bluuebunny/crossref_metadata_2025 huggingface dataset:
alpha-Difluoromethylornithine attenuates monocrotaline-induced airway/lung dysfunction
Authors: Zhou K. R. , Lai Y. L.
Published: December 2017

On the basis of the previous findings that alpha-difluoromethylornithine (DFMO, an inhibitor of ornithine decarboxylase, which is the rate-limiting enzyme in polyamine biosynthesis) treatment prevents monocrotaline-(MCT) induced pulmonary hypertension and that ventilatory dysfunction precedes pulmonary hypertension in MCT-treated rats, we hypothesize that MCT-induced changes in airway/lung function are polyamine dependent. To evaluate this hypothesis, in phase 1, 48 young Sprague-Dawley rats were evenly divided into four groups: control, DFMO, MCT, and DFMO + MCT. Each DFMO rat received DFMO in its drinking water (2%) for 11 days, with additional injections (400 mg/kg sc) on the 5th day. Each MCT rat received a single injection of MCT (60 mg/kg sc) 1 wk before the functional study. Each DFMO + MCT rat received the same DFMO and MCT treatments as above, and MCT was administered on the 5th day of the DFMO treatment. In the MCT group, there were marked rightward shifts in pressure-volume and maximal flow-static recoil (MFSR) curves and significant decreases in dynamic and quasi-static compliance, the maximal expiratory flow, slope of the MFSR curve, and the carbon monoxide diffusing capacity, as well as a significant increase in alveolar wall thickness. However, in rats treated with DFMO + MCT, most of MCT-induced changes were significantly attenuated. To evaluate whether MCT causes bronchoconstriction, a bronchodilator, terbutaline (0.2 mg/kg i.v.), was administered to control (n = 7) and MCT (n = 11) rats in phase 2. Terbutaline significantly reversed MCT-induced decreases in maximal expiratory flow and slope of the MFSR curve, whereas it did not alter these parameters in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of longitudinal laparotomy on respiratory system, lung, and chest wall mechanics
Authors: Santos R. L. , Santos M. A. , Sakae R. S. , Saldiva P. H. , Zin W. A.
Published: December 2017

In six sedated, anesthetized, paralyzed, and mechanically ventilated guinea pigs, total respiratory system (RT,rs), lung, and chest wall resistances and respiratory system (Est,rs), lung, and chest wall (Est,w) elastances were determined before and after longitudinal laparotomy. Furthermore the resistances were also split into their initial and difference components, with the former reflecting the Newtonian resistances and the latter representing the viscoelastic/inhomogeneous pressure dissipations in the system. For such purpose the end-inflation occlusion during constant inspiratory flow method was used. During laparotomy, a statistically significant increase in respiratory system difference resistance (from 0.086 to 0.101 cmH2O.ml-1.s) significantly augmented RT,rs (from 0.157 to 0.167 cmH2O.ml-1.s). The former was entirely secondary to a significant increase in chest wall difference resistance (0.019 to 0.034 cmH2O.ml-1.s), which naturally raised chest wall total resistance (from 0.030 to 0.047 cmH2O.ml-1.s). Est,rs and Est,w also increased (14.7 and 13.1%, respectively) after abdominal incision. It can be concluded that the midline xiphipubic laparotomy accompanied by the bilateral ventrodorsal infracostal incision increases RT,rs as a consequence of augmented chest wall difference resistance and Est,rs as a result of higher Est,w.
Time course of glycogen accumulation after eccentric exercise
Authors: Widrick J. J. , Costill D. L. , McConell G. K. , Anderson D. E. , Pearson D. R. , Zachwieja J. J.
Published: December 2017

This study examined the time course of glycogen accumulation in skeletal muscle depleted by concentric work and subsequently subjected to eccentric exercise. Eight men exercised to exhaustion on a cycle ergometer [70% of maximal O2 consumption (VO2max)] and were placed on a carbohydrate-restricted diet. Approximately 12 h later they exercised one leg to subjective failure by repeated eccentric action of the knee extensors against a resistance equal to 120% of their one-repetition maximum concentric knee extension force (ECC leg). The contralateral leg was not exercised and served as a control (CON leg). During the 72-h recovery period, subjects consumed 7 g carbohydrate.kg body wt-1.day-1. Moderate soreness was experienced in the ECC leg 24–72 h after eccentric exercise. Muscle biopsies from the vastus lateralis of the ECC and CON legs revealed similar glycogen levels immediately after eccentric exercise (40.2 +/- 5.2 and 47.6 +/- 6.4 mmol/kg wet wt, respectively; P greater than 0.05). There was no difference in the glycogen content of ECC and CON legs after 6 h of recovery (77.7 +/- 7.9 and 85.1 +/- 4.9 mmol/kg wet wt, respectively; P greater than 0.05), but 18 h later, the ECC leg contained 15% less glycogen than the CON leg (90.2 +/- 8.2 vs. 105.8 +/- 8.9 mmol/kg wet wt; P less than 0.05). After 72 h of recovery, this difference had increased to 24% (115.8 +/- 8.0 vs. 153.0 +/- 12.2 mmol/kg wet wt; P less than 0.05). These data confirm that glycogen accumulation is impaired in eccentrically exercised muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain adaptation to chronic hypobaric hypoxia in rats
Authors: LaManna J. C. , Vendel L. M. , Farrell R. M.
Published: December 2017

