bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular permeability and epithelial transport effects on lung edema formation in ischemia and reperfusion
Authors: Khimenko P. L. , Barnard J. W. , Moore T. M. , Wilson P. S. , Ballard S. T. , Taylor A. E.
Published: December 2017

To determine the role of various Na+ transport systems in the edema fluid accumulation after ischemia and reperfusion in the lung, we evaluated the effect of amiloride (a Na+ channel blocker), ouabain (a Na(+)-K(+)-adenosinetriphosphatase blocker), and phloridzin (a Na(+)-glucose cotransport blocker) in isolated rat lungs. Ischemia and reperfusion (I/R) significantly increased the edema accumulation, with the wet-to-dry weight ratios increasing to 10.14 +/- 0.58 from 6.03 +/- 0.05 in control lungs (P < 0.04). Amiloride significantly augmented the amount of edema fluid (wet-to-dry weight ratio 12.26 +/- 0.77), and ouabain further increased the amount of edema (wet-to-dry weight ratio 18.58 +/- 1.00). Phloridzin did not significantly affect edema formation associated with I/R. Isoproterenol decreased the amount of edema formation in the presence and absence of amiloride. This occurred because the endothelial permeability as assessed by filtration coefficient was restored to normal values and less edema formed. The present study indicates that Na+ channels and Na(+)-K(+)-adenosinetriphosphatase, components of the active Na+ absorption transport system, are very important in opposing edema fluid accumulation in rat lungs subjected to I/R injury and operate as an edema safety factor. However, if the endothelial damage associated with I/R is allowed to persist, then the transport processes, even if operative, are insufficient to prevent continuous edema accumulation.
Physical determinants of bronchial mucosal folding
Authors: Lambert R. K. , Codd S. L. , Alley M. R. , Pack R. J.
Published: December 2017

It has recently been proposed, on the basis of a theoretical analysis, that the folding of the mucosa provides a significant component of airway stiffness. The model predicted that the stiffness of an airway was directly related to the number of epithelial folds that developed. In this study we examine the possibility that the folding pattern is determined by the physical requirements that the folding membrane must stay within the boundary of the smooth muscle wall, that the submucosal mass is constant, and that the strain energy of the folding membrane is the minimum possible within the geometric constraints. Model predictions are compared with morphometric data from the noncartilaginous airways of 17 sheep lungs. The data are in agreement with our predictions, which are based on the assumption that the folding membrane thickness is proportional to the submucosal thickness (in a fully dilated airway). The outcome of this analysis is that the increase in intrinsic stiffness of the folding membrane resulting from the increased thickness outweighs the decrease in stiffness conferred by the fewer folds required by the thicker submucosa. It is suggested that the increase in folding membrane thickness observed in asthma could be viewed as a protective mechanism that tends to reduce hyperresponsiveness.
Effects of inhaled substance P on airway responsiveness to methacholine in asthmatic subjects in vivo
Authors: Cheung D. , van der Veen H. , den Hartigh J. , Dijkman J. H. , Sterk P. J.
Published: December 2017

We tested the hypothesis that the inhaled tachykinin substance P (SP) can induce hyperresponsiveness to methacholine in asthmatic subjects in vivo. Nine atopic nonsmoking asthmatic males with normal forced expiratory volume in 1 s (FEV1; > 80% predicted) and increased methacholine sensitivity [provocative concn causing 20% fall in FEV1 (PC20) < 8 mg/ml] participated in a two-period placebo-controlled crossover study. Dose-response curves to SP (0.25–8 mg/ml) and placebo were recorded on 2 randomized days at least 1 wk apart, and methacholine tests were done 24 h before and 2 and 24 h after these challenges. The responses were measured by FEV1 (%fall from baseline). The position of the methacholine dose-response curves was expressed by the PC20 FEV1 and by the maximal response by the plateau level (MFEV1). SP caused a dose-dependent fall in FEV1 (P < 0.001). There was a slight increase in the PC20 FEV1 at 2 and 24 h, which was not significantly different between placebo and SP. Similarly, there was a reduction in MFEV1 at 2 h after both pretreatments. However, at 24 h after SP inhalation, MFEV1 increased compared with placebo. These changes in MFEV1 were significantly different between SP and placebo by 5.2 +/- 2.2% fall (SE) (P < 0.05). We conclude that 1) a bronchoconstrictive dose of SP, compared with placebo, enhances maximal airway narrowing to methacholine in asthma 24 h after inhalation and 2) tolerance develops to high doses of inhaled methacholine. These findings are suggestive of a role of SP in causing excessive airway narrowing in asthma by inflammatory mechanisms.
Effects of spaceflight on morphology of the rat adenohypophysis
Authors: Thapar K. , Kovacs K. , Horvath E. , Stefaneanu L. , Chambers E. , Mortimer A. J.
Published: December 2017

