bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracheobronchial perfusion during exercise in ponies
Authors: Manohar M.
Published: December 2017

Tracheobronchial circulation during exercise has previously not been examined. Therefore blood flow to the trachea and bronchi (up to 7th generation of branching) was studied in seven healthy adult ponies at rest and during the 3rd and 10th min of exercise performed at a treadmill speed setting of 25 km/h. The ambient air temperature varied from 19 to 20 degrees C and humidity from 35 to 45%. To determine blood flow radionuclide-labeled 15-microns-diameter microspheres were injected into the left ventricle via a catheter advanced from the left carotid artery (exposed using local anesthesia), and a reference sample was obtained from the aorta. Adequate mixing of microspheres with blood was demonstrated by similar perfusion values for left and right kidneys. Exercise increased heart rate (194 +/- 9 and 200 +/- 7 beats/min) and mean aortic pressure (169 +/- 8 and 156 +/- 4 mmHg) of ponies at 3rd and 10th min. Tracheal blood flow (6.7 +/- 0.5 ml.min-1 x 100 g-1) of resting ponies was only one-third of the bronchial blood flow (21.6 +/- 4.9 ml.min-1 x 100 g-1) Significant changes in tracheal perfusion did not occur at 3rd or 10th min of exercise. Although bronchial perfusion also did not change at the 3rd min of exercise, it rose dramatically to 202.8 +/- 30.3 ml.min-1 x 100 g-1 during the 10th min. Concomitantly, renal blood flow decreased at 10th min of exertion. The large increase in bronchial blood flow at 10th min of exertion may have been necessitated by the need to help dissipate body heat.
Pulmonary diffusing capacities for nitric oxide and carbon monoxide determined by rebreathing in dogs
Authors: Meyer M. , Schuster K. D. , Schulz H. , Mohr M. , Piiper J.
Published: December 2017

Pulmonary diffusing capacities (DL) of NO and CO were determined simultaneously from rebreathing equilibration kinetics in anesthetized paralyzed supine dogs (mean body wt 20 kg) after denitrogenation (replacement of N2 by Ar). During rebreathing the dogs were ventilated in closed circuit with a gas mixture containing 0.06% NO, 0.06% 13C18O, and 1% He in Ar for 15 s, with tidal volume of 0.5 liter and frequency of 60/min. The partial pressures of NO, 13C18O, 16O18O, N2, Ar, CO2, and He in the trachea were continuously analyzed by mass spectrometry. Measurements were performed at various O2 levels characterized by the mean end-expired PO2 during rebreathing (PE'O2). In control conditions ('normoxia,” PE'O2 = 67 +/- 8 Torr) the following mean +/- SD values were obtained (in ml.min-1.Torr-1): DLNO = 52.4 +/- 11.0 and DLCO = 15.4 +/- 2.9. In hypoxia (PE'O2 = 24 +/- 7 Torr) DLNO increased by 11 +/- 8% and DLCO by 19 +/- 10%, and in hyperoxia (PE'O2 = 390 +/- 26 Torr) DLNO decreased to 87 +/- 3% and DLCO to 56 +/- 8% with respect to values in normoxia. DLNO/DLCO of 3.24 +/- 0.06 (hypoxia), 3.38 +/- 0.31 (normoxia), and 5.54 +/- 1.04 (hyperoxia) were significantly higher than the NO/CO Krogh diffusion constant ratio (1.92) predicted for simple diffusion through aqueous layers. With increasing O2 uptake elicited by 2,4-dinitrophenol, DLNO and DLCO increased and DLNO/DLCO remained close to unchanged. The results suggest that the combined effects of diffusion and chemical reaction with hemoglobin limit alveolar-capillary transport of CO. If it is assumed that reaction kinetics of NO with hemoglobin (known to be extremely fast) are not rate limiting for NO uptake, the contribution of the slow chemical reaction with hemoglobin to the total CO uptake resistance (= 1/DLCO) was estimated to be 38% in hypoxia, 41% in normoxia, and 64% in hyperoxia. The various factors expected to restrict the validity of this analysis are discussed, in particular the effects of functional inhomogeneity.
Respiratory burst in alveolar macrophages of diabetic rats
Authors: Mohsenin V. , Latifpour J.
Published: December 2017

Bactericidal ability of alveolar macrophages is depressed in rats with diabetes mellitus. To define the mechanism of this abnormality, we measured the parameters of respiratory burst in alveolar macrophages, peripheral blood monocytes, and neutrophils of rats 8 wk after the induction of diabetes by streptozocin. Superoxide anion (O2-.) generation during basal conditions and after stimulation with phorbol myristate acetate (PMA) was measured as superoxide dismutase-inhibitable cytochrome c reduction. NADPH, the principal substrate for NADPH-oxidase-dependent O2-. generation, was measured in the alveolar macrophages and quick-frozen lungs by the enzyme-cycling method. O2-. generation after PMA was significantly lower in the alveolar macrophages of diabetics than in the controls (14.4 +/- 2.0 nmol.10(6) cells-1.20 min-1 vs. 26.2 +/- 1.9, P less than 0.05). Conversely the peripheral blood monocytes of diabetics demonstrated an enhanced O2-. production after PMA stimulation. There was no significant difference in the neutrophil O2-.-generation between the groups. The alveolar macrophage NADPH (control 0.44 +/- 0.15 nmol/10(6) cells vs. diabetic 0.21 +/- 0.04, P less than 0.05) and lung tissue NADPH levels (control 81.4 +/- 16.3 nmol/g dry wt vs. diabetic 35.8 +/- 20.5, P less than 0.05) were significantly lower in the diabetics than in the controls. These data indicate that the O2-.-generating capacity of alveolar macrophages is markedly depressed in diabetes, whereas their precursors, monocytes, are primed to generate O2-. with PMA stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of serotonin on expiratory pulmonary resistance in cats
Authors: Skaburskis M. , Shardonofsky F. , Milic-Emili J.
Published: December 2017