Rats were exposed to hypobaric hypoxia (0.5 atm) for up to 3 wk. Hypoxic rats failed to gain weight but maintained normal brain water and ion content. Blood hematocrit was increased by 48% to a level of 71% after 3 wk of hypoxia compared with littermate controls. Brain blood flow was increased by an average of 38% in rats exposed to 15 min of 10% normobaric oxygen and by 23% after 3 h but was not different from normobaric normoxic rats after 3 wk of hypoxia. Sucrose space, as a measure of brain plasma volume, was not changed under any hypoxic conditions. The mean brain microvessel density was increased by 76% in the frontopolar cerebral cortex, 46% in the frontal motor cortex, 54% in the frontal sensory cortex, 65% in the parietal motor cortex, 68% in the parietal sensory cortex, 68% in the hippocampal CA1 region, 57% in the hippocampal CA3 region, 26% in the striatum, and 56% in the cerebellum. The results indicate that hypoxia elicits three main responses that affect brain oxygen availability. The acute effect of hypoxia is an increase in regional blood flow, which returns to control levels on continued hypoxic exposure. Longer-term effects of continued moderate hypoxic exposure are erythropoiesis and a decrease in intercapillary distance as a result of angiogenesis. The rise in hematocrit and the increase in microvessel density together increase oxygen availability to the brain to within normal limits, although this does not imply that tissue PO2 is restored to normal.
Effects of pharyngeal lubrication on the opening of obstructed upper airway
Authors: Miki H. , Hida W. , Kikuchi Y. , Chonan T. , Satoh M. , Iwase N. , Takishima T.
Published: December 2017

We examined the effect of electrical stimulation of the hypoglossal nerve and pharyngeal lubrication with artificial surfactant (Surfactant T-A) on the opening of obstructed upper airway in nine anesthetized supine dogs. The upper airway was isolated from the lower airway by transecting the cervical trachea. Upper airway obstruction was induced by applying constant negative pressures (5, 10, 20, and 30 cmH2O) on the rostral cut end of the trachea. Peripheral cut ends of the hypoglossal nerves were electrically stimulated by square-wave pulses at various frequencies from 10 to 30 Hz (0.2-ms duration, 5–7 V), and the critical stimulating frequency necessary for opening the obstructed upper airway was measured at each driving pressure before and after pharyngeal lubrication with artificial surfactant. The critical stimulation frequency for upper airway opening significantly increased as upper airway pressure became more negative and significantly decreased with lubrication of the upper airway. These findings suggest that greater muscle tone of the genioglossus is needed to open the occluded upper airway with larger negative intraluminal pressure and that lubrication of the pharyngeal mucosa with artificial surfactant facilitates reopening of the upper airway.
Metabolic and febrile responses to typhoid vaccine in humans: effect of beta-adrenergic blockade
Authors: Cooper A. L. , Horan M. A. , Little R. A. , Rothwell N. J.
Published: December 2017

Fever and activation of acute phase responses were induced in human volunteers by intramuscular injection of typhoid vaccine. Vaccine injection caused a rapid (within 1 h) and sustained rise in metabolic rate (peak response 16%, 6–8 h), followed by later increases in white blood cell count (3–4 h), skin temperature (4–5 h), oral temperature (5–6 h), heart rate (6–8 h), and plasma cortisol (5–8 h). A peak fever [1.2 +/- 0.2 degree C (SE) rise] was recorded 12 h after vaccine injection. The involvement of the sympathetic nervous system in the development of these responses was investigated by the oral administration of propranolol before (80 mg) and 3 h after (40 mg) vaccine injection. Propranolol prevented the increases in metabolic rate, heart rate, and skin temperature but did not inhibit the rise in oral temperature or white cell count after vaccine administration. These data indicate that the sympathetic nervous system is responsible for the rise in energy expenditure associated with fever in humans. However, the rise in body temperature can develop in the absence of this increase in metabolic rate possibly by changes in heat loss.
Substrate and endocrine responses during exercise at selected stages of pregnancy
Authors: Bonen A. , Campagna P. , Gilchrist L. , Young D. C. , Beresford P.
Published: December 2017

To determine whether the concomitant effects of pregnancy and exercise yield substrate and endocrine patterns different from those expected during exercise alone, we compared the responses of glucose, lactate, free fatty acids, insulin, epinephrine (EP), norepinephrine (NE), human chorionic gonadotropin (HCG), human placental lactogen (HPL), estriol, and progesterone (P) in nonpregnant women (NP; n = 7) and pregnant women in the second (TR2; n = 6) and third trimester (TR3; n = 8) of pregnancy, before, during, and after 30 min of bicycle ergometer exercise at heart rates of 130–140 beats/min. In general, all substrates and hormone concentrations increased with exercise (P less than 0.05), except insulin, which decreased (P less than 0.05), and HCG, which did not change (P = 0.08). Differences in selected hormone concentrations (P, estriol, HCG, and HPL) among groups were already present at rest because of the different stages of pregnancy. Differences among groups at rest were also found in insulin and NE (P less than 0.05). Significantly different responses to exercise (i.e., group x time interactions) were as follows. NP vs. TR2:P, estriol, HCG, HPL, EP, and NE (P less than 0.05); NP vs. TR3: glucose, EP, and NE (P less than 0.05); TR2 vs. TR3: lactate, EP, and NE (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Response of laryngeal mechanoreceptors to high-frequency pressure oscillation
Authors: Zhang S. , Mathew O. P.
Published: December 2017

