bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II 1 receptor-mediated contraction of pulmonary artery and its modulation by prolylcarboxypeptidase
Authors: Tamaoki J. , Sugimoto F. , Tagaya E. , Isono K. , Chiyotani A. , Konno K.
Published: December 2017

To determine the subtype of angiotensin II (ANG II) receptor involved in the contraction of pulmonary artery and to elucidate its possible modulation by endogenous peptidases, we studied canine isolated pulmonary arterial rings under isometric conditions in vitro. Addition of ANG II caused a concentration-dependent contraction, an effect that was not altered by the ANG II 2 receptor antagonist EXP655 but was depressed by the ANG II 1 receptor antagonist DuP 753 so that the ANG II response curves were displaced to higher concentration by 1.5–2.0 log U (P < 0.001). Pretreatment of tissues with the prolylcarboxypeptidase (PCP) inhibitor p-methylphenyl sulfonyl-fluoride potentiated the ANG II-induced contraction, with the concentration required to produce a half-maximal effect of ANG II being decreased from 4.1 +/- 0.9 x 10(-9) to 3.8 +/- 0.5 x 10(-10) M (P < 0.001), whereas other peptidase inhibitors such as p-chloromercuriphenyl sulfonic acid, amastatin, and phosphoramidon had no effect. The p-methylphenyl sulfonylfluoride-induced potentiation was abolished by the removal of endothelium, but it was still observed in the presence of NG-nitro-L-arginine methyl ester in the endothelium-intact tissues. The PCP activity in the tissues was reduced by the removal of endothelium from 645 +/- 88 to 91 +/- 29 nmol.mg protein-1.h-1 (P < 0.001), and cultured endothelium had the activity of 404 +/- 39 nmol.mg protein-1.h-1. These results suggest that ANG II contracts pulmonary artery via ANG II 1 receptor and that PCP localized to the endothelium may have a modulatory role in the ANG II-induced pulmonary vasoconstriction.
Metabolic-ventilatory interaction in conscious rats: effect of hypoxia and ambient temperature
Authors: Saiki C. , Matsuoka T. , Mortola J. P.
Published: December 2017

Previous studies have indicated that the hypometabolic response to hypoxia depends on ambient temperature (Ta), being more pronounced in the cold. If metabolic rate were an important contributor to the level of ventilation (VE), the magnitude of the hyperpneic response to hypoxia should also depend on Ta. We tested this hypothesis on adult conscious male rats. In normoxia, a drop in Ta from 25 to 10 degrees C increased O2 consumption and CO2 production (VO2 and VCO2, respectively, measured by an open-flow technique) and VE (measured with the barometric method) by 80 and 60%, respectively, with no changes in blood gases. At both Ta, hypoxia (10% inspired O2, 33–35 Torr arterial PO2) induced the same degree of hyperventilation, i.e., the same drop in arterial PCO2 (about -13 Torr). The hyperventilation at 25 degrees C Ta was achieved exclusively by an increase in VE, whereas at 10 degrees C Ta the hyperpnea was minimal (+15%) and accompanied by a drop (-30%) in VO2 and VCO2. Diaphragmatic electromyograms confirmed the VE results. Changes in blood pressure were similar at both Ta. Addition of 3% CO2 to the inspired air further increased VE, indicating that the hypoxic rat was not breathing at its maximal VE at either Ta. We conclude that, in the rat, changes in metabolic rate play an important role in the VE response to hypoxia and that Ta influences the response because of its effect on the degree of hypoxic hypometabolism.
Exercise training improves metabolic response after ischemia in isolated working rat heart
Authors: Bowles D. K. , Starnes J. W.
Published: December 2017

Hearts from treadmill-trained and sedentary rats were perfused in the working heart mode. Mechanical and metabolite status was evaluated before ischemia, after 25 min of global ischemia, and after 30 min of retrograde reperfusion. After reperfusion, hearts from trained rats were found to have better recovery of contractile function, lower diastolic stiffness, greater efficiency of work, and greater extracellular calcium responsiveness than hearts from sedentary rats. Training had no significant impact on bioenergetic status before or at the end of ischemia. However, after reperfusion, both phosphocreatine and ATP were significantly higher in hearts from trained rats than from sedentary control rats. Mitochondrial function in both subsarcolemmal and intermyofibrillar subpopulations was unaffected by ischemia-reperfusion. 45Ca2+ uptake during reperfusion was significantly higher in hearts from sedentary rats than from exercise-trained rats. No differences were found in free radical production or tolerance due to training. Therefore, hearts from exercise-trained rats demonstrated an increased metabolic tolerance to ischemic-reperfusion damage, which may contribute to the improved postischemic functional recovery.
Inhomogeneity of pulmonary ventilation during sustained microgravity as determined by single-breath washouts
Authors: Guy H. J. , Prisk G. K. , Elliott A. R. , Deutschman R. A. , West J. B.
Published: December 2017

Gravity is known to cause inhomogeneity of ventilation. Nongravitational factors are also recognized, but their relative contribution is not understood. We therefore studied ventilatory inhomogeneity during sustained microgravity during the 9-day flight of Spacelab SLS-1. All seven crew members performed single-breath nitrogen washouts. They inspired a vital capacity breath of 100% oxygen with a bolus of argon at the start of inspiration, and the inspiratory and expiratory flow rates were controlled at 0.5 l/s. Control measurements in normal gravity (1 G) were made pre- and postflight in the standing and supine position. Compared with the standing 1-G measurements, there was a marked decrease in ventilatory inhomogeneity during microgravity, as evidenced by the significant reductions in cardiogenic oscillations, slope of phase III, and height of phase IV for nitrogen and argon. However, argon phase IV volume was not reduced, and considerable ventilatory inhomogeneity remained. For example, the heights of the cardiogenic oscillations during microgravity for nitrogen and argon were 44 and 24%, respectively, of their values at 1 G, whereas the slopes of phase III for nitrogen and argon were 78 and 29%, respectively, of those at 1 G. The presence of a phase IV in microgravity is strong evidence that airway closure still occurs in the absence of gravity. The results were qualitatively similar to those found previously during short periods of 0 G in parabolic flight.
Prediction of carboxyhemoglobin formation due to transient exposure to carbon monoxide
Authors: Benignus V. A. , Hazucha M. J. , Smith M. V. , Bromberg P. A.
Published: December 2017