In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow (IVPF) relationships of the lung were studied under control conditions and during serotonin-induced bronchoconstriction. At the end of a tidal inspiration, airway opening pressure was set between +3 and -15 cmH2O for single tidal expirations. After control measurements, animals were treated with progressively increasing doses of intravenous serotonin (10, 20, 50, and 100 micrograms.kg-1.min-1) and all measurements were repeated at each dose. No animal became flow limited during passive expiration against atmospheric pressure. Disregarding flow-limited segments, IVPF plots for three lung volumes showed that the resistive pressure-flow relationships were curvilinear under all conditions, thus fitting Rohrer's equation. Under control conditions and during the lowest dose of serotonin, the volume dependence of pulmonary resistance (RL) tended to balance its flow dependence so that during lung deflation against atmospheric pressure RL remained nearly constant. However, as bronchoconstriction became more pronounced, RL often increased disproportionately at the lower lung volumes. Changes in expiratory RL with serotonin relative to control values varied according to the flow rates used to make comparisons. The technique used to determine RL will partly determine the results obtained.
Triacylglycerol metabolism in rat skeletal muscle after exercise
Authors: Pearsall D. , Palmer W. K.
Published: December 2017

The temporal relationships between triacylglycerol (TG) content and TG lipase activity in slow-twitch (STR) and fast-twitch red (FTR) muscles were determined in rats during recovery from a 2-h swim. Immediately after the exercise, plasma free fatty acid (FFA) was elevated and glycogen concentrations were decreased. TG content was decreased 40% in STR muscle and reduced 45% in FTR muscle. The TG concentration of STR muscle increased in a linear fashion throughout recovery so that control levels were reached within the first 24 h after exercise. TG lipase activity of STR muscle was elevated 36% above control immediately after the swim and continued to increase to 84% above control 24 h after the work. In STR muscle there was a net synthesis of TG, while lipase activity was elevated above that measured in muscle of control rats. TG content of FTR muscle remained 45% below control throughout the first 24 h of recovery, and TG lipase activity increased from 26% (P greater than 0.05) greater than control immediately after exercise to threefold above control 24 h after work. All parameters returned to control levels by 48 h of recovery. These data indicated that a net TG synthesis occurs in STR muscle when lipolytic activity is elevated. In FTR muscle, however, a gradual increase in TG lipase activity that occurs during the first 24 h of recovery accompanies a TG concentration well below the control level throughout this same time frame.(ABSTRACT TRUNCATED AT 250 WORDS)
Attenuation of reflex pressor and ventilatory responses to static muscular contraction by intrathecal opioids
Authors: Hill J. M. , Kaufman M. P.
Published: December 2017

We have tested the hypothesis that intrathecal injections of opioid peptides attenuate the reflex pressor and ventilatory responses to static contraction of the triceps surae muscles of chloralose-anesthetized cats. We found that before intrathecal injections of [D-Ala2]Met-enkephalinamide (100 micrograms in 0.2 ml), static contraction increased mean arterial pressure and ventilation by 32 +/- 5 (SE) mmHg and 227 +/- 61 (SE) ml/min, whereas after injection of this opioid peptide, static contraction increased mean arterial pressure and ventilation by only 15 +/- 5 mmHg and 37 +/- 33 ml/min, respectively. The attenuation of both the pressor and ventilatory responses to static contraction by [D-Ala2]Met-enkephalinamide were statistically significant (P less than 0.05). Moreover, the attenuation was probably not caused by an opioid-induced withdrawal of sympathetic outflow because [D-Ala2]Met-enkephalinamide had no effect on the pressor and ventilatory responses evoked by high-intensity electrical stimulation of the central cut end of the sciatic nerve. In addition, intrathecal injection of peptides that were highly selective agonists for either the opioid mu- or delta-receptor attenuated the reflex responses to static contraction. Naloxone (1,000 micrograms), injected intrathecally, prevented the attenuation of the reflex responses to contraction by opioid peptides. We speculate that the opioid-induced attenuation of the reflex pressor and ventilatory responses to static contraction may have been due to suppression of substance P release from group III and IV muscle afferents.
Postural effects on measurements of tidal volume from body surface displacements
Authors: Paek D. , Kelly K. B. , McCool F. D.
Published: December 2017

