not differ between young and senescent diaphragm muscles. However, the senescent diaphragm exhibited greater passive force compared with the young (P < 0.05) at lengths > 110% of L(o). High-pressure liquid chromatography analysis revealed a higher concentration of HYP in the senescent compared with the young diaphragm (9.32 +/- 0.83 and 6.59 +/- 0.78 g HYP/mg dry wt, respectively; P < 0.05). Additionally, the content of HP was greater in the senescent compared with the young diaphragm (1.16 +/- 0.05 and 0.91 +/- 0.05 mol HP/mol collagen, respectively; P < 0.05). These results suggest that diaphragm collagen metabolism, maturation, and the passive length-force characteristics of the muscle are altered with senescence.
Modification of a whole room indirect calorimeter for measurement of rapid changes in energy expenditure
Authors: Sun M. , Reed G. W. , Hill J. O.
Published: December 2017

Whole room indirect calorimeters are among the most accurate devices for measurement of human energy expenditure and have provided useful data about determinants of total daily energy expenditure. However, a limitation of whole room indirect calorimeters has been the inability to detect acute (usually < 10–15 min) changes in energy expenditure. This precludes using these devices to study the acute effects of food, drugs, or exercise on energy expenditure. We describe modifications made to our whole room indirect calorimeter (respiratory chamber) to allow accurate measurement of energy expenditure over time periods as short as 1 min. The modifications involve changes in the system design and use of signal processing techniques. With these modifications, we can measure energy expenditure in 1-min intervals throughout the day. This allows accurate study of the acute effects of food, exercise, or drugs on energy expenditure in subjects moving freely inside the respiratory chamber. The ability to use respiratory chambers for these types of studies should improve our understanding of how body weight is regulated.
Influence of intralaryngeal CO2 on the response of laryngeal afferents to upper airway negative pressure
Authors: Ghosh T. K. , Mathew O. P.
Published: December 2017

Effects of intralaryngeal CO2 on the response of superior laryngeal afferents to negative pressure were investigated in 20 anesthetized spontaneously breathing adult cats. Single-fiber action potentials were recorded from the peripheral cut end of the superior laryngeal nerve. The larynx was exposed to negative pressure during inspiration when the animal breathed against an occluded upper airway. Among the 99 receptors evaluated, 54 were respiratory modulated and 45 were nonmodulated endings. The effect of intralaryngeal CO2 on the response of 39 receptors responding to negative pressure was determined by exposure of the larynx to CO2 or air for 1 min followed immediately by upper airway occlusion. The mean discharge frequency of 22 fibers inhibited by negative pressure was 32.4 +/- 2.6 Hz during air trials compared with 29.9 +/- 2.6 Hz during CO2 trials (P < 0.005). During occlusion of the upper airway after the warm humidified air trial, the discharge frequency of these endings decreased to 24.2 +/- 2.3 Hz compared with 17.5 +/- 2.2 Hz after CO2 trial (P < 0.001). The mean discharge frequencies of 17 fibers stimulated by negative pressure were 3.7 +/- 2.6 and 4.4 +/- 1.8 Hz, respectively, during air and CO2 trials. The mean frequencies increased to 14.7 +/- 3.5 Hz (air) and 18.6 +/- 4.0 Hz (CO2) during upper airway occlusions (P < 0.01). We conclude that intralaryngeal CO2 can alter the response of pressure-sensitive laryngeal afferents, thereby having a role in the maintenance of upper airway patency.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung tissue viscoelasticity: a mathematical framework and its molecular basis
Authors: Suki B. , Barabasi A. L. , Lutchen K. R.
Published: December 2017

Recent studies indicated that lung tissue stress relaxation is well represented by a simple empirical equation involving a power law, t-beta (where t is time). Likewise, tissue impedance is well described by a model having a frequency-independent (constant) phase with impedance proportional to omega-alpha (where omega is angular frequency and alpha is a constant). These models provide superior descriptions over conventional spring-dashpot systems. Here we offer a mathematical framework and explore its mechanistic basis for using the power law relaxation function and constant-phase impedance. We show that replacing ordinary time derivatives with fractional time derivatives in the constitutive equation of conventional spring-dashpot systems naturally leads to power law relaxation function, the Fourier transform of which is the constant-phase impedance with alpha = 1 - beta. We further establish that fractional derivatives have a mechanistic basis with respect to the viscoelasticity of certain polymer systems. This mechanistic basis arises from molecular theories that take into account the complexity and statistical nature of the system at the molecular level. Moreover, because tissues are composed of long flexible biopolymers, we argue that these molecular theories may also apply for soft tissues. In our approach a key parameter is the exponent beta, which is shown to be directly related to dynamic processes at the tissue fiber and matrix level. By exploring statistical properties of various polymer systems, we offer a molecular basis for several salient features of the dynamic passive mechanical properties of soft tissues.
Adenosine infusion does not improve maximal O2 uptake in isolated working dog muscle
Authors: Kurdak S. S. , Hogan M. C. , Wagner P. D.
Published: December 2017

