bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of radiolabeled neutrophils in swine
Authors: Ohgami M. , Doerschuk C. M. , English D. , Dodek P. M. , Hogg J. C.
Published: December 2017

The kinetics of radiolabeled neutrophils (PMNs) as they pass through the lungs of swine were evaluated and compared with those in rabbits (J. Appl. Physiol. 63: 1806–1815, 1987) and dogs (J. Appl. Physiol. 63: 1253–1261, 1987; 65: 1217–1225, 1988) previously reported from our laboratory. 111In-labeled PMNs (111In-PMNs) and 99mTc-labeled erythrocytes were simultaneously injected into the right atrium, and the 111In-PMN percent extraction on the first passage through the lung was determined by the indicator-dilution technique. After 10 min of circulation the distribution of 111In-PMNs in selected organs was determined. The extraction of 111In-PMNs in swine was 88 +/- 3%, which was significantly greater than that of rabbits (78 +/- 3%) or dogs (72 +/- 2%). The recovery of the 111In-PMNs in the lungs of swine was 60 +/- 7%, which was two to three times higher than the recovery in lungs of rabbits or dogs. These results show that radiolabeled PMNs injected intravenously are less able to pass through the pulmonary vasculature and are retained much more within the lung in swine than in rabbits or dogs. This difference could be the result of the presence of pulmonary intravascular macrophages in the lungs of swine.
Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs
Authors: Lee L. Y. , Kou Y. R. , Frazier D. T. , Beck E. R. , Pisarri T. E. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

Inhalation of cigarette smoke into the lower airway via a tracheostomy evokes immediate apnea, bradycardia, and systemic hypotension in dogs. These responses can still be evoked when conduction in myelinated vagal fibers is blocked preferentially by cooling but are abolished by vagotomy, suggesting that they are mediated by afferent vagal C-fibers. To examine this possibility, we recorded impulses in pulmonary C-fibers in anesthetized, open-chest dogs and delivered 120 ml cigarette smoke to the lungs in a single ventilatory cycle. Pulmonary C-fibers were stimulated within 1 or 2 s of the delivery of smoke generated by high-nicotine cigarettes, activity increasing from 0.3 +/- 0.1 to a peak of 12.6 +/- 1.3 (SE) impulses/s, (n = 60); the evoked discharge usually lasted 3–5 s. Smoke generated by low-nicotine cigarettes evoked a milder stimulation in 33% of pulmonary C-fibers but did not significantly affect the overall firing frequency (peak activity = 2.2 +/- 1.1 impulses/s, n = 36). Hexamethonium (0.7–1.2 mg/kg iv) prevented C-fiber stimulation by high-nicotine cigarette smoke (n = 12) but not stimulation by right atrial injection of capsaicin. We conclude that pulmonary C-fibers are stimulated by a single breath of cigarette smoke and that nicotine is the constituent responsible.
Plateau in muscle blood flow during prolonged exercise in miniature swine
Authors: McKirnan M. D. , Gray C. G. , White F. C.
Published: December 2017

Cardiovascular, metabolic, and thermoregulatory responses were studied in eight male miniature swine during a prolonged treadmill run. Each animal underwent 8–10 wk of exercise training, thoracic surgery, and 3 wk of retraining before the experimental run. This regimen enabled the animals to run at 65% of the heart rate range (210–220 beats/min) for approximately 100 min. Skin wetting and a fan were used to cool the pigs during the run. Regional blood flow was significantly altered with the onset of exercise; however, hindlimb muscle and total gastrointestinal blood flow were unchanged throughout the exercise period. Compared with 5-min values, heart rate and cardiac output were significantly elevated by 17 beats/min and 31 ml.min-1.kg-1 at 60 min and by 20 beats/min and 33 ml.min-1.kg-1 at end exercise, respectively. Core temperatures increased between 5 and 30 min of exercise (39.4 vs. 39.9 degrees C) but then remained unchanged to the end of exercise. Mean arterial pressure, O2 consumption, and blood lactate did not change during the exercise bout. These data indicate that limiting increases in core temperature during prolonged exercise was associated with a plateau in active muscle blood flow.
Electrolyte and other chemical concentrations in tracheal airway surface liquid and mucus
Authors: Robinson N. P. , Kyle H. , Webber S. E. , Widdicombe J. G.
Published: December 2017

With the ferret in vitro tracheal preparation, we measured the electrolyte and chemical composition of airway surface liquid (ASL) under control conditions and when drugs were added to promote submucosal gland secretion and to change epithelial ion transport. Control ASL was hyperosmolar (342 +/- 2.8 mosmol/kg) compared with ferret plasma and surrounding buffer. Higher values were also found for sodium (167 +/- 1.7 mmol/l), potassium (9.0 +/- 0.05 mmol/l), total calcium (3.46 +/- 0.11 mmol/l), and ionized calcium (2.55 +/- 0.18 mmol/l). pH was lower (7.12 +/- 0.03) than in plasma or buffer. Addition of methacholine to the surrounding buffer increased flow of ASL and potential difference across the mucosa and lowered pH, calcium, sodium, and chloride concentrations. Potassium concentration was increased. Phenylephrine increased flow and decreased calcium concentrations. Salbutamol (albuterol) had no effect on flow but decreased pH and increased calcium and potassium concentrations. Histamine increased flow and calcium concentrations and decreased pH. These changes are presumably due to changes in gland secretion and epithelial transport. Methacholine and phenylephrine increased the sugar content of the secretions, the changes with phenylephrine being larger. Thus resting ASL is hyperosmolar and relatively acid, with high cation contents, and administration of drugs changes its composition by actions on submucosal glands and epithelium.
Reduction of lung perfusion increases VA/Q heterogeneity
Authors: Ohlsson J. , Middaugh M. , Hlastala M. P.
Published: December 2017