Tidal volume measurements based on the sum of volume displacements of the rib cage (RC) and abdomen (Ab) are limited in accuracy when changes in posture occur. To elucidate the underlying sources of error, five subjects performed spinal flexion-extension isovolume maneuvers and then performed Konno-Mead isovolume maneuvers at different lung volumes while erect, with the spine fully flexed, and at intermediate degrees of spinal flexion. RC and Ab dimensions were measured with respiratory inductance plethysmograph belts, and spinal flexion was assessed by a pair of magnetometers measuring the xiphi-Ab distance (Xi). RC and Ab volume-motion coefficients (alpha and beta, respectively) were calculated from the slope (-beta/alpha) of the Konno-Mead isovolume lines. We found that 1) spinal flexion with constant lung volume mainly increases the RC dimension, thereby displacing the Konno-Mead isovolume lines, and 2) spinal flexion decreases the -beta/alpha by decreasing beta. The error related to displacement averaged 28.4 +/- 15% of vital capacity, whereas the error related to changes in beta averaged 14 +/- 6% (SD). The systematic relationship of these errors with the degree of spinal flexion provides a mechanism whereby the addition of Xi to RC and Ab displacements significantly (P less than 0.001) improves volume estimates.
Left ventricular hemodynamics during exercise recovery
Authors: Johnson E. C. , Hudson T. L. , Greene E. R.
Published: December 2017

The directional response of human left ventricular stroke volume during exercise recovery is unclear. Stroke volume has been reported to increase and decrease over exercise values during early recovery. The confounding variable may be posture. With the use of pulsed Doppler ultrasound, we tested the hypothesis that there is a significant difference between seated and supine stroke index (SI) during passive recovery from seated ergometer exercise. Thirteen subjects aged 26 +/- 2 yr performed two seated cycle ergometer exercise tests to 70% of predicted maximum heart rate (HR). Recovery was supine on one test and seated on the other. Cardiac index (CI), HR, and SI were calculated during rest, exercise, and 10 min of recovery. At rest, SI and CI were significantly (P less than 0.01) less and HR significantly (P less than 0.01) greater when the subjects were seated than when they were supine. At the last exercise work load, no significant differences were found in any measured variable between tests. During recovery, supine SI was maximal 180 s postexercise (99 +/- 14 ml/m2) and exceeded (P less than 0.01) resting supine (81 +/- 14 ml/m2) and peak exercise (77 +/- 14 ml/m2) SI by 22 and 29%, respectively. Seated SI was constant at peak exercise levels for 2 min. Seated and supine recovery CI never exceeded exercise values. Systolic and diastolic blood pressure recovery curves were similar in the two postures. We conclude that posture significantly affects SI during recovery from submaximal seated exercise. These results have implications for choice of recovery posture after stress testing in cardiac patients where it is desirable to minimize ventricular loading.
Mechanical alterations in sensitized canine saphenous vein
Authors: Wang Z. , Seow C. Y. , Kepron W. , Stephens N. L.
Published: December 2017

Because it is likely that antigen sensitization is not restricted to airway smooth muscle but probably involves all tissues in the animal, we decided to test the hypothesis that saphenous vein from pollen extract-sensitized dogs is sensitized and is, in addition, mechanically altered. To this end, we studied responses to specific antigen challenge and length-tension and force-velocity relationships in sensitized (SSV) and control saphenous veins (CSV). The antigen challenge revealed that the venous smooth muscle was strongly sensitized and developed a Schultz-Dale response, the two main mediators of which were histamine and norepinephrine. Length-tension relationship studies showed that whereas there is no difference in maximum isometric tension development between SSV and CSV [93.95 +/- 7.34 and 87.86 +/- 4.00 (SE) mN/mm2, respectively], SSV exhibited a significantly greater maximum isotonic shortening capacity of 0.613 +/- 0.009 optional length (lo) vs. 0.578 +/- 0.012 lo for CSV. Unloaded shortening velocity (Vo), which reflects the cross-bridge cycling rate, was determined at different times after the onset of electrical stimulation. Maximum Vo was attained early (5 s) in the contraction; a 15% decline in Vo was observed at the plateau of the contraction (15 s). At 5 s, Vo of SSV (0.316 +/- 0.019 lo/s) was significantly higher than that of CSV (0.269 +/- 0.018 lo/s), although Vos were same at 15 (0.249 +/- 0.021 lo/s for SSV and 0.237 +/- 0.019 lo/s for CSV). The increase in shortening likely results from th e increase in the early cross-bridge cycling rate because our studies show that the bulk of shortening occurs in the first 5 s.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of CPAP on respiratory effort and dyspnea during exercise in severe COPD
Authors: Petrof B. J. , Calderini E. , Gottfried S. B.
Published: December 2017

Recent work has demonstrated the ability of continuous positive airway pressure (CPAP) to relieve dyspnea during exercise in patients with severe chronic obstructive pulmonary disease (COPD). The present study examined the effects of CPAP (7.5-10 cmH2O) on the pattern of respiratory muscle activation and its relationship to dyspnea during constant work load submaximal bicycle exercise [20 +/- 4.8 (SE) W] in eight COPD patients (forced expiratory volume in 1 s = 25 +/- 3% predicted). Tidal volume, respiratory rate, minute ventilation, and end-expiratory lung volume increased with exercise as expected. There was no change in breathing pattern, end-expiratory lung volume, or pulmonary compliance and resistance with the addition of CPAP. CPAP reduced inspiratory muscle effort, as indicated by the pressure-time integral of transdiaphragmatic (integral of Pdi.dt) and esophageal pressure (integral of Pes.dt, P less than 0.01 and P less than 0.05, respectively). In contrast, the pressure-time integral of gastric pressure (integral of Pga.dt), used as an index of abdominal muscle recruitment during expiration, increased (P less than 0.01). Dyspnea improved with CPAP in five of the eight patients. The amelioration of dyspnea was directly related to reductions in integral of Pes.dt (P less than 0.001) but inversely related to increases in integral of Pga.dt (P less than 0.01). In conclusion, CPAP reduces inspiratory muscle effort during exercise in COPD patients. However, the expected improvement in dyspnea is not seen in all patients and may be explained by more marked increases in expiratory muscle effort in some individuals.
Effects on breathing of rostral pons glutamate injection during opossum development
Authors: Farber J. P.
Published: December 2017