Fifteen men were exposed to 6,683 ppm C18O for 3.09–6.65 min. Arterial and antecubital vein blood samples were drawn at 1-min intervals beginning at the start of C18O inhalation and ending 10 min later. Simultaneously, alveolar ventilation was calculated from the measured values of minute ventilation and dead space. All other parameters of the Coburn-Forster-Kane equation (CFKE), except the Haldane affinity ratio, were measured separately in each subject. Means of CFKE predictions of increases in venous HbCO (delta HbCO) in samples collected approximately 2 min after cessation of exposure were accurate, but the range in errors of prediction for individual subjects was +/- 3.8% HbCO, depending on the time after exposure cessation. Increases in venous and arterial HbCO were inaccurately predicted during and immediately after HbCO formation, however. Venous blood was overestimated during CO uptake because of a delayed appearance of HbCO. Individual subjects differed markedly in the degree of delay of HbCO appearance in venous blood. Arterial delta HbCO was consistently underestimated either by the CFKE or by predictions based on venous blood samples. Thus, exposure of such organs as brain or heart to HbCO may be substantially higher than expected during transient high-level CO exposure.
Evaluating the oxygen diffusing capacity of maximally stimulated canine muscle
Authors: Gainer J. L.
Published: December 2017

A series of studies over the past several years has been concerned with O2 consumption in the gastrocnemius muscle of the dog. Those experiments indicate that the maximal O2 consumption may be diffusion limited and suggest that such data can be correlated using a parameter, the O2 diffusing capacity, that combines different effects. An analysis of those data is presented here with use of multiple linear regression techniques, which indicate that, even if the experimental conditions are different, the diffusing capacity can be quantitatively evaluated if the blood flow rate, hemoglobin content, and blood pressure are known. Although the data are for a specific tissue, similar results might be expected when O2 consumption is considered in other tissues.
Total blood volume in healthy young and older men
Authors: Davy K. P. , Seals D. R.
Published: December 2017

The primary aim of this investigation was to test the general hypothesis that aging does not influence total blood volume in humans. To accomplish this, we measured supine resting plasma volume (modified Evans blue dye technique) and hematocrit in healthy nonobese young (24.7 +/- 1.2 yr, n = 7) and older (66.1 +/- 1.8 yr, n = 7) men carefully matched for body size and daily energy expenditure. Estimated body fat was greater (23 +/- 2 vs. 17 +/- 1%, P < 0.01) and maximal O2 consumption was lower (32.4 +/- 2.1 vs. 48.7 +/- 1.5 ml.kg-1.min-1, P < 0.001) in the older men than in the young controls. Absolute levels of total blood volume were 24% lower (P < 0.01) in the older men than in the young controls (4,749 +/- 333 vs. 6,234 +/- 318 ml). The lower absolute level of total blood volume in the older men was due to a 21% lower (P < 0.01) plasma volume (2,956 +/- 194 vs. 3,745 +/- 176 ml) and a 28% lower (P < 0.01) erythrocyte volume (1,792 +/- 148 vs. 2,488 +/- 158 ml) than in the young controls. Total blood volume, plasma volume, and erythrocyte volume also were lower (P < 0.01) in the older than in the young men when expressed relative to body weight, body surface area, or estimated fat-free mass. These findings suggest that total blood volume decreases with age in healthy men of similar size and chronic physical activity levels.
Cardiopulmonary adaptations to pneumonectomy in dogs. III. Ventilatory power requirements and muscle structure
Authors: Hsia C. C. , Herazo L. F. , Ramanathan M. , Claassen H. , Fryder-Doffey F. , Hoppeler H. , Johnson R. L.
Published: December 2017

Static and dynamic mechanical characteristics of the respiratory system were measured in five adult foxhounds 6–15 mo after right pneumonectomy (R-PNX) and in five matched foxhounds that underwent right thoracotomy without pneumonectomy (Sham). In R-PNX dogs, elastic recoil was lower than that in the left lung of Sham dogs. On exercise, absolute ventilatory power requirements of the lung and its components were measured, i.e., power requirements to overcome elastic and viscous resistances of the lung as well as power requirements during inspiration and expiration. All components were higher for a given minute ventilation in R-PNX dogs than in both lungs of Sham dogs. Ventilatory power requirements after R-PNX were also higher than in three adult foxhounds after left PNX studied previously by the same techniques. After R-PNX, the mass of the right costal diaphragm and total mass of inspiratory muscles were greater than in Sham dogs. There were no significant differences in ultrastructural features of the costal diaphragm. The unilateral increase in muscle mass is likely the result of chronic elevation and stretch of the right costal diaphragm after R-PNX.
Contribution of lymphatic myogenic activity and respiratory movements to pleural lymph flow
Authors: Negrini D. , Ballard S. T. , Benoit J. N.
Published: December 2017