This study addresses the hypothesis that decreases in lung perfusion rate independently worsen gas exchange efficiency in an isolated left lower lobe in zone 2 conditions. In seven anesthetized dogs, the left lower lobe was isolated, leaving the bronchus and bronchial vasculature intact. Blood was taken from the femoral arteries and reinfused at a controlled rate into the pulmonary artery of the left lower lobe. The flow rate was varied between 100 and 400 ml/min. The multiple inert gas elimination technique was used to quantitate the matching of ventilation to perfusion. Reduction in lobe blood flow resulted in a significant increase in perfusion-related indexes of alveolar ventilation-perfusion heterogeneity, such as the log standard deviation of the perfusion distribution, the retention component of the arterial-alveolar difference area, and the retention dispersion index. The increased heterogeneity suggests a worsening of the intraregional matching between the ventilation and the perfusion when perfusion is less than normal.
High-frequency ventilation-induced apnea: interaction of frequency, volume, FRC, and CO2
Authors: Davenport P. W. , Dalziel D. J.
Published: December 2017

Apnea is often observed during high-frequency oscillatory ventilation (HFOV). This study on anesthetized dogs varied the oscillator frequency (f) and determined the stroke volume (SV) at which apnea occurred. Relaxation functional residual capacity (FRC) and the eupneic breathing end-tidal CO2 level were held constant. Airway pressure and CO2 were measured from a side port of the tracheostomy cannula. An arterial cannula was inserted for blood gas analysis. Diaphragm electromyogram (EMG) was recorded with bipolar electrodes. Apnea was defined as the absence of phasic diaphragm EMG activity for a minimum of 60 s. During HFOV, SV was increased at each f (5–40 Hz) until apnea occurred. The apnea inducing SV decreased as f increased. SV was minimal at 25–30 Hz. Frequencies greater than 30 Hz required increased SV to produce apnea. The f-SV curve was defined as the apneic threshold. Increased FRC resulted in a downward shift (less SV at the same f) in the apneic threshold. Elevated CO2 caused an upward shift (more SV at the same f) in the apneic threshold. These results demonstrate that the apnea elicited by HFOV is dependent on the interaction of oscillator f and SV, the FRC, and CO2.
Solubility of Freon 22 in human blood and lung tissue
Authors: Varene N. , Choukroun M. L. , Marthan R. , Varene P.
Published: December 2017

The solubility of Freon 22 in human blood and lung tissue was determined using the chromatographic method of Wagner et al. (J. Appl. Physiol. 36: 600–605, 1974). In normal human blood, the mean Bunsen coefficient of solubility (alpha B) was 0.804 cm3 STPD.cm-3.ATA-1 at 37 degrees C. It increased with hematocrit (Hct) according to the equation alpha B = 0.274 Hct + 0.691. Tissue homogenates were prepared from macroscopically normal lung pieces obtained at thoracotomy from eight patients undergoing resection for lung carcinoma. The Bunsen solubility coefficients were 0.537 +/- 0.068 and 0.635 +/- 0.091 in washed and unwashed lung, respectively. These values can be used in the determination of both cardiac output and pulmonary tissue volume in humans by use of the rebreathing technique.
Effects of incomplete pulmonary gas exchange on VO2 max
Authors: Powers S. K. , Lawler J. , Dempsey J. A. , Dodd S. , Landry G.
Published: December 2017

Recent evidence suggests that heavy exercise may lower the percentage of O2 bound to hemoglobin (%SaO2) by greater than or equal to 5% below resting values in some highly trained endurance athletes. We tested the hypothesis that pulmonary gas exchange limitations may restrict VO2max in highly trained athletes who exhibit exercise-induced hypoxemia. Twenty healthy male volunteers were divided into two groups according to their physical fitness status and the demonstration of exercise-induced reductions in %SaO2 less than or equal to 92%: 1) trained (T), mean VO2max = 56.5 ml.kg-1.min-1 (n = 13) and 2) highly trained (HT) with maximal exercise %SaO2 less than or equal to 92%, mean VO2max = 70.1 ml.kg-1.min-1 (n = 7). Subjects performed two incremental cycle ergometer exercise tests to determine VO2max at sea level under normoxic (21% O2) and mild hyperoxic conditions (26% O2). Mean %SaO2 during maximal exercise was significantly higher (P less than 0.05) during hyperoxia compared with normoxia in both the T group (94.1 vs. 96.1%) and the HT group (90.6 vs. 95.9%). Mean VO2max was significantly elevated (P less than 0.05) during hyperoxia compared with normoxia in the HT group (74.7 vs. 70.1 ml.kg-1.min-1). In contrast, in the T group, no mean difference (P less than 0.05) existed between treatments in VO2max (56.5 vs. 57.1 ml.kg-1.min-1). These data suggest that pulmonary gas exchange may contribute significantly to the limitation of VO2max in highly trained athletes who exhibit exercise-induced reductions in %SaO2 at sea level.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of progressive hypoxia on parasternal, costal, and crural diaphragm activation
Authors: Darian G. B. , DiMarco A. F. , Kelsen S. G. , Supinski G. S. , Gottfried S. B.
Published: December 2017