To determine whether pathways from the rostral pons, capable of influencing breathing, were present in immature mammals, the excitatory amino acid glutamate (sodium salt) was pressure injected in very small volumes into the rostral pons of suckling and adult opossums. The youngest animals tested were approximately 3 wk old (1.5-2.9 g). Animals were anesthetized with the thiobarbituric acid derivative, Inactin, and the electromyogram of the diaphragm was used to assess changes in breathing rhythm and ventilatory output. Glutamate concentrations of 50, 150, and 1,000 mM were injected into the rostral pons. Active sites were generally located between parabrachial and either lateral lemniscal or trigeminal nuclei. Effects of glutamate in opossums of all ages included changes in diaphragm activity and respiratory timing over several breaths. In the youngest animals, a very high incidence of apnea occurred as an initial response (17 of 20 sites) at the 1,000 mM concentration. The high incidence of apneic response in the youngest animals suggests that strong activation of rostral pontine neurons can more easily disrupt respiratory output; a physiological circumstance of such activation might include a diving response stimulated by trigeminal afferents.
Pulmonary microcirculatory kinetics of neutrophils deficient in leukocyte adhesion-promoting glycoproteins
Authors: Yoder M. C. , Checkley L. L. , Giger U. , Hanson W. L. , Kirk K. R. , Capen R. L. , Wagner W. W.
Published: December 2017

The mechanism that causes neutrophils to sequester in the pulmonary circulation is unknown. Because the CD11/CD18 glycoprotein family on the surface membrane of neutrophils participates in many adhesive interactions with the endothelium, we investigated the role of these proteins in the intravascular sequestration of pulmonary neutrophils. Neutrophils were isolated from normal dogs and from the only living dog known to have leukocyte adhesion deficiency disease, an inherited deficiency of the CD11/CD18 adhesion family. The neutrophils were labeled with fluorescein dye, injected into normal recipient dogs, and their passage through the pulmonary microcirculation was recorded by in vivo videofluorescence microscopy through a transparent thoracic window. Transit times for normal and deficient neutrophils were similar over a wide range of hemo-dynamic conditions. Activation by zymosan-activated plasma, which increases the surface membrane expression of CD11/CD18, prolonged the transit of normal neutrophils but did not alter the transit time of the deficient neutrophils. These results indicate that neutrophil CD11/CD18 adhesion-promoting glycoproteins are not involved in the normal pulmonary sequestration of neutrophils but have a significant role in the arrest of activated neutrophils in the pulmonary capillaries.
In vitro tracheal responses from mice chosen for in vivo lung cholinergic sensitivity
Authors: Weinmann G. G. , Black C. M. , Levitt R. C. , Hirshman C. A.
Published: December 2017

We selected two inbred strains of mice based on their different in vivo lung responses to intravenous acetylcholine for studies on the in vitro tracheal responses to contractile and relaxing agents. In addition, we studied the role of cyclooxygenase products on the in vitro responses. Tracheal rings were contracted with increasing concentrations of carbachol and KCl and relaxed with increasing concentrations of isoproterenol after contraction with carbachol at the concentration that produced 30, 50, and 70% of the maximal contraction (EC30, EC50, and EC70, respectively) and KCl at the EC50. Half the tracheae simultaneously underwent the same protocols after pretreatment with indomethacin (3 X 10(-6) M). Despite a severalfold difference in the maximal response to cholinergic agents in vivo, there were no significant differences between the strains in the tracheal responses to carbachol (P = 0.78) or KCl (P = 0.13) in vitro. Both strains showed inhibition of the isoproterenol relaxation by carbachol (P less than 0.0001). Multiple linear regression analysis showed that the strain that was more sensitive to carbachol in vivo was also more sensitive to isoproterenol in vitro after carbachol contraction (P = 0.014). The greater isoproterenol sensitivity of the tracheae from this strain was not present after contraction with KCl, nor were these tracheae more sensitive to relaxation with sodium nitroprusside. Indomethacin pretreatment of the tissues in vitro augmented the maximal response and the sensitivity to carbachol (P less than 0.001) and KCl (P = 0.0006), and this effect was similar in both strains. Evaluation of isoproterenol relaxation after indomethacin pretreatment was confounded by the lower concentrations of carbachol needed for contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Nature of pulmonary hypertension in canine oleic acid pulmonary edema
Authors: Leeman M. , Lejeune P. , Closset J. , Vachiery J. L. , Melot C. , Naeije R.
Published: December 2017