High-frequency pressure oscillations (HFPO) in the upper airway induce arousal, activation of genioglossus muscle, and bronchoconstriction. The present study was designed to determine the response of superior laryngeal nerve afferent fibers to HFPO. In 10 anesthetized dogs spontaneously breathing through a tracheal cannula, the upper airway was converted to a closed system. The activity of thin bundles separated from the peripheral cut end of the superior laryngeal nerve was monitored. Of 104 mechanoreceptors identified, 87 were classified as respiratory modulated and 17 as non-respiratory modulated on the basis of their response to transmural pressure change and muscle activity. The responses of these fibers to HFPO of +/- 2.5 cmH2O at 10, 20, and 30 Hz were determined. Among the respiratory-modulated receptors, 86 of 87 increased their activity in response to HFPO. Of the 17 non-respiratory-modulated receptors, 12 receptors showing a random or tonic activity did not respond to HFPO, whereas the 5 that were silent during control condition responded exclusively to HFPO. Our results show that HFPO of similar frequency but much less magnitude than snoring is capable of activating the vast majority of laryngeal mechanoreceptors. Pressure-sensitive respiratory-modulated endings appear to mediate the arousal and genioglossal response, whereas non-respiratory-modulated receptors responding to HFPO presumably mediate the bronchoconstrictive response.
Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease
Authors: Hiatt W. R. , Wolfel E. E. , Regensteiner J. G. , Brass E. P.
Published: December 2017

Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS)
A signal-averaging technique for the analysis of human muscle sympathetic nerve activity
Authors: Birkett C. L. , Ray C. A. , Anderson E. A. , Rea R. F.
Published: December 2017

We present a signal-averaging technique for analysis of human muscle sympathetic nerve activity (SNA). Nerve traffic was averaged by coupling signal acquisition to electrocardiographic R waves. The amplitude of the averaged waveform was multiplied by the number of R waves sampled to provide a measure of SNA in arbitrary units. This was compared with SNA measured by manual digitization of hard-copy records. In nine volunteers, SNA was increased or decreased with stepwise infusions of nitroprusside or phenylephrine: there were 10 5-min periods of data in each subject. Across all subjects, the correlation between manual and signal-averaged measures of SNA was excellent during both nitroprusside (r = 0.98) and phenylephrine infusions (r = 0.91) and the slopes of the regression lines were near unity. In three periods of data collection, electrical artifacts were added randomly at frequencies of 0.5 and 0.07 Hz during playback of the signal into the computer. Signal-averaged estimates of SNA were unaffected by artifacts. This technique provides reliable observer-independent measures of SNA.
Effects of hyperphosphatemia on diaphragmatic strength and endurance
Authors: Bark H. , Nizri M. , Tarasuik A. , Heimer D.
Published: December 2017

Effects of an infusion of Na2HPO4 on diaphragm strength, endurance, and magnitude of recovery were evaluated in in situ canine diaphragm strips. Results showed no effect on maximal isometric tetanic tension. Twitch tension and tension in the low- (10-Hz) frequency range were significantly increased (P less than 0.01). Time to fatigue (endurance) increased by 38 +/- 4.5% in the group that received phosphorus compared with its control and decreased by 18.5 +/- 2.5% in the group that received dextrose compared with its control (P less than 0.005). Recovery from fatigue was also significantly improved after the phosphorus infusion. Serum ATP and 2,3-diphosphoglycerate levels were unchanged throughout the experiment. The results of this study support the notion that hyperphosphatemia improves diaphragmatic endurance and recovery from fatigue. The mechanisms involved may in part be due to the phosphate-buffering effects, which limit the extent of the muscle intracellular acidosis produced with fatigue.
Central neural mechanisms of progesterone action: application to the respiratory system
Authors: Bayliss D. A. , Millhorn D. E.
Published: December 2017

Around the turn of the century, it was recognized that women hyperventilate during the luteal phase of the menstrual cycle and during pregnancy. Although a causative role for the steroid hormone progesterone in this hyperventilation was suggested as early as the 1940s, there has been no clear indication as to the mechanism by which it produces its respiratory effects. In contrast, much mechanistic information has been obtained over the same period about a different effect of progesterone, i.e., the facilitation of reproductive behaviors. In this case, the bulk of the evidence supports the hypothesis that progesterone acts via a genomic mechanism with characteristics not unlike those predicted by classic models for steroid hormone action. We recently, therefore, undertook a series of experiments to test predictions of those same models with reference to the respiratory effects of progesterone. Here we highlight the results of those studies; as background to and precedent for our experiments, we briefly review previous work in which effects of progesterone on respiration and reproductive behaviors have been studied. Our results indicate that the respiratory response to progesterone is mediated at hypothalamic sites through an estrogen- (E2) dependent progesterone receptor- (PR) mediated mechanism requiring RNA and protein synthesis, i.e., gene expression. The E2 dependence of the respiratory response to progesterone is likely a consequence of the demonstrated induction of PR mRNA and PR in hypothalamic neurons by E2. In short, we found that neural mechanisms underlying the stimulation of respiration by progesterone were similar to those mediating its reproductive effects.
Effort sensation, chemoresponsiveness, and breathing pattern during inspiratory resistive loading
Authors: Clague J. E. , Carter J. , Pearson M. G. , Calverley P. M.
Published: December 2017