To determine the effects of spaceflight on the anterior pituitary gland, the adenohypophyses of rats after a 7-day spaceflight aboard the space shuttle Endeavor (STS-54) were investigated by histology, immunohistochemistry, morphometry, electron microscopy, and in situ hybridization and were compared with synchronous control rats. Morphometry revealed the corticotrophs of space-flown rats to be significantly enlarged, demonstrating 46–48% increases in mean cell, nuclear, and cytoplasmic areas. These corticotrophs also exhibited striking ultrastructural signs of heightened secretory activity. Furthermore, their expression of proopiomelanocortin mRNA, the transcript encoding the precursor protein from which adrenocorticotropic hormone is posttranslationally cleaved, was also significantly enhanced, a finding consistent with their hypersecretory state. Gonadotrophs also exhibited significant increments in mean nuclear, cell, and cytoplasmic areas of 22, 45, and 51%, respectively; however, they were not accompanied by ultrastructural evidence of increased secretory function. There were no morphological changes in somatotrophs, lactotrophs, or thyrotrophs, nor were there any significant changes in the overall frequency of any one adenohypophyseal cell type in comparison with control. The structural integrity of all adenohypophyseal secretory and vascular elements was preserved after spaceflight, as there was neither evidence of necrosis nor other forms of cellular injury in spaceflown specimens. Capillaries were patent, and neither endothelial damage nor thrombosis was noted. These data suggest that spaceflight is accompanied by a selective morphological response in the anterior pituitary, one characterized by hypertrophy of both corticotrophs and gonadotrophs and by enhanced endocrine activity of the former.
Effect of increasing work rate on metabolic responses of the donkey (Equus asinus)
Authors: Mueller P. J. , Jones M. T. , Rawson R. E. , van Soest P. J. , Hintz H. F.
Published: December 2017

Oxygen consumption (VO2) and concentration of venous blood metabolites were measured in donkeys trained to run and to pull loads on a treadmill. VO2 in two donkeys running at maximal speed on a 9.8% slope was 110 +/- 2 ml.min-1.kg-1, approximately 22 times preexercise VO2. Average heart rate at maximal VO2 (VO2max) was 223 +/- 2 beats/min, five times the preexercise heart rate. Blood lactate increased 14-fold, and blood glucose did not change (P > 0.05). Animals running up a 4% incline and incremental draft loading of five donkeys walking on the level were also studied. The total energy cost of walking unloaded was 2.86 +/- 0.06 J.m-1.kg live wt-1. During low- to medium-intensity draft work for 25 min, glucose fell below preexercise values (P < 0.05), whereas plasma hematocrit and cortisol increased (P < 0.05). Blood lactate remained unchanged up to approximately 40% VO2 max but increased 170% at approximately 60% VO2max. The responses in donkeys are similar to those of exercising horses except for the rapid decline in blood glucose observed during low-intensity exercise and the lower lactate levels at both the high-intensity exercise and the apparent anaerobic threshold.
Physiological dead space increases during initial hours of chronic hypoxemia with or without hypocapnia
Authors: Olson E. B.
Published: December 2017

A whole body plethysmograph was used to determine the minute ventilation-to-CO2 production ratio (VE/VCO2) of intact unrestrained unanesthetized adult male Sprague-Dawley rats during 7 days of hypoxemia (arterial PO2 approximately 50 Torr). In one set of rats, normocapnia (arterial PCO2 approximately 40 Torr) was maintained. Arterial blood gases and acid-base status were determined, and arterial PCO2 was used to calculate alveolar ventilation-to-VCO2 ratio (VA/VCO2) in all situations when inhaled CO2 was not elevated. In normoxia VE/VCO2 = 25 +/- 1 (mean +/- 95% confidence limits); after 12 h of hypoxemia, VE/VCO2 was maximal, 61 +/- 5 in hypoxemic hypocapnia and 200 +/- 55 in hypoxemic normocapnia. Between 2 and 7 days of hypoxemia, VE/VCO2 had plateaued, 42 +/- 3 in hypoxemic hypocapnia and 95 +/- 19 in hypoxemic normocapnia. Dead space-to-tidal volume ratio (VD/VT) = (VE/VCO2 - VA/VCO2)/(VE/VCO2), and in normoxia VD/VT = 0.17 +/- 0.04. In hypoxemic hypocapnia, VD/VT measured between 1 and 5 h was 0.38 +/- 0.04. It remained elevated at 0.29 +/- 0.04 after 24 h, but after 4-7 days in hypoxemic hypocapnia, VD/VT had recovered to 0.15 +/- 0.03. It is postulated that the disproportionate increase in VE/VCO2 observed during the first 24 h of exposure to hypoxemic normocapnia (compared with elevated steady-state plateau levels maintained from 2 to 7 days sojourn) reflects an immediate transient increase of physiological dead space on exposure to hypoxemia.
Prior exercise suppresses the plasma tumor necrosis factor response to bacterial lipopolysaccharide
Authors: Bagby G. J. , Sawaya D. E. , Crouch L. D. , Shepherd R. E.
Published: December 2017

This study was initiated to determine the effect of physical exercise on the in vivo tumor necrosis factor-alpha (TNF) response to Escherichia coli lipopolysaccharide (LPS). Rats familiarized with treadmill running and surgically implanted with vascular catheters were either not exercised or exercised to near exhaustion (mean run time of 102 +/- 13 min) before intravenous LPS challenge (1 mg/kg; lethality of dose is 10–20% in 24 h). Compared with time-matched nonexercised control rats, exercised rats had increased heart rates, plasma lactate, and plasma corticosterone and decreased plasma glucose at the conclusion of exercise. In response to LPS, both groups became hypotensive, exhibited transient hyperglycemia, and sustained hyperlactacidemia. By 30 min post-LPS, plasma corticosterone levels were similar in the two groups. Nonexercised rats exhibited a normal plasma TNF response to LPS with the peak value (10,400 +/- 2,000 U/ml) occurring 90 min after LPS challenge. In contrast, the TNF response in rats exercised before LPS administration was blunted to 17% of the nonexercised group, with the peak occurring at an earlier time after LPS. Addition of recombinant murine TNF to postexercise plasma was fully expressed. The TNF response remained attenuated when LPS was administered up to 6 h after completion of exercise, but it returned to normal in rats allowed to recover for 24 h. The results demonstrate that exercise, perhaps as a stress modality, markedly suppresses the systemic TNF response that is normally observed in response to LPS challenge.
Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle
Authors: Marone J. R. , Falduto M. T. , Essig D. A. , Hickson R. C.
Published: December 2017

