bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue viscance during induced constriction in rabbit lungs: morphological-physiological correlations
Authors: Nagase T. , Lei M. , Robatto F. M. , Eidelman D. H. , Ludwig M. S.
Published: December 2017

Tissue viscance (Vti), the pressure drop across the lung tissues in phase with flow, increases after induced constriction. To gain information about the possible site of response, we induced increases in Vti with methacholine (MCh) and attempted to correlate these changes with alterations in lung morphology. We measured tracheal (Ptr) and alveolar pressure (PA) in open-chest rabbits during mechanical ventilation [frequency = 1 Hz, tidal volume = 5 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] under control conditions and after administration of saline or MCh (32 or 128 mg/ml) aerosols. We calculated lung elastance (EL), lung resistance (RL), Vti, and airway resistance (Raw) by fitting the equation of motion to changes in Ptr and PA. The lungs were then frozen in situ with liquid nitrogen (PEEP = 5 cmH2O), excised, and processed using freeze substitution techniques. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed area (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), the standard deviation of Lm (SDLm), and an atelectasis index (ATI) derived by calculating the ratio of tissue to air space using computer image analysis. RL, Vti, and EL were significantly increased after MCh, and Raw was unchanged. A/Ar, Lm, SDLm, and ATI all changed significantly with MCh. Log-normalized change (% of baseline) in Vti significantly correlated with A/Ar (r = -0.693), Lm (r = 0.691), SDLm (r = 0.648), and ATI (r = 0.656). Hence, changes in lung tissue mechanics correlated with changes in morphometric indexes of parenchymal distortion and airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of protein requirements for trained strength athletes
Authors: Tarnopolsky M. A. , Atkinson S. A. , MacDougall J. D. , Chesley A. , Phillips S. , Schwarcz H. P.
Published: December 2017

Leucine kinetic and nitrogen balance (NBAL) methods were used to determine the dietary protein requirements of strength athletes (SA) compared with sedentary subjects (S). Individual subjects were randomly assigned to one of three protein intakes: low protein (LP) = 0.86 g protein.kg-1.day-1, moderate protein (MP) = 1.40 g protein.kg-1.day-1, or high protein (HP) = 2.40 g protein.kg-1.day-1 for 13 days for each dietary treatment. NBAL was measured and whole body protein synthesis (WBPS) and leucine oxidation were determined from L-[1–13C]leucine turnover. NBAL data were used to determine that the protein intake for zero NBAL for S was 0.69 g.kg-1.day-1 and for SA was 1.41 g.kg-1.day-1. A suggested recommended intake for S was 0.89 g.kg-1.day-1 and for SA was 1.76 g.kg-1.day-1. For SA, the LP diet did not provide adequate protein and resulted in an accommodated state (decreased WBPS vs. MP and HP), and the MP diet resulted in a state of adaptation [increase in WBPS (vs. LP) and no change in leucine oxidation (vs. LP)]. The HP diet did not result in increased WBPS compared with the MP diet, but leucine oxidation did increase significantly, indicating a nutrient overload. For S the LP diet provided adequate protein, and increasing protein intake did not increase WBPS. On the HP diet leucine oxidation increased for S. These results indicated that the MP and HP diets were nutrient overloads for S. There were no effects of varying protein intake on indexes of lean body mass (creatinine excretion, body density) for either group. In summary, protein requirements for athletes performing strength training are greater than for sedentary individuals and are above current Canadian and US recommended daily protein intake requirements for young healthy males.
N omega-nitro-L-arginine influences cerebral metabolism in awake sheep
Authors: Iwamoto J. , Yang S. P. , Yoshinaga M. , Krasney E. , Krasney J.
Published: December 2017

Experiments were carried out on decerebrate cats to identify transsynaptic mediators of spontaneous postsynaptic inhibition of bulbar inspiratory and postinspiratory neurons. Somatic membrane potentials were recorded through the central micropipette of a coaxial multibarreled electrode. Blockers of type A gamma-aminobutyric acid (GABA-A) and glycine receptors were iontophoresed extracellularly from peripheral micropipettes surrounding the central pipette. Effective antagonism was demonstrated by iontophoresis of agonists with antagonists; application of strychnine antagonized the action of glycine but not GABA, and application of bicuculline antagonized the action of GABA but not glycine. In both types of neurons, iontophoresis of either antagonist depolarized the somatic membrane and increased input resistance throughout the respiratory cycle. Bicuculline preferentially depolarized the somatic membrane in both types of neurons during inactive phases. Strychnine increased the firing rate of inspiratory neurons during inspiration despite maintenance of somatic membrane potential at preiontophoresis levels. Tetrodotoxin reduced the effects of iontophoresed bicuculline and strychnine, suggesting that the action of the antagonists required presynaptic axonal conduction. The present results suggest that presynaptic release of both GABA and glycine contributes to tonic postsynaptic inhibition of bulbar respiratory neurons. GABA-A receptors appear to contribute to inhibition during inactive phases in inspiratory and postinspiratory neurons, whereas glycinergic mechanisms appear to contribute to inspiratory inhibition in inspiratory neurons.
Effects of daily physical activity on insulin action in the elderly
Authors: Yamanouchi K. , Nakajima H. , Shinozaki T. , Chikada K. , Kato K. , Oshida Y. , Osawa I. , Sato J. , Sato Y. , Higuchi M. , et al.
Published: December 2017