Although inspiratory resistive loading (IRL) reduces the ventilatory response to CO2 (VE/PCO2) and increases the sensation of inspiratory effort (IES), there are few data about the converse situation: whether CO2 responsiveness influences sustained load compensation and whether awareness of respiratory effort modifies this behavior. We studied 12 normal men during CO2 rebreathing while free breathing and with a 10-cmH2O.l-1.s IRL and compared these data with 5 min of resting breathing with and without the IRL. Breathing pattern, end-tidal PCO2, IES, and mouth occlusion pressure (P0.1) were recorded. Free-breathing VE/PCO2 was inversely related to an index of effort perception (IES/VE; r = -0.63, P less than 0.05), and the reduction in VE/PCO2 produced by IRL was related to the initial free-breathing VE/PCO2 (r = 0.87, P less than 0.01). IRL produced variable increases in inspiratory duration (TI), IES, and P0.1 at rest, and the change in tidal volume correlated with both VE/PCO2 (r = 0.63, P less than 0.05) and IES/VE (r = -0.69, P less than 0.05), this latter index also predicting the changes in TI with loading (r = -0.83, P less than 0.01). These data suggest that in normal subjects perception of inspiratory effort can modify free-breathing CO2 responsiveness and is as important as CO2 sensitivity in determining the response to short-term resistive loading. Individuals with good perception choose a small-tidal volume and short-TI breathing pattern during loading, possibly to minimize the discomfort of breathing.
Mechanical properties of small airways in excised pony lungs
Authors: Olson L. E.
Published: December 2017

We evaluated the pressure-flow relationships in collaterally ventilating segments of excised pony lungs by infusing N2, He, Ne, or SF6 at known flows (V) through a catheter wedged in a peripheral airway. Measurements were made at segment- (Ps) to-airway opening (Pao) pressure differentials of 3–15 cmH2O when the lungs were held at transpulmonary pressures of 5, 10, and 15 cmH2O. The data were analyzed both by calculating collateral resistance (Ps-Pao/V) and by constructing Moody-type plots of normalized pressure drop [(Ps-Pao)/(1/2 rho U2, where rho is density and U is velocity)] against Reynolds number to assess the pattern of flow through the segment and the change in dimension of the flow channels as Ps and Pao were changed. The interpretations from these analyses were compared with radiographic measurements of the diameters of small airways within the collaterally ventilating lung segment at similar pressures. Collateral resistance increased as Ps-Pao increased at high Reynolds numbers, i.e., high flows or dense gas (SF6). Analysis of the Moody-type plots revealed that flow was density dependent at Reynolds number greater than 100, which frequently occurred when N2 was the inflow gas. The radiographic data revealed that small airway diameter increased as Ps-Pao increased at all lung volumes. In addition, at 5 cmH2O Pao, small-airway diameter was smaller for a given Ps in the nonhomogeneous case (Ps greater than Pao) than small-airway diameter for the same Ps in the homogeneous case (Ps = Pao). We interpret these data to suggest that the surrounding lung prevented the segment from expanding in the nonhomogeneous case.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute and chronic pulmonary vasoconstriction after left lung autotransplantation in conscious dogs
Authors: Murray P. A. , Stuart R. S. , Fraser C. D. , Fehr D. M. , Chen B. B. , Rock P. , Desai P. M. , Nyhan D. P.
Published: December 2017

We investigated the acute and chronic effects of left lung autotransplantation (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in conscious dogs. Continuous LP/Q plots were generated in chronically instrumented conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented normal conscious dogs were studied at equal time points post-surgery. LLA had little or no effect on baseline systemic hemodynamics or blood gases. In contrast, compared with normal conscious dogs, striking active flow-independent pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/- 0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post-LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial blood gases were unchanged when total pulmonary blood flow was directed to exclusively perfuse the transplanted left lung. Thus, LLA results in both acute and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a useful stable experimental model to assess the specific effects of surgical transplantation on pulmonary vascular regulation.
PEEP is necessary for exogenous surfactant to reduce pulmonary edema in canine aspiration pneumonitis
Authors: Zucker A. R. , Holm B. A. , Crawford G. P. , Ridge K. , Wood L. D. , Sznajder J. I.
Published: December 2017

Alveolar edema inactivates surfactant, and surfactant depletion causes edema by reducing lung interstitial pressure (Pis). We reasoned that surfactant repletion might reduce edema by raising Pis after acute lung injury and that positive end-expiratory pressure (PEEP) might facilitate this effect. One hour after tracheal administration of hydrochloric acid in 18 anesthetized dogs with transmural pulmonary capillary wedge pressure of 8 Torr, the animals were randomized into three groups: in the SURF + PEEP group, 50 mg/kg of calf lung surfactant extract (CLSE) was instilled into each main stem bronchus with 8 cmH2O of PEEP; in the SAL + PEEP group, PEEP was followed by an equal volume of saline (SAL); in the SURF group, CLSE was given without PEEP. After 5 h, edema in excised lungs (wet-to-dry weight ratios) was significantly less in the SURF + PEEP group (9.1 +/- 1.0) than in the other groups (11.3 +/- 1.8 and 11.3 +/- 1.8, respectively). In the SURF + PEEP group, pulmonary venous admixture fell by 6%; this change was different from the 7% increase in the SAL + PEEP group and 40% increase in the SURF group (P less than 0.05). Airway secretions obtained in the SURF + PEEP group had normal minimum surface tensions of 4 +/- 2 mN/m, a value much lower than in SAL + PEEP and SURF groups (32 +/- 4 and 22 +/- 7 mN/m, respectively). We conclude that surfactant normalizes surface tension and decreases transcapillary hydrostatic forces in this lung injury model, thereby reducing edema formation and improving gas exchange. These benefits occur only if surfactant is given with PEEP, allowing surfactant access to the alveoli and/or minimizing its inhibition by edema proteins.
Reductions of neural activities to upper airway muscles after elevations in static lung volume
Authors: St John W. M. , Zhou D.
Published: December 2017