We asked whether maximally working muscle could increase O2 extraction at fixed O2 delivery [i.e., improve maximal O2 uptake (VO2max)] when vascular resistance was decreased with adenosine (A) infusion. We postulated that a reduction in vascular resistance at the same blood flow (Q) might result in more uniform vascular perfusion and also possibly increase red blood cell transit time, thereby potentially improving the ability of the tissue to extract O2. Pump-perfused isolated dog gastrocnemius muscle (n = 6) was stimulated maximally at each of two levels of Q: 110 +/- 3 and 54 +/- 4 (SE) ml.100 g-1.min-1 [normal control (C) and ischemia (I), respectively], both before and after giving 10(-2) M of A solution in each case. Arterial and venous blood samples were taken to measure blood gases, and the Fick principle was used to calculate O2 uptake. Resistance decreased significantly after A treatment in both groups (1.2 +/- 0.1 vs. 0.9 +/- 0.1 and 1.3 +/- 0.1 vs. 1.1 +/- 0.1 mmHg.ml-1.100 g.min for C vs. C + A and I vs. I + A, respectively; P < 0.01). O2 delivery was lower with I but did not change at either perfusion rate when A was infused. VO2max also decreased significantly with I but was no different when A was added (13.8 +/- 0.7 vs. 13.8 +/- 0.9 and 8.4 +/- 0.5 vs. 8.2 +/- 0.6 ml.100 g-1.min-1 for C vs. C + A and I vs. I + A, respectively). These results show that the decrease in resistance with A did not lead to changes in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)
Loss of diaphragm glutathione is associated with respiratory failure induced by resistive breathing
Authors: Borzone G. , Julian M. W. , Merola A. J. , Clanton T. L.
Published: December 2017

It has been suggested that oxidant stress may contribute to dysfunction of respiratory muscles undergoing severe work loads. We examined changes in glutathione content and redox status in the diaphragm and intercostal muscles of anesthetized Sprague-Dawley rats exposed to prolonged inspiratory resistive loading while breathing 70% O2. These results were compared with those from control groups breathing air or 70% O2. Changes in liver glutathione were also examined. Freeze-clamping and an enzymatic recycling assay were used. Results show that 1) in controls, glutathione content was higher in the diaphragm than in the intercostals, 2) severe hypercapnic acidosis without hypoxemia was present with loading, 3) total diaphragm glutathione decreased approximately 35% with no increase in glutathione oxidation with resistive breathing, whereas intercostal and liver glutathione remained unchanged, and 4) the drop in diaphragm glutathione correlated significantly with the drop in minute ventilation and the increase in arterial PCO2, whereas it was not directly related to intensity of respiratory muscle activity. In conclusion, although diaphragm susceptibility to oxidant stress may be increased with resistive breathing, it is unlikely that the modest decrease in total glutathione contributed significantly to respiratory failure in this model.
Endothelin-1 infusion reduces splanchnic glucose production in humans
Authors: Ahlborg G. , Weitzberg E. , Lundberg J. M.
Published: December 2017

Two groups of six healthy subjects received an intravenous endothelin-1 (ET-1) infusion (4 pmol.kg-1.min-1 for 20 min) in the basal state. Blood was drawn from catheters in an artery (n = 12), a hepatic vein (n = 12), and a renal vein (n = 6) for determinations of blood flows and substrate exchanges. During the ET-1 infusion, splanchnic and renal blood flows were reduced by approximately 50 (P < 0.01) and 25% (P < 0.001), respectively. Arterial glucose concentration and splanchnic glucose production fell by approximately 4 (P < 0.01) and 55% (P < 0.001), respectively. The latter was still 30% below basal level 3 h after the infusion (P < 0.001). Arterial glycerol increased by 64% (P < 0.01), whereas arterial lactate was unchanged. Splanchnic uptakes of lactate and glycerol were unchanged. Arterial insulin and glucagon showed transient falls with a maximal drop of approximately 35% (P < 0.001) during the infusion. In conclusion, ET-1 infusion causes reduced splanchnic glucose production due to reduced glycogen-derived glucose release. The latter could partly be connected with the transient fall in arterial glucagon, but the prolonged suppressive effect on splanchnic glycogenolysis seems to be linked with other ET-1-related factors. We propose that the underlying mechanism to the transient falls in both arterial glucagon and insulin might be coupled to the ET-1-arginine-NO system.
An ATP-sensitive potassium channel blocker decreases diaphragmatic circulation in anesthetized dogs
Authors: Comtois A. , Sinderby C. , Comtois N. , Grassino A. , Renaud J. M.
Published: December 2017

The goal of this study was to determine whether in the dog ATP-sensitive K+ channels blocked with glibenclamide affect diaphragmatic blood flow [phrenic arterial blood flow (Qpa)] during both spontaneous breathing at rest and increased diaphragmatic activity. A control group (no glibenclamide; n = 4) and an experimental group (50 mg/kg of glibenclamide; n = 5) were studied. During spontaneous breathing at rest, Qpa was 15.0 ml.min-1 x 100 g-1 and decreased by 5% in the presence of glibenclamide. Diaphragmatic pacing (30 min-1) generated by phrenic nerve pacing produced an initial diaphragmatic tension-time index of 0.25 in both groups. A 50% decay in transdiaphragmatic pressure was reached at 165 s in the experimental group compared with 421 s in the control group. Diaphragmatic pacing increased Qpa by 46% in the experimental group and 65% in the control group, yielding a 63% greater vascular resistance in the experimental group. Phrenic vein K+ content at rest was unchanged by the presence of glibenclamide, being 3.6 +/- 0.16 mmol/l compared with 3.5 +/- 0.19 mmol/l in the control group. Phrenic nerve pacing in the control group produced a 13% increase in phrenic vein K+ content, whereas in the experimental group a 16% decrease was observed. We suggest that ATP-sensitive K+ channels play an important role in the modulation of Qpa.