It has recently been suggested that pulmonary hypertension secondary to oleic acid lung injury mainly results from an increase in the critical closing pressure of the pulmonary vessels [Boiteau et al., Am. J. Physiol. 251 (Heart Circ. Physiol. 20): H1163-H1170, 1986]. To further test this hypothesis, we studied 1) the pulmonary arterial pressure- (Ppa) flow (Q) relationship with left atrial pressure (Pla) kept constant (n = 7) and 2) the Ppa-Pla relationship with Q kept constant (n = 9) in intact anesthetized and ventilated dogs before and after lung injury induced by oleic acid (0.09 ml/kg iv). Q was manipulated by use of a femoral arteriovenous bypass and a balloon catheter inserted in the inferior vena cava. Pla was manipulated with a balloon catheter placed by thoracotomy in the left atrium. Ppa-Q plots were rectilinear before as well as after oleic acid. Before oleic acid, the extrapolated pressure intercept of the Ppa-Q plots approximated Pla. Oleic acid administration resulted in a parallel shift of the Ppa-Q plots to higher pressure; i.e., the pressure intercept increased, whereas the slope was not modified. Increasing Pla at constant Q before oleic acid led to a proportional augmentation of Ppa. After oleic acid, however, changes in Pla over the same range affected Ppa only at the highest levels of Pla. These results suggest that oleic acid lung injury increases the critical closing pressure that exceeds Pla, becomes the effective outflow pressure of the pulmonary circulation, and is responsible for the pulmonary hypertension.
Impact of reduced cytochrome oxidase activity on peak oxygen consumption of muscle
Authors: McAllister R. M. , Ogilvie R. W. , Terjung R. L.
Published: December 2017

The impact of reduced muscle oxidative capacity on peak oxygen consumption and isometric performance was evaluated using an isolated rat hindlimb preparation perfused with a high oxygen delivery. Capacity for electron transport was reduced with chloramphenicol (CAP), an inhibitor of mitochondrial gene-coded protein synthesis. The activity of cytochrome oxidase, a mitochondrial cristae component, was reduced approximately 45% (P less than 0.005) in the mixed-fiber-type plantaris muscle. Several facets of muscle remodeling were also evident with the 10- to 14-day CAP treatment, including decreased citrate synthase activity, increased capillarity, and increased numbers of type IIc fibers. Perfusion of CAP (n = 6) and control (n = 7) rat hindlimbs of similar size with similar total flows (10-11 ml/min) and oxygen contents (20-21 vol%) resulted in similarly high oxygen deliveries to contracting muscles of the hindlimbs (CAP, 9.66 +/- 0.83 mumols.min-1.g-1; control, 8.74 +/- 0.75). Performance of the gastrocnemius-plantaris-soleus group declined in a similar fashion for both groups during increasingly intense near-steady-state tetanic contraction (100 ms at 100 Hz) conditions of 4, 8, 15, 30, 45, and 60 per minute. Oxygen consumption was similar for both groups at rest and increased similarly at each contraction condition. Peak oxygen consumption was not different between CAP (5.34 +/- 0.55 mumols.min-1.g-1) and control (5.74 +/- 0.43) groups and required only 56-68% of the oxygen delivered. This implies that rat skeletal muscle can suffer a significant reduction in its electron transport capacity without impairing peak oxygen consumption and muscle performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Association between muscle acetyl-CoA and acetylcarnitine levels in the exercising horse
Authors: Carlin J. I. , Harris R. C. , Cederblad G. , Constantin-Teodosiu D. , Snow D. H. , Hultman E.
Published: December 2017

Treadmill exercise of 2-min duration and increasing intensity resulted in increased formation of acetyl-CoA and acetylcarnitine in working muscle of Thoroughbred horses. At high work intensities a plateau was reached for both acetyl-CoA (approximately 50 mumols/kg dry muscle) and acetylcarnitine (approximately 20 mmol/kg dry muscle). Postexercise concentrations were significantly (P less than 0.001) correlated; [acetylcarnitine] = 349.[acetyl-CoA] + 2.4. The results indicate that approximately 350 mumols acetylcarnitine were accumulated for every 1 mumol acetyl-CoA. Under the conditions of exercise used it is probable that most of the acetyl-CoA formed is generated through the intramitochondrial decarboxylation of pyruvate. The acetyl groups of acetyl-CoA are apparently redistributed throughout the whole cell through formation of acetylcarnitine, which readily transverses the mitochondrial membrane. Despite the redistribution, however, the close correlation between acetylcarnitine and acetyl-CoA would indicate that equilibrium was maintained and that neither acetylcarnitine transferase nor carnitine/acetylcarnitine translocase were rate limiting. There is some question as to whether the changes observed relate directly to exercise itself or to the state in muscle 10 s or more after exercise.
Exercise-induced swelling of rat soleus muscle: its relationship with intramuscular pressure
Authors: Peeze Binkhorst F. M. , Slaaf D. W. , Kuipers H. , Tangelder G. J. , Reneman R. S.
Published: December 2017