In 11 anesthetized spontaneously breathing rabbits, we studied the contribution to total pleural lymph flow of myogenic activity of pleural lymphatics (“intrinsic mechanism”) and the effect due to mechanical action of respiratory movements (“extrinsic mechanism”). Isoncotic saline solution (5 ml) containing 100 microCi of 125I-lactate dehydrogenase (LDH) was injected into right pleural space; in all but three control rabbits, injectate contained 1 mM amiloride in dimethyl sulfoxide to induce relaxation of smooth muscle tone. At 3 h, rabbits were killed and pleural fluid was collected and its volume measured. LDH radioactivity in pleural liquid and parietal pleural tissue was counted. In control rabbits, net pleural liquid flow (Jnet) at 3 h was -0.17 +/- 0.04 (SD) ml.kg-1.h-1; LDH concentration (C) and quantity (Q) decreased by 40.3 and 51.1% of initial value, respectively; total pleural lymphatic flow (Jl), calculated from LDH clearance, was 0.58 +/- 0.01 ml.kg-1.h-1. In amiloride-treated rabbits, Jnet was 0.01 +/- 0.1 ml.kg-1.h-1, C decreased by 34.4% and Q by 33.1%, and Jl averaged 0.39 +/- 0.02 ml.kg-1.h-1. C in parietal pleura, rich in lymphatics, was 13-fold higher in control than in amiloride-treated animals. The significant decrease of pleural lymphatic flow observed with amiloride (-40% relative to control) resulted from impairment of intrinsic mechanism, whereas, at comparable breathing frequencies, extrinsic mechanism remained unaltered. The direct effect of topical application of 1 mM amiloride was confirmed on exposed mesenteric collecting lymphatic ducts (data from 5 rats): amiloride reduced lymph flow by 40% by decreasing stroke volume without greatly affecting contraction rate of lymphatic walls.
Treatment of mild immersion hypothermia by direct body-to-body contact
Authors: Giesbrecht G. G. , Sessler D. I. , Mekjavic I. B. , Schroeder M. , Bristow G. K.
Published: December 2017

Body-to-body contact is often recommended for rewarming mildly hypothermic victims in the field. This procedure involves a euthermic individual donating heat to the recipient by direct contact in an insulated bag. However, this technique has not been critically evaluated and may not be beneficial because there is limited direct contact between recipient and donor, peripheral vasoconstriction may impair heat transfer to the core, skin warming may blunt the recipient's shivering response, and cold stress to the donor may be excessive. The present study was designed to evaluate whether donation of heat by a donor would be sufficient to enhance rewarming of a hypothermic subject (recipient). Six pairs of recipients (5 men, 1 woman) and donors (2 men, 4 women) participated in the study. Esophageal and skin temperatures, cutaneous heat flux, and oxygen consumption were measured. Recipients were immersed in 8 degrees C water until esophageal temperature decreased to a mean of 34.6 +/- 0.7 degrees C (SD). They then were rewarmed by one of three methods: rewarming by the endogenous heat generated by shivering only (SH), body-to-body rewarming (BB), or rewarming with a constant-heat source manikin (MAN). Mean afterdrop for the three conditions was 0.54 +/- 0.2, 0.54 +/- 0.2, and 0.57 +/- 0.2 degrees C for SH, BB, and MAN, respectively (NS), and the rate of rewarming was 2.40 +/- 0.8, 2.46 +/- 1.1 and 2.55 +/- 0.9 degrees C/h for SH, BB, and MAN, respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
A new function for lactate in the toad Bufo marinus
Authors: Portner H. O. , Branco L. G. , Malvin G. M. , Wood S. C.
Published: December 2017

In the amphibian Bufo marinus, progressive hypoxia below a critical PO2 elicits a transient 50% increase in O2 consumption that coincides with the onset of lactate formation. The present study was designed to test the hypothesis that lactate causes the observed rise in metabolic rate. Arterial bolus infusions of pH-neutral sodium lactate solutions (4 mmol/kg body wt) in toads maintained under hypoxia actually elicit a similar increase in metabolic rate. The application of adrenergic antagonists (bretylium tosylate, phentolamine, propranolol, and reserpine) inhibits this response, suggesting that catecholamines are involved. Moreover, animals injected with lactate move to a cooler environment (behavioral hypothermia), a behavioral response that is beneficial during hypoxia. We hypothesize that, in accordance with Cannon's concept of an emergency response, lactate may function as an alarm signal during hypoxia. However, the signal function of lactate is observed in animals both under hypoxia and under normoxia and should thus be considered in future studies whenever elevated lactate levels are present, e.g., during and after exercise.
Inhaled nicotine in humans: effect on the respiratory and cardiovascular systems
Authors: Hansson L. , Choudry N. B. , Karlsson J. A. , Fuller R. W.
Published: December 2017

Inhalation of nicotine (0–64 mg/ml) and capsaicin (2 x 10(-6)-2.5 x 10(-4) M) in 24 healthy nonsmoking subjects produced a concentration-dependent cough response. Two subjects coughed to capsaicin but not to nicotine. The mean (95% confidence interval) nicotine concentrations causing two and five coughs were 5.5 (3.5–8.7) and 15.8 (10.0–25.1) mg/ml, respectively, and were reproducible over 3 different days. Capsaicin inhalation did not alter the response to nicotine and vice versa. Both agents increased respiratory resistance, but the response was more rapid to capsaicin. Inhalation of nicotine (0–8 mg/ml) over 5 min caused increases in heart rate and blood pressure and a decrease in skin temperature. Inhaled ipratropium bromide (0.50 mg) had an antitussive effect and also inhibited the nicotine-induced bronchoconstriction, indicating a vagally mediated effect. Sodium cromoglycate (0.20 mg) did not affect cough or airway resistance changes caused by nicotine. This study shows that inhaled nicotine produces a concentration-dependent cough and airway obstruction in healthy subjects, probably because of stimulation of afferent nerve endings in the bronchial mucosa and mediated through parasympathetic cholinergic pathways. Respiratory reflexes evoked by nicotine are similar to those produced by capsaicin, but it is unclear whether these reflexes are mediated by the same type of sensory nerves.
Opioid antagonism alters blood glucose homeostasis during exercise in humans
Authors: Hickey M. S. , Trappe S. W. , Blostein A. C. , Edwards B. A. , Goodpaster B. , Craig B. W.
Published: December 2017