The effects of daily physical activity on peripheral insulin action were investigated in aged individuals. Glucose infusion rates (GIR) during the euglycemic insulin clamp procedure in aged bedridden, aged controls, and aged athletes were compared with those in young controls and young athletes at insulin infusion rates of 40 and 400 mU.m-2.min-1 to estimate insulin action at physiological and maximal insulin concentrations, respectively. At both insulin infusion rates, GIR was significantly higher in aged athletes and significantly lower in aged bedridden subjects than in aged controls. Although there was no statistical difference in GIR at 400 mU.m-2 x min-1 between young athletes and young controls, GIR at 40 mU.m-2 x min-1 was higher in young athletes than in young controls. Comparison of the aged and young groups showed that although GIR at 400 mU.m-2 x min-1 was significantly lower in aged controls than in young controls, there was no significant difference between the aged athletes and the young athletes. We conclude that insulin responsiveness (insulin action at the postreceptor binding site) may decrease with the aging process and may be further affected by physical inactivity. Although physical training may improve insulin responsiveness in aged individuals up to levels similar to those in young athletes, physical training in young individuals may improve only insulin sensitivity.
Acid-base changes in the running greyhound: contributing variables
Authors: Pieschl R. L. , Toll P. W. , Leith D. E. , Peterson L. J. , Fedde M. R.
Published: December 2017

To determine the factors responsible for changes in [H+] during and after sprint exercise in the racing greyhound, Stewart's quantitative acid-base analysis was applied to arterial blood plasma samples taken at rest, at 8-s intervals during exercise, and at various intervals up to 30 min after a 402-m spring (approximately 30 s) on the track. [Na+], [K+], [Cl-], [total Ca], [lactate], [albumin], [Pi], PCO2, and pH were measured, and the [H+] was calculated from Stewart's equations. This short sprint caused all measured variables to change significantly. Maximal changes were strong ion difference decreased from 36.7 meq/l at rest to 16.1 meq/l; [albumin] increased from 3.1 g/dl at rest to 3.7 g/dl; PCO2, after decreasing from 39.6 Torr at rest to 27.9 Torr immediately prerace, increased during exercise to 42.8 Torr and then again decreased to near 20 Torr during most of recovery; and [H+] rose from 36.6 neq/l at rest to a peak of 76.6 neq/l. The [H+] calculated using Stewart's analysis was not significantly different from that directly measured. In addition to the increase in lactate and the change in PCO2, changes in [albumin], [Na+], and [Cl-] also influenced [H+] during and after sprint exercise in the running greyhound.
Vagal afferent and reflex responses to changes in surface osmolarity in lower airways of dogs
Authors: Pisarri T. E. , Jonzon A. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

In anesthetized dogs we examined the sensitivity of afferent vagal endings in the lungs to changes in airway fluid osmolarity. Injection of 0.25–0.5 ml/kg water or hyperosmotic sodium chloride solutions (1,200–2,400 mmol/l) into a lobar bronchus caused bradycardia, arterial hypotension, apnea followed by rapid shallow breathing, and contraction of tracheal smooth muscle. All effects were abolished by vagotomy. We examined the sensory mechanisms initiating these effects by recording afferent vagal impulses arising from the lung lobe into which the liquids were injected. Water stimulated pulmonary and bronchial C-fibers and rapidly adapting receptors; isosmotic saline and glucose solutions were ineffective. Hyperosmotic saline (1,200–9,600 mmol/l, 0.25–1 ml/kg) stimulated these afferents in a concentration-dependent manner. Stimulation began 1–10 s after the injection and sometimes continued for several minutes. Responses of slowly adapting stretch receptors varied. Our results suggest that non-isosmotic fluid in the lower airways initiates defense reflexes by stimulating pulmonary and bronchial C-fibers and rapidly adapting receptors. Conceivably, stimulation of these afferents as a result of evaporative water loss from airway surface liquid could contribute to exercise-induced asthma.
Effects of repeated cycles of starvation and refeeding on lungs of growing rats
Authors: Sahebjami H. , Domino M.
Published: December 2017

Adult male rats were subjected to four cycles of mild starvation (2 wk) and refeeding (1 wk) and were compared with a fed group. Starvation was induced by giving rats one-third of their measured daily food consumption. During each starvation cycle, rats lost approximately 20% of their body weight. Despite catch-up growth and overall weight gain, starved rats had lower final body weight than fed rats. Lung dry weight and lung volumes were also reduced in the starved group. The mechanical properties of air- and saline-filled lungs did not change significantly with repeated cycles of starvation. Mean linear intercept was similar in the two groups, but alveolar surface area was reduced in the starved rats. Total content of crude connective tissue and concentration per lung dry weight of hydroxyproline and crude connective tissue were reduced in starved rats. We conclude that lung growth is retarded in growing rats subjected to repeated cycles of mild starvation and refeeding, as manifested by smaller lung volume and reduced alveolar surface area. Because alveolar size is unchanged, a reduced number of alveoli is most likely responsible for decreased lung volumes.
Effects of hypoxia on the discharge of group III and IV muscle afferents in cats
Authors: Hill J. M. , Pickar J. G. , Parrish M. D. , Kaufman M. P.
Published: December 2017

The reflex pressor response evoked by static muscular contraction is widely believed to be caused by the stimulation of group III and IV afferents. Although the specific nature of the contraction-induced stimulus to these thin-fiber afferents is unknown, they are thought to be stimulated in part by a condition arising from a mismatch between blood supply and demand in the exercising muscle. Hypoxia, a condition found in skeletal muscle during such a mismatch, may stimulate these afferents. We have therefore tested the hypothesis that perfusion of the triceps surae muscles with hypoxic blood stimulates group III and IV afferents in barbiturate-anesthetized cats. We found that 3–3.5 min of hypoxia with the triceps surae muscles at rest significantly (P < 0.05) increased the average discharge rate of contraction-sensitive group IV afferents but had no effect on the average discharge rate of contraction-sensitive group III afferents. Hypoxia had only trivial effects on the discharge of contraction-insensitive group III and IV afferents. Hypoxia stimulated 4 of 11 contraction-sensitive group IV afferents and 2 of 13 contraction-sensitive group III afferents. The responses of the afferents stimulated by hypoxia were small in magnitude. Hypoxia with the muscles at rest appeared to have no effect on either hydrogen or lactate ion concentrations in the femoral venous blood. In addition, hypoxia increased the responses to contraction in only 3 of 22 group III and 4 of 21 group IV afferents tested. We conclude that muscle tissue hypoxia is a minor stimulus to afferents that sense a mismatch between blood supply and demand during static contraction.
Vasoconstrictor-mediated release of lactate from the perfused rat hindlimb
Authors: Hettiarachchi M. , Parsons K. M. , Richards S. M. , Dora K. A. , Rattigan S. , Colquhoun E. Q. , Clark M. G.
Published: December 2017

The effects of different vasomodulators on lactate release by the constant-flow-perfused rat hindlimb were examined and compared with that by perfused mesenteric artery, incubated preparations of aortas, soleus and epitrochlearis muscles, and perifused soleus muscles. Infusion of vasopressin (0.5 nM), angiotensin II (5 nM), norepinephrine (50 nM), and methoxamine (10 microM) into the hindlimbs of 180- to 200-g rats increased the perfusion pressure by 112–167% from 30.4 +/- 0.8 mmHg, O2 consumption by 26–68% from 6.4 +/- 0.2 mumol.g-1 x h-1, and lactate efflux by 148–380% from 5.41 +/- 0.25 mumol.g-1 x h-1. Hindlimbs of 100- to 120-g rats responded similarly to angiotensin II. Isoproterenol (1 microM) had no effect on O2 uptake or perfusion pressure but increased lactate release by 118%. Nitroprusside (0.5 mM) markedly inhibited the vasoconstrictor-mediated increases in lactate release, perfusion pressure, and O2 consumption by the hindlimb but had no effect on isoproterenol-mediated lactate efflux. Serotonin (6.7 microM) increased lactate release from the perfused mesenteric artery by 120% from 5.48 mol.g-1 x h-1. Lactate release by incubated aorta was increased by angiotensin II (50 nM), isoproterenol (1 microM), and mechanical stretch. The increase mediated by angiotensin II was blocked by glycerol trinitrate (2.2 microM), which had no effect on lactate release by isoproterenol. Neither angiotensin II (5 nM) nor vasopressin (0.5 nM) increased lactate release from incubated soleus and epitrochlearis muscles; however, lactate release was increased by isoproterenol, and this increase was unaffected by glycerol trinitrate (2.2 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Brain glutamate metabolism during metabolic alkalosis and acidosis
Authors: Ang R. C. , Hoop B. , Kazemi H.
Published: December 2017

Glutamate modifies ventilation by altering neural excitability centrally. Metabolic acid-base perturbations may also alter cerebral glutamate metabolism locally and thus affect ventilation. Therefore, the effect of metabolic acid-base perturbations on central nervous system glutamate metabolism was studied in pentobarbital-anesthetized dogs under normal acid-base conditions and during isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid transfer rates of radiotracer [13N]ammonia and of [13N]glutamine synthesized de novo via the reaction glutamate+NH3-->glutamine in brain glia were measured during normal acid-base conditions and after 90 min of acute isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid [13N]ammonia and [13N]glutamine transfer rates decreased in metabolic acidosis. Maximal glial glutamine efflux rate jm equals 85.6 +/- 9.5 (SE) mumol.l-1 x min-1 in all animals. No difference in jm was observed in metabolic alkalosis or acidosis. Mean cerebral cortical glutamate concentration was significantly lower in acidosis [7.01 +/- 0.45 (SE) mumol/g brain tissue] and tended to be larger in alkalosis, compared with 7.97 +/- 0.89 mumol/g in normal acid-base conditions. There was a similar change in cerebral cortical gamma-aminobutyric acid concentration. Within the limits of the present method and measurements, the results suggest that acute metabolic acidosis but not alkalosis reduces glial glutamine efflux, corresponding to changes in cerebral cortical glutamate metabolism. These results suggest that glutamatergic mechanisms may contribute to central respiratory control in metabolic acidosis.
Vascular effects of platelet-activating factor in lambs: role of cyclo- and lipoxygenase
Authors: Toga H. , Hibler S. , Ibe B. O. , Raj J. U.
Published: December 2017

In adult sheep, platelet-activating factor (PAF) effects include systemic hypotension and pulmonary hypertension. To identify developmental differences in vascular responses to PAF, we studied the effects of C18- and C16-PAF in 49 +/- 2- (SE) day-old lambs. Responses of upstream (arteries and microvessels) and venous segments of the lung to C18-PAF were determined both in vivo and in isolated lungs. In isolated lungs, the role of eicosanoids in PAF effects was also determined. In vivo, both C18- and C16-PAF caused a significant increase in systemic and pulmonary vascular resistance. The magnitude of vascular responses to C16-PAF was greater than that to C18-PAF. C18-PAF constricted both upstream and venous segments of the pulmonary circulation. Cyclooxygenase inhibition in isolated lungs attenuated arterial constriction to C18-PAF, whereas simultaneous cyclooxygenase and lipoxygenase inhibition completely blocked the effects of C18-PAF. In summary, in contrast to PAF effects in adult sheep, PAF constricts both systemic and pulmonary vessels in lambs, with significant pulmonary venous constriction. Eicosanoids, especially lipoxygenase products, play a major role in mediating PAF effects in the lung.
Evaluation of human dynamic contraction by phonomyography
Authors: Petitjean M. , Maton B. , Cnockaert J. C.
Published: December 2017

Phonomyogram (PMG, or acoustic myogram) is known to increase with force in isometric contractions. We investigated this relationship for dynamic contractions against different inertias. PMG and surface electromyogram (EMG) from biceps brachii and brachioradialis muscles were simultaneously recorded with the angular acceleration of elbow flexions. These were self-initiated movements (30 degrees) toward a fixed target and performed against two different inertias. PMG and EMG were integrated from the onset of the signal to the end of the acceleration phase. Phono- and electromechanical delays were also measured. For integrated EMG (iEMG), there was a linear relationship between integrated PMG (iPMG) and force, the slope of which did not depend on inertia. There was also a linear relationship between iPMG or iEMG and angular acceleration, with a higher slope for the highest inertia condition. There was also a family of linear relationships between iPMG or iEMG and angular acceleration, and their slopes depended on inertia. Measurements of the phono- and electromechanical delays showed that onset of PMG followed that of EMG but preceded onset of acceleration. It is suggested that PMG expresses tension of the underlying muscle contractile elements. Given the simplicity of the PMG method, we conclude that PMG allows convenient evaluation of muscle tension during human dynamic contraction.
Relationship between arterial oxygen desaturation and ventilation during maximal exercise
Authors: Miyachi M. , Tabata I.
Published: December 2017

The purpose of the present study was to investigate the contribution of ventilation to arterial O2 desaturation during maximal exercise. Nine untrained subjects and 22 trained long-distance runners [age 18–36 yr, maximal O2 uptake (VO2max) 48–74 ml.min-1 x kg-1] volunteered to participate in the study. The subjects performed an incremental exhaustive cycle ergometry test at 70 rpm of pedaling frequency, during which arterial O2 saturation (SaO2) and ventilatory data were collected every minute. SaO2 was estimated with a pulse oximeter. A significant positive correlation was found between SaO2 and end-tidal PO2 (PETO2; r = 0.72, r2 = 0.52, P < 0.001) during maximal exercise. These statistical results suggest that approximately 50% of the variability of SaO2 can be accounted for by differences in PETO2, which reflects alveolar PO2. Furthermore, PETO2 was highly correlated with the ventilatory equivalent for O2 (VE/VO2; r = 0.91, P < 0.001), which indicates that PETO2 could be the result of ventilation stimulated by maximal exercise. Finally, SaO2 was positively related to VE/VO2 during maximal exercise (r = 0.74, r2 = 0.55, P < 0.001). Therefore, one-half of the arterial O2 desaturation occurring during maximal exercise may be explained by less hyperventilation, specifically for our subjects, who demonstrated a wide range of trained states. Furthermore, we found an indirect positive correlation between SaO2 and ventilatory response to CO2 at rest (r = 0.45, P < 0.05), which was mediated by ventilation during maximal exercise. These data also suggest that ventilation is an important factor for arterial O2 desaturation during maximal exercise.
Separate effects of ischemia and reperfusion on vascular permeability in ventilated ferret lungs
Authors: Becker P. M. , Pearse D. B. , Permutt S. , Sylvester J. T.
Published: December 2017

In systemic organs, ischemia-reperfusion injury is thought to occur during reperfusion, when oxygen is reintroduced to hypoxic ischemic tissue. In contrast, the ventilated lung may be more susceptible to injury during ischemia, before reperfusion, because oxygen tension will be high during ischemia and decrease with reperfusion. To evaluate this possibility, we compared the effects of hyperoxic ischemia alone and hyperoxic ischemia with normoxic reperfusion on vascular permeability in isolated ferret lungs. Permeability was estimated by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb), using methods that did not require reperfusion to make these measurements. Kf and sigma alb in control lungs (n = 5), which were ventilated with 14% O2–5% CO2 after minimal (15 +/- 1 min) ischemia, averaged 0.033 +/- 0.004 g.min-1.mmHg-1.100 g-1 and 0.69 +/- 0.07, respectively. These values did not differ from those reported in normal in vivo lungs of other species. The effects of short (54 +/- 9 min, n = 10) and long (180 min, n = 7) ischemia were evaluated in lungs ventilated with 95% O2–5% CO2. Kf and sigma alb did not change after short ischemia (Kf = 0.051 +/- 0.006 g.min-1.mmHg-1.100 g-1, sigma alb = 0.69 +/- 0.07) but increased significantly after long ischemia (Kf = 0.233 +/- 0.049 g.min-1 x mmHg-1 x 100 g-1, sigma alb = 0.36 +/- 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Edema clearance in isolated sheep lungs
Authors: Pearse D. B. , Wagner E. M. , Sylvester J. T.
Published: December 2017

Edema may be cleared from the lung by lymphatic drainage, transudation across the visceral pleural, vascular reabsorption, and movement into the mediastinum. To determine the quantity and mechanisms of edema clearance associated with spontaneous edema formation in isolated sheep lungs, we perfused six lungs for 180 min with blood (100 ml.kg-1.min-1) at subatmospheric left atrial pressure (Pla) from a weighed reservoir. In six other lungs, Pla was increased to 20 mmHg at 30–75 min to further augment edema. Fluid drainage from the lung was fractionated into blood and water components by serial measurements of drainage and perfusate hematocrit. Changes in weight of circulating intravascular blood and extravascular lung water (EVLW) were also directly measured by dye dilution and standard gravimetric techniques, respectively. From these measurements, we calculated that 3.04 +/- 0.53 g/g blood-free dry lung of water filtered into the extravascular space during perfusion. Of this amount, 42% was reabsorbed into the pulmonary vasculature; 18% drained from the lung via lymphatics, visceral pleura, and mediastinum; and 40% was retained in the lung. Compared with low Pla lungs, transient elevation of Pla increased lung hemorrhage and the final change in reservoir weight, but the quantity and clearance of cumulative filtered water and the final values of EVLW and wet-to-dry weight ratio (WW/DW) were not altered. These results suggest that 1) significant edema clearance occurred in isolated sheep lungs, primarily by vascular reabsorption, and 2) measurements of EVLW and WW/DW under-estimated injury in the presence of lung hemorrhage and significant edema clearance.
Regional blood flow during closed-chest cardiac resuscitation in rats
Authors: Duggal C. , Weil M. H. , Gazmuri R. J. , Tang W. , Sun S. , O'Connell F. , Ali M.
Published: December 2017

Quantitative measurement of regional blood flow during cardiac arrest and resuscitation has been confined to large animals. We report on a rodent model utilizing radioactive microspheres during cardiac arrest and resuscitation for investigation of regional blood flow. Ventricular fibrillation was electrically induced in 10 pentobarbital-anesthetized Sprague-Dawley rats. Resuscitation was attempted by precordial compression followed by external direct current countershock. During precordial compression, cardiac output corresponded to 12% of prearrest flow. Similarly low flows were observed in the myocardium and brain. However, much lower flows were observed in the adrenal glands, kidneys, intra-abdominal viscera, skin, and skeletal muscle. Five of ten animals were successfully resuscitated. During precordial compression, resuscitated animals had significantly higher cardiac output (13.1 +/- 4.1 vs. 8.6 +/- 1.46 ml/min), myocardial blood flow (0.70 +/- 0.24 vs. 0.22 +/- 0.15 ml.min-1.g-1), cerebral blood flow (0.17 +/- 0.04 vs. 0.06 +/- 0.02 ml.min-1.g-1), and adrenal blood flow (1.09 +/- 0.60 vs. 0.27 +/- 0.16 ml.min-1.g-1). Thirty minutes after successful resuscitation, cardiac output and myocardial, cerebral, renal, and adrenal blood flows and blood flow to splanchnic viscera (with the exception of the spleen) had returned to > or = 70% of prearrest flows. These studies confirm the conclusion of earlier investigations in larger animals that visceral blood flow during cardiac arrest and precordial compression is preferentially distributed to the brain and myocardium. Successful cardiac resuscitation is contingent on threshold levels of myocardial blood flow that exceed 0.4 ml.min-1.g-1.
Alveolar liquid and protein clearance in the absence of blood flow or ventilation in sheep
Authors: Sakuma T. , Pittet J. F. , Jayr C. , Matthay M. A.
Published: December 2017

The primary objective of these studies was to test the contribution of ventilation and blood flow to the removal of excess liquid from the air spaces and interstitium of the lung. First, after eliminating ventilation by clamping the left main bronchus in anesthetized sheep, alveolar and lung liquid clearance was not altered over 4 h compared with control sheep that were ventilated normally. Thus, removal of excess liquid across the alveolar epithelium was independent of the change in the transalveolar hydrostatic pressure gradient produced by ventilation. Second, to determine the effect of removing all blood flow to the lung, we developed a new in situ sheep lung model in which lung lymph flow was measured over 4 h with or without ventilation after the sheep had been exsanguinated. Alveolar liquid clearance, as measured by the percent increase in alveolar protein concentration over 4 h, was similar between sheep without blood flow (31 +/- 18%) compared with sheep with normal blood flow to the lungs (31 +/- 17%). Lung lymph flow contributed to only 10–15% of the clearance of the excess alveolar liquid that was transported to the interstitium, indicating that nonlymphatic pathways accounted for most of the excess lung liquid clearance in the absence of microvascular filtration. Third, because ouabain completely inhibited alveolar liquid clearance in this in situ sheep lung model, these data provide evidence that alveolar liquid clearance depends on an intact Na(+)-K(+)-ATPase-dependent pump mechanisms. Finally, this in situ model represents a unique experimental preparation that can be used to study the alveolar epithelial barrier without blood flow or ventilation for a short time (4 h) interval.
Cooling the pulmonary blood in dogs alters activity of pulmonary vagal afferents
Authors: Giesbrecht G. G. , Pisarri T. E. , Coleridge J. C. , Coleridge H. M.
Published: December 2017

In open-chest anesthetized dogs with left and right lungs ventilated separately, we recorded changes in firing of right lung vagal receptors when 1.25 ml/kg cold (5 degrees C, 20 degrees C) blood were injected into the nonperfused right pulmonary artery. With the right lung inflated at constant pressure, effects of cold blood on individual pulmonary stretch receptors (PSRs) were frequency dependent, with discharge increasing or remaining unchanged if control frequency was low and decreasing if it was high. Consequently average PSR discharge was unchanged by cold blood when airway pressure was maintained at 5 cmH2O, but it decreased at pressures of 10 and 15 cmH2O. Cold blood stimulated rapidly adapting receptors (RARs) at all three pressures. Injection of blood at 37 degrees C had no effect. We conclude that changes in PSR activity account for the tachypnea induced by pulmonary arterial injection of cold blood (G. G. Giesbrecht and M. Younes. J. Appl. Physiol. 69: 1435–1441, 1990). With the right lung phasically ventilated, cold blood decreased PSR discharge in inflation, caused high-threshold PSRs to fire in deflation, and stimulated RARs. Pulmonary C-fibers were unaffected by cold blood. We suggest that PSRs and RARs initiate respiratory changes during hypothermia or exercise-induced asthma.
Protection against platelet-activating factor-induced injury by interferon inducer in perfused rabbit lung
Authors: Huang Y. C. , Kennedy T. P. , Su Y. F. , Watkins W. D. , Whorton A. R. , Piantadosi C. A.
Published: December 2017

Platelet-activating factor (PAF) and the interferons (IFN) are released during sepsis and the adult respiratory distress syndrome. The proinflammatory nature of PAF and anti-inflammatory property of IFN led us to investigate interactions between these two mediators in an isolated perfused lung (IPL) preparation. In the IPL, mean pulmonary arterial pressure (Ppa), lung weight gain, and peak airway pressure (Paw) were monitored continuously for 1 h in six groups of rabbits: 1) control, 2) the IFN-alpha/beta inducer polyinosinic:cytidylic acid (polyI:C) alone, 3) PAF alone, 4) polyI:C + PAF, 5) indomethacin + PAF, and 6) AA861 (a 5-lipoxygenase inhibitor) + PAF. At the end of 1 h, microvascular pressure was determined by double-occlusion technique and partition of total pulmonary vascular resistance (RT) was calculated. Serial eicosanoid concentrations in the perfusate also were measured. PAF increased Ppa, Paw, lung weight gain, and RT. These changes were associated with increased thromboxane B2 and decreased leukotriene production. PolyI:C, which induced high levels of serum IFN in rabbits, blocked the PAF-induced increase in Ppa, Paw, lung weight gain, and RT, similar to indomethacin and AA861. PolyI:C suppressed PAF-stimulated release of thromboxane B2 and increased leukotriene levels in the perfusate. The PAF-induced lung responses also were attenuated by pretreatment with human recombinant IFN. These data indicate that polyI:C protects against PAF-induced responses in the rabbit IPL, most likely via its induction of IFN. This effect is related in part to inhibition of thromboxane A2 production stimulated by PAF and leukotrienes.
Atypical beta-adrenoceptor- (beta 3-adrenoceptor) mediated relaxation of canine isolated bronchial smooth muscle
Authors: Tamaoki J. , Yamauchi F. , Chiyotani A. , Yamawaki I. , Takeuchi S. , Konno K.
Published: December 2017

To determine whether atypical beta-adrenoceptors (beta 3-adrenoceptors) exist in the airway smooth muscle, we studied isolated bronchial segments from dogs under isometric conditions in vitro. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 10(-5) M acetylcholine, rank-order potency being isoproterenol (1) > or = salbutamol (0.95) > or = BRL 37344, a beta 3-selective adrenoceptor agonist (0.83) > norepinephrine (0.10). Under the condition that alpha- and beta 1-adrenoceptors had been blocked, the relaxant response to salbutamol was competitively antagonized by the beta 2-adrenoceptor antagonist ICI 118551 and the pA2 was 7.01 +/- 0.25 (SE), whereas the response to BRL 37344 was resistant, with an apparent pA2 of 5.66. However, cyanopindolol, an antagonist for atypical beta-adrenoceptors, antagonized the BRL-induced relaxation in a competitive manner, with a pA2 of 6.74 +/- 0.11. This pA2 was lower than that when salbutamol was used as an agonist (P < 0.05). Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were increased by BRL 37344 in a concentration-dependent fashion. These results suggest that beta 3-adrenoceptors may exist in canine bronchial smooth muscle and that the stimulation of this type of receptor causes a bronchodilation through a cAMP-dependent pathway.
Peripheral chemoreceptor function in children with the congenital central hypoventilation syndrome
Authors: Gozal D. , Marcus C. L. , Shoseyov D. , Keens T. G.
Published: December 2017

In children with the congenital central hypoventilation syndrome (CCHS), some patients require mechanical ventilation during sleep, whereas others need respiratory assistance even when awake. The cause of this disparity is unclear. We hypothesized that differences in peripheral chemoreceptor response (PCR) could provide an explanatory mechanism for this disparity in clinical manifestations. PCR was measured in five children with CCHS and five sex- and age-matched controls by measuring the ventilatory responses induced by 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 5% and 15% CO2 in O2 and 5% CO2–95% N2. Tidal breathing of 100% O2 resulted in similar ventilatory responses in CCHS patients and controls with various changes dependent on the method of analysis of response used. Acute hypoxia by N2 tidal breathing resulted in a 39.2 +/- 22% increase in respiratory rate in CCHS patients and a 15.1 +/- 11.1% increase in controls (P < 0.05), with similar increases in minute ventilation (VE) of 124 +/- 69% and 85 +/- 11%, respectively. Vital capacity breaths of each of the CO2-containing gas mixtures induced similar increases in VE in CCHS patients and controls. The changes in VE obtained with 15% CO2–85% O2 and with 5% CO2–95% N2 were significantly greater than those with 5% CO2–95% O2, suggesting a dose-dependent response as well as additive effects of hypercapnic and hypoxic stimuli. We conclude that the PCR, when assessed by acute hypoxia, hyperoxia, or hypercapnia, is present and intact in CCHS children who are able to sustain adequate ventilation during wakefulness.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of 5-hydroxytryptamine and 5-hydroxytryptophan infusion on the human cough reflex
Authors: Stone R. A. , Worsdell Y. M. , Fuller R. W. , Barnes P. J.
Published: December 2017

In some species serotonin (5-HT) has been shown to act as a central modulator of the cough reflex. To investigate whether serotonergic mechanisms influence the control of the human cough reflex, we have induced cough responses before and during infusions of 5-HT; its precursor 5-hydroxytryptophan (5-HTP), which, in contrast to 5-HT, crosses the blood-brain barrier; and saline control. At the start of each study day, eight normal male volunteers were challenged with a single inhalation of a solution lacking chloride ions (0.15 M sodium bicarbonate) and a single breath of capsaicin during a sham infusion. After 3 h they received repeat cough challenges during experimental infusions of 5-HT, 5-HTP, or saline control, which were given randomly and single blind. Heart rate, respiratory rate, and blood pressure were measured before, during, and after each infusion. Both 5-HT and 5-HTP reduced cough responses to the chloride-deficient solution (P = 0.035 and P = 0.017, respectively) with respect to saline control, whereas neither infusion reduced responses to capsaicin. 5-HT caused a transient increase in heart rate that was not observed with a similar dose of 5-HTP or saline (P < 0.01). Respiratory rate and blood pressure were not affected by experimental infusions but rose during cough challenge. We conclude that 5-HT exerts an inhibitory influence over the human cough reflex at peripheral and possibly central sites.
Protective effects of anti-O polysaccharide and anti-lipid A monoclonal antibodies on pulmonary hemodynamics
Authors: Chen T. Y. , Warren H. S. , Greene E. , Black K. M. , Frostell C. G. , Robinson D. R. , Zapol W. M.
Published: December 2017

Monoclonal antibodies (MAbs) directed to endotoxin can protect in some animal models against the pathophysiological effects of endotoxin infusion. When 0.02 microgram/kg of lipopolysaccharide (LPS) derived from Escherichia coli O111:B4 was incubated in vitro for 2 h with the murine immunoglobulin G MAb, 5B10, directed against the O-polysaccharide antigenic domain of E. coli O111:B4 and then the mixture was infused into sheep, we noted significant protection. The second temperature peak was decreased (P < 0.05 vs. LPS control). The acute pulmonary arterial pressure elevation was diminished (mean peak pulmonary arterial pressure 23.2 +/- 2.5 mmHg, P < 0.05 vs. LPS control), and the peak plasma thromboxane B2 level was reduced (mean peak thromboxane B2 level 0.50 +/- 0.15 ng/ml, P < 0.05 vs. LPS control). In contrast, preincubation of the LPS with a human immunoglobulin M MAb, HA-1A, directed against the core glycolipid of the LPS molecule provided no protective effects in this sheep model. This finding is in agreement with recent studies reporting HA-1A may bind to antibiotic-treated bacteria but not to purified smooth LPS.
Lactate kinetics in resting and exercising forearms during moderate-intensity supine leg exercise
Authors: Catcheside P. G. , Scroop G. C.
Published: December 2017

Arterial blood lactate was elevated by supine leg exercise (20 min at approximately 65% maximal oxygen uptake) in five untrained male subjects, and the contribution to blood lactate removal from passive uptake vs. metabolic disposal was compared in resting and lightly exercising (15% maximal voluntary contraction static handgrip) forearm skeletal muscle. An integrated form of the Fick equation was used to predict venous lactate levels resulting solely from passive equilibration of lactate between incoming arterial blood and the forearm muscles. In the resting forearm, predicted and measured venous lactate levels were closely correlated during the exercise period (r = 0.995, P < 0.001), indicating that lactate removal could be accounted for in terms of passive uptake alone. In the lightly exercising forearm, measured venous lactate levels were higher than both the arterial and predicted venous levels, indicating net lactate production. It was concluded that most of the blood lactate generated by moderate-intensity supine leg exercise is taken up passively and not metabolized by resting skeletal muscle and that the rate of lactate disposal is unlikely to be enhanced in lightly exercising muscle.
Airway and vascular effects of 8-epi-prostaglandin F2 alpha in isolated perfused rat lung
Authors: Kang K. H. , Morrow J. D. , Roberts L. J. , Newman J. H. , Banerjee M.
Published: December 2017

The effects of 8-epi-prostaglandin (PG) F2 alpha, a recently discovered noncyclooxygenase free radical-catalyzed product of arachidonic acid, on pulmonary vascular and airway tone, its potency, and its mechanism of action were studied. Progressively increasing bolus doses (1.0, 5.0, 10.0, and 20.0 micrograms) of 8-epi-PGF2 alpha were injected into the pulmonary artery catheter of 18 isolated rat lungs, and a single dose (40.0 micrograms) was injected into 7 additional rat lungs. The lungs were perfused with Krebs-Henseleit buffer solution containing 3% bovine serum albumin at 50 ml.kg-1.min-1 during ventilation with 21% O2–5% CO2–74% N2. 8-Epi-PGF2 alpha caused rapid pulmonary vascular and airway constrictor responses, which were followed by a gradual return over 10 min to baseline levels. Double vascular occlusion at peak rise in pulmonary arterial pressure (Ppa) revealed a 28% increase in arterial resistance. The rise in Ppa with 20 micrograms of 8-epi-PGF2 alpha was approximately twofold greater than with 20 micrograms of the cyclooxygenase-derived prostaglandin PGF2 alpha. The addition of 100 microM N-nitro-L-arginine, a blocker of endothelium-derived relaxing factor, in the perfusate potentiated the rise in Ppa by 244%. Injection of 40 micrograms of rat atrial natriuretic factor at peak response to 20 micrograms of 8-epi-PGF2 alpha accelerated the return to baseline Ppa, resistance to airflow across the lung, and dynamic lung compliance values.(ABSTRACT TRUNCATED AT 250 WORDS)
Fast-response whole body indirect calorimeters for infants
Authors: Moon J. K. , Jensen C. L. , Butte N. F.
Published: December 2017

Portable whole body indirect calorimeters were constructed for full-term (2.5- to 8-kg) and preterm (1- to 2.5-kg) infants. A new calibration system significantly increased the accuracy of flowmeters and gas analyzers. Performance tests with N2 and CO2 infusions and butane combustion demonstrated that the error of individual measurements of O2 consumption and CO2 production were within +/- 2%. The measured error was close to the theoretical uncertainty of approximately +/- 1% calculated from test results of the flowmeters and gas analyzers. System response to a step change in butane combustion rate exceeded 90% within 2 min. Error of +/- 2% and response of 2 min are likely to be the practical lower limits for whole body infant indirect calorimeters with current technology. The calorimeters demonstrated a rapid increase in O2 consumption after feeding (preterm infants) and in the transition from non-rapid-eye-movement to rapid-eye-movement sleep stages (full-term infants).
Breathing, transcutaneous blood gases, and CO2 response in SIDS siblings and control infants during sleep
Authors: Schafer T. , Schafer D. , Schlafke M. E.
Published: December 2017

Age-related changes of 20 variables describing breathing patterns, transcutaneous blood gases, and estimated CO2 response during sleep were examined in a cross-sectional study of 30 healthy control infants and 150 healthy siblings of sudden infant death syndrome victims within the first 18 mo of life. Whole-night measurements were performed using noninvasive respiratory induction plethysmography and transcutaneous blood gas electrodes. Each candidate for the study was extensively screened and found to be healthy. Mean transcutaneous PCO2 (PtcCO2, median 40.3 Torr) and maximum PtcCO2 (median 44.8 Torr), as well as the estimated ventilatory response to inhalation of 2% CO2 in air during regular breathing, causing a 20–36% increase of ventilation per Torr PtcCO2, were not related to postnatal age. In contrast, paradoxical breathing decreased from 49.5 to 0% of total sleep time (TST), periodic breathing from 5.5 to 0% TST, and respiratory rate during regular breathing from 40 to 22 breaths/min; the portion of regular breathing increased from 32 to 55% TST and mean and minimum transcutaneous PO2 from 65.4 and 47 to 69.7 and 52 Torr with increasing stability. The largest changes occurred in the first 6 mo of life. Maximum apnea duration (9.5 s, maximum 16 s), mean apnea duration (3.74 s, breathing pauses > or = 2 s), and time spent apneic per hour of irregular breathing (199 s/h) were not related to age. The comparison of data from siblings and controls showed similarities in the above-mentioned variables. No significant differences were found among the groups. Also a comparison of 30 pairs of siblings and controls, matched for age, gender, birth, and actual body weight, did not show significant differences. The present study extends the knowledge of development of breathing control beyond the first 6 mo of life.
Mean circulatory filling pressure: its meaning and measurement
Authors: Rothe C. F.
Published: December 2017

The volume-pressure relationship of the vasculature of the body as a whole, its vascular capacitance, requires a measurement of the mean circulatory filling pressure (Pmcf). A change in vascular capacitance induced by reflexes, hormones, or drugs has physiological consequences similar to a rapid change in blood volume and thus strongly influences cardiac output. The Pmcf is defined as the mean vascular pressure that exists after a stop in cardiac output and redistribution of blood, so that all pressures are the same throughout the system. The Pmcf is thus related to the fullness of the circulatory system. A change in Pmcf provides a uniquely useful index of a change in overall venous smooth muscle tone if the blood volume is not concomitantly changed. The Pmcf also provides an estimate of the distending pressure in the small veins and venules, which contain most of the blood in the body and comprise most of the vascular compliance. Thus the Pmcf, which is normally independent of the magnitude of the cardiac output, provides an estimate of the upstream pressure that determines the rate of flow returning to the heart.
Vascular conductance and aerobic power in sedentary and active subjects and heart failure patients
Authors: Reading J. L. , Goodman J. M. , Plyley M. J. , Floras J. S. , Liu P. P. , McLaughlin P. R. , Shephard R. J.
Published: December 2017

The relationship between peak aerobic power and a strain-gauge determination of local skeletal muscle vascular conductance 10–13 s after calf exercise to fatigue was examined in 21 middle-aged adults (age 38.1 +/- 2.5 yr): seven physically active men (A), seven sedentary men (S), and six men and one woman with compensated idiopathic heart failure (HF). The three subgroups were chosen as differing widely in peak O2 intake [48.2 +/- 1.2, 32.9 +/- 1.6, and 16.1 +/- 1.3 (SE) ml.kg-1 x min-1, respectively]. Calf vascular conductance showed a gradation with aerobic power: 64.8 +/- 3.8, 40.7 +/- 4.3, and 30.7 +/- 6.1 (SE) ml/min local flow per 10 liters of tissue per unit of blood pressure. There was a strong positive correlation between O2 intake and vascular conductance for the overall group (VO2 = 0.614 G + 3.5; r = 0.75, P < 0.001) and for the 14 normal subjects (VO2 = 0.377 G + 20.6; r = 0.74, P < 0.002). The mean conductance was smaller in HF (P < 0.001), with no significant slope in relation to O2 intake. There was no relationship between the resting cardiac ejection fraction [74.4 +/- 4.1% (SE) for A, 74.3 +/- 4.2% for S, and 25.8 +/- 5.2% for HF] and either peak aerobic power or calf vascular conductance. We conclude that peak aerobic power is strongly associated with local vascular conductance during peripherally limited exercise involving the calf muscles of one leg and that vascular conductance is particularly low in subjects with compensated idiopathic heart failure.