bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric reflex responses of the nasal and tracheal vasculatures of the dog
Authors: Dylewska K. , Sahin G. , Widdicombe J. G.
Published: December 2017

Both sides of the nasal vasculature of the dog in vivo were perfused separately, with measurement of vascular resistance responses to stimulation of various nerves. Stimulation of the central end of a cut superior laryngeal nerve caused an ipsilateral vasodilation (-4.98%) and a contralateral vasoconstriction (+3.96%), the difference being statistically significant (P < 0.01). Stimulation of a glossopharyngeal nerve caused vasodilation on both sides, the ipsilateral (-17.52%) being greater than the contralateral (-6.33%) response (P < 0.05). Mechanical stimulation of the nasal mucosa caused little ipsilateral change (+0.47%) and a weak contralateral vasoconstriction (+3.78%; P < 0.01). Stimulation of the central end of a cervical vagus nerve caused vasodilations on both sides, the ipsilateral (-9.75%) being greater than the contralateral (-5.73%) change (P < 0.05). With bilateral perfusions of the cervical tracheal arteries, stimulation of a superior laryngeal nerve caused vasodilation on both sides, the ipsilateral (-10.1%) being greater than the contralateral (-7.4%) response (P < 0.05). Stimulation of the central end of a vagus nerve caused vasoconstrictions on both the sides, the ipsilateral (+37.4%) being greater than the contralateral (+10.8%) change (P < 0.05). Thus various nervous inputs from the nose, pharynx, larynx, and vagal distribution cause asymmetric vascular responses both in the nose and in the cervical trachea.
Ventilatory sensitivity to CO2 in hyperoxia and hypoxia in older aged humans
Authors: Poulin M. J. , Cunningham D. A. , Paterson D. H. , Kowalchuk J. M. , Smith W. D.
Published: December 2017

Findings from studies of the effects of aging on the human respiratory controller are equivocal. This study assessed the ventilatory response to CO2 in hyperoxia and hypoxia in groups of younger (YS) and older (OS) humans. Two protocols were used. In the first, end-tidal PCO2 (PETCO2) was clamped at 1–2 Torr above rest (eucapnia), and, in the second, PETCO2 was clamped at 7–8 torr above resting PETCO2 (moderate hypercapnia). End-tidal PO2 was clamped at 100 Torr throughout except for two 2-min periods at 500 and 50 Torr. The ventilatory responses for each subject at each PO2 were fitted to the linear equation, VE = S(PETCO2 - B), where VE is minute ventilation, S is the response curve slope, and B is the response curve threshold. In eucapnia, there were no differences in hypoxic and hyperoxic VE between YS and OS. In hypercapnia, hypoxic VE was 24% lower in OS [39.93 +/- 2.71 (SE) l/min] than in YS (52.16 +/- 3.17 l/min). In hypoxia, S was significantly lower in OS (3.25 +/- 0.38 l.min-1.Torr-1) than in YS (4.76 +/- 0.37 l.min-1.Torr-1). We conclude that, in older humans, VE is lower in hypoxia during moderate hypercapnia, resulting mainly from a decreased peripheral chemoreflex CO2 sensitivity.
Postnatal maturation of carotid chemoreceptor responses to O2 and CO2 in the cat
Authors: Carroll J. L. , Bamford O. S. , Fitzgerald R. S.
Published: December 2017

This study aimed to characterize neural responses of the carotid chemoreceptors of the maturing cat to natural stimuli and to determine the time course of carotid chemoreceptor development from the neonatal period to adulthood. Carotid sinus nerve (CNS) responses to O2 and CO2 were studied in cats at 1, 4, and 8 wk of age and in adult cats (n = 6 at each age). Pentobarbital sodium-anesthetized cats were exposed to three levels of O2 (arterial PO2 = 40–45, 80–90, and > 300 Torr) at five levels of arterial PCO2 (22, 35, 48, 63, and 75 Torr) while the moving average of whole nerve output from the CSN was recorded. Ganglioglomerular nerves were sectioned. All cats at every age increased CSN activity during hypoxia. However, the CSN response to hypoxia was not sustained in some immature cats. Of the cats that sustained CSN activity during hypoxia, four of the six 1-wk-old cats showed a biphasic pattern of response, with an initial overshoot followed by a steady level of discharge. Older cats did not exhibit this pattern. CNS sensitivity to hypoxia was weakest in 1-wk-old kittens but increased to nearly adult levels by 4 wk of age. Carotid chemoreceptor responses to CO2 were also smallest in 1-wk-old kittens and increased with maturation. However, unlike hypoxia responses, CO2 sensitivity during hypoxia continued to develop between 8 wk and adulthood. O2-CO2 interaction did not become significant until after 4 wk of age. Thus, carotid chemoreceptor responses to both O2 and CO2 are weak in newborn cats and increase during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased endothelin and creatine kinase after electrical stimulation of paraplegic muscle
Authors: Robergs R. A. , Appenzeller O. , Qualls C. , Aisenbrey J. , Krauss J. , Kopriva L. , DePaepe J.
Published: December 2017