We evaluated the hypothesis that the tonic discharge of pulmonary stretch receptors significantly influences the respiratory-modulated activities of cranial nerves. Decerebrate and paralyzed cats were ventilated with a servo-respirator, which produced changes in lung volume in parallel with integrated phrenic activity. Activities of the facial, hypoglossal, and recurrent laryngeal nerves and nerves to the thyroarytenoid muscle and triangularis sterni were recorded. After a stereotyped pattern of lung inflation, tracheal pressure was held at 1, 2, 4, or 6 cmH2O during the subsequent ventilatory cycle. Increases in tracheal pressure caused progressive reductions in both inspiratory and expiratory cranial nerve activities and progressive elevations in triangularis sterni discharge; peak levels of phrenic activity declined modestly. Similar changes were observed in normocapnia and hypercapnia. We conclude that the tonic discharge of pulmonary stretch receptors is an important determinant of the presence and magnitude of respiratory-modulated cranial nerve activity. This reflex mechanism may maintain upper airway patency and also regulate expiratory airflow.
Acute and long-term TNF-alpha administration increases pulmonary vascular reactivity in isolated rat lungs
Authors: Stevens T. , Janssen P. L. , Tucker A.
Published: December 2017

Tumor necrosis factor-alpha (TNF-alpha) causes pulmonary hypertension and arterial hypoxemia, but the mechanisms are unknown. We conducted two experiments to test the hypothesis that TNF-alpha alters pulmonary vascular reactivity, which in turn could cause either pulmonary hypertension or arterial hypoxemia. In experiment 1, rats were given acute or long-term injections of TNF-alpha (recombinant human) in vivo. Rats treated acutely received either saline or TNF-alpha (40 micrograms/kg iv in saline) 3 min (TNF-3 min; n = 8), 20 min (TNF-20 min; n = 8), or 24 h (TNF-24 h; n = 5) before the lungs were isolated. Rats treated chronically received injections of either saline or TNF-alpha (250 micrograms/kg ip in saline) two times per day for 7 days (TNF-7 days; n = 9). Lungs were isolated and perfused with Earle's salt solution (+2 g/l NaHCO3 + 4 g/100 ml Ficoll), and vascular reactivity was tested with acute hypoxia (3 min; 3% O2) and angiotensin II (ANG II; 0.025–0.40 micrograms). Pulmonary pressor responses to hypoxia were greater (P less than 0.05) in TNF-20 min and TNF-7 day groups. ANG II responses were increased (P less than 0.05) in TNF-7 day rats. In experiment 2, lungs were isolated and perfused and received direct pulmonary arterial injections of TNF-alpha (0.2, 2.0, and 20 micrograms) or saline, after stable responses to hypoxia and ANG II (0.10 microgram) were attained. Reactivity was not different between control and TNF-alpha rats before the injections, but TNF-alpha increased (P less than 0.05) responses to hypoxia and ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of regular voluntary exercise on resting cardiovascular responses in SHR and WKY pregnant rats
Authors: Jones M. T. , Norton K. I. , Black D. M. , Graham R. E. , Armstrong R. B.
Published: December 2017

The purpose of this study was to assess the influence of regular voluntary exercise in pregnant normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats on 1) uteroplacental perfusion and mean arterial pressure in the resting conscious condition and 2) fetal number, fetal weight, and number of fetal resorptions. WKYs and SHRs were randomly assigned to standard cages [CWKY (n = 10); CSHR (n = 6)] or cages with activity wheels [EWKY (n = 7); ESHR (n = 8)]. EWKYs and ESHRs exercised for 12 wk, and then all rats were bred and experiments were conducted on gestational day 17. Resting blood flow (microspheres), heart rate (HR), and mean arterial pressure (Pa) were measured. No significant difference was found in Pa, HR, uterine blood flow (ESHRs 52 +/- 8 ml.min-1.100 g-1; CSHRs 28 +/- 6 ml.min-1.100 g-1), or maternal placental blood flow (ESHRs, 122 +/- 31 ml.min-1.100 g-1; CSHRs 78 +/- 21 ml.min-1.100 g-1) among the groups. Exercise altered the relationship between maternal placental and uterine blood flow and Pa in the SHR; SHRs with lower Pa maintained higher placental and uterine blood flow after training. Before gestation ESHRs ran on average more kilometers per week than EWKYs (43 +/- 3 vs. 34 +/- 4), but during gestation ESHRs averaged fewer kilometers per week than EWKYs (16 +/- 4 vs. 22 +/- 4). Succinate dehydrogenase activity was higher in the white vastus lateralis (1.02 +/- 0.2 mumol cytochrome c reduced.min-1.g wet wt-1) and vastus intermedius (3.1 +/- 0.5 mumol cytochrome c reduced.min-1.g wet wt-1) muscles of ESHRs.(ABSTRACT TRUNCATED AT 250 WORDS)
Urinary leukotriene E4 excretion in exercise-induced asthma
Authors: Taylor I. K. , Wellings R. , Taylor G. W. , Fuller R. W.
Published: December 2017