The distribution of motor drive to the costal and crural diaphragm and parasternal intercostal muscles was evaluated during progressive isocapnic hypoxia in anesthetized dogs. Bipolar stainless steel wire electrodes were placed unilaterally into the costal and crural portions of the diaphragm and into the parasternal intercostal muscle in the second or third intercostal space. Both peak and rate of rise of electromyographic activity of each chest wall muscle increased in curvilinear fashion in response to progressive hypoxia. Both crural and parasternal intercostal responses, however, were greater than those of the costal diaphragm. The onset of crural activation preceded that of the costal portion of the diaphragm and parasternal intercostal muscle activation. Despite differences in the degree of activation among the various chest wall muscles, the rate of increase in activation for any given muscle was linearly related to the rate of increases for the other two. This suggests that respiratory drive during progressive hypoxia increases in fixed proportion to the different chest wall inspiratory muscles. Our findings lend further support to the concept that the costal and crural diaphragm are governed by separate neural control mechanisms and, therefore, may be considered separate muscles.
Plasma protein binding and endothelial enzyme interactions in the lung
Authors: Linehan J. H. , Dawson C. A. , Bongard R. D. , Bronikowski T. A. , Roerig D. L.
Published: December 2017

The influence of plasma albumin binding of the synthetic angiotensin-converting enzyme (ACE) substrate [3H]benzoyl-phenylalanyl-alanyl-proline (BPAP) on BPAP hydrolysis by pulmonary endothelial ACE was studied in isolated rabbit lungs perfused with a salt solution containing either 5% bovine serum albumin (BSA) or 5% dextran. The single-pass indicator-dilution method was used to measure the fraction (M) of [3H]BPAP hydrolyzed. Lung M was greater with albumin-free perfusate than when BSA was present. M decreased as the time (ti) that the BPAP was in contact with the BSA before reaching the lung was increased, suggesting that some BSA binding sites for BPAP were not in equilibrium during bolus transit through the lungs. The M vs. ti data were correlated using a model incorporating both rapid and slow binding kinetics of BPAP and BSA. For the slow BPAP-BSA interaction, the dissociation rate constant was approximately 0.015 s-1, and the fraction of the BPAP bound to these slowly equilibrating sites at equilibrium was approximately 22%. The results indicate that transient plasma protein binding kinetics can affect lung BPAP hydrolysis.
Inhibition of neutral endopeptidase potentiates neurogenic inflammation in the rat trachea
Authors: Umeno E. , Nadel J. A. , Huang H. T. , McDonald D. M.
Published: December 2017

The present study was performed to determine whether neurogenic inflammation in the rat trachea can be exaggerated by inhibiting neutral endopeptidase, an enzyme that degrades tachykinins that are believed to mediate neurogenic inflammation. Neurogenic inflammation was produced by antidromic electrical stimulation of one vagus nerve (2.5 Hz, 1 ms, 5 V for 5 min) in the presence of atropine or by an intravenous injection of capsaicin (100 micrograms/kg). Neutrophils that adhered to the endothelium of venules were visualized and counted in tracheal whole mounts that were stained by a histochemical reaction for myeloperoxidase. Neural inflammation increased the number of adherent neutrophils. Pretreatment with the neutral endopeptidase inhibitor phosphoramidon (1.0 or 2.5 mg/kg iv) increased neutrophil adhesion induced by neural inflammation. As assessed by the amount of extravasation of Monastral blue pigment, neural inflammation also increased vascular permeability, and this change was potentiated by phosphoramidon. These results are consistent with the concept that neuropeptides released from sensory nerves in the tracheal mucosa cause neutrophils to adhere to venules and increase vascular permeability and that these effects are modulated by neutral endopeptidase.
Sequence of interstitial liquid accumulation in liquid-inflated sheep lung lobes
Authors: Conhaim R. L. , Lai-Fook S. J. , Eaton A.
Published: December 2017

In the initial stages of pulmonary edema, liquid accumulates in the lung interstitium and appears as cuffs around pulmonary vessels. To determine the pattern, rate, and magnitude of cuff formation, we inflated sheep lungs to capacity with liquid (inflation pressure 19 cmH2O) for 3–300 min. After freezing the lobes in liquid N2, we measured perivascular cuff size and total perivascular volume in frozen blocks of each lobe and compared the results with previous measurements in dog lungs. Total cuff volume in sheep lungs reached a maximum value of 5% of air space volume, compared with 9% in dog lungs. In sheep lungs 94% of vessels greater than or equal to 0.5 mm diam and 16% of smaller vessels were surrounded by cuffs. In dog lungs these values were 99 and 47%, respectively. The ratio of cuff area to vessel area reached a maximum of 2.3 in sheep lungs and 3.4 in dog lungs. In an electrical analogue model designed to simulate cuff growth, estimated interstitial resistance to liquid flow was 6–15 times higher than similar estimates in dog lungs. These species differences might be the result of differences in the composition of the interstitial gel or to differences in the mechanical linkage between the lung parenchyma and vessel wall.
Static contraction increases arachidonic acid levels in gastrocnemius muscles of cats
Authors: Rotto D. M. , Massey K. D. , Burton K. P. , Kaufman M. P.
Published: December 2017