The purpose of this study was to assess changes in creatine kinase (CK) and endothelin (ET) in individuals with spinal cord injury (SCI) after computerized functional electrical stimulation leg ergometry (CFES LE). Eight subjects (7 male and 1 female) with complete spinal cord lesions (C7 to L1) completed zero-loaded CFES LE tests at baseline, after 3, 6, and 12 wk of CFES LE training (30 min, 3 times/wk), and also after detraining (DT) (n = 5). Venous blood samples were drawn 24, 48, and 72 h after CFES LE for measurement of ET and CK. The CK response was largest (peak CK) 72 h after baseline tests (28.2 +/- 6.0 to 895.7 +/- 345.9 ktals/l) and was no different from baseline by weeks 3, 6, and 12. After DT, CK was similar before and after CFES LE (153.8 +/- 19.0 and 189.7 +/- 34.5 ktals/l, respectively). CFES LE also significantly increased peak ET after baseline (from 11.7 +/- 1.5 to 18.0 +/- 2.5 pg/ml). During the subsequent training, peak ET remained significantly higher than the baseline value at weeks 3, 6, and 12 (20.2 +/- 1.8, 18.0 +/- 1.1, and 16.9 +/- 2.2 pg/ml, respectively). After DT, peak ET increased significant relationship (r = 0.44) existed between ln peak CK activity and peak ET. In summary, the increase in circulating ET in spinal cord-injured individuals may have implications for baroreceptor function and therefore blood pressure control in SCI. Further research into CFES LE, ET, and baroreceptor function in SCI is warranted.
Systemic deficiency of glutathione in cystic fibrosis
Authors: Roum J. H. , Buhl R. , McElvaney N. G. , Borok Z. , Crystal R. G.
Published: December 2017

Cystic fibrosis (CF), a disorder characterized by mutations of the CF transmembrane regulator gene, is characterized in the lung by chronic inflammation, leading to progressive damage to the airway epithelium, bronchiectasis, and chronic obstructive lung disease. One process contributing to the airway derangement is the chronic burden of oxidants released by inflammatory cells on the respiratory epithelial surface. With this background, we hypothesized that glutathione in respiratory epithelial lining fluid (ELF) in CF patients might be oxidized and/or diminished in amount compared with that in normal subjects. Recovery of ELF by bronchoalveolar lavage from young adults with CF (n = 21) and normal subjects (n = 25) demonstrated marked neutrophil-dominated inflammation in ELF in CF patients. As predicted, ELF in CF patients was characterized by a deficiency of glutathione (P < 0.001), but this was secondary to a reduction in reduced glutathione (P < 0.001), inasmuch as there were no differences in ELF levels of oxidized glutathione (P > 0.2). Unexpectedly, there was also a marked deficiency of reduced glutathione in plasma (P < 0.02); i.e., the glutathione "deficiency" observed in ELF in CF patients is not limited to the site of the inflammation but is systemic. Although the etiology of this generalized deficiency of extracellular glutathione is unknown, it is important in considering options for treating the concomitant and devastating lung pathology in this disorder.
Tissue resistance in the guinea pig at baseline and during methacholine constriction
Authors: Ingenito E. P. , Davison B. , Fredberg J. J.
Published: December 2017

Total lung resistance (RL), airway resistance (Raw), and tissue resistance (Rti) were measured in unconstricted and methacholine (MCh)-constricted guinea pigs while tidal volume, lung volume, and breathing frequency were varied. Measurements were made in tracheostomized ventilated guinea pigs with use of alveolar capsules. Relationships between Raw and Rti at different breathing frequencies, lung volumes, tidal volumes, and levels of constriction were compared with previously reported values in other species. Our results demonstrate that, at fixed tidal volume, Rti was inversely related to breathing frequency (Rti approximately f-0.64, where f is breathing frequency in Hz) and increased with increasing lung volume. Rti was a significantly greater percentage of RL after MCh administration (40–50%) than at baseline (15–35%), indicating a greater tissue than airway constrictor response. Rti was also 0.5 log dose more responsive to intravenous MCh than Raw on the basis of the dose required to produce 100% increase in resistance from baseline (PD100). These data show that, in the guinea pig, Rti changes with lung volume, breathing frequency, and constrictor tone in a manner similar to other species previously reported and that Rti can be an important determinant of lung dysfunction during constriction, even in species for which it is small in relation to Raw at baseline.
Effects of acetylsalicylic acid on pulmonary vascular tone and membrane permeability in blood-perfused dog lung
Authors: Kambara K. , Arakawa M. , Segawa T. , Ando F. , Ohno M. , Kano A.
Published: December 2017

We studied the effects of acetylsalicylic acid (ASA) on pressor response, microvascular filtration coefficient (Kf), extravascular lung water, and plasma concentrations of cyclooxygenase- and 5-lipoxygenase-derived products in 21 blood-perfused dog lungs with constant flow. The lungs were perfused for 1 h with an intrapulmonary injection of saline as vehicle (n = 5), a low dose of ASA [136 +/- 25 (SD) micrograms/ml perfusate; n = 5], a high dose of ASA (1,006 +/- 278 micrograms/ml perfusate; n = 6), or alloxan (1,000 mg; n = 5). Alloxan significantly increased Kf and extravascular lung water, whereas neither the low nor high dose of ASA increased Kf or extravascular lung water. The ASA-induced increase in vascular resistance did not correlate with the extent of the decrease in perfusate 6-keto-prostaglandin F1 alpha or the ratio of perfusate 6-ketoprostaglandin F1 alpha to thromboxane B2. Moreover, ASA did not enhance the generation of perfusate leukotrienes B4, D4, or E4. We conclude that pulmonary microvascular permeability is unaltered by ASA and that neither the decrease in plasma prostacyclin nor the increase in plasma sulfidopeptide leukotrienes may account for ASA-induced pulmonary vasoconstriction.
Activation-induced reduction of SDH activity in diaphragm muscle fibers
Authors: Johnson B. D. , Sieck G. C.
Published: December 2017