Recent evidence suggests that the cysteinyl-leukotrienes (LTC4, LTD4, and LTE4) may be important in the pathogenesis of exercise-induced asthma. To evaluate the role of these mediators further, nine asthmatic subjects with exercise-induced bronchoconstriction were studied on two occasions. On visit 1, subjects performed 6 min of treadmill exercise; the mean maximal percent fall in FEV1 was 38.0 +/- 5.3%. On visit 2, maximal bronchoconstriction observed after exercise was matched with aerosolized methacholine. Urine was collected in two 90-min fractions (0–90 and 90–180 min) after challenges and analyzed by high-performance liquid chromatography-radioimmunoassay for LTE4. There were no significant differences in urinary LTE4 excretion between exercise and methacholine challenges for the periods 0-90 min (16.9 +/- 5.4 vs. 20.4 +/- 4.2 ng/mmol urinary creatinine), 90–180 min (24.9 +/- 8.2 vs. 20.1 +/- 5.5), or 0-180 min (21.5 +/- 6.5 vs. 18.8 +/- 4.1). Thus in contrast to allergen-induced bronchoconstriction, there is little evidence for enhanced cysteinyl-leukotriene generation in exercise-induced bronchoconstriction as assessed by urinary LTE4. If local release and subsequent participation of functionally active cysteinyl-leukotrienes in the pathways that ultimately lead to bronchoconstriction after exercise challenge do occur, these are of insufficient magnitude to perturb urinary LTE4 excretion.
Photoaffinity labeling of regulatory subunits of protein kinase A in cardiac cell fractions of rats
Authors: Mednieks M. I. , Popova I. , Grindeland R. E.
Published: December 2017

The regulatory (R) subunits of adenosine 3′,5′,-cyclic monophosphate-dependent protein kinase were measured by photoaffinity labeling in heart tissue of rats flown on COSMOS 2044. Densitometric analyses showed a significant decrease of RII subunits in the particulate cell fraction extract (S2; P less than 0.05 in all cases) when extracts of tissue samples from vivarium controls were compared with those from flight animals. Photoaffinity labeling of the soluble fraction (S1) was unaffected by spaceflight or any of the simulation conditions. This was previously observed in heart muscle of rats flown on Spacelab 3 and COSMOS 1887 missions. A change in either the number or reactivity of the R subunits apparently results from some aspect of spaceflight. Proteins of the S2 fraction constitute a minor (less than 10%) component of the total, whereas the S1 fraction contained most of the cell proteins. No changes were seen when total incorporation of photoaffinity label was calculated on the basis of adrenal gland weights. A negative correlation resulted on comparison of controls with flight, synchronous control, and a tail-suspended simulation group of animals when incorporation of total counts due to azido labeling was based on body weights. Environmental factors that influence organismic responses may alter individual hormonal responses and may be reflected on the molecular level of organization. Conversely, changes in a relatively minor aspect of adenosine 3′,5′-cyclic monophosphate-mediated reactions may be representative of a metabolic effect on an organismic level.
Effect of spaceflight on the extracellular matrix of skeletal muscle after a crush injury
Authors: Stauber W. T. , Fritz V. K. , Burkovskaya T. E. , Ilyina-Kakueva E. I.
Published: December 2017

The organization and composition of the extracellular matrix were studied in the crush-injured gastrocnemius muscle of rats subjected to 0 G. After 14 days of flight on COSMOS 2044, the gastrocnemius muscle was removed and evaluated by histochemical and immunohistochemical techniques from the five injured flight rodents and various Earth-based treatment groups. In general, the repair process was similar in all injured muscle samples with regard to the organization of the extracellular matrix and myofibers. Small and large myofibers were present within an expanded extracellular matrix, indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of nonmuscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well organized and contained more macrophages and blood vessels in the repair region, indicative of a delayed repair process, but did not demonstrate any chronic inflammation. Myofiber repair did vary in muscles from the different groups, being slowest in the flight animals and most complete in the tail-suspended ones.
Respiration and measurement of cardiac output by thermodilution and central or peripheral dye dilution
Authors: Delhaas T. , Mook G. A. , Zijlstra W. G.
Published: December 2017

Cardiac output as measured by indicator dilution methods during artificial ventilation shows differences up to +/- 35%. We studied the influence of spontaneous breathing on measurement of cardiac output by thermodilution (TD) and central (CDD) and peripheral dye dilution (PDD) in seven anesthetized dogs. Injection of indicator was timed at one of five chosen moments in a respiratory cycle. The indicator for TD was also used as solvent for indocyanine green. Results were normalized by the value obtained with injection at inspiratory onset. Results of the central dilution methods showed a slight but not significant difference between values measured with injection at 25 and 75% of the respiratory cycle: 105.7 and 98.0%, respectively, (TD) and 102.3 and 97.2% (CDD). Mean cardiac output determined by TD, CDD, or PDD was not significantly different. We conclude that 1) a reasonable estimate of cardiac output may be obtained by means of a single indicator-dilution curve and 2) the choice of the dilution method may be determined by practical considerations.
Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles in normal men
Authors: Tangel D. J. , Mezzanotte W. S. , Sandberg E. J. , White D. P.
Published: December 2017