In an attempt to clarify the role of endogenous opioid peptides in substrate mobilization and hormonal responses to dynamic exercise, eight trained cyclists completed exercise trials at 90% of maximal O2 consumption (VO2max) until exhaustion and at 70% VO2max for 90 min. Trials were conducted after intravenous administration of the opiate antagonist naloxone (NAL, 0.1 mg/kg bolus + 0.1 mg.kg-1.h-1) or volume-matched saline (SAL) at each intensity. Serum glucose was maintained at significantly higher levels at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and at all points during exercise and at 30 and 60 min of recovery in the 90%-NAL than in the 90%-SAL trial. The serum insulin response to exercise was not altered by NAL administration at either intensity. Serum C-peptide was approximately 50% higher at 60 and 90 min of exercise in the 70%-NAL than in the 70%-SAL trial but was significantly lower during exercise in the 90%-NAL than in the 90%-SAL trial. The plasma glucagon response to exercise at 70% VO2max was not altered by NAL administration but was significantly elevated in the 90%-NAL vs. the 90%-SAL trial. Plasma epinephrine was 50–150% (approximately 2–3 nM) higher during exercise from 30 to 90 min of exercise in the 70%-NAL than in the 70%-SAL trial and was higher at termination (4.9 +/- 2.1 vs. 2.7 +/- 1.7 nM) in the 90%-NAL than in the 90%-SAL trial, although the difference in the 90% trial was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of brief exercise on circulating insulin-like growth factor I
Authors: Cappon J. , Brasel J. A. , Mohan S. , Cooper D. M.
Published: December 2017

An acute insulin-like growth factor I (IGF-I) response to 10 min of above-lactate threshold cycle ergometer exercise was studied in 10 subjects (age 22–35 yr). Each subject exercised on three separate mornings after ingesting one of two isocaloric isovolemic liquid meals high in either fat or glucose or an isovolemic noncaloric placebo. The high-fat meal attenuated the growth hormone (GH) response (Cappon et al., J. Clin. Endocrinol. Metab. 76: 1418–1422, 1993). In contrast, IGF-I increased equally for all protocols [e.g., after the placebo meal IGF-I increased from 21,716 (SE) ng/ml preexercise to 25,316 ng/ml at 10 min of exercise; P < 0.05]. IGF-I peaked by the 10th min of exercise, like GH, and remained significantly elevated for only 20 min of recovery. We tested for possible GH-dependent mechanisms in which circulating IGF-I would increase 12-24 h after exercise. Ten subjects (age 23–32 yr) performed 10 min of above-lactate threshold exercise at 9, 10, and 11 A.M. GH was elevated after the first exercise bout (peak GH 6.05 +/- 1.45 ng/ml; P < 0.001) but was significantly reduced for the second and third bouts (peak GH 2.52 +/- 0.76 and 1.50 +/- 0.40 ng/ml, respectively). No increase in IGF-I was observed by 8 A.M. on the following day. Heavy ergometer exercise led to brief and small increases in circulating IGF-I that were independent of circulating GH.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of muscle length and force on endurance and pressor responses to isometric exercise
Authors: Ng A. V. , Agre J. C. , Hanson P. , Harrington M. S. , Nagle F. J.
Published: December 2017

Experiments were performed to determine whether endurance time, mean arterial pressure, or heart rate was related to either muscle length or external torque production in humans during isometric knee extension. Eight men and nine women performed isometric knee extension to the endurance limit at each of three muscle lengths, determined by knee angles of 40 degrees (0.698 rad, shortest), 60 degrees (1.047 rad, intermediate), and 90 degrees (1.571 rad, longest), and at intensities of 30 and 50% maximal voluntary contraction (MVC). Knee extension forms an ascending-descending length-torque curve, and lengths were chosen to result in different external torques. MVC was greatest at a knee angle of 60 degrees (P < 0.05 vs. 40 degrees, 90 degrees), with no significant difference between 90 degrees and 40 degrees. Endurance time was inversely related to muscle length, independent of torque production, at 30% MVC [40 degrees, 395 +/- 139 (SE); 60 degrees, 237 +/- 60; 90 degrees, 165 +/- 51 s; P < 0.05 vs. each other] and 50% MVC (40 degrees, 176 +/- 64; 60 degrees, 137 +/- 40; 90 degrees, 85 +/- 23 s; P < 0.05 vs. each other). Evidence is presented that endurance is a function of internal muscle force and not resultant external torque. The experimental design allowed the relationship of external torque and cardiovascular responses to be examined independent of exercise intensity. Muscle mass was also controlled in that the same muscle group was involved in all contractions. There were no differences in mean arterial pressure, heart rate, or rating of perceived exertion at any percentage of endurance time under any condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Diphenyleneiodonium inhibits both potassium and calcium currents in isolated pulmonary artery smooth muscle cells
Authors: Weir E. K. , Wyatt C. N. , Reeve H. L. , Huang J. , Archer S. L. , Peers C.
Published: December 2017