Static contraction of hind-limb muscles is well known to increase reflexly cardiovascular function. Recently, blockade of cyclooxygenase activity has been reported to attenuate the reflex pressor response to contraction, a finding which suggests that working skeletal muscle releases arachidonic acid metabolites. Therefore, we measured the effects of static contraction and ischemia on arachidonic acid levels in the gastrocnemius muscles of barbiturate-anesthetized cats treated with indomethacin. Unesterified arachidonic acid levels were measured by high-pressure liquid chromatography. We found that static contraction of freely perfused gastrocnemius muscles increased arachidonic acid levels from 4.4 +/- 1.0 to 10.3 +/- 2.2 nmol/g wet wt (n = 12; P less than 0.005). Likewise, static contraction of gastrocnemius muscles made ischemic for 2 min before the onset of the contraction period increased arachidonic acid levels from 12.6 +/- 2.3 to 21.0 +/- 2.0 nmol/g wet wt (n = 12; P less than 0.01). Lastly, 2 min of ischemia with the gastrocnemius muscles at rest increased arachidonic acid levels from 5.9 +/- 1.1 to 10.5 +/- 3.0 nmol/g wet wt (n = 18; P less than 0.02). We conclude that both static contraction and ischemia increase arachidonic acid levels in working hindlimb muscle.
Exercise-induced focal skeletal muscle fiber degeneration and capillary morphology
Authors: Peeze Binkhorst F. M. , Kuipers H. , Heymans J. , Frederik P. M. , Slaaf D. W. , Tangelder G. J. , Reneman R. S.
Published: December 2017

The relationship between exercise-induced focal muscle fiber degeneration and changes in capillary morphology was investigated in male Wistar rats. Untrained animals ran on a treadmill for 1 h at submaximal intensity and were killed 0, 6, or 24 h after running. Nonexercised rats served as controls. In situ perfused soleus muscles were prepared for electron microscopy. Micrographed cross sections were quantitatively analyzed for parameters indicative of capillary blood flow or transcapillary exchange. Capillary lumina were ovally rather than circularly shaped, and no indications for obstruction of blood flow at the capillary level were found. Endothelial cells and their organelles had a normal appearance in all groups. However, immediately after exercise, capillaries showed a decreased thickness of their endothelium and basal membrane, probably caused by dehydration. Six hours after exercise, muscle fibers were swollen (28% increase in cross-sectional area), resulting in a slightly increased diffusion distance. This fiber swelling was not associated with an increase in muscle water content, a finding for which no explanation could be found. Twenty-four hours after the animals ran, capillaries located near degenerated muscle fibers had an increased cross-sectional luminal area and an increased luminal circumference. This effect decreased gradually with increasing distance from the degenerated fiber area. The present morphometric results do not support the hypothesis that changes in capillary morphology primarily contribute to exercise-induced focal muscle fiber degeneration.
Oleic acid reduces pulmonary microvascular sieving capacity in sheep
Authors: Smith L. , Andreasson S. , Bergdahl S. , Rippe B. , Risberg B.
Published: December 2017

Changes in pulmonary microvascular permeability in sheep, after oleic acid injection, were studied using estimations of the osmotic reflection coefficient (sigma d) for total protein, albumin, immunoglobulins (Ig) G and M and calculation of the equivalent small and large pores of the microvessels. A chronic lung fistula was prepared in eight sheep. After a base-line period, left atrial pressure (Pla) was increased. Oleic acid (0.05 mg/kg body wt) was injected after a filtration-independent state had been obtained, and the spontaneously ventilating animals were then followed for 2 h. The sigma d for the normal lung was 0.65 +/- 0.03, 0.59 +/- 0.02, 0.72 +/- 0.04, and 0.84 +/- 0.02 for total protein, albumin, IgG, and IgM, respectively. The equivalent pore radii were 54 and 225 A. After oleic acid infusion, arterial pressure and arterial O2 tension decreased and leukocytes and platelets were consumed. At the end of the experiment, sigma d's were 0.27 +/- 0.04, 0.24 +/- 0.07, 0.33 +/- 0.06, and 0.55 +/- 0.04 for total protein, albumin, IgG, and IgM, respectively. The equivalent pore radii were 54 and 275 A, and the number of large pores was increased by 195%. The results indicate that oleic acid produces an increased vascular permeability by increasing the size and the numbers of large pores of the pulmonary microvascular walls.
Effect of papaverine on pulmonary vascular permeability to proteins
Authors: Maron Michael B. , Pilati Cahrles F.
Published: December 2017

Page 1367–1371: Michael B. Maron and Charles F. Pilati. “Effect of papaverine on pulmonary vascular permeability to proteins.” Page 1370: right-hand column, sentence beginning on line 23 should read: For example, we previously found that histamine does not decrease sigma in this preparation, although we found it to do so in an isolated perfused canine forelimb preparation (11).
Adenine nucleotide degradation in human skeletal muscle during prolonged exercise
Authors: Broberg S. , Sahlin K.
Published: December 2017

Eight healthy men cycled at a work load corresponding to approximately 70% of maximal O2 uptake (VO2max) to fatigue (exercise I). Exercise to fatigue at the same work load was repeated after 75 min of rest (exercise II). Exercise duration averaged 65 and 21 min for exercise I and II, respectively. Muscle (quadriceps femoris) content of glycogen decreased from 492 +/- 27 to 92 +/- 20 (SE) mmol/kg dry wt and from 148 +/- 17 to 56 +/- 17 (SE) mmol/kg dry wt during exercise I and II, respectively. Muscle and blood lactate were only moderately increased during exercise. The total adenine nucleotide pool (TAN = ATP + ADP + AMP) decreased and inosine 5′-monophosphate (IMP) increased in the working muscle during both exercise I (P less than 0.001) and II (P less than 0.01). Muscle content of ammonia (NH3) increased four- and eight-fold during exercise I and II, respectively. The working legs released NH3, and plasma NH3 increased progressively during exercise. The release of NH3 at the end of exercise II was fivefold higher than that at the same time point in exercise I (P less than 0.001, exercise I vs. II). It is concluded that submaximal exercise to fatigue results in a breakdown of the TAN in the working muscle through deamination of AMP to IMP and NH3. The relatively low lactate levels demonstrate that acidosis is not a necessary prerequisite for activation of AMP deaminase. It is suggested that the higher average rate of AMP deamination during exercise II vs. exercise I is due to a relative impairment of ATP resynthesis caused by the low muscle glycogen level.
NADH shuttle enzymes and cytochrome b5 reductase in human skeletal muscle: effect of strength training
Authors: Schantz P. G. , Kallman M.
Published: December 2017