In this study, we examined whether exhaustive activation reduces succinate dehydrogenase (SDH) activity in diaphragm muscle fibers. In adult male rats (approximately 300 g), the costal diaphragm was excised and positioned in a chamber perfused with mammalian Ringer solution kept at 26 degrees C and oxygenated with 95% O2–5% CO2. The muscle was stimulated directly at 10 or 75 Hz in trains of 500 ms duration (1/s) for 8 min. An adjacent unstimulated segment of muscle served as control. The two muscle segments were frozen, and serial sections were stained for myofibrillar adenosinetriphosphatase activity after alkaline and acid preincubation to classify type I, IIa, and IIb fibers. The extent of glycogen utilization was also examined histochemically to confirm exhaustive activation of muscle fibers. SDH activity was quantified using a microdensitometric procedure implemented on an image-processing system. Exhaustive activation at both 10 and 75 Hz caused a significant decrease in SDH activity of all fiber types, with the decrease after 10-Hz stimulation being greater than that after 75-Hz stimulation. At both stimulation frequencies, type IIb fibers demonstrated the greatest decrease in SDH activity (36% after 10-Hz and 27% after 75-Hz stimulation), whereas type I and IIa fibers both displayed reductions of approximately 27 and approximately 19% after 10- and 75-Hz stimulation, respectively. The greater reduction of SDH activity in type IIb fibers indicates an inverse relationship between activation-induced reductions in SDH activity and fiber oxidative capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans
Authors: Wilson J. R. , Kapoor S.
Published: December 2017

Release of endothelium-derived relaxing factor (EDRF) from the vascular endothelium may contribute to skeletal muscle arteriolar vasodilation during exercise. The present study was undertaken to test this hypothesis. Ten normal subjects underwent brachial arterial catheter insertion and instrumentation of their forearm to measure plethysmographic forearm blood flow. Forearm blood flow was then measured at rest, during two levels of wrist flexion exercise (0.2 and 0.4 W), and during 0.4-W exercise with concurrent infusion of norepinephrine (100 ng.min-1 x 100 ml forearm volume-1). Measurements were made with and without infusion of N-monomethyl-L-arginine (L-NMMA) (0.1–0.2 mg.min-1 x 100 ml forearm volume-1), a specific inhibitor of EDRF synthesis. Infusion of L-NMMA reduced resting forearm blood flow (control: 2.5 +/- 0.4 vs. L-NMMA: 1.5 +/- 0.1 ml.min-1 x 100 ml-1) and markedly reduced forearm blood flow response to acetylcholine (5 micrograms.min-1 x 100 ml forearm volume-1) (control: 20.2 +/- 2.9 vs L-NMMA: 4.0 +/- 1.0 ml.min-1 x 100 ml-1; both P < 0.01). However, L-NMMA had no significant effect on flow responses to exercise (0.2 W: 8.3 +/- 1.1 vs. 8.3 +/- 1.2; 0.4 W: 13.8 +/- 1.7 vs. 13.5 +/- 1.7; 0.4 W + norepinephrine: 10.3 +/- 2.4 vs. 9.4 +/- 2.6 ml.min-1 x 100 ml-1; all P = NS). These findings suggest that release of EDRF from the vascular endothelium contributes to skeletal muscle arteriolar vasodilation at rest but does not contribute to the arteriolar vasodilation produced by exercise.
Microdialysis probe for transcutaneous monitoring of ethanol and glucose in humans
Authors: De Boer J. , Plijter-Groendijk H. , Korf J.
Published: December 2017

A heated (42 degrees C) microdialysis probe and its application for continuous transcutaneous sampling of ethanol and glucose through cellophane-stripped forearm skin are described. Ethanol and glucose concentration in the dialysate were measured on-line with continuous-flow analysis and compared with blood values in human volunteers after ethanol consumption (n = 4) and oral glucose testing (n = 5), respectively. For ethanol and glucose, the dialysate and blood concentrations were linearly related in each subject (r > or = 0.91, P < 0.005), although the dialysate-to-blood ratio varied among subjects. The recovery in vivo was 22.4 +/- 22.7 and 4.7 +/- 2.3% (SD) of the recovery in vitro for ethanol and glucose, respectively. The dialysate glucose concentration was independent of blood flow. When the probe temperature was increased from 32 to 42 degrees C, the dialysate-to-blood glucose ratio increased, with 2.4 +/- 1.4%/degrees C (SD) in fasting subjects (n = 4), which was similar to an increase of 2.1 +/- 0.045%/degree C in dialysate-to-medium ratio in vitro. The present approach for transcutaneous sampling may possibly be used for other substances of low molecular weight as well.
Evaluation of perilla ketone-induced unilateral lung injury using external gamma scanning
Authors: Abernathy V. J. , Pou N. A. , Parker R. E. , Roselli R. J.
Published: December 2017

We used a modified external gamma scanning technique to quantitate right and left lung permeability changes to iodinated sheep albumin before and after perilla ketone (PK)-mediated unilateral lung injury in seven anesthetized sheep. Three portable gamma scintillation probes containing 2-in. NaI crystals detected radioactivities of 51Cr-labeled red blood cells and 125I-labeled albumin over the right and left lungs and blood, respectively. Radioactivities were monitored for 1 h before and 3 h after infusion of 25 mg/kg PK into a single lung. Calculation of normalized slope index (NSI) (Roselli and Riddle, J. Appl. Physiol. 67: 2343–2350, 1989) over the 30-min interval before PK and over the 60- to 90-min interval after PK for each lung revealed a four- to five-fold NSI increase in lungs receiving PK (0.00237 +/- 0.00065 to 0.0109 +/- 0.0016 min-1) and no increase in contralateral control lungs (0.00214 +/- 0.00065 to 0.00201 +/- 0.00032 min-1). Observed changes in NSI were consistent with postmortem evaluations of each lung. Lungs receiving PK had significantly higher wet-to-dry lung weight ratios and extravascular lung water volumes than contralateral control lungs. Measured bloodless wet-to-dry lung weight ratios were 5.68 +/- 0.39 and 3.27 +/- 0.27 (P < 0.05) for PK and control lungs, respectively.
Ventilatory responses to inspiratory threshold loading and role of muscle fatigue in task failure
Authors: Eastwood P. R. , Hillman D. R. , Finucane K. E.
Published: December 2017