Diphenyleneiodonium (DPI) blocks hypoxic vasoconstriction in the pulmonary vasculature. Because one of the actions of DPI is the inhibition of NADPH oxidase, this has led to the suggestion that NADPH oxidase acts as an oxygen tension sensor in pulmonary smooth muscle cells. We investigated the effects of DPI on potassium and calcium currents in freshly isolated pulmonary artery smooth muscle cells by using whole cell patch-clamp recordings, since these ionic currents are known to be involved in hypoxic pulmonary vasoconstriction. DPI (3 and 10 microM) reversibly inhibited potassium currents, and in its presence, residual currents appeared markedly more transient than under control conditions. The actions of DPI could not be reversed by 4.4 mM hydrogen peroxide, the product of NADPH oxidase. Calcium channel currents were also reversibly inhibited by 3 microM DPI. Thus DPI is a nonselective blocker of ionic channels in pulmonary smooth muscle cells, and its mechanism of action does not appear to involve inhibition of hydrogen peroxide formation. The ability of DPI to block calcium currents can explain its inhibition of hypoxic pulmonary vasoconstriction.
Musculotendinous stiffness: its relationship to eccentric, isometric, and concentric performance
Authors: Wilson G. J. , Murphy A. J. , Pryor J. F.
Published: December 2017

The purpose of this study was to quantify the relationship between musculotendinous stiffness and performance in eccentric, isometric, and concentric activities. Thirteen trained subjects performed a series of maximal effort eccentric, concentric, and isometric muscular contractions in a bench press-type movement. Additionally, subjects performed a series of quasi-static muscular contractions in a bench press movement. A brief perturbation was applied to the bar while these isometric efforts were maintained, and the resulting damped oscillations provided data pertaining to each subject's musculotendinous stiffness. Musculotendinous stiffness was significantly related to isometric and concentric performance (r = 0.57–0.78) but not to eccentric performance. These results are interpreted as demonstrating that the optimal musculotendinous stiffness for maximum concentric and isometric activities was toward the stiff end of the elasticity continuum. A stiffer musculotendinous unit may facilitate such performances by improving the force production capabilities of the contractile component, due to a combination of improved length and rate of shortening, and additionally by enhancing initial force transmission.
Cardiac protein content and synthesis in vivo after voluntary running or head-down suspension
Authors: Henriksen E. J. , Munoz K. A. , Aannestad A. T. , Tischler M. E.
Published: December 2017

The adaptive responses of myocardial protein metabolism to chronic increases in work load were evaluated in juvenile female Sprague-Dawley rats. Rats were studied under four conditions: normal weight bearing (N), voluntary wheel running (WR) for < or = 4 wk, head-down-tilt suspension for 7 days (HS), or wheel running (2 or 3 wk) followed by 7 days of suspension (WR-HS). WR activity plateaued after 2 wk at 16 km/day and was maintained through week 4. WR did not affect normal whole body growth. Protein metabolism was studied by measuring heart protein content and in vivo fractional rate of protein synthesis with the [3H]phenylalanine “flooding dose” method. Two weeks of WR increased (P < 0.05) absolute heart protein content (22%) and protein synthesis (21%) relative to age-matched N group values. These differences in protein content and synthesis were maintained for > or = 4 wk. Rats failed to gain significant body weight during suspension. Heart protein content increased (P < 0.05) by 12% to 26% as did protein synthesis (14% to 22%) in HS compared with N group. In WR-HS group, cardiac protein content and protein synthesis were maintained at significantly elevated levels. These findings indicate that 1) high-volume WR by young rats provides a convenient noninvasive method for producing rapid and substantial cardiac hypertrophy, which results, at least in part, from enhanced cardiac protein synthesis; and 2) head-down suspension of sedentary juvenile rats leads to increased cardiac protein synthesis, which helps to increase cardiac protein content despite a lack of whole body growth.
Adductor pollicis muscle fatigue during acute and chronic altitude exposure and return to sea level
Authors: Fulco C. S. , Cymerman A. , Muza S. R. , Rock P. B. , Pandolf K. B. , Lewis S. F.
Published: December 2017

Large muscle exercise performance is impaired during acute exposure to normobaric or hypobaric hypoxia, but the effects of hypoxic conditions on fatigue of isolated smaller muscle groups per se are poorly defined. We studied how acute and chronic altitude (ALT) exposure and post-ALT return to sea level (SL) affects voluntary strength and fatigue of the adductor pollicis muscle. Eight healthy men (mean age 28 yr) were studied on five separate occasions: at SL, on days 1 (acute) and 13 (chronic) at ALT (4,300 m), and on days 1 (post 1) and 3 or 4 (post 2) at SL after 20 days of residence at ALT. On each day, maximal voluntary contractions (MVCs) of the adductor pollicis were obtained before and at the end of each minute of submaximal intermittent contractions of the adductor pollicis (50% of MVC of rested muscle, 5 s of contraction/5 s of rest) until exhaustion, defined as the inability to exert or maintain 50% of rested MVC. MVC of rested muscle did not differ among days. Time to exhaustion was shorter at acute ALT [5.1 +/- 0.5 (SE) min] than at SL (7.4 +/- 0.8 min, P < 0.05) and tended to be shorter than at chronic ALT (6.6 +/- 0.7 min, P > 0.05). Compared with acute and chronic ALT, time to exhaustion was prolonged during post 1 (9.0 +/- 1.2 min, P < 0.05) but not post 2 (6.1 +/- 0.5 min, P > 0.05). We conclude that 1) MVC of rested adductor pollicis muscle is not impaired during or after ALT exposure, 2) compared with SL conditions, acute but not chronic ALT exposure leads to a more rapid decline in adductor pollicis MVC associated with submaximal contractions, and 3) time to exhaustion is prolonged for > or = 1 day after return from ALT.
Effects of training on blood lactate-running speed relationship in thoroughbred racehorses
Authors: Von Wittke P. , Lindner A. , Deegen E. , Sommer H.
Published: December 2017