The main aim of this study was to investigate whether enzyme levels of the malate-aspartate and alpha-glycerophosphate shuttles and of cytochrome b5 reductase in human skeletal muscle are affected by strength training. Muscle biopsy samples from the deltoid muscle of the nondominant arm in untrained (n = 12) and strength-trained (n = 12) subjects were compared. The strength-trained muscles were characterized by a tendency to a higher percentage of type I fibers (67 vs. 59%), a lower percentage of type IIb fibers (12 vs. 18%), 34% larger mean fiber areas, and 19% more capillaries per fiber (P less than 0.1). No difference was noted in levels of enzymes representing the citric acid cycle, fatty acid oxidation, and glycolysis, nor in the number of capillaries per square millimeter. Neither did the levels of malate-aspartate and alpha-glycerophosphate shuttle enzymes nor cytochrome b5 reductase differ. Levels of cytochrome b5 reductase correlated (r = 0.59, P less than 0.01) with levels of the mitochondrial marker enzyme citrate synthase. It is concluded that strength training does not appear to result in increased levels of NADH shuttle enzymes and cytochrome b5 reductase.
Use of doubly labeled water technique in soldiers training for jungle warfare
Authors: Forbes-Ewan C. H. , Morrissey B. L. , Gregg G. C. , Waters D. R.
Published: December 2017

The doubly labeled water method was used to estimate the energy expended by four members of an Australian Army platoon (34 soldiers) engaged in training for jungle warfare. Each subject received an oral isotope dose sufficient to raise isotope levels by 200–250 (18O) and 100–120 ppm (2H). The experimental period was 7 days. Concurrently, a factorial estimate of the energy expenditure of the platoon was conducted. Also, a food intake-energy balance study was conducted for the platoon. Mean daily energy expenditure by the doubly labeled water method was 4,750 kcal (range 4,152–5,394 kcal). The factorial estimate of mean daily energy expenditure was 4,535 kcal. Because of inherent inaccuracies in the food intake-energy balance technique, we were able to conclude only that energy expenditure, as measured by this method, was greater than the estimated mean daily intake of 4,040 kcal. The doubly labeled water technique was well tolerated, is noninvasive, and appears to be suitable in a wide range of field applications.
Mechanical and metabolic alterations in rat diaphragm during electrical stimulation
Authors: Massarelli P. S. , Green H. J. , Hughson R. L. , Sharratt M. T.
Published: December 2017

To investigate the hypothesis that the rate of fatigue development is not influenced by the absolute duration of contraction (train duration) and relaxation (off-phase of duty cycle) at constant duty cycle, strips of the diaphragm from 36 male adult rats (mean +/- SD wt 152 +/- 21 g) were stimulated directly for periods of 180, 250, and 320 ms at a constant duty cycle of 50%. The frequency of stimulation was adjusted to produce 40% of maximal tetanic tension at supramaximal voltages. After 30 min of stimulation, analysis of twitch characteristics between control and experimental groups indicated a prolongation of contraction time of 9% (P less than 0.05), an increase in relaxation time of 75% (P less than 0.05), and a decrease in twitch tension by 78% (P less than 0.05). Similarly, reductions (P less than 0.05) in isometric force output at high stimulation frequency (100 Hz) of 58% and at low frequency (20 Hz) of 67% were also noted. These changes were accompanied by an approximately 60% reduction in the maximal velocity of shortening. No difference was observed for any of the mechanical measures between experimental conditions. After 30-min stimulation, decreases of between 43 and 46% were noted for ATP (P less than 0.05) and increases of between three- and fourfold noted for IMP (P less than 0.05). No changes were found for either ADP or AMP. Total adenine nucleotide concentrations declined (P less than 0.05) an average of 24%. As with the mechanical data, no differences were found between the different stimulation conditions. It is concluded that for the conditions studied, fatigue mechanisms become manifest early in the stimulation period and are only minimally altered by the duration of specific contractions provided the relaxation period is of equal duration.
Thermal and metabolic responses to cold by men and by eumenorrheic and amenorrheic women
Authors: Graham T. E. , Viswanathan M. , Van Dijk J. P. , Bonen A. , George J. C.
Published: December 2017

Previous work has suggested that men (M) are more sensitive to cold stress than women. There have also been observations that suggest that amenorrheic women (AW) are less thermally responsive than eumenorrheic women (EW). We investigated the hypothesis that M, EW, and AW would have different responses to cold stress. The subjects (6/group) were tested four times: twice at rest for 60 min (5 and 22 degrees C) and twice in a progressive exercise test (5 and 22 degrees C). At rest at 22 degrees C AW had a lower O2 uptake (VO2) than M and lower rectal (Tre) and finger temperatures than EW. At rest at 5 degrees C both AW and EW had lower skin temperature (Tsk) than M, but there were no group differences in peripheral Tsk sites. M increased VO2 after 10 min and EW after 20 min of cold stress; however, AW did not increase metabolism until 60 min. In the two exercise tests Tre increased in proportion to relative work load; in the 5 degrees C test there was little evidence that exercise increased Tsk sites above rest levels. Few of the metabolic or thermal differences could be accounted for by body fatness, body surface area (BSA), or BSA/kg. The data support the hypothesis that M, EW, and AW have different responses to cold stress.
Effect of elevated vascular pressure transients on protein permeability in the lung
Authors: Maron M. B.
Published: December 2017