To examine respiratory muscle recruitment pattern during inspiratory loading and role of fatigue in limiting endurance, we studied seven normal subjects on 17 +/- 6 days during breathing against progressive inspiratory threshold load. Threshold pressure (Pth) was progressively increased 14 +/- 5 cmH2O every 2 min until voluntary cessation (task failure). Subjects could adopt any breathing pattern. Tidal volume (VT), chest wall motion, end-tidal PCO2, and arterial O2 saturation were measured. At moderate loads [50–75% of maximum Pth (Pthmax)], inspiratory time (TI) decreased and VT/TI and expiratory time increased, increasing time for recovery of muscles between inspirations. At high loads (> 75% Pthmax), VT/TI decreased, which, with progressive decrease in end-expiratory lung volume (EELV) throughout, increased potential for inspiratory force development. Progressive hypoxia and hypercapnia occurred at higher work loads. Immediately after task failure all subjects could recover at high loads and still reachieve initial Pthmax on reimposition of progressive loading. Respiratory pressures were measured in subgroup of three subjects: transdiaphragmatic pressure response to 0.1-ms bilateral supramaximal phrenic nerve stimulation at end expiration initially increased with increasing load/decreasing EELV, consistent with increasing mechanical advantage of diaphragm, but decreased at highest loads, suggesting diaphragm fatigue. Full recovery had not occurred at 30 min after task failure. We demonstrated that progressive threshold loading is associated with systematic changes in breathing pattern that act to optimize muscle strength and increase endurance. Task failure occurred when these compensatory mechanisms were maximal. Inspiratory muscles appeared relatively resistant to fatigue, which was late but persistent.
alpha-Trinositol decreases lung edema formation after smoke inhalation in an ovine model
Authors: Nakazawa H. , Gustafsson T. O. , Traber L. D. , Herndon D. N. , Traber D. L.
Published: December 2017

Inhalation injury is a dominant cause of mortality in thermally injured individuals. After acute lung injury induced by smoke inhalation, lung lymph flow (QL) increased and pulmonary microvascular reflection coefficient to protein (sigma) decreased. alpha-Trinositol (PP56, 1D-myo-inositol 1,2,6-trisphosphate) can decrease edema formation after thermal injury. We therefore tested the hypothesis that alpha-trinositol could decrease the pulmonary edema noted with inhalation injury. Seven days after surgical preparation, sheep were insufflated with smoke from burning cotton towels. The alpha-trinositol group (n = 8) were treated with alpha-trinositol (2 mg/kg + 3.5 mg.kg-1 x h-1). The sham group (n = 7) received an equal volume of 0.9% NaCl. The sham group showed a large increase in QL (9.3 +/- 1.7 to 54.1 +/- 8.8 ml/h) and a decrease in sigma (0.79 +/- 0.03 to 0.48 +/- 0.03) 24 h after smoke inhalation. alpha-Trinositol attenuated the increase in QL (8.1 +/- 1.2 to 25.6 +/- 6.9 ml/h) and the decrease in sigma (0.76 +/- 0.03 to 0.60 +/- 0.03) noted with smoke inhalation. alpha-Trinositol thus decreased the changes in pulmonary microvascular permeability and transvascular fluid flux noted with inhalation injury.
Regional effects of myocardial ischemia on epicardially recorded canine first heart sounds
Authors: Wood J. C. , Festen M. P. , Lim M. J. , Buda A. J. , Barry D. T.
Published: December 2017

To determine whether focal changes in myocardial material properties are important in determining the response of first heart sound acceleration amplitude and frequency to myocardial ischemia, cardiac vibrations were simultaneously recorded from ischemic and nonischemic regions of canine epicardium by use of ultralight acceleration transducers. Cardiac acceleration and hemodynamics were recorded before and 5 min, 15 min, 1 h, and 2 h after left circumflex coronary artery occlusion. Peak-to-peak amplitude declined transiently in the nonischemic zone during early occlusion (P < 0.05) but was not decreased at any time in the ischemic myocardium. The median frequency of first heart sound vibrations in the ischemic region increased 31% within 5 min after occlusion (P < 0.01) and remained elevated for 2 h (P < 0.05). Nonischemic zone frequency was not statistically different from baseline at any time point. The disparate regional response of first heart sound vibrational frequency to myocardial ischemia suggests that propagating mechanical transients and myocardial contractile acceleration, rather than resonant vibrations, produce the first heart sound.
Cerebral pressure-flow and metabolic responses to sustained hypoxia: effect of CO2
Authors: Yang S. P. , Bergo G. W. , Krasney E. , Krasney J. A.
Published: December 2017

This study was designed to determine the role of CO2 in the cerebral hemodynamic, metabolic, and fluid shift responses in a conscious sheep model of acute mountain sickness (AMS). Ewes were instrumented chronically with left ventricular, aortic, inferior vena cava, sagittal sinus, and epidural catheters and exposed to 96 h of hypoxia in an environmental chamber in two groups: 1) hypocapnic [HH; n = 12; arterial PO2 (PaO2) = 40 Torr, arterial PCO2 (PaCO2) = 27 Torr] and 2) eucapnic (EH; n = 9; PaCO2 = 40 Torr, PaCO2 = 37 Torr). AMS, estimated from food and water intakes and behavior, occurred in 9 of 12 HH and 9 of 9 EH sheep. Intracranial pressure (Picp) and the pressure gradient between Picp and sagittal sinus (Psag) increased in AMS sheep only. Total and regional cerebral blood flows, except in the choroid plexus (Qcp), were elevated significantly (P < 0.05) throughout hypoxia in all sheep; cerebral blood flow was greater in EH sheep (P < 0.05). Qcp decreased in HH (P < 0.05) but remained unchanged in EH sheep. Cerebral O2 and glucose uptakes were not altered in either group. Brain edema, reflected by elevated wet-to-dry tissue weight ratios (P < 0.0001), occurred only in AMS sheep. We conclude 1) AMS is associated with cerebral edema and normal brain aerobic metabolism, 2) decreased Qcp and increased Picp-Psag gradients during HH likely compensate the increased intracranial volume in AMS, and 3) CO2 supplementation at constant PaO2 did not reduce AMS, Picp, or brain tissue edema.
Ventilatory afterdischarge and central respiratory drive interactions in the awake goat
Authors: Engwall M. J. , Smith C. A. , Dempsey J. A. , Bisgard G. E.
Published: December 2017