This investigation was undertaken to evaluate whether the mitochondrial disfunction associated with glucocorticoid treatment is expressed at the level of cytochrome-c oxidase (COX) and whether endurance training attenuates this response. Adult female rats were administered cortisol acetate (100 mg/kg body wt) or an equal volume of the vehicle solution for 11 days. Endurance training was performed by treadmill running up to 28 m/min (with intervals at 50 m/min for 2 min every 15 min), for 90 min/day, 6 days/wk, for 8–10 wk. During hormone treatments, the training animals ran every day. Exercise prevented 43–55% of the hormone-induced atrophy in various fast-twitch muscles or muscle groups. Cortisol acetate treatment produced no significant effects on COX enzyme activities or subunit mRNA content in deep red or superficial white quadriceps or mixed plantaris muscles. The levels of COX were increased as a result of training by 70–110% in plantaris and red quadriceps muscles, but no changes were seen in white quadriceps muscles. Both nuclear-encoded (COX IV) and mitochondrial-encoded (COX III) mRNAs were increased approximately twofold by the exercise program in these same muscles. These data indicate that the impaired mitochondrial functioning associated with glucocorticoids is not observed at the COX step of electron transport. The prolonged endurance-training regimen appears to induce relatively parallel increases in COX enzyme activity and mRNA expression with coordinate changes in nuclear and mitochondrial mRNAs.
Effect of aminophylline on plasma [K+] and hypoxic ventilatory response during mild exercise in men
Authors: Igarashi T. , Nishimura M. , Akiyama Y. , Yamamoto M. , Miyamoto K. , Kawakami Y.
Published: December 2017

To examine the role of endogenous adenosine on the hypoxic ventilatory response (HVR) enhanced during exercise, we measured HVR at rest and during mild exercise (12.5 W) in nine healthy men in a supine position after pretreatment with aminophylline (5 mg/kg), an adenosine receptor blocker, or dipyridamole (0.6 mg/kg), an adenosine uptake blocker, by using a 3-day double-blind placebo-controlled design. Although HVR was enhanced during exercise on all occasions, HVR with aminophylline [0.42 +/- 0.07 (SE) l.min-1.%fall-1 of arterial O2 saturation] was significantly lower than that with placebo (0.64 +/- 0.13 l.min-1.%fall-1) or dipyridamole (0.64 +/– 0.08 l.min-1.%fall-1) during exercise (P < 0.05 for both) at similar end-tidal PCO2 on the 3 days but not at rest. We then examined the changes in plasma K+ concentration ([K+]) and catecholamines, the other possible endogenous potentiators of the carotid body activity. The exercise- and hypoxia-induced increases in plasma [K+] were significantly lower with aminophylline (0.23 +/- 0.09 meq/l) than with the placebo (0.51 +/- 0.10 meq/l) or dypyridamole (0.58 +/- 0.13 meq/l) (P < 0.05 for both). We therefore conclude that aminophylline attenuates the enhancement of HVR during mild exercise and that this might be due to its attenuating effect on exercise- and hypoxia-associated increases in plasma [K+] rather than due to its antagonizing effect on endogenous adenosine.
Spaceflight alters autonomic regulation of arterial pressure in humans
Authors: Fritsch-Yelle J. M. , Charles J. B. , Jones M. M. , Beightol L. A. , Eckberg D. L.
Published: December 2017

Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4–5 days) impairs one neural mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8–14 days. We found the following changes between preflight and landing day: 1) orthostatic tolerance decreased; 2) R-R interval spectral power in the 0.05 to 0.15-Hz band increased; 3) plasma norepinephrine and epinephrine levels increased; 4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and 5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevant reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.
Muscle lactate metabolism in recovery from intense exhaustive exercise: impact of light exercise
Authors: Bangsbo J. , Graham T. , Johansen L. , Saltin B.
Published: December 2017

This study examined the effect of low-intensity exercise on lactate metabolism during the first 10 min of recovery from high-intensity exercise. Subjects exercised (61.0 +/- 5.4 W) one leg to exhaustion (approximately 3.5 min), and after 1 h of rest they performed the same exhaustive exercise with the other leg. For one leg the intense exercise was followed by rest [passive (P) leg], and for the other leg the exercise was followed by a 10-min period with low-intensity exercise at a work rate of 10 W [active (A) leg]. The muscle lactate concentration after the intense exercise was the same in the P and A legs, but after 10 min of recovery, the lactate concentration and the arterial blood lactate level were higher for the P leg than for the A leg (both P < 0.05). During the recovery, the mean blood flow was lower for the P leg than for the A leg (P < 0.05), whereas the mean lactate efflux was not significantly different. During the 10 min of recovery, lactate release accounted for approximately 60% of the change in muscle lactate for either leg. The leg excess postexercise O2 consumption during 10 min of recovery was 440 and 750 ml for the P and A legs, respectively. The present data suggest that a lowered blood lactate level during active recovery is due to an elevated muscle lactate metabolism and is not caused by a transient higher release of lactate from the exercising muscles coupled with greater uptake in other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased peak oxygen consumption of trained muscle requires increased electron flux capacity
Authors: Robinson D. M. , Ogilvie R. W. , Tullson P. C. , Terjung R. L.
Published: December 2017