Exercise-induced tissue swelling and its possible consequence for tissue pressure were studied in rat soleus muscle. Rats ran for 75 min on a belt with a 10 degree positive incline. Wet weights of cryofixed soleus muscles were increased at 3 (16%), 6 (28%), 9 (16%), and 24 (16%) h after running compared with those of nonexercised controls. The transient increase in muscle wet weight correlated in time with an increase in muscle volume. Muscle fiber swelling accounted for most of the muscle swelling in absolute terms because of the large proportion (approximately 90%) of the muscle volume composed of fibers, but swelling of the interstitium was about twofold larger than fiber swelling per unit area. Muscle fiber degeneration was most frequently found at the end of the observation period, i.e., 24 h after running. The muscle swelling was not associated with an increase in intramuscular pressure. During the postexercise measuring period (18 min to 24 h after exercise), intramuscular pressures of exercised rats (1.3 +/- 0.3 mm Hg) did not differ significantly from control values (1.0 +/- 0.2 mm Hg). These findings indicate that increased intramuscular pressure is not responsible for the muscle fiber degeneration found in rat soleus muscle 24 h after endurance running.
Effects of tracheal irritation and hypercapnia on tracheal smooth muscle in humans
Authors: Nishino T. , Sugimori K. , Hiraga K. , Honda Y.
Published: December 2017

Both hypercapnia and tracheal irritation are known to constrict the airways in animals. To see whether similar responses occur in humans, we investigated tracheal smooth muscle (TSM) responses to hypercapnia and tracheal irritation with water in 14 paralyzed and anesthetized humans. TSM tone was monitored by measuring the pressure in the saline-filled cuff of the endotracheal tube. Although, tracheal irritation caused TSM constriction in 10 of 14 patients, 4 patients showed no TSM response. Administration of intravenous atropine attenuated the TSM constriction response. Hypercapnia did not cause any change in TSM tone in any of the 14 patients. These results indicate that in paralyzed and anesthetized humans, there exist interindividual differences in the TSM responses to tracheal irritation and that hypercapnia cannot be an effective stimulus for the TSM constriction.
Mucus-depleted frog palate as a model for the study of mucociliary clearance
Authors: Rubin B. K. , Ramirez O. , King M.
Published: December 2017

To better understand the frog palate model of mucociliary transport, we measured the transport rate of mucus (MTR) from the leopard frog, Rana pipiens, and from the bullfrog, R. catesbeiana, recorded the stability of the MTR over a period of hours and days and over the course of 1 yr, and measured the viscoelasticity, percent solid composition, and spinnability (filance) of mucus from both species. Bullfrog mucus was less rigid than leopard frog mucus (log G* at 1 rad/s 2.09 vs. 2.61; P less than 0.01) and had a higher viscosity-to-elasticity ratio (tan delta at 1 rad/s 0.36 vs. 0.26; P less than 0.05). It also had a lower solids content (8.71 vs. 13.72%; P = 0.02), and there was a trend to lower spinnability for bullfrog mucus (filance 26.7 vs. 33.5 mm). These data suggest that bullfrog mucus has viscoelastic properties similar to normal mammalian respiratory mucus and leopard frog mucus has viscoelasticity similar to sputum samples. MTR was significantly slower in the winter than in the summer months (17 vs. 30 mm/min; P less than 0.0001). Although the leopard frog palate could be used for at least 7 consecutive days without exhaustion, bullfrog palates could be used for only 5 days. Palates of either species could generally be tested for 6 h/day without a significant decrease in MTR. These data clarify some of the sources of variability in the use of this system and suggest methods of standardization.
Beta-blockade with intrinsic sympathetic activity modifies favorably exercise-induced changes in plasma lipoproteins
Authors: Van Nguyen P. , Cleroux J. , Peterson M. , Leenen F. H.
Published: December 2017

The effects of beta-blockade on acute exercise-induced changes in plasma lipoprotein levels were investigated in 12 healthy normotensive subjects by use of beta-blockers of three types: a nonselective agent, a beta 1-selective agent, and a nonselective agent with intrinsic sympathomimetic activity (ISA) or partial agonist activity. Each subject received each drug and a placebo for 1 wk each according to a randomized double-blind crossover design. After placebo, exercise caused 10-20% increases in total plasma cholesterol and the high-density lipoprotein (HDL)-cholesterol fraction. The total-to-HDL cholesterol ratio fell, particularly during the 30-min recovery phase. Pindolol treatment increased resting values of HDL cholesterol (from 43 +/- 4 to 48 +/- 4 mg/dl) and potentiated the response to exercise (to 59 +/- 5 vs. 51 +/- 4 mg/dl after placebo). The total-to-HDL cholesterol ratio was significantly lower after pindolol treatment than after placebo. In contrast, neither atenolol nor timolol affected exercise-induced changes in plasma lipoprotein levels. The effects of pindolol on other study parameters (exercise endurance and exercise-induced increases in systolic blood pressure, heart rate, and potassium) were similar to the effects of the nonselective agent, timolol. We conclude that the effects of pindolol on the plasma lipid profile are due to its ISA and that the process activated (possibly plasma lecithin-cholesterol acyltransferase activity) is under minimal sympathetic control and, therefore, sensitive to the expression of ISA both at rest and in response to exercise.
Effects of sleep-induced increases in upper airway resistance on ventilation
Authors: Henke K. G. , Dempsey J. A. , Kowitz J. M. , Skatrud J. B.
Published: December 2017

To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Segmental vascular resistance in postobstructive pulmonary vasculopathy
Authors: Michel R. P. , Hakim T. S. , Petsikas D.
Published: December 2017