We have previously established the existence of ventilatory afterdischarge (VAD) in the awake goat by means of an isolated perfused carotid body (CB) technique. In the present series of experiments we used this animal preparation to examine the effects of systemic (central nervous system) hypoxia, mild hypercapnia, and hypocapnia on the manifestation of VAD in ventilatory variables and respiratory muscle electromyogram activity after hypoxic stimulation of the isolated CB. With systemic isocapnic normoxia, inspired minute ventilation remains above control for 30–40 s (time constant = 16.8 s) after termination of CB hypoxia; however, with systemic hypocapnia, VAD is short (time constant = 5.5 s) and hypoventilation is common after removal of CB stimulation. During mild systemic hypercapnia, VAD is prolonged (time constant = 39.9 s). However, systemic (central nervous system) hypoxia did not decrease VAD (time constant = 17.0 s). These results indicate that the manifestation of VAD is more sensitive to the level of arterial PCO2 and central chemoreceptor activity than it is to the state of central oxygenation. Inspiratory and expiratory muscle electromyogram activities qualitatively tracked ventilation during CB stimulation and during the VAD period in all conditions.
Adenosine, an endogenous anti-inflammatory agent
Authors: Cronstein B. N.
Published: December 2017

Adenosine receptors are present on most cells and organs, yet, although the physiological effects of adenosine were first described over 60 years ago, the potential therapeutic uses of adenosine have only been recognized and realized recently. A decade ago the potent anti-inflammatory effects of adenosine were first described; adenosine, acting at specific A2 receptors, inhibits some, but not all, neutrophil functions. Adenosine inhibits phagocytosis, generation of toxic oxygen metabolites, and adhesion (to some surfaces and to endothelial cells) but does not inhibit degranulation or chemotaxis. Occupancy of adenosine A2 receptors modulates leukocyte function by a novel mechanism. Although adenosine A2 receptors are classically linked to heterotrimeric GS signaling proteins and stimulation of adenylate cyclase, adenosine 3′,5′-cyclic monophosphate does not act as the second messenger for inhibition of leukocyte function. By a mechanism that still remains obscure, occupancy of adenosine A2 receptors on neutrophils “uncouples” chemoattractant receptors from their stimulus-transduction proteins. The concentrations of adenosine that inhibit inflammatory cell function are similar to those observed in vivo and suggest a role for adenosine in the modulation of inflammation in vivo. Indeed, recent studies indicate that nonmetabolized adenosine receptor agonists are potent anti-inflammatory agents, and other studies indicate that methotrexate, a commonly used anti-inflammatory agent, diminishes inflammation by increasing adenosine release at inflamed sites. The observations reviewed here suggest that adenosine and agents that act through adenosine are excellent candidates for development as anti-inflammatory agents.
Cardiac receptors modulate the renal sympathetic response to dynamic exercise in rabbits
Authors: O'Hagan K. P. , Bell L. B. , Mittelstadt S. W. , Clifford P. S.
Published: December 2017

Activation of cardiac sensory receptors with vagal afferents can result in inhibition of sympathetic outflow to the peripheral circulation. This study investigated whether the regulation of renal sympathetic nerve activity (RSNA) during dynamic exercise was modulated by cardiac sensory receptors. RSNA, blood pressure, and heart rate were measured in seven New Zealand White rabbits during treadmill exercise while cardiac receptors were intact (saline), during cardiac neural block with 2% procaine (2% PCN), and during cardiac efferent receptor block with methscopolamine and atenolol (M + A). Drugs were infused into the pericardial space via a chronic catheter. Two exercise protocols were used: 7 m/min (5 min) and 12 m/min (2 min) at 0% grade. The increases in HR during exercise at 7 and 12 m/min were attenuated with 2% PCN or M + A. At 12 m/min, blood pressure was significantly lower with 2% PCN (76 +/- 4 mmHg) or M + A (76 +/- 3 mmHg) than with saline (86 +/- 2 mmHg). Abolition of cardiac afferent input with 2% PCN resulted in a potentiated RSNA response to exercise at 7 m/min (+134 +/- 37%) and 12 m/min (+234 +/- 45%) relative to saline (+62 +/- 24 and +101 +/- 28%) or M + A (+19 +/- 9 and +52 +/- 19%, P < 0.05). These results suggest that cardiac sensory receptors attenuate sympathetic drive to the kidney during dynamic exercise in conscious rabbits.
Stress wave velocity measured in intact pig lungs with cross-spectral analysis
Authors: Jahed M. , Lai-Fook S. J.
Published: December 2017

In anesthetized pigs (25–40 kg), we generated stress waves in the lung by rapid deflation of an esophageal balloon. The source distortion was measured by an accelerometer (1 g wt) bonded to the balloon. Stress waves were detected by three accelerometers bonded to intercostal muscle and to the skin near midchest. The distance between the source and chest receivers were measured radiographically. Cross-spectral analysis was used to calculate transit times. We measured stress wave velocities at airway pressures of 0 (functional residual capacity) and 25 cmH2O. Transpulmonary pressure (Ptp) was measured by an esophageal balloon. In vivo, stress wave velocities increased from 291 +/- 117 (SD) cm/s at 3.0 +/- 0.9 cmH2O Ptp to 573 +/- 73 cm/s at 13.8 +/- 3.5 cmH2O Ptp (n = 6). These velocities agreed with longitudinal wave velocities measured in isolated sheep lungs and predictions based on the elastic moduli of lung parenchyma. Post-mortem edema was induced by intratracheal instillation of 200 ml of saline, resulting in a wet-to-dry weight ratio of 7.7 +/- 1.4 (n = 5). At 15 cmH2O Ptp, stress wave velocities decreased from 565 +/- 155 cm/s before edema to 445 +/- 130 cm/s after edema. This decrease correlated well with predictions based on the increased lung density, as dictated by elasticity theory.
Exposure of immature rats to hyperoxia increases tracheal smooth muscle stress generation in vitro
Authors: Hershenson M. B. , Wylam M. E. , Punjabi N. , Umans J. G. , Schumacker P. T. , Mitchell R. W. , Solway J.
Published: December 2017