In this study the effects of training history on the results of a standardized two-speed test in competing Thoroughbreds were investigated during a racing season. For nine Thoroughbreds, 1,755 training days were recorded. Within the observation period each horse completed a two-speed field test at intervals of 6–8 wk to determine its running velocity (v) eliciting blood lactate concentrations of 4 (v4) and 12 mmol/l (v12). Horses performed 29 two-speed tests. Changes of v4 and v12 in a horse between two consecutive tests were used to assess effects of training history variables calculated for the period between two consecutive tests. The percentage of days with gallop workouts between two consecutive tests showed a significant correlation with changes in v4 (r = 0.71, P < 0.01) and v12 (r = 0.56, P < 0.05). The number of gallop workouts (r = 0.60, P < 0.05) and the total time of training (r = 0.58, P < 0.05) correlated with the change of v4. Furthermore the percentage of days without training was negatively correlated to changes of v4 (r = -0.75, P < 0.01) and v12 (r = -0.56, P < 0.05). Therefore the actual training caused changes in the blood lactate-running speed relationship despite its relatively low volume, intensity, and frequency. Future studies have to evaluate how the training variables can be changed to improve the training effects on the blood lactate-running speed relationship of competing Thoroughbreds.
N-acetylcysteine depresses contractile function and inhibits fatigue of diaphragm in vitro
Authors: Khawli F. A. , Reid M. B.
Published: December 2017

We have previously shown that antioxidant enzymes (superoxide dismutase and catalase) depress contractility of unfatigued diaphragm fiber bundles and inhibit development of acute fatigue. In the present study, we tested for similar effects of N-acetyl-cysteine (NAC), a nonspecific antioxidant approved for clinical use. Diaphragms were excised from deeply anesthetized rats. Fiber bundles were removed, mounted isometrically at 37 degrees C, and stimulated directly using supramaximal current intensity. Studies of unfatigued muscle showed that 10 mM NAC reduced peak twitch stress (P < 0.0001), shortened time to peak twitch stress (P < 0.002), and shifted the stress-frequency curve down and to the right (P < 0.05). Fiber bundles incubated in 0.1–10 mM NAC exhibited a dose-dependent decrease in relative stresses developed during 30-Hz contraction (P < 0.0001) with no change in maximal tetanic (200 Hz) stress. NAC (10 mM) also inhibited acute fatigue. Throughout 10 min of intermittent contraction at 30–40 Hz, treated bundles developed higher stresses than time-matched control bundles (P < 0.0001). NAC concentrations > or = 30 mM were toxic, causing a prompt irreversible decrease in maximal tetanic stress (P < 0.0001). Because NAC effects mimic the effects of other antioxidant agents with different mechanisms of action, we conclude that exogenous antioxidants exert stereotypical effects on contractile function that differ between unfatigued and fatiguing muscle. Unlike antioxidant enzymes, however, NAC has been approved for clinical use and may be used in future studies of human muscle fatigue.
No lung toxicity after repeated aerosol or intravenous delivery of plasmid-cationic liposome complexes
Authors: Canonico A. E. , Plitman J. D. , Conary J. T. , Meyrick B. O. , Brigham K. L.
Published: December 2017

The safety aspects of human gene therapy are of paramount importance in developing an ideal system for gene transfer. Lipofection using DNA in the form of a plasmid has been shown to successfully transfect the lungs when administered either intravenously or by aerosol. We have shown that repeated intravenous or aerosol administration of a plasmid containing the recombinant human alpha 1-antitrypsin gene and a cytomegalovirus promoter complexed to cationic liposomes results in no adverse effects on pulmonary histology, lung compliance, lung resistance, or alveolar-arterial oxygen gradient. Immunohistochemistry and Western blot analysis confirm successful gene transfer using this delivery system. We conclude that plasmids complexed to cationic liposomes may be a safe and efficacious delivery system for in vivo gene transfer to the lungs. Using this delivery system, in vivo gene therapy to the lungs can be achieved by either intravenous or aerosol administration of the transgene.
Cardiorespiratory changes during microwave-induced lethal heat stress and beta-adrenergic blockade
Authors: Jauchem J. R. , Frei M. R.
Published: December 2017

Ketamine-anesthetized Sprague-Dawley rats were exposed to 2,450-MHz microwaves at an average power density of 60 mW/cm2 (whole body specific absorption rate of approximately 14 W/kg) until lethal temperatures were attained. The effects of propranolol (2 or 10 mg/kg body wt), nadolol (10 mg/kg), and labetalol (10 mg/kg) on physiological responses (including changes in body temperature, heart rate, blood pressure, and respiratory rate) were examined. Lethal temperatures in the labetalol and both propranolol groups were significantly lower than in saline controls. Survival time was significantly less only in the high-dose propranolol group. In all groups, heart rate increased continuously during exposure; blood pressure increased until colonic temperature reached 41–41.5 degrees C and then decreased. These heart rate and blood pressure changes were similar to those that occur during environmental heat stress. Heart rate and blood pressure changes among groups were similar. Respiratory rate, however, was significantly elevated during most of the exposure period in the high-dose propranolol animals. This change in respiration, coupled with the significantly lower survival time in these animals, suggests a vital role of respiration in susceptibility to microwave-induced heating.
Contributions of capillary pathway size and neutrophil deformability to neutrophil transit through rabbit lungs
Authors: Wiggs B. R. , English D. , Quinlan W. M. , Doyle N. A. , Hogg J. C. , Doerschuk C. M.
Published: December 2017