Chronic unilateral pulmonary arterial ligation has been touted as a model of arteriopathy resulting in a tremendous increase in anastomotic bronchial flow (Qbr) via collaterals. To investigate its effects on the pulmonary vasculature, we ligated the left main pulmonary artery of seven dogs and 120 days later pump perfused their left lower lobes (LLL) via a cannula in the pulmonary artery at pulmonary arterial flow (Qpa) of 250 ml/min. We measured Qbr (330 ml/min) and compared LLL with control contralateral right lower lobes (RLL) and three LLL from normal dogs. Pressure-flow (P-Q) curves were obtained by varying Qpa. With arterial and venous occlusion we measured total, arterial, venous, and middle segment resistances under baseline conditions, after serotonin and histamine, either with or without Qpa and with antegrade and retrograde Qbr. Light microscopy was done postmortem. The slope of the P-Q curve was 33.4 mmHg.l-1.min in the ligated lobes compared with 15.9 in the controls, attributable by the occlusion technique mainly to a rise in arterial resistance (22.4 mmHg.l-1.min compared with 7.4 in the controls) with a small rise in venous resistance. This was explained by significant arterial medial muscle thickening and some loss of LLL volume. The arterial segment was markedly hypersensitive to serotonin, and the venous segment was mildly hypersensitive to histamine compared with controls. The occlusion data also enabled us to model the point of entry of the bronchial circulation into the pulmonary circuit at the precapillary level and to calculate bronchial vascular resistance. We conclude that postobstructive vasculopathy substantially raises pulmonary vascular resistance, mainly upstream from the site of entry of the bronchial circulation. The role of the latter may be to keep it from rising excessively in the segments it perfuses, i.e., the middle and venous ones.
Collagenase activity in anterior cruciate ligament: protective role of the synovial sheath
Authors: Amiel D. , Billings E. , Harwood F. L.
Published: December 2017

To evaluate the protective role of the synovial sheath of the anterior cruciate ligament (ACL), we have developed a synovectomy model that exposes the ACL substance to the intra-articular environment with and without hemarthrosis. Histology and the level of collagenase activity were studied to assess intrinsic ligament alterations. The treatment groups studied were as follows: ACLs of sham-operated knees receiving arthrotomy only, ACLs of knees receiving arthrotomy and acute hemarthrosis, ACLs of knees that underwent synovectomy, and ACLs of knees that underwent both synovectomy and acute hemarthrosis. All animals were killed 10 days postoperatively for gross, histological, and biochemical assessment. Histologically at 10 days ACLs experiencing synovectomy and ACLs having synovectomy plus hemarthrosis revealed marked hypocellular areas. Biochemical results indicate that synovectomy is the treatment mainly responsible for the observed increase in ACL collagenase activity. Hemarthrosis alone clearly had no effect, although hemarthrosis coupled with synovectomy appeared to further increase the amount of active collagenase present in the ACLs. This study indicates that, with exposure of the ACL substance to the synovial fluid or with hemarthrosis after synovectomy, there is an increase in the degradative activity of the ACL. The protective role of the synovial sheath suggests that the synovial sheath injury associated with acute ACL rupture may allow for exposure of the ligament substance to the degradative effects of the synovial environment and associated hemarthrosis.
Experimental cardiac tamponade: correlation of pressure, flow velocity, and echocardiographic changes
Authors: Cohen M. L.
Published: December 2017

Seven episodes of experimental cardiac tamponade were induced in five anesthetized closed-chest dogs. Simultaneous pericardial and intracavitary pressures were synchronized with superior vena caval and transvalvular pulsed-Doppler flow tracings. The earliest indication of tamponade was the development of a negative transmural right atrial pressure that occurred during early ventricular diastole and was associated with echocardiographic evidence of right atrial collapse. This was also associated with reversal of diastolic flow in the superior vena cava and with diminished early diastolic flow velocity across the tricuspid as well as the mitral valve. During more advanced cardiac tamponade, the transmural right atrial pressure became negative during both early and late ventricular diastole as well as during isovolumic ventricular systole. This was associated with a disappearance of early diastolic ventricular filling and right ventricular diastolic collapse as observed on two-dimensional echocardiography. In hypotensive cardiac tamponade (cardiac output diminished by 70%), the decreased transmural right atrial pressure that developed during ventricular systole was accompanied by diminished antegrade flow in the superior vena cava. In advanced and hypotensive tamponade, ventricular filling occurred mainly during atrial contraction.
Muscle buffer capacity estimated from pH changes during rest-to-work transitions
Authors: Adams G. R. , Foley J. M. , Meyer R. A.
Published: December 2017