The importance of the training-induced increase in mitochondrial capacity in realizing the increase in maximal O2 consumption (VO2max) of trained muscle was evaluated using an isolated perfused rat hindlimb preparation at a high blood flow (approximately 80 ml.min-1.100 g-1) during tetanic contractions. Rats trained for 8-–12 wk by treadmill running exhibited an approximately 25% increase in muscle VO2max (5.62 +/- 0.31 to 7.06 +/- 0.64 mumol.min-1.g-1), an increase in mitochondrial enzyme activity (approximately 70% for cytochrome oxidase and approximately 55% for NADH cytochrome-c reductase), and an increase in tissue capillarity (14%) that is expected to increase the O2 exchange capacity of the tissue. Muscle VO2max of sedentary (n = 34) and trained (n = 30) animals was determined, and electron transport capacity was acutely managed with myxothiazol, a tight-binding inhibitor of complex III. Inhibition of complex III was similar among 1) the low- and high-oxidative fibers and 2) the superficial and deep mitochondrial populations within muscle. Inhibition of NADH cytochrome-c reductase activity resulted in reductions in muscle VO2max with similar dose responses (mean effective dose of approximately 0.2 microM) of myxothiazol added to the perfusion medium. The extraction of O2 by the contracting muscle decreased as VO2max declined. The increase in muscle VO2max observed in the muscle of trained animals was eliminated when its electron transport capacity was reduced to that observed in normal sedentary rat muscle. Thus, the exercise-induced adaptation of an increased muscle mitochondrial content appears to be essential for trained muscle to exhibit its increased O2 flux capacity. The results of the present experiment illustrate the importance of mitochondrial adaptations in muscle remodeled by exercise training.
Fatigue of rapid and slow onset in isolated perfused rat and mouse diaphragms
Authors: Kolbeck R. C. , Nosek T. M.
Published: December 2017

Muscle fatigue was studied in the isolated perfused rat (66% oxidative fibers) and mouse (99% oxidative fibers) diaphragms. Both muscles displayed two fatigue patterns when exposed to 333-ms trains of 20-Hz stimulation. A rapid fatigue pattern appeared within each contractile train as an immediate progressive twitch-by-twitch diminution in contractility [a decrease in maximal isometric twitch tension (T) and maximal rate of T development]. An intertrain slow fatigue pattern also appeared as a progressive train-by-train diminution in contractility and an increased maximal rate of relaxation normalized to T. A reduction in the stimulatory frequency from 20 to 2 Hz caused a considerable diminution in the rapid fatigue pattern. These data suggest that rapid fatigue results from the time course of mechanical restitution, the time necessary for the Ca2+ channels of the sarcoplasmic reticulum to recover from inactivation. The slow fatigue pattern, on the other hand, is thought to be due to changes in the intracellular milieu. The difference in sensitivity of the rat and mouse diaphragms to rapid and slow fatigue is apparently related to differences in their fiber type composition. Thus, as would be expected, the mouse diaphragm, composed of only oxidative fibers, is less susceptible to slow fatigue compared with the rat diaphragm. On the other hand, it is more susceptible to rapid fatigue.
Atrial septal defect blunts the impairment of left ventricular function during the Mueller maneuver
Authors: Virolainen J. , Ventila M. , Kupari M.
Published: December 2017

To investigate whether atrial septal defect (ASD) modifies the left ventricular (LV) hemodynamic response to a fall of intrathoracic pressure (Mueller maneuver), we studied 15 patients with an uncomplicated ASD and 16 healthy control subjects. LV function was measured by M-mode and Doppler echocardiography at rest and during the maneuver. Indicator-dilution technique was used to quantify the pulmonary-to-systemic flow ratio. During comparable changes (means +/- SE) of intrathoracic pressure (-33 +/- 2 mmHg in persons with ASD vs. -34 +/- 2 mmHg in those without), LV systolic function and filling diminished in both groups but patients with ASD showed smaller reductions in LV stroke dimension (-0.9 +/- 0.5 vs. -2.5 +/- 0.4 mm; P = 0.016), peak diameter shortening rate (-4 +/- 2 vs. -12 +/- 2 mm/s; P = 0.007), transmitral velocity-time integral (-1.0 +/- 0.3 vs. -2.2 +/- 0.4 cm; P = 0.022), and cardiac output (-6 +/- 3 vs. -18 +/- 3%; P = 0.029). The pulmonary-to-systemic flow ratio increased from 2.1 +/- 0.1 to 2.6 +/- 0.2 in the ASD group (P = 0.014). In conclusion, LV function diminishes significantly in healthy persons during the Mueller maneuver. In patients with ASD, the changes are directionally similar but quantitatively smaller. An interatrial communication mitigates the impairment of LV function after an acute and sustained drop of intrathoracic pressure.
Continuous measurements of changes in pulmonary capillary surface area with 201Tl infusions
Authors: Effros R. M. , Hacker A. , Jacobs E. , Audi S. , Murphy C.
Published: December 2017