Neutrophil margination within the pulmonary capillary is due to a delay in their transit compared with that of red blood cells (RBC). This delay has been attributed to the large fraction of capillary segments that are narrower than spherical neutrophils and differences between the time required for deformation of neutrophils and that required for deformation of RBC. This study investigated the characteristics of neutrophil deformation in vivo and the perfusion patterns of segments within capillary pathways. Studies comparing the extraction of neutrophils with that of nondeformable microspheres in one transit through the pulmonary circulation suggest that neutrophils can undergo a rapid deformation from 6.4 to 5.0–5.1 microns, whereas larger deformations require a delay. Effective diameters of the perfused capillary pathways were larger than expected for a random distribution of capillary segment diameters within these pathways. The longer transit times of neutrophils in the upper regions of the lung were associated with a greater fraction of pathways containing narrow segments. These studies suggest that neutrophil deformability and capillary pathway diameters are important in determining the size of the marginated pool of neutrophils within the pulmonary capillaries.
Stimulus-response curve of hypoxic pulmonary vasoconstriction in intact dogs: effects of ASA
Authors: Brimioulle S. , Lejeune P. , Vachiery J. L. , Delcroix M. , Hallemans R. , Leeman M. , Naeije R.
Published: December 2017

Hypoxic pulmonary vasoconstriction (HPV) has been reported to decrease during severe hypoxia in isolated lungs, but it remains unknown whether this decrease occurs in the intact animal and how it is affected by cyclooxygenase inhibition. We investigated the HPV stimulus-response relationship in eight pentobarbital sodium-anesthetized intact dogs with a naturally occurring response to hypoxia (“responders”). The pulmonary arterial minus wedge pressure difference (Ppa-Ppw) was measured at 11 inspired O2 fraction (FIO2) values between 0.40 and 0.04 while ventilation, cardiac output, and acid-base status were kept constant. Ppa-Ppw increased by 8 +/- 1 mmHg between FIO2 of 0.40 and 0.10 (alveolar PO2 of approximately 40 Torr) and decreased by 3 +/- 1 mmHg between FIO2 of 0.10 and 0.04. To assess the effects of cyclooxygenase inhibition, similar stimulus-response curves were obtained after administration of 20 mg/kg of acetylsalicylic acid (ASA) in 16 more dogs selected as either nonresponders or responders to hypoxia. ASA restored HPV in nonresponders and enhanced HPV in responders, with the difference between Ppa-Ppw at FIO2 of 0.10 and 0.40 increasing from 1 +/- 1 to 8 +/- 1 mmHg (P < 0.001) and from 7 +/- 1 to 10 +/- 1 mmHg (P < 0.05), respectively. In both groups, the shape of the stimulus-response curve after ASA was comparable to that of spontaneous HPV, with a maximum at FIO2 of 0.10 and a significant decrease at lower FIO2. We conclude that severe hypoxia attenuates HPV in the intact animal and that ASA restores or enhances HPV by affecting the magnitude of the hypoxic response and not the sensitivity to hypoxia.
Contractile properties of the developing diaphragm correlate with myosin heavy chain phenotype
Authors: Johnson B. D. , Wilson L. E. , Zhan W. Z. , Watchko J. F. , Daood M. J. , Sieck G. C.
Published: December 2017

The objective of this study was to determine the relationship between developmental transitions in myosin heavy chain (MHC) composition and changes in maximum unloaded shortening velocity (Vo) and maximum specific force (Po) of the rat diaphragm muscle. The diaphragm was excised at postnatal days 0, 3, 7, 14, 21, and 28 and in adults. MHC isoform expression was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and laser densitometry. In muscle fiber bundles, Vo was determined at 15 degrees C by use of the “slack” test. Isometric Po was determined at 15 and 26 degrees C. Simple and stepwise regressions were used to evaluate the correlations between Vo, Po, and MHC phenotype transitions and the various developmental ages. The progressive increases in Vo and Po with age were found to be inversely correlated to MHC-neonatal isoform expression (r2 = -0.84 and -0.63, respectively) and positively correlated to MHC-2X (r2 = 0.78 and 0.57) and MHC-2B (r2 = 0.51 and 0.40) isoform expression (P < 0.001). Changes in MHC-neonatal isoform expression contributed to most of the developmental variance in Vo and Po, with changes in MHC-2X and MHC-2B expression also contributing significant increments to total variance. The postnatal increase in Vo most likely relates to differences in the actomyosin adenosinetriphosphatase activity between neonatal and adult fast MHC phenotypes. The increase in Po may reflect inherent differences in myofibrillar density, cross-bridge cycling kinetics, and/or the force produced per cross bridge among fibers composed of the different MHC isoforms.
Simultaneous in vivo measurements of HbO2 saturation and PCr kinetics after exercise in normal humans
Authors: McCully K. K. , Iotti S. , Kendrick K. , Wang Z. , Posner J. D. , Leigh J. , Chance B.
Published: December 2017