Recently, we demonstrated that chronic exposure to hyperoxia causes in vivo airway muscarinic receptor hyperresponsiveness in the developing rat [Am. J. Physiol. 262 (Lung Cell. Mol. Physiol. 6): L263-L269, 1992]. To test whether airway cholinergic hyperresponsiveness might result from intrinsic alterations in smooth muscle contractility, we measured the effect of in vivo hyperoxia on the contractile force elicited by acetylcholine (ACh) of isometrically mounted tracheal rings in vitro. Tracheal rings were obtained from 3-wk-old rats exposed to air or to > 95% O2 for 8 days. Muscarinic responses were determined by measuring the force elicited by exposure to increasing concentrations of ACh. Responses were normalized to the morphometrically determined tracheal smooth muscle cross-sectional area in a plane perpendicular to the axis of force generation. In vivo O2 exposure significantly increased maximal ACh-induced stress generation (response to 10(-3) M ACh: air, 15.92 +/- 1.37 g/mm2; O2, 21.78 +/- 1.52 g/mm2; P = 0.010). The ACh-induced stress generation of cylinders from hyperoxic rats was substantially reduced by both epithelial removal and treatment with the cyclooxygenase inhibitor indomethacin. We conclude that in vivo hyperoxic exposure increases tracheal smooth muscle contractile function in vitro and that epithelium-derived prostaglandin(s) contributes to the observed increase in maximal contractile responsiveness.
Dietary supplements affect the anabolic hormones after weight-training exercise
Authors: Chandler R. M. , Byrne H. K. , Patterson J. G. , Ivy J. L.
Published: December 2017

To examine the effect of carbohydrate and/or protein supplements on the hormonal state of the body after weight-training exercise, nine experienced male weight lifters were given water (Control) or an isocaloric carbohydrate (CHO; 1.5 g/kg body wt), protein (PRO; 1.38 g/kg body wt), or carbohydrate-protein (CHO/PRO; 1.06 g carbohydrate/kg body wt and 0.41 g protein/kg) supplement immediately and 2 h after a standardized weight-training workout. Venous blood samples were drawn before and immediately after exercise and during 8 h of recovery. Exercise induced elevations in lactate, glucose, testosterone, and growth hormone. CHO and CHO/PRO stimulated higher insulin concentrations than PRO and Control. CHO/PRO led to an increase in growth hormone 6 h postexercise that was greater than PRO and Control. Supplements had no effect on insulin-like growth factor I but caused a significant decline in testosterone. The decline in testosterone, however, was not associated with a decline in luteinizing hormone, suggesting an increased clearance of testosterone after supplementation. The results suggest that nutritive supplements after weight-training exercise can produce a hormonal environment during recovery that may be favorable to muscle growth by stimulating insulin and growth hormone elevations.
51Cr-RBCs and 125I-albumin as markers to estimate lymph drainage of the peritoneal cavity in sheep
Authors: Yuan Z. Y. , Rodela H. , Hay J. B. , Oreopoulos D. , Johnston M. G.
Published: December 2017

The purpose of this study was to compare the use of 125I-labeled human serum albumin (125I-HSA) and autologous 51Cr-labeled red blood cells (51Cr-RBCs) as lymph flow markers to estimate lymph drainage of the peritoneal cavity in conscious sheep. In one group, we assessed lymph drainage from the appearance of intraperitoneally administered tracer in the bloodstream. To determine distribution of drainage into discrete lymph compartments, in a second group of studies, lymph was collected from the caudal mediastinal lymph node and the thoracic duct, both of which are involved in lymphatic drainage of the ovine peritoneal cavity. Ringer lactate solution (50 ml/kg) containing 8–10 microCi each of 125I-HSA and 51Cr-RBCs was infused into the peritoneal cavity. Lymph drainage was calculated by dividing the change in mass of tracer in the blood or lymph compartments by the average intraperitoneal tracer concentration. In noncannulated animals, lymph drainage averaged over 6 h was higher with 125I-HSA as tracer (1.35 +/- 0.12 vs. 0.62 +/- 0.19 ml.h-1.kg-1 with 51Cr-RBCs). A similar pattern was noted in terms of drainage into the caudal lymphatic (0.89 +/- 0.23 and 0.52 +/- 0.19 ml.h-1.kg-1 with 125I-HSA and 51Cr-RBCs, respectively) and thoracic duct (0.16 +/- 0.06 and 0.05 +/- 0.02 ml.h-1.kg-1 with 125I-HSA and 51Cr-RBCs, respectively). Analysis of 125I-HSA and 51Cr-RBC concentrations in lymph and intraperitoneal fluid suggested sieving of RBCs at the diaphragmatic stomata or lymph nodes. Using 125I-HSA as tracer and combining data from noncannulated and cannulated sheep, we estimated peritoneal lymph drainage to be 1.35 ml.h-1.kg-1, with 66% of this flow drained by the caudal vessel, 22% by the parasternal pathway (right lymph duct), and 12% by the thoracic duct.
Structural response of growing bone to exercise and disuse
Authors: Biewener A. A. , Bertram J. E.
Published: December 2017