The impact of physiological and pathological processes on metabolism and transport of a variety of substances traversing the pulmonary vasculature depends in part on the capillary surface area available for exchange, and a reliable method for detecting changes in this parameter is needed. In this study, a continuous-infusion approach was used to investigate the response of the pulmonary capillary surface area to increases in flow and left atrial pressure. Isolated rat lungs were perfused with an acellular perfusion solution containing 125I-labeled albumin (an intravascular indicator) and 201Tl, a K+ analogue which is concentrated within lung cells. The extraction of 201Tl from the perfusate was 61% greater at low flow (8.5 ml/min) than at high flow (26 ml/min), and rapid changes in extraction were observed when flow was altered. In contrast, the permeability-surface area product was 76% greater when lungs were perfused at high flow than at low flow, suggesting comparable increases in pulmonary capillary surface area in these zone 2 lungs (airway pressure = 5 cmH2O, left atrial pressure < 0 cmH2O). In a second group of experiments, increases in left atrial pressure to 14 cmH2O (zone 3 lungs) at a constant flow of 8.5 ml/min increased the permeability-surface area product by only 18% despite increases in average intravascular pressure that were at least as high as those associated with high perfusion rates. 201Tl infusions provide a useful method for detecting and quantifying changes in pulmonary capillary surface area.
Decreasing stimulation frequency-dependent length-force characteristics of rat muscle
Authors: Roszek B. , Baan G. C. , Huijing P. A.
Published: December 2017

Effects of decreasing stimulation frequency on length-force characteristics were determined for rat medial gastrocnemius muscle. The peripheral nerve was stimulated supramaximally with a succession of twitch and frequencies of 100, 50, 40, 30, and 15 Hz. Active peak tetanic and twitch forces and active muscle geometry were analyzed. Optimal muscle length and active slack length shifted significantly (P < 0.05) to higher muscle length by a maximum of 2.8 and 3.2 mm, respectively. Further significant effects were found for distal fiber length and mean sarcomere length of distal fiber (increases) and for fiber angle and aponeurosis length (decreases). Neither muscle length range between active slack and optimal length nor aponeurosis angle was altered significantly. We concluded that decreasing stimulation frequency-dependent length-force characteristics are affected by a complex interaction of length-dependent calcium sensitivity, potentiation of the contractile system, distribution of sarcomere length, and interactions between force exerted and aponeurosis length. Length-dependent calcium sensitivity seems to be a major factor determining the magnitude of the shift of optimal muscle length.
Diaphragmatic pressure-flow relationship during hemorrhagic shock: role of nitric oxide
Authors: Ward M. E. , Hussain S. N.
Published: December 2017

In the vascularly isolated resting and contracting (3 Hz) canine hemidiaphragm, we studied the effect of intra-arterial infusion of the nitric oxide (NO) inhibitor NG-nitro-L-arginine (LNA) on the relationship between phrenic arterial perfusion pressure (Pphr) and blood flow (Qphr). In separate groups of animals, either saline or LNA (final concn 6 x 10(-4) M) was infused into the phrenic artery over 20 min. The diaphragm was then autoperfused by diverting flow from the left femoral artery. Arterial blood pressure was reduced in stages by controlled hemorrhage. The Pphr-to-Qphr relationship was plotted for each animal, and the third-order polynomial of best fit was determined by least squares regression. The inflection point of this relationship was determined for each animal. In the contracting and resting diaphragms, the inflection point corresponded to Pphr values of 83.6 +/- 4.7 and 72.5 +/- 6.8 mmHg, respectively, in the saline-treated group compared with 86.2 +/- 2.7 and 76.8 +/- 5.1 mmHg, respectively, in the LNA-treated group. In the contracting diaphragm, LNA reduced Qphr uniformly across the entire range of perfusion pressures. In the resting diaphragm, the effect of LNA was not uniform. At perfusion pressures below the inflection point, the flow was reduced in proportion to the reduction in inflection point flow. At higher perfusion pressures, Qphr was decreased to a greater extent than could be accounted for by the change in inflection point flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Ventilatory output and acetylcholine: perturbations in release and muscarinic receptor activation
Authors: Burton M. D. , Nouri K. , Baichoo S. , Samuels-Toyloy N. , Kazemi H.
Published: December 2017

Cholinergic transmission may be part of the normal neurochemical processes that support spontaneous ventilation. If this is true, perturbations in acetylcholine (ACh) turnover should alter ventilatory output in a predictable manner. With the use of the isolated perfused brain stem-spinal axis from the neonatal rat, the effects of modifiers of ACh release and blockers of muscarinic receptors on spontaneous C4 (phrenic) output were determined. Vesamicol and cetiedil, inhibitors of ACh release, caused depression and cessation of the C4 output in a dose-dependent manner when added to the perfusate. Muscarinic blockers, particularly M1 and M3 blockers, caused a similar depression. 4-Aminopyridine and tetraethylammonium chloride, facilitators of ACh release, caused stimulation of C4 (phrenic) output. The depressive effects of the blockers and inhibitors were reversible with facilitation of ACh release except in the case of cetiedil. These findings are consistent with the view that the synaptic turnover of endogenous ACh is an important part of the normal neurochemical process that supports and modulates ventilation.
Longitudinal development of young talented speed skaters: physiological and anthropometric aspects
Authors: de Koning J. J. , Bakker F. C. , de Groot G. , van Ingen Schenau G. J.
Published: December 2017