Neurogenic pulmonary edema (NPE) may develop in individuals with head trauma or seizures and is generally thought to have a hydrostatic basis in the severe degree of pulmonary hypertension that occurs. Recently, it has been suggested that vascular pressures may rise to levels that damage the vessels, leaving the patient at risk for further edema development. The objective of this study was to determine if pulmonary vascular protein permeability is increased in a canine isolated perfused left lower lung lobe (LLL) preparation by pressure transients that may occur in NPE. Venous pressure (Pv) was transiently raised to values ranging from 8 to 102 Torr in 19 LLL. One Pv transient was studied per LLL. After Pv was returned to normal, the osmotic reflection coefficient (sigma d) for total proteins was determined by the hematocrit-protein double indicator technique. No reduction in sigma d was observed until microvascular pressure exceeded 70 Torr. The average sigma d for the 11 LLL in which the peak microvascular pressure was less than 70 Torr was 0.74 +/- 0.03 (SE). Above this level sigma d fell linearly with increasing Pv, with a value of 0.26 being observed after the highest Pv transient. These results suggest that protein permeability may increase in patients with NPE who develop very large increases in pulmonary vascular pressures but may not be a universal occurrence in this disorder.
Analysis of bronchoconstrictor responses to platelet-activating factor in the cat
Authors: Underwood D. C. , Kadowitz P. J.
Published: December 2017

Bronchoconstrictor responses to platelet-activating factor (PAF) were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of PAF caused dose-dependent increases in lung resistance (RL) and decreases in dynamic compliance (Cdyn) and systemic arterial (aortic) pressure (PAO). The increases in RL and decreases in Cdyn in response to PAF were markedly reduced by sodium meclofenamate, a cyclooxygenase inhibitor, whereas the decreases in PAO were unchanged. Increases in RL and decreases in Cdyn but not PAO in response to PAF were reduced by SQ 29,548, a thromboxane (Tx) receptor blocking agent. CV 3988, a PAF receptor antagonist, reduced bronchoconstrictor and aortic depressor responses to PAF but had no effect on responses to the Tx mimic, U 46619, or to the prostaglandin precursor, arachidonic acid. The present studies suggest that bronchoconstrictor responses but not the hypotensive response to PAF are mediated in large part by the release of arachidonic acid from cell membrane phospholipids and the formation of cyclooxygenase products including TxA2. These data indicate that although airway and vasodepressor responses to PAF in the cat are mediated by different mechanisms, a similar PAF-CV 3988-sensitive receptor is involved.
Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion
Authors: Richalet J. P. , Le-Trong J. L. , Rathat C. , Merlet P. , Bouissou P. , Keromes A. , Veyrac P.
Published: December 2017

A decrease in heart rate response to isoproterenol (IP) infusion has been previously described in humans exposed to acute (2–3 days) or chronic (21 days) exposure to altitude hypoxia (J. Appl. Physiol. 65: 1957–1961, 1988). To evaluate this cardiac response in subacute (8 days) hypoxia and to explore its reversal with restoration of normoxia, six subjects received an IP infusion under normoxia (condition N), after 8 days in altitude (4,350 m, condition H8), on the same day in altitude after inhalation of O2 restoring normoxic arterial O2 saturation (SaO2, condition HO), and 6–11 h (condition RN) and 4–5 mo (condition ND) after the return to sea level. Cardiac chronotropic response to IP, evaluated by the mean increase in heart rate from base value (delta HR, min-1), was lower in condition H8 [mean 30 +/- 13 (SD)] than in condition N (50 +/- 14, P less than 0.03); it was slightly higher in condition HO (38 +/- 14) or condition RN (42 +/- 15) than condition H8 but still significantly different from condition N (P less than 0.03), despite normal values of SaO2. delta HR in condition ND (55 +/- 10) returned to base N value. These findings confirm the hypothesis of a hypoxia-induced decrease in cardiac chronotropic function. Two possible mechanisms are suggested: an O2-dependent one, rapidly reversible with recent restoration of normoxia, and a more slowly reversible mechanism, probably a downregulation of the cardiac beta-receptors.
Furosemide and cerebrospinal fluid ions during acute respiratory acidosis
Authors: Javaheri S. , Freidel J. F. , Davis P. J.
Published: December 2017

The purpose of this study was to investigate the effects of furosemide, an inhibitor of NaCl cotransport, on cisternal cerebrospinal fluid (CSF) acid-base balance during acute respiratory acidosis (ARA). We measured blood and CSF acid-base variables in two groups (n = 7 in each) of anesthetized, paralyzed, and mechanically ventilated dogs with bilateral ligation of renal pedicles (to eliminate saluresis). After base-line samples were obtained (-1 h), furosemide (50 mg/kg) was administered intravenously within 15 min (group II); group I received an equal volume of half-normal saline. ARA was induced 1 h later (0 h) and arterial CO2 tension was maintained between 55 and 60 Torr for 5 h. Mean cisternal CSF PCO2 was 42.8 +/- 2.6 and 39.5 +/- 1.7 Torr, respectively in groups I and II and rose approximately 20 Torr during ARA. In group I, CSF [HCO3-] was 22.0 +/- 1.0, 24.8 +/- 0.6, and 25.4 +/- 1.6 meq/l, respectively at 0, 2.5, and 5 h. Respective values for group II were 22.2 +/- 1.3, 24.3 +/- 1.8, and 24.6 +/- 1.0 meq/l. These values were not significantly different from each other. In each group, CSF [Na+-Cl-] increased significantly during ARA, but the changes were not significantly different when the two groups were compared. We conclude that furosemide at the dose used in the present study does not change ionic composition and acid-base balance of cisternal CSF compared with control. Because changes in CSF [Na+-Cl-] during ARA were similar in both groups, any inhibition of Cl- influx into CSF by furosemide should have been proportional to that of Na+.
In vivo regional diaphragm function in dogs
Authors: Sprung J. , Deschamps C. , Hubmayr R. D. , Walters B. J. , Rodarte J. R.
Published: December 2017

