bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of total peripheral resistance during hyperthermia in rats
Authors: Takamata A. , Nose H. , Mack G. W. , Morimoto T.
Published: December 2017

To elucidate the effect of blood volume on the circulatory adjustment to heat stress, we studied alpha-chloralose-anesthetized rats at three levels of blood volume: normovolemia (NBV), hypervolemia (HBV; +32% plasma volume by isotonic albumin solution infusion), and hypovolemia (LBV; -16% plasma volume by furosemide administration). Body surface heating was performed with an infrared lamp to raise arterial blood temperature (Tb) at the rate of approximately 0.1 degree C/min. Before heating, central venous pressure (CVP) was significantly higher in HBV (0.41 +/- 0.25 mmHg) and lower in LBV (-1.44 +/- 0.22 mmHg) than in NBV (-0.41 +/- 0.10 mmHg). The Tb at which CVP started to decrease was approximately 40 degrees C in HBV, approximately 41 degrees C in NBV, and approximately 42 degrees C in LBV, and it decreased by 1.53 +/- 0.14, 1.92 +/- 0.24, and 0.62 +/- 0.14 mmHg from 37 to 43 degrees C of Tb in HBV, NBV, and LBV, respectively. Stroke volume was closely correlated with CVP, and this relationship was not affected by Tb. Heart rate responses to the raised Tb were similar among the three groups. Mean arterial pressure (MAP) was not affected by blood volume modification or CVP and was maintained at preheating (Tb 37 degrees C) level until Tb rose to 40 degrees C. Above this Tb, MAP increased until Tb reached 43 degrees C (+30-40 mmHg) for all three groups. Total peripheral resistance (TPR) was inversely correlated with CVP, and the slope of the linear relationship between TPR and CVP in LBV was three- to fourfold steeper than in NBV or HBV.(ABSTRACT TRUNCATED AT 250 WORDS)
Extracellular matrix disruption and pain after eccentric muscle action
Authors: Stauber W. T. , Clarkson P. M. , Fritz V. K. , Evans W. J.
Published: December 2017

Pain, stiffness, and indicators of muscle damage occur at different times after eccentric muscle action. After a single bout of maximal resisted lengthening of the elbow flexors, elbow position, pain perception, and indicators of cellular damage were measured. Immediately postexercise, a significant decrease in resting muscle length was observed that continued to 48 h. At this time, an increase in perceived muscle soreness was noted (P less than 0.05), and a biopsy of the biceps brachii revealed mast cell degranulation, separations of the extracellular matrix from myofibers, and increased plasma constituents in the extracellular space. It is proposed that myofiber disruption allows intracellular proteins to escape and extracellular proteins and ions to enter, causing swelling, whereas the disrupted extracellular matrix initiates the inflammatory response, which includes the release of mast cell granules seen at 48 h postexercise. Thus the delayed sensation of pain (soreness) after repeated eccentric muscle actions probably results from inflammation in response to extracellular matrix disruption.
Bradykinin release from contracting skeletal muscle of the cat
Authors: Stebbins C. L. , Carretero O. A. , Mindroiu T. , Longhurst J. C.
Published: December 2017

Results of previous studies from our laboratory suggest that bradykinin has a role in the exercise pressor reflex elicited by static muscle contraction. The purpose of this study was to quantify the release of bradykinin from contracting skeletal muscle. In 18 cats, blood samples were withdrawn directly from the venous effluent of the triceps surae muscles immediately before and after 30 s of static contraction producing peak muscle tensions of 33, 50, and 100% of maximum electrically stimulated contraction. Contractions producing muscle tensions of 50 and 100% of maximum increased muscle venous bradykinin levels by 27 +/- 9 and 19 +/- 10 pg/ml, respectively. Conversely, 33% maximum contraction did not alter muscle venous bradykinin concentrations. However, when captopril was administered to slow the degradation of bradykinin, muscle venous bradykinin increased from 68 +/- 15 pg/ml at rest to 106 +/- 18 after contractions of 33% of maximum. When muscle ischemia was induced by 2 min of arterial occlusion before and during 30 s of 33% of maximum contraction, muscle venous bradykinin increased by 15 +/- 5 pg/ml. In addition, contraction-induced changes in muscle venous pH and lactate strongly correlated with bradykinin concentrations (r = 0.80 and 0.83, respectively). These data demonstrate that static contraction of relatively high intensity evokes the release of bradykinin from skeletal muscle and that ischemia, decreased pH, and increased lactate are strongly correlated with this release.
Splanchnic and muscle fructose metabolism during and after exercise
Authors: Ahlborg G. , Bjorkman O.
Published: December 2017

Regional substrate exchange was studied in 12 healthy males during 90 min of bicycle exercise at 30% of maximal O2 consumption with a 20-min recovery. Six subjects received an intravenous fructose infusion (8.5 mmol/min) from 40 min of exercise to the end of recovery. Splanchnic glucose output, muscle glucose uptake, arterial glucose, and insulin were uninfluenced by the infusion. The respiratory exchange ratio rose to 0.93 +/- 0.04, and arterial free fatty acids fell by 50% (P less than 0.05). Fructose was taken up by splanchnic tissues (45% of administered load), leg muscle (28%), and resting muscle (28%). During infusion, arterial lactate and pyruvate rose two- to threefold, and these substrates were released from splanchnic tissues and taken up by exercising and resting muscle. Splanchnic release of lactate, pyruvate, and glucose accounted for 78% of fructose uptake at 90 min of exercise. Uptake of fructose, lactate, and pyruvate accounted for 55% and together with glucose for 103% of the total oxidative metabolism by exercising muscle. The regional fructose uptakes and lactate exchanges persisted throughout recovery. The present results indicate that fructose infusion during leg exercise 1) results in increased carbohydrate oxidation from fructose, lactate, and pyruvate in exercising muscle, 2) exerts a glycogenic effect in resting muscle and liver during exercise and in liver and muscle recovering from exercise, and 3) does not interfere with glucose metabolism, and that fructose transport into muscle differs from that of glucose.
Almitrine mimics hypoxia in fetal sheep with lateral pontine lesions
Authors: Johnston B. M. , Moore P. J. , Bennet L. , Hanson M. A. , Gluckman P. D.
Published: December 2017

Almitrine bimesylate is a potent and long-lasting respiratory stimulant in adult species. It acts by stimulating the peripheral chemoreceptors, where it has been shown to accumulate specifically, although its exact mechanism of action is uncertain. In the fetal lamb, however, it produces a profound inhibition of breathing even after denervation of