A longitudinal analysis of a group of speed skaters was done to identify the performance-determining factors for a successful speed skating career. This paper presents both the physiological and anthropometric results of this longitudinal study. Twenty-four athletes from the Dutch National Junior Speed Skating Team were followed from age 16–17 yr to age 20–21 yr. During the development from junior to senior speed skater, a number of anthropometric and physiological variables changed. There were no differences between successful and unsuccessful speed skaters from an anthropometric perspective; consequently, it was not possible to distinguish successful from unsuccessful athletes on anthropometric grounds. The longitudinal data showed that at a younger age the successful speed skaters had similar oxygen consumption, mechanical efficiency, and power output values compared with the unsuccessful speed skaters. Later in the study, successful speed skaters distinguished themselves by the ability to produce higher power output values. There were no anthropometric or physiological relationships found in this study on which performance at the age of 20–21 yr could be predicted with measurements at a junior age.
Effect of sternothyrohyoid myectomy on upper airway mechanics in normal horses
Authors: Holcombe S. J. , Beard W. L. , Hinchcliff K. W. , Robertson J. T.
Published: December 2017

The effect of transection of the sternothyroideus and sternohyoideus muscles on upper airway mechanics was investigated in exercising horses. Upper airway mechanics of six Standardbred horses were measured at rest and during exercise before and 24 h and 2 wk after sternothyrohyoid myectomy. Transnasal tracheal and pharyngeal catheters connected to differential pressure transducers were used to measure tracheal and pharyngeal pressures. A pneumotachograph mounted on the rostral end of an airtight face mask was used to measure airflow. Horses ran at 50, 75, and 100% of maximal O2 consumption on a treadmill. Twenty-four hours after sternothyrohyoid myectomy, no significant difference was detected in tracheal, pharyngeal, or translaryngeal inspiratory and expiratory pressures and impedances, inspiratory and expiratory flows, and respiratory frequency. Two weeks after sternothyrohyoid myectomy, there was a statistically significant increase in translaryngeal inspiratory pressure (P = 0.035) and tracheal inspiratory pressure (P = 0.032) compared with preoperative measurements. Two weeks after sternothyrohyoid myectomy, there was a statistically significant increase in translaryngeal inspiratory resistance (P = 0.017) and tracheal inspiratory resistance (P = 0.023) compared with preoperative values. Increased translaryngeal and tracheal inspiratory pressures and resistances after sternothyrohyoid myectomy suggest that the sternothyroideus and sternohyoideus muscles act to increase or maintain upper airway patency and stability in normal horses.
The need to scale for differences in body size and mass: an explanation of Kleiber's 0.75 mass exponent
Authors: Nevill A. M.
Published: December 2017

When modeling intraspecific relationships between selected measurements (Y) for differences in body mass (m) using the allometric equation Y = amb (where a is a constant and b is the exponent parameter), various studies have reported exponents greater than the anticipated 2/3, often closer to the exponent 0.75 identified by Kleiber. A possible explanation for these exponents is proposed based on the findings of Alexander et al. (J. Zool. Lond. 194: 539–552, 1981), who observed that, within a variety of species, larger mammals have a greater proportion of proximal leg muscle mass in relation to their body mass, m1.1. If subjects that are used to record Y exhibit a similar disproportionate increase in muscle mass with body size, then the allometric equation is likely to identify both a contribution proportional to the subject's body mass and a contribution from the disproportionate increase in muscle mass within the group. These confounding influences in Y can be identified separately by incorporating a body size parameter as well as a mass component in the allometric equation. The factor “body size“ can be introduced either by partitioning the sample into discrete subgroups according to body size or, in studies involving human subjects, by introducing height as a continuous covariate. In both studies reported involving human maximal exercise, these methods were able to identify a systematic increase in Y with body size, leaving the subject's body mass component, found to be proportional to m2/3, independent of body size.
Role of nonenzymatically generated prostanoid, 8-iso-PGF2 alpha, in pulmonary oxygen toxicity
Authors: Vacchiano C. A. , Tempel G. E.
Published: December 2017

Oxygen delivery at higher than ambient concentrations is in frequent clinical use, yet prolonged exposure can produce pulmonary edema in humans and animals. The specific mediators of oxygen toxicity are unknown, although evidence suggests that oxygen-based radicals such as superoxide anion contribute to this injury. Recently, 8-iso-prostaglandin F2 alpha (PGF2 alpha), an F2-isoprostane formed by free radical-initiated lipid peroxidation of arachidonic acid, has been implicated in pulmonary injury. Nitric oxide (NO) also contributes to tissue oxygen radical load, and although believed to be beneficial, its metabolites may play a pathophysiological role by participating in lipid peroxidation and isoprostane formation. We hypothesized that 8-iso-PGF2 alpha and NO levels increase in high oxygen concentrations and that 8-iso-PGF2 alpha is associated with lung injury and accumulation of plasma albumin in pulmonary extravascular space. Levels of 8-iso-PGF2 alpha in bronchial alveolar lavage fluid (BALF) of rats exposed to 90% O2 at 1 atmosphere for 48 h (56 +/- 3 pg/ml) or 60 h (70 +/- 5 pg/ml) were significantly increased compared with levels in ambient air-exposed control rats (36 +/- 5 pg/ml). NO levels in BALF of rats exposed to 90% O2 at 1 atmosphere for 60 h were increased 50% compared with NO levels in BALF of rats exposed to ambient air or 48 h of 90% O2 (P < 0.05). Accumulation of radiolabeled plasma albumin in lung parenchyma of rats inhaling 8-iso-PGF2 alpha was also examined.(ABSTRACT TRUNCATED AT 250 WORDS)
Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury in rats
Authors: Shen C. Y. , Wang D. , Chang M. L. , Hsu K.
Published: December 2017