A biplane videofluorographic system was used to track the position of metallic markers affixed to the abdominal surface of the left hemidiaphragm in supine anesthetized dogs. Regional shortening was determined from intermarker distances of rows of markers placed along muscle bundles in the ventral, middle, and dorsal regions of the costal diaphragm and of one row on the crural diaphragm. Considerable variability of regional shortening was seen in a given row, which was reproducible on repeat study in individual dogs but which differed between mechanical ventilation and spontaneous breathing. There were no consistent patterns among dogs. Regional shortening obtained from the change in length of rows extending from chest wall to central tendon showed no consistent differences among dogs during spontaneous breathing. At equal tidal volumes, all regions (except the ventral costal diaphragm) shortened more during spontaneous breathing than during mechanical ventilation.
Pulmonary rapidly adapting receptors reflexly increase airway secretion in dogs
Authors: Yu J. , Schultz H. D. , Goodman J. , Coleridge J. C. , Coleridge H. M. , Davis B.
Published: December 2017

We attempted to determine whether stimulation of pulmonary rapidly adapting receptors (RARs) increase tracheal submucosal gland secretion in anesthetized open-chest dogs. Electroneurographic studies of pulmonary afferents established that RARs but not lung C-fibers were stimulated by intermittent lung collapse during deflation, collapse being produced by removing positive end-expiratory pressure (PEEP, 4 cmH2O) or by applying negative end-expiratory pressure (NEEP, -4 cmH2O). We measured tracheal secretion by the “hillocks” method. Removing PEEP or applying NEEP for 1 min increased secretion from a base line of 6.0 +/- 1.1 to 11.8 +/- 1.7 and 22.0 +/- 2.8 hillocks.cm-2.min-1, respectively (P less than 0.005). After PEEP was restored, dynamic lung compliance (Cdyn) was 37% below control, and secretion remained elevated (P less than 0.05). A decrease in Cdyn stimulates RARs but not other pulmonary afferents. Hyperinflation, which restored Cdyn and RAR activity to control, returned secretion rate to base line. Secretory responses to lung collapse were abolished by vagal cooling (6 degrees C), by pulmonary vagal section, or by atropine. We conclude that RAR stimulation reflexly increases airway secretion. We cannot exclude the possibility that reduced input from slowly adapting stretch receptors contributed to the secretory response.
Effect of regional alveolar hypoxia on gas exchange in dogs
Authors: Domino K. B. , Hlastala M. P. , Eisenstein B. L. , Cheney F. W.
Published: December 2017

We studied the effects of left lower lobe (LLL) alveolar hypoxia on pulmonary gas exchange in anesthetized dogs using the multiple inert gas elimination technique (MIGET). The left upper lobe was removed, and a bronchial divider was placed. The right lung (RL) was continuously ventilated with 100% O2, and the LLL was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Whole lung and individual LLL and RL ventilation-perfusion (VA/Q) distributions were determined. LLL hypoxia reduced LLL blood flow and increased the perfusion-related indexes of VA/Q heterogeneity, such as the log standard deviation of the perfusion distribution (log SDQ), the retention component of the arterial-alveolar difference area [R(a-A)D], and the retention dispersion index (DISPR*) of the LLL. LLL hypoxia increased blood flow to the RL and reduced the VA/Q heterogeneity of the RL, indicated by significant reductions in log SDQ, R(a-A)D, and DISPR*. In contrast, LLL hypoxia had little effect on gas exchange of the lung when evaluated as a whole. We conclude that flow diversion induced by regional alveolar hypoxia preserves matching of ventilation to perfusion in the whole lung by increasing gas exchange heterogeneity of the hypoxic region and reducing heterogeneity in the normoxic lung.
Effects of angiotensin blockade on the splanchnic circulation in normotensive humans
Authors: Stadeager C. , Hesse B. , Henriksen O. , Christensen N. J. , Bonde-Petersen F. , Mehlsen J. , Giese J.
Published: December 2017

The effects of angiotensin-converting enzyme inhibition (ACE-I) by enalapril on splanchnic (n = 10) and central hemodynamics (n = 9) were examined in moderately salt-depleted healthy volunteers, at rest and during 15–20 min of lower body negative pressure (LBNP), reducing mean arterial pressure by 10 mmHg. During LBNP before ACE-I, both splanchnic and total peripheral vascular resistances increased. During ACE-I, splanchnic and total peripheral vascular resistances decreased. After enalapril administration, splanchnic vascular resistance did not increase during LBNP. Total peripheral vascular resistance still increased but not to the same extent as during LBNP before ACE-I. The increases in heart rate and plasma norepinephrine during LBNP were attenuated after ACE-I compared with LBNP before ACE-I. The effectiveness of the ACE-I was clearly demonstrated by unchanged and low plasma angiotensin II levels during ACE-I. We conclude that, in normal sodium-depleted humans, acute ACE-I decreases splanchnic vascular resistance at rest and abolishes splanchnic vasoconstriction during LBNP. Furthermore, it may interfere with autonomic nervous system control of the circulation.
Inhalation of adenosine 5'-monophosphate increases methacholine airway responsiveness
Authors: Rosati G. , Hargreave F. E. , Ramsdale E. H.
Published: December 2017