The limbs of growing chicks (2–12 wk of age) were subjected to differing conditions of mechanical use to examine the effect of extrinsic loading on bone modeling early in postnatal growth. One group of chicks was subjected to intensive exercise by running on a treadmill 5 days/wk at 60% maximum speed while carrying on their trunk a load equal to 20% of body weight (EXER). In a second group, weight-bearing function was eliminated by sciatic denervation of one hindlimb at 2 wk of age (DNV). A third group grew under sedentary conditions (SED). Comparisons among groups were made on the basis of bone mass and length, cortical cross-sectional area and second moment of area, cortical thickness, longitudinal curvature, and % ash. After normalizing for growth-related differences in body mass among the three groups, we found that exercise led to an overall 16 +/- 13% increase in cortical cross-sectional area and a 26 +/- 21% increase in second moment of area measured at proximal, midshaft, and distal levels of the bone compared with values of SED animals. These increases in cortical geometry corresponded to a 10% increase in total bone mass and were generally established by 8 wk of age (6 wk of training) and maintained to 12 wk of age. When deprived of functional use, the growing bones of DNV animals were reduced in mass (-19%), cortical area (-8 +/- 7%), and second moment of area (-11 +/- 9%) compared with SED animals. DNV tibiotarsi were also significantly shorter (7% at 8 wk and 14% at 12 wk); however, the contralateral load-bearing tibiotarsus of the DNV animals was similarly reduced compared with SED and EXER animals, suggesting a general reduction of growth in the DNV group. Even more pronounced than the reductions in bone mass and area, however, were the loss of normal longitudinal curvature and an increase in the variability of cross-sectional shape and cortical thickness of the DNV tibiotarsi compared with SED and EXER animals.
Natural surfactant and hyperoxic lung injury in primates. II. Morphometric analyses
Authors: Fracica P. J. , Caminiti S. P. , Piantadosi C. A. , Duhaylongsod F. G. , Crapo J. D. , Young S. L.
Published: December 2017

Diffuse lung injury is accompanied by low compliance and hypoxemia with histological evidence of endothelial and alveolar epithelial cell disruption. The histological effects of treatment of an acute diffuse lung injury with a natural surfactant product were evaluated in a primate model because surfactant function and content have been shown to be abnormal in diffuse lung injury in both animals and humans. Ten baboons were ventilated with 100% O2 for 96 h, and 5 were given an aerosol of natural porcine surfactant. Physiological and biochemical measurements of the effects of hyperoxia and surfactant treatment are presented in a companion paper. After O2 exposure, lungs were fixed and processed for quantitative electron microscopy. The responses to O2 included epithelial and endothelial cell injuries, interstitial edema, and inflammation. The hyperoxic animals treated with surfactant were compared with the untreated animals; the treatments altered neutrophil distribution, fibroblast proliferation, and changes in the volumes of type I epithelial cells and endothelial cells. Surfactant-treated animals also had decreased lamellar body volume density in type II epithelial cells and preservation of endothelial cell integrity. These changes suggest complex effects of natural surfactant on the pulmonary response to hyperoxia, including protection against epithelial and endothelial cell destruction as well as significant interstitial inflammation and fibroblast proliferation. We conclude that natural surfactant treatment of hyperoxic lung injury in primates resulted in partial protection of epithelial and endothelial cells but also increased the accumulation of fibroblasts in the lung.
Kinetics of lactate transport in sarcolemmal giant vesicles obtained from human skeletal muscle
Authors: Juel C. , Kristiansen S. , Pilegaard H. , Wojtaszewski J. , Richter E. A.
Published: December 2017

We developed a method that allows the measurement of muscle lactate transport in humans. The transport studies were carried out with giant (1.8- to 36-microns-diam) sarcolemmal vesicles obtained by collagenase treatment of needle biopsy material. Marker enzyme analyses demonstrated that the vesicular membrane is predominantly of sarcolemmal origin, contamination with sarcoplasmic reticulum membranes is very low, and mitochondrial membranes are not a major contaminant. The vesicles were loaded with labeled lactate, and the efflux was measured. The system displayed saturation kinetics and inhibitor sensitivity. In equilibrium exchange experiments (pH 7.4, 21 degrees C), the Michaelis-Menten constant (Km) for the carrier-mediated flux was 30 +/- 8 (SD) mM and maximal transport rate (Vmax) was 184 +/- 24 pmol.cm-2.s-1 (142 nmol.mg protein-1.min-1). In zero-trans efflux experiments, Km was 24 +/- 8 mM and Vmax was 81 +/- 11 pmol.cm-2.s-1 (63 nmol.mg protein-1.min-1). In infinite-cis experiments with a variable lactate concentration on the outside of the vesicles, Km was 8 +/- 4 mM and Vmax was 136 +/- 9 pmol.cm-2.s-1 (105 nmol.mg protein-1.min-1). Thus, the system displayed transacceleration. Low pH (6.4) had no significant effect on equilibrium exchange experiments, whereas in zero-trans experiments low pH at the trans side inhibited the flux by 50%. We concluded that lactate transport can be studied in giant vesicles obtained from a single human muscle biopsy. Our data provide evidence for the existence of a lactate carrier in human sarcolemma. This transport system must be taken into account in models of human lactate kinetics.
Skeletal muscle adaptations during early phase of heavy-resistance training in men and women
Authors: Staron R. S. , Karapondo D. L. , Kraemer W. J. , Fry A. C. , Gordon S. E. , Falkel J. E. , Hagerman F. C. , Hikida R. S.
Published: December 2017