Mepacrine, a cell membrane stabilizer and inhibitor of phospholipase A2 (PLA2), exerts a protective effect on ischemia-reperfusion injury in heart; however, its effect in lungs has not been examined. This study aimed to determine whether mepacrine pretreatment attenuates ischemia-reperfusion lung injury simulated by hypoxia reoxygenation and to identify possible mechanisms for such protection. Acute lung injury was induced in Sprague-Dawley rats by ventilation with 5% CO2–95% N2 and 5% CO2–95% air. Pretreatment with 0.06 mM mepacrine significantly attenuated the acute lung injury. Capillary filtration coefficient, lung weight gain, and protein concentration of lung lavage fluid were significantly lower in mepacrine-treated rats than in rats exposed to hypoxia reoxygenation alone. Steroid dexamethasone, another potential PLA2 inhibitor, had almost no protective effect. Mepacrine but not dexamethasone caused dose-dependent attenuation of the increase in leukocyte chemiluminescence produced by exposure to phorbol myristate acetate. Mepacrine also dose-dependently inhibited production of tumor necrosis factor-alpha (TNF-alpha) by human monocytes; dexamethasone was much less effective in decreasing TNF-alpha production. We conclude that mepacrine but not dexamethasone can significantly attenuate a hypoxia-reoxygenation-induced injury of the lung. This protective effect of mepacrine may not be the result of its inhibition of PLA2 but rather of its downregulation of oxygen radical production by circulating or resident leukocytes or its attenuation of TNF-alpha production by macrophages.
Basal fat oxidation decreases with aging in women
Authors: Calles-Escandon J. , Arciero P. J. , Gardner A. W. , Bauman C. , Poehlman E. T.
Published: December 2017

The present study tested the hypothesis that a decrease in basal fat oxidation in aging women is related to a loss of fat-free mass. Thirty-two nonsmoking women with a wide range of age (18–73 yr) were characterized for body composition (underwater weight), maximal aerobic capacity, and basal fat oxidation (indirect calorimetry). Results showed that fat oxidation was negatively correlated with age (r2 = 0.17, P = 0.017) but was positively correlated with the fat-free mass (r2 = 0.48, P < 0.0001) and with the level of aerobic fitness (maximal aerobic capacity) (r2 = 0.22, P = 0.007). Unexpectedly, fat oxidation had no relationship with fat mass (r2 = 0.07, P = 0.136). Partial correlation analysis showed that the decline in fat-free mass, and not the age or maximal O2 consumption, was the best single predictor of the decline in basal fat oxidation. These results support the theory that a decrease in fat oxidation with advancing age in healthy women is associated with a decrease in the fat-free mass and not age per se. Interventions that increase or preserve the quantity of fat-free mass (e.g., exercise training) may enhance fat oxidation and thus lessen the age-associated adiposity in women.
Effects of strength and endurance training on thigh and leg muscle mass and composition in elderly women
Authors: Sipila S. , Suominen H.
Published: December 2017

The effects of 18 wk of intensive strength and endurance training on knee extensor, knee flexor, and lower leg muscle mass and composition were studied in 76- to 78-yr-old women. Muscle cross-sectional area (CSA), lean tissue CSA, and relative proportion of fat were determined using computed tomography. The strength-trained women increased their total muscle lean tissue CSA of the thigh (1.5%; P = 0.035), quadriceps CSA (4.5%; P = 0.021), quadriceps lean tissue CSA (5.8%, P = 0.009), and mean Hounsfield unit of the lower leg muscles (11.2%; P = 0.035) compared with the changes that occurred in the control group during the experiment. The change in quadriceps lean tissue CSA because of the strength training was also significant compared with that in the endurance group. The relative proportion of fat within the quadriceps muscle decreased due to the strength training compared with the changes that occurred in the endurance group. The results show that intensive strength training can induce skeletal muscle hypertrophy in elderly women and thereby also reduce the relative amount of intramuscular fat, whereas the effects of endurance training are negligible.
Hypoxic effects on exercise-induced diaphragmatic fatigue in normal healthy humans
Authors: Babcock M. A. , Johnson B. D. , Pegelow D. F. , Suman O. E. , Griffin D. , Dempsey J. A.
Published: December 2017

We examined the effects of hypoxia on exercise-induced diaphragmatic fatigue. Eleven subjects with a mean maximal O2 uptake of 52.4 +/- 0.7 ml.kg-1.min-1 completed one normoxic (arterial O2 saturation 96-94%) and one hypoxic (inspiratory O2 fraction = 0.15; arterial O2 saturation 83–77%) exercise test at 85% maximal O2 uptake to exhaustion on separate days. Supramaximal bilateral phrenic nerve stimulation (BPNS) was used to determine the pressure generation of the diaphragm pre- and postexercise at 1, 10, and 20 Hz. There was increased flow limitation during hypoxic vs. normoxic exercise. There was a decrease in hypoxic exercise time (normoxic 24.9 +/- 0.7 min vs. hypoxic 15.8 +/- 0.8 min; P < 0.05). After exercise the BPNS transdiaphragmatic pressure (Pdi) was significantly reduced at 1 and 10 Hz after both exercise tests. The BPNS Pdi was recovered to control values by 60 min postnormoxic exercise but was still reduced 90 min posthypoxic exercise. The mean percent fall in the stimulated BPNS Pdi was similar (normoxic -24.8 +/- 4.7%; hypoxic -18.8 +/- 3.0%) after both exercise conditions. Experiencing the same amount of diaphragm fatigue in a shorter time period in hypoxic exercise may have been due to 1) the increased expiratory flow limitation and diaphragmatic muscle work, 2) decreased O2 transport to the diaphragm, and/or 3) increased levels of circulating metabolites.
Sulfide-induced perturbations of the neuronal mechanisms controlling breathing in rats
Authors: Greer J. J. , Reiffenstein R. J. , Almeida A. F. , Carter J. E.
Published: December 2017