Airway hyperresponsiveness is a characteristic feature in asthmatic subjects, but the mechanism of the hyperresponsiveness is not known. The purpose of this study was to investigate whether methacholine airway responsiveness was increased 24 h after inhalation of adenosine 5′-monophosphate (AMP). Ten atopic asthmatic subjects and six atopic normal subjects were studied on 4 study days. On the 1st day, a methacholine inhalation test was performed, followed within 48 h by an AMP inhalation test. Seven days later the second AMP test was performed, and 24 h later the methacholine inhalation test was repeated. Response was measured using partial flow-volume curves, and the concentration required to cause a 40% fall in the partial flow-volume curve (PC40) was calculated. The geometric mean methacholine PC40 fell from 1.36 mg/ml on day 1 (before AMP inhalation) to 0.71 mg/ml on day 4 (24 h after AMP inhalation, P less than 0.01). There was no change in the mean PC40 for adenosine on the 2 study days (5.82 and 7.06 mg/ml, P greater than 0.1). These findings suggest that adenosine release may contribute to the increase in airway responsiveness after allergen challenge.
Detection of a lactate threshold during incremental exercise?
Authors: Morton R. H.
Published: December 2017

An important question in the study of the exercise response is the real or imaginary nature of the anaerobic threshold, and mathematical modeling techniques have been invoked to assist in resolving this issue. Two opposing views with competing data models recently published in this journal are criticized. One view suggests a segmented model with a discontinuous first derivative at the threshold. The other suggests a continuous model over the whole work load range, implying the anaerobic threshold to be imaginary. However, neither group of authors has devoted proper rigorous attention to the models they use. Had this been done, some of the divergence of opinion may have been avoided. Ideal data from an alternate segmented model that has a continuous first derivative at the threshold are considered for comparative purposes. This suggests that the log-log transformation method may well lead to improved detection of a threshold when one exists, although the estimates of the threshold value obtained are unreliable. Modeling methodology is a useful approach to the resolution of scientific issues, but there exist fundamental implications and alternatives that must be fully recognized.
Effect of fenoldopam on preconstricted isolated salt-perfused rat lungs
Authors: Polak M. J. , Knight M. E. , Gause G. E. , Bucciarelli R. L. , Drummond W.
Published: December 2017

Using an in situ isolated salt-perfused rat lung preparation, we investigated the pulmonary vascular response to fenoldopam (a highly selective dopamine (DA1) agonist) infused at six different doses ranging from 0.1 to 10,000 micrograms/kg, during prostaglandin F2 alpha- (PGF2 alpha) induced pulmonary vasoconstriction. These experiments were repeated after selective DA1-blockade with SCH 23390. Twelve experiments were performed to evaluate the effect of fenoldopam on base-line hemodynamics. Sixty experiments were performed after PGF2 alpha vasoconstriction. Thirty lung preparations were pretreated with SCH 23390. PGF2 alpha was infused into the pulmonary inflow catheter at 2.5 micrograms.kg-1.min-1 to give a sustained rise in mean pulmonary arterial pressure (5.0 +/- 1.0 mmHg). Fenoldopam, at doses of 0.1, 1, 10, 100, 1,000, or 10,000 micrograms/kg, was injected into the pulmonary artery (n = 5 blocked and n = 5 unblocked at each dose). Fenoldopam had no effect on hemodynamics in the absence of PGF2 alpha. In the unblocked group, after PGF2 alpha vasoconstriction, fenoldopam infusion resulted in a dose-dependent decrease in the mean pulmonary arterial pressure with a dose-response curve characteristic for a drug-receptor interaction [Response = -1.0 (log Dose) -1.6]. In the DA1-blocked group after PGE2 alpha vasoconstriction, the dose-response curve was shifted to the right but parallel to the unblocked group, indicating competitive receptor blockade [Response -0.8 (log Dose) -0.05]. We conclude that vasodilatory DA1-receptors are responsible for the observed results.
Determinants and limits of pressure-preset ventilation: a mathematical model of pressure control
Authors: Marini J. J. , Crooke P. S. , Truwit J. D.
Published: December 2017

In recent years, four square-wave modes of pressure-preset mechanical ventilation (PPV)--pressure control, pressure support, inverse ratio, and airway pressure release ventilation--have been introduced to clinical practice. Conceptually, they share important features. Yet, because there remains widespread uncertainty regarding their ventilatory characteristics, efficacy, and appropriate use, the potential range of application is only now being investigated. To construct a unifying mathematical model of PPV, we developed a system of equations for prediction of the major “outcome” variables of PPV--tidal volume, minute ventilation, auto-positive end-expiratory pressure, mean alveolar pressure, and mechanical work--from the primary clinical “inputs” from patient (resistance, compliance) and clinician (applied pressure, frequency, inspiratory time fraction). Our analysis revealed distinct bounding limits for the outcome variables of ventilation and pressure and important implications for their clinical determinants. Although simplifying assumptions were required to enable construction of this mathematical analogue of respiratory system behavior, this model provides a firm conceptual framework for understanding the physiological interactions between PPV and the patients they are intended to help.