Gated phosphorus nuclear magnetic resonance (31P-NMR) spectra were acquired after 5 or 9 s of 5-Hz stimulation in rat and cat skeletal muscles, respectively. Net phosphocreatine (PCr) hydrolysis was associated with an intracellular alkalinization of 0.08 +/- 0.01 and 0.05 +/- 0.003 pH units in isolated perfused cat biceps and soleus, respectively, and 0.12 +/- 0.02 in the superficial predominantly fast-twitch white portion of gastrocnemius of anesthetized rats. The net change in [H+] expected from PCr hydrolysis was calculated, and apparent buffer capacity (beta) in intact muscles was calculated from beta = delta [H+]/delta pH. The beta of the same muscle types was also estimated from titration of muscle homogenates between pH 6.0 and 8.0. The contribution of Pi to total beta of the homogenates was subtracted to ascertain the non-Pi beta for each muscle. The non-Pi beta values were added to the actual amount of Pi present in the stimulated muscles to calculate a predicted beta at pH 7. The apparent beta calculated from PCr and pH changes in intact muscles and the predicted beta from homogenate titrations were in good agreement (38 +/- 9 vs. 38 slykes in cat biceps, 21 +/- 7 vs. 30 in cat soleus, and 30 +/- 6 vs. 27 in rat gastrocnemius). The results indicate that changes in pH during the first few seconds of contraction can be entirely accounted for by proton consumption via net PCr hydrolysis.
Structural and mechanical adaptations of immature trabecular bone to strenuous exercise
Authors: Hou J. C. , Salem G. J. , Zernicke R. F. , Barnard R. J.
Published: December 2017

Effects of strenuous exercise on immature bone were examined in two clinically important regions, femoral neck (FN) and lumbar vertebra (L6). Female Sprague-Dawley rats (n = 20, 8 wk of age, 150-170 g) were exercised progressively 5 days/wk for approximately 1 h/day for 10 wk at 75-80% of maximum oxygen capacity on a motor-driven treadmill. Caged age-matched rats served as controls (n = 20). Rat FNs were tested in cantilever bending, and vertebral bodies were compressed to 50% of their initial height at a fast strain rate. In response to the strenuous exercise, the relative area of the FN trabecular core increased significantly at the expense of the cortical shell. With that structural change, the exercised FN had significantly less energy to proportional limit than controls. The FN material properties (normal stresses at proportional limit and maximum) were significantly diminished after 10 wk of strenuous exercise. At the same time, no differences were found in vertebral geometry or structural and material properties. In the immature rate, the differential responses of the FN vs. L6 may relate to load history rather than a general systemic response to the strenuous exercise.
Effect of exercise and obesity on skeletal muscle amino acid uptake
Authors: Friedman J. E. , Lemon P. W. , Finkelstein J. A.
Published: December 2017

The genetically obese Zucker rat has a reduced capacity to deposit dietary protein in skeletal muscle. To determine whether amino acid uptake by muscle of obese Zucker rats is impaired, soleus strip (SOL) and epitrochlearis (EPI) muscles from 10-wk-old lean and obese Zucker rats were studied in vitro by use of [14C]alpha-aminoisobutyric acid (AIB). Muscles from fasted rats were incubated under basal conditions at rest or after a 1-h treadmill run at 8% grade. To equate total work completed, lean and obese rats ran at 27 and 20 m/min, respectively. Muscles were pinned at resting length, preincubated for 30 min at 37 degrees C in Krebs-Ringer bicarbonate buffer containing 5 mM glucose under 95% O2-5% CO2, and then incubated up to 3 h in Krebs-Ringer bicarbonate with 0.5 mM AIB, [14C]AIB, and [3H]inulin as a marker of extracellular fluid. Basal AIB uptake in EPI and SOL from obese rats was significantly reduced by 40 and 30% (P less than 0.01), respectively, compared with lean rats. For both lean and obese rats, exercise increased (P less than 0.05) basal AIB uptake in EPI and SOL, but the relative increases were greater in the obese rats (EPI 54% and SOL 71% vs. EPI 32% and SOL 37%). These results demonstrate that genetically obese Zucker rats have reduced basal skeletal muscle amino acid uptake and suggest that physical inactivity may partially contribute to this defect.
Acetazolamide alters temperature regulation during submaximal exercise
Authors: Brechue W. F. , Stager J. M.
Published: December 2017

Acetazolamide (ACZ), a potent carbonic anhydrase inhibitor, is known to decrease submaximal exercise tolerance under normoxic and hypoxic conditions. These decrements in performance occur despite the maintenance of O2 consumption and CO2 removal. Because ACZ is a diuretic, it induces a moderate hypohydration that may have a role in reducing the ability to sustain exercise through cardiovascular and thermoregulatory impairment. To investigate this potential impairment, seven healthy males between 21 and 35 yr of age were studied in a double-blind crossover design (placebo vs. ACZ). ACZ was administered in three 250-mg oral doses 14, 8, and 2 h before exercise. Subjects exercised at 70% peak O2 uptake for 30 min on a cycle ergometer in a normoxic thermoneutral environment (25 degrees C, 40% relative humidity). Results indicate that exercise minute ventilation was greater but O2 uptake, CO2 output, and respiratory exchange ratio did not differ with ACZ. ACZ led to lower mean skin (0.7 degrees C), higher rectal (0.6 degrees C), and higher mean body temperatures (0.4 degrees C) after 30 min of exercise. Whole-body sweat loss was reduced 23%, and heat storage during the exercise bout was increased 55%. Stroke volume decreased 25%, and arteriovenous O2 difference increased 15%. A significant inverse relationship (r = -0.63) between heart rate and stroke volume was observed. It is concluded that previously reported decreases in the ability to sustain submaximal exercise with ACZ may be related to hypohydration-induced impairment of the cardiovascular and thermoregulatory systems.
Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema
Authors: Lotvall J. O. , Lemen R. J. , Hui K. P. , Barnes P. J. , Chung K. F.
Published: December 2017

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.