The effects of sulfide on neonatal rat respiration were studied. Two in vitro experimental models were utilized: the isolated brain stem-spinal cord preparation and the medullary slice preparation containing respiratory rhythm-generating regions from neonatal rats. Plethysmographic measurements of the effects of sulfide on the breathing patterns of unanesthetized neonatal rats were also made to compare the sensitivities of neonatal and adult rats to sulfide toxicity. In vitro, sulfide acted at sites within the ventrolateral medulla to depress the frequency of respiratory rhythmic discharge by approximately 50–60%. However, the neuronal network underlying respiratory rhythmogenesis continued to function in the presence of concentrations of sulfide far beyond those deemed to be lethal in vivo. Intraperitoneal administration of sulfide caused a dose-dependent decrease in the frequency and amplitude of breathing of neonatal rats of all ages (0–19 days postnatal), although the sensitivity to sulfide increased with age. We hypothesize that the rapid suppression of breathing caused by sulfide is due to changes in neuronal excitability within respiratory rhythm-generating centers rather than, as previously hypothesized, to perturbations of cellular oxidative metabolism.
Effect of blood and albumin on pulmonary hypertension and edema in perfused rabbit lungs
Authors: Kraft S. A. , Fujishima S. , McGuire G. P. , Thompson J. S. , Raffin T. A. , Pearl R. G.
Published: December 2017

Perfusate composition may alter pulmonary hemodynamics and edema formation in perfused lungs. Perfusion for 3 h with Krebs-Henseleit solution with 3% bovine serum albumin did not produce pulmonary hypertension, pulmonary edema (assessed by lung wet-to-dry wt ratio), or increased macromolecular permeability (assessed by 125I-albumin uptake). Addition of blood to hematocrit levels of 10 or 20% resulted in pulmonary hypertension during the final hour of perfusion but not pulmonary edema or increased macromolecular permeability. Pulmonary hypertension during blood perfusion was primarily due to increased precapillary resistance. Perfusion with buffer solution without albumin produced edema and increased macromolecular permeability but not pulmonary hypertension. In lungs perfused with blood (20% hematocrit), thromboxane B2 levels increased in parallel with the pulmonary hypertension, and inhibition of cyclooxygenase or thromboxane synthase with indomethacin or dazmegrel prevented pulmonary hypertension. Perfusion with leukopenic blood (from prior nitrogen mustard administration or from filtration) also prevented pulmonary hypertension. We conclude that blood perfusion produces pulmonary hypertension via thromboxane A2 generation, which depends on leukocyte activation, and that perfusion with buffer solutions without albumin produces edema and increased permeability without pulmonary hypertension.
Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep
Authors: Bednarik J. A. , May C. N.
Published: December 2017

The accuracy of transit-time ultrasonic flow probes for measurement of regional blood flow and cardiac output was evaluated after long-term implantation in sheep. Transit-time flow probes (3, 4, 6, and 20 mm) accurately measured flow in vitro. Recalibration in vivo demonstrated that this accuracy was maintained after 1–9 mo of implantation on the left circumflex coronary (3-mm probe), cranial mesenteric (6-mm probe), left renal (4-mm probe), and left external iliac (6-mm probe) arteries of sheep. The flow probes also showed good zero stability. However, a transit-time flow probe (20 mm) chronically implanted on the pulmonary trunk significantly underestimated cardiac output compared with thermodilution or timed collection of blood. Although this flow probe underestimated flow, the response was linear. Bilateral carotid occlusion caused mesenteric, renal, and iliac vasoconstrictions, confirming that innervation of these vascular beds was undamaged. For experimental purposes, regional blood flow was measured with transit-time flow probes and cardiac output was measured with electromagnetic flow probes calibrated against thermodilution. In summary, transit-time flow probes reliably and accurately measure regional blood flow over many months in adult sheep, but, to measure cardiac output in sheep, the probes must be calibrated in vivo against another reference technique.
Hyperpnea with dry air causes time-dependent alterations in mucosal morphology and bronchovascular permeability
Authors: Omori C. , Schofield B. H. , Mitzner W. , Freed A. N.
Published: December 2017

This study examines the morphological and physiological changes that occur in canine peripheral airways after hyperpnea with dry air. Peripheral airways were exposed to a 5-min 2,000 ml/min dry air challenge (DAC) at 24, 6, 2, or 1 h before or 60 s after (0 h) the injection of colloidal carbon. After recording the dry air-induced increase in peripheral airway resistance, the lungs were removed and prepared for morphometric analysis (n = 5). Light microscopy revealed that 50% of the airway perimeter appeared damaged at 0, 1, and 2 h after DAC, and repair was evident 6–24 h after the challenge. The average goblet-to-ciliated cell ratio decreased from 0.34 before DAC to 0.15 after DAC and recovered within 24 h. Dry air-induced bronchovascular leakage occurred immediately after DAC and persisted for > or = 24 h. DAC decreased mast cell number only in regions where the mucosa was damaged, and this decrease was inversely correlated with bronchovascular leakage. Finally, leukocyte infiltration was evident 1–2 h after DAC and continued throughout the 24-h period. We conclude that hyperpnea with dry air causes mucosal injury, inflammation, and microvascular leakage and that these dry air-induced effects persist for > or = 24 h after DAC.