Simultaneous measurements of phosphocreatine (PCr) and oxyhemoglobin (HbO2) saturation were made during recovery from exercise in calf muscles of five male subjects. PCr was measured using magnetic resonance spectroscopy in a 2.0-T 78-cm-bore magnet with a 9-cm-diam surface coil. Relative HbO2 saturation was measured as the difference in absorption of 750- and 850-nm light with use of near-infrared spectroscopy. The light source and detectors were 3 cm apart. Exercise consisted of isokinetic plantar flexion in a supine position. Two 5-min submaximal protocols were performed with PCr depletion to 60% of resting values and with pH values of > 7.0. Then two 1-min protocols of rapid plantar flexion were performed to deplete PCr values to 5–20% of resting values with pH values of < 6.8. Areas of PCr peaks (every 8 s) and HbO2 saturation (every 1 s) were fit to a monoexponential function, and a time constant was calculated. The PCr time constant was larger after maximal exercise (68.3 +/- 10.5 s) than after submaximal exercise (36.0 +/- 6.5 s), which is consistent with the effects of low pH on PCr recovery. HbO2 resaturation approximated submaximal PCr recovery and was not different between maximal (29.4 +/- 5.5 s) and submaximal (27.6 +/- 6.0 s) exercise. We conclude that magnetic resonance spectroscopy measurements of PCr recovery and near-infrared spectroscopy measurements of recovery of HbO2 saturation provide similar information as long as muscle pH remains near 7.0.
Effects of GABA receptor blockage on the respiratory response to hypoxia in sedated newborn piglets
Authors: Huang J. , Suguihara C. , Hehre D. , Lin J. , Bancalari E.
Published: December 2017

Brain gamma-aminobutyric acid (GABA) levels increase during hypoxia, which may modulate the ventilatory response to hypoxia. To test the possibility that the depressed neonatal ventilatory response to hypoxia may be related to increased central nervous system GABA activity, 26 sedated spontaneously breathing newborn piglets (age 5 +/- 1 day, wt 1.7 +/- 0.4 kg) were studied. Minute ventilation (VE), oxygen consumption, heart rate, arterial blood pressure, and arterial blood gases were measured in room air and after 1, 5, and 10 min of hypoxia (inspired O2 fraction 0.10) before drug intervention. Immediately after these measurements, an infusion of saline or the GABA alpha-receptor blocker (bicuculline, 0.3 mg/kg iv) or beta-receptor blocker (CGP-35348, 100–300 mg/kg iv) was administered while animals were hypoxic. All measurements were repeated at 1, 5, and 10 min after initiation of the drug infusion. Basal VE was similar among groups. During hypoxia, VE increased significantly in the animals that received either a GABA alpha- or beta-receptor blocker but not in those receiving saline. Changes in arterial Po2, oxygen consumption, heart rate, and arterial blood pressure were similar among groups before and after saline or GABA antagonist infusion. These results suggest that the decrease in ventilation during the biphasic ventilatory response to hypoxia in the neonatal piglet is in part mediated through the depressant effect of GABA on the central nervous system.
31P-MRS and simultaneous quantification of dynamic human quadriceps exercise in a whole body MR scanner
Authors: Rodenburg J. B. , de Boer R. W. , Jeneson J. A. , van Echteld C. J. , Bar P. R.
Published: December 2017

An ergometer for dynamic quadriceps exercise in a magnetic resonance (MR) scanner is physiologically validated, and its technical aspects are presented. The reproducibility of heart rate (HR), O2 consumption (VO2), and power (P) during two graded exercises on the MR ergometer was good (n = 8). Graded exercises on the MR ergometer and on a cycle ergometer (n = 17) were similar with respect to the regression lines between 1) HR and VO2 and 2) HR and P; also peak P did not differ significantly (280 +/- 37 and 298 +/- 41 W, respectively). Peak HR (171 +/- 14 and 184 +/- 15 beats/min, respectively), peak VO2 (3.00 +/- 0.51 and 3.54 +/- 0.44 l/min, respectively), and the slope of the regression line between P and VO2 were lower for MR exercise (P < 0.01). During quadriceps exercise in an MR scanner (n = 12), peak P was 64–143 W for the right leg, with corresponding inorganic phosphate-to-phosphocreatine ratios of 0.85–7.2. It is concluded that continuous noninvasive assessment of energy metabolism with 31P-MR spectroscopy and quantification of power output can be performed simultaneously during dynamic quadriceps exercise, without major reduction of the spectral resolution or the signal-to-noise ratio, and that exercise on this MR ergometer currently is the best possible approximation of cycling exercise for MR purposes.
Impaired plasma FFA oxidation imposed by extreme CHO deficiency in contracting rat skeletal muscle
Authors: Turcotte L. P. , Hespel P. J. , Graham T. E. , Richter E. A.
Published: December 2017

The extent to which carbohydrate (CHO) availability affects free fatty acid (FFA) metabolism in contracting skeletal muscle is not well characterized. To study this question, rats were depleted of glycogen by swimming exercise and lard feeding 24 h before perfusion of their isolated hindquarters. After 20 min of preperfusion with a medium containing no glucose, palmitate (600 or 2,000 microM), and [1–14C]palmitate, flow was restricted to one hindlimb, which was electrically stimulated for 2 min to further deplete muscles of glycogen. After 2 min of recovery, glucose was added to the perfusate at final concentrations of 0, 6, or 20 mM, and after another 3 min muscles were stimulated for 30 min. At 6 and 2,000 microM palmitate, glucose uptake after 30 min of stimulation averaged 23.5 +/- 9.3 and 45.9 +/- 10.6 mumol.g-1.h-1 with 6 and 20 mM glucose, respectively. At 6 and 2,000 microM palmitate, palmitate uptake was lower (30–37%, P < 0.05) with 0 than with 6 or 20 mM glucose. At 600 microM palmitate, percent palmitate oxidation was higher (27%, P < 0.05) with 0 than with 6 or 20 mM glucose, resulting in similar total palmitate oxidation with the three glucose concentrations (0.28 +/- 0.01 mumol.g-1.h-1). At 2,000 microM palmitate, percent palmitate oxidation was not significantly different among glucose concentrations, resulting in a significantly lower rate of palmitate oxidation with 0 (0.62 +/- 0.18 mumol.g-1.h-1) than with 6 or 20 mM glucose (0.77 +/- 0.25 and 0.78 +/- 0.20 mumol.g-1.h-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)