Studies of sleep influences on human pharyngeal and other respiratory muscles suggest that the activity of these muscles may be affected by non-rapid-eye-movement (NREM) sleep in a nonuniform manner. This variable sleep response may relate to the pattern of activation of the muscle (inspiratory phasic vs. tonic) and peripheral events occurring in the airway. Furthermore, the ability of these muscles to respond to respiratory stimuli during NREM sleep may also differ. To systematically investigate the effect of NREM sleep on respiratory muscle activity, we studied two tonic muscles [tensor palatini (TP), masseter (M)] and two inspiratory phasic ones [genioglossus (GG), diaphragm (D)], also measuring the response of these muscles to inspiratory resistive loading (12 cmH2O.l-1.s) during wakefulness and NREM sleep. Seven normal male subjects were studied on a single night with intramuscular electrodes placed in the TP and GG and surface electrodes placed over the D and M. Sleep stage, inspiratory airflow, and moving time average electromyograph (EMG) of the above four muscles were continuously recorded. The EMG of both tonic muscles fell significantly (P less than 0.05) during NREM sleep [TP awake, 4.3 +/- 0.05 (SE) arbitrary units, stage 2, 1.1 +/- 0.2; stage 3/4, 1.0 +/- 0.2. Masseter awake, 4.8 +/- 0.6; stage 2, 3.3 +/- 0.5; stage 3/4, 3.1 +/- 0.5]. On the other hand, the peak phasic EMG of both inspiratory phasic muscles (GG and D) was well maintained.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypoxic bronchodilation
Authors: Wetzel R. C. , Herold C. J. , Zerhouni E. A. , Robotham J. L.
Published: December 2017

Recent advances in computed tomographic imaging provide a unique method to serially and directly visualize acute physiological response in the lung. To directly investigate the airway response to hypoxia, high-resolution computed tomographic scans of the lungs of eight intact anesthetized minipigs were serially repeated before, during, and after ventilation with a hypoxic gas mixture (inspired fraction of O2 congruent to 0.07). This approach demonstrated an acute reversible 56 +/- 8% (SE) dilation in large airways (greater than 2 mm diam) and a 90 +/- 15% dilation in small airways (less than 1.99 mm diam) with decreased inspired O2 tension. Of the airways studied, 70 of 76 dilated. Hypoxic bronchodilation may interact with hypoxic pulmonary vasoconstriction in the fundamental physiological process of ventilation-perfusion matching in the lung.
Late potentials in an ovine model of acute transmural myocardial infarction
Authors: Kreiner G. , Gottlieb C. D. , Furukawa S. , Simson M. B. , Tyson G. S. , Edmunds L. H.
Published: December 2017

The development of slow conduction during the first hours of acute transmural myocardial infarction (ATMI) was studied by signal-averaged electrocardiograms (SAE) in 19 adult anesthetized sheep. SAEs were recorded before and after intravenous infusions of lidocaine and bretylium were begun and 10, 30, and 60 min after ATMI produced by ligation of the left anterior descending and second diagonal coronary arteries. Four sheep died promptly of ventricular tachyarrhythmias; two others developed sustained ventricular arrhythmias, which precluded additional data. Biphasic changes in QRS duration, root mean square voltage of the terminal 40 ms of the QRS complex, and duration of terminal low-amplitude (less than 30 microV) signal were observed. Peak changes in conduction occurred 30 min after infarction and regressed toward baseline thereafter. At 30 min, all animals developed late potentials, which were defined as signals that exceeded both after-drug QRS duration and duration of terminal low-amplitude signal less than 30 microV by more than two standard deviations. At 60 min, only 3 of 13 (23%) animals had late potentials. Conduction is slowest 30 min after ATMI in sheep but may not be related to development of ventricular arrhythmias. In five of six sheep (83%), ventricular arrhythmias occurred within 15 min of infarction before peak slowing was observed by SAE.
Breathing patterns during varied activities
Authors: Paek D. , McCool F. D.
Published: December 2017

The level of ventilation attained and breathing patterns adopted during activity have important implications for the distribution and deposition of particles that are inhaled. However, breathing patterns and levels of ventilation adopted during specific physical activities are unknown. We used a noninvasive means of measuring ventilation in subjects performing a variety of activities (bicycling, arm ergometry, lifting, and pulling) during unencumbered (no mouthpiece) breathing and while breathing through a mouthpiece. Minute ventilation (VE), tidal volume (VT), inspiratory time (TI), and total breathing cycle time (TT) were measured initially both spirometrically and from body surface displacements. When a mouthpiece was used, VE and breathing patterns were significantly altered during all activities such that VE, VT, and TT increased by 16, 34, and 20%, respectively. This mouthpiece effect was attenuated at the higher levels of VE. A task dependency of breathing pattern was also noted such that there was much greater variability of VT and TI for a given VE during the lifting activity compared with bicycling (coefficient of variation for VT of 0.39 +/- 0.09 vs. 0.20 +/- 0.07, P less than 0.01; and for TI of 0.38 +/- 0.08 vs. 0.21 +/- 0.08, P less than 0.01). We conclude that a mouthpiece significantly alters breathing pattern during varied types and intensities of activities, and breathing patterns may differ significantly from one activity to another. When the total dose of particulates inhaled in the lung are assessed, the mouthpiece effect and activity effect on breathing pattern must be considered.
Prolonged pulmonary hypertension caused by platelet-activating factor and leukotriene C4 in the rat lung
Authors: Davidson D. , Drafta D.
Published: December 2017