An 8-wk progressive resistance training program for the lower extremity was performed twice a week to investigate the time course for skeletal muscle adaptations in men and women. Maximal dynamic strength was tested biweekly. Muscle biopsies were extracted at the beginning and every 2 wk of the study from resistance-trained and from nontrained (control) subjects. The muscle samples were analyzed for fiber type composition, cross-sectional area, and myosin heavy chain content. In addition, fasting blood samples were measured for resting serum levels of testosterone, cortisol, and growth hormone. With the exception of the leg press for women (after 2 wk of training) and leg extension for men (after 6 wk of training), absolute and relative maximal dynamic strength was significantly increased after 4 wk of training for all three exercises (squat, leg press, and leg extension) in both sexes. Resistance training also caused a significant decrease in the percentage of type IIb fibers after 2 wk in women and 4 wk in men, an increase in the resting levels of serum testosterone after 4 wk in men, and a decrease in cortisol after 6 wk in men. No significant changes occurred over time for any of the other measured parameters for either sex. These data suggest that skeletal muscle adaptations that may contribute to strength gains of the lower extremity are similar for men and women during the early phase of resistance training and, with the exception of changes in the fast fiber type composition, that they occur gradually.
Behavioral effects of carbon monoxide: meta analyses and extrapolations
Authors: Benignus V. A.
Published: December 2017

In the absence of reliable data, this work was performed to estimate the dose-effects function of carboxyhemoglobin (HbCO) on behavior in humans. Meta analysis is the quantitative analysis of the combined findings of a number of research reports. By meta analysis, an HbCO-behavior dose-effects function was estimated for rats and corrected for effects of hypothermia (which accompanies acute HbCO increases in rats but not in humans). By use of pulmonary function models and blood gas equations, equivalent HbCO values were calculated for data in the literature on hypoxic hypoxia and behavior. Another meta analysis was performed to fit a dose-effects function to the equivalent HbCO data and to correct for the behavioral effects of hypocapnia (which usually occurs during hypoxic hypoxia but not with HbCO elevation). The two extrapolations agreed closely and indicated that, for healthy sedentary persons, 18–25% HbCO would be required to produce a 10% decrement in behavior. Confidence intervals are computed to characterize the uncertainty. Frequent reports of lower-level effects are discussed.
Airway reopening pressure in isolated rat lungs
Authors: Naureckas E. T. , Dawson C. A. , Gerber B. S. , Gaver D. P. , Gerber H. L. , Linehan J. H. , Solway J. , Samsel R. W.
Published: December 2017

In a previous modeling study, we predicted that the yield pressure for airway reopening (Pyield) should depend on airway fluid surface tension (gamma) and airway radius (R), according to the relationship Pyield = 8.3 gamma/R. To test this prediction, we studied tantalum bronchograms of isolated perfused rat lungs from three rats by using microfocal X-ray imaging. Thirty-two airways with diameters ranging from 300 to 2,400 microns were recorded as the airways were collapsed and reinflated. Airway pressure was reduced transiently to -40 cmH2O to produce airway closure. Airway pressure was then slowly increased from 0 to 25 cmH2O. In each airway, the observed diameter remained constant until a Pyield was reached; at this pressure, airways were seen to “pop” open, allowing clear identification of airway reopening pressure. When Pyield was plotted against diameter at maximum inflation, the experimental data were in approximate agreement with predictions of Pyield made assuming a gamma of 35 dyn/cm. The close correspondence of the measured values with these predictions suggests that surfactant is present in these airways and facilitates airway reopening.
Quantification of nasal involvement in a guinea pig plethysmograph
Authors: Finney M. J. , Forsberg K. I.
Published: December 2017

We have developed a technique for measuring lung function in conscious guinea pigs using a whole body plethysmograph. Because guinea pigs breathe through the nose, a technique was also developed to measure nasal and lower respiratory system conductance simultaneously in anesthetized animals. The upper and the lower airways could be challenged separately and studied in a manner similar to the conditions in the plethysmograph. Aerosols of histamine, carbachol, or ovalbumin delivered to the nose in sensitized animals had no effect on nasal conductance, even in doses 100 times higher than that required to reduce lower respiratory system conductance. However, intravenous histamine increased nasal conductance. Thus, although nasal resistance constitutes the majority of the total respiratory system resistance measured in the plethysmograph, nasal resistance is unaffected by the aerosol drugs studied. We therefore consider changes in resistance measured in the plethysmograph to originate at or below the larynx. The plethysmographic technique described here is a reliable, reproducible, and rapid technique that enables repeated measurement in animals and minimizes animal trauma.
Eccentric contraction-induced injury of mouse soleus muscle: effect of varying [Ca2+]o
Authors: Lowe D. A. , Warren G. L. , Hayes D. A. , Farmer M. A. , Armstrong R. B.
Published: December 2017

The objective of this study was to determine the effect of varying extracellular Ca2+ concentration ([Ca2+]o) on eccentric contraction-induced muscle injury. Isolated mouse soleus muscles (n = 64) performed either 20 eccentric or 20 isometric contractions over a 40-min period in a Krebs buffer containing 0.5, 1.25, or 5.0 mM Ca2+. Measurements of contractile function and lactate dehydrogenase accumulation in the buffer were then made every 15 min for 2 h. Prostaglandin E2, leukotriene B4, and tyrosine accumulation in the incubation medium and total muscle [Ca2+] were measured at the end of the experiment. Reductions in maximal isometric tetanic force for muscles immediately after performance of 20 eccentric and 20 isometric contractions were 21.1 +/- 1.4 and 1.2 +/- 0.7%, respectively. Total muscle [Ca2+] was 28–37% higher in muscles that performed eccentric contractions than in those that performed isometric contractions. However, estimates made with a confocal laser scanning microscope and fluo 3 do not indicate that there was a difference in free cytosolic [Ca2+] between fibers from injured and control muscles. Also, leukotriene B4, prostaglandin E2, and tyrosine accumulation in the buffer from muscles that performed eccentric contractions was not elevated over that from muscles that performed isometric contractions. Furthermore, lactate dehydrogenase accumulation and reductions of contractile function over the 2-h incubation period were not enhanced by higher [Ca2+]o or influenced by the type of contraction. These findings suggest that muscles that were injured by eccentric contractions were able to buffer the increased influx of extracellular Ca2+, maintain a normal free cytosolic [Ca2+], and avoid activation of Ca(2+)-sensitive degradative pathways.