Platelet-activating factor (PAF) and leukotrienes (LTs) are potent pulmonary hypertensive and inflammatory mediators produced by the lung. Previously we showed that a rapid injection of PAF into the pulmonary artery of an isolated rat lung produced an extended elevation in mean pulmonary arterial pressure (PAP). The objective of the present study was to determine whether the extended pressor response induced by PAF was caused by prolonged activation of the 5-lipoxygenase pathway or slow clearance of LTs from the lung parenchyma. Rat lungs were perfused with a nonrecirculating physiological salt solution that contained indomethacin and albumin. Five minutes after a rapid injection of PAF into the pulmonary artery catheter, the following elevations (mean % above baseline) were observed: PAP (83%), LTB4 (3,260%), LTC4 (1,490%), LTD4 (970%), and LTE4 (1,500%). At 20 min these levels declined but were still significantly elevated above baseline. The 5-lipoxygenase inhibitor diethylcarbamazine (DEC), administered before the PAF injection, inhibited the elevations of PAP and all LTs. DEC administration that began 5 min after PAF reduced PAP and only LTC4 levels at 20 min in comparison to lungs with no DEC. The 5-lipoxygenase-activating protein inhibitor MK886, administered orally 2–6 h before perfusion, also inhibited the pressor response to PAF as well as LT production, as did DEC. We conclude that 1) the extended pulmonary hypertension induced by PAF was caused mainly by prolonged activation of 5-lipoxygenase with LTC4 production, 2) the relative overall lung clearance of LTB4, LTD4, and LTE4 was slower than that of LTC4, and 3) LTB4, LTD4, and LTE4 had no appreciable pressor effect.
Microvascular damage in the cortex of cat brain from middle cerebral artery occlusion and reperfusion
Authors: Wilson D. F. , Gomi S. , Pastuszko A. , Greenberg J. H.
Published: December 2017

Oxygen-dependent quenching of phosphorescence provides an extraordinarily powerful method for examining the effects of ischemia/hypoxia on the cortex of the brain. Video camera technology has permitted imaging, through a window in the skull, of the phosphorescence of an oxygen probe, Pd meso-tetra-(4-carboxyphenyl)-porphine, bound to albumin in the blood of anesthetized animals. Images of the phosphorescence taken at different times after the flash of excitation light were used to generate high-resolution two-dimensional maps of the oxygen pressure. These maps show that cortical oxygenation is spatially heterogeneous and that there is dynamic time-dependent modulation of regional oxygen pressures. When the middle cerebral artery was occluded, the region for which it supplied blood became hypoxic, the severity of the hypoxia varying among animals. Release after 60 min of occlusion resulted in a rapid rise of the oxygen pressure to above-normal levels followed by onset of a delayed period of hypoxia. This period is characterized by generally low tissue oxygen pressures with local regions of more severe hypoxia. The delayed period of hypoxia appears to result from damage to the microvasculature, and this microvascular damage is proposed to be an important determinant of the extent of irreversible brain damage.
Reflex bronchodilation produced by phasic ventilation of the lungs
Authors: Coon R. L.
Published: December 2017

The primary purpose of this work was to demonstrate whether oscillation of tracheal pressure in the range of normal breathing frequencies is more effective than static lung inflation in producing reflex bronchodilation. Secondarily, studies were conducted to determine a single factor that would integrate the reflex bronchodilator effects of frequency and tidal volume. Dogs were anesthetized and placed on cardiopulmonary bypass. After tracheal tone had been reflexly enhanced by chemoreceptor stimulation, oscillatory patterns of ventilation were produced around static pressure lung inflations of approximately 5.0 mmHg. The reflex bronchodilation produced by oscillation of lung volume was compared with that produced by static pressure lung inflation. Reflex bronchodilation produced by oscillation of lung volume was greater than that produced by static pressure inflation of the lungs and was strongly related to the maximum first time derivative of pressure (dP/dt, mmHg/s) observed, irrespective of whether the changes in the maximum dP/dt were produced by changes in the frequency or amplitude of the oscillations of tracheal pressure.
Respiratory load compensation. I. Role of the cerebrum
Authors: Xu F. , Taylor R. F. , McLarney T. , Lee L. Y. , Frazier D. T.
Published: December 2017

This study examines the extent to which the cerebrum and other suprapontine structures modulate the respiratory response to added mechanical resistive loads to breathing. Nine adult cats were anesthetized with thiopental sodium, tracheotomized, and instrumented with diaphragm electromyographic (EMGdi) recording electrodes. Two levels of resistive loads and tracheal occlusion were applied at the onset of inspiration in random order before and after decerebration. The integrated signal of the EMGdi (integral of EMGdi) was used to detect changes in respiratory timing and as an index of respiratory motor drive. The results showed that, compared with intact cats, decerebration did not significantly change baseline values for peak integral of EMGdi, respiratory timing, systemic blood pressure, or arterial blood gases. Although the percent changes in the peak integral of EMGdi elicited by the added loads were still significantly greater than those elicited by unloaded control breaths after decerebration, the magnitude of the responses was significantly attenuated at all load levels compared with the intact preparation. It is concluded that the cerebrum and/or other suprapontine structures provide information that is facilitatory to the respiratory pattern generator with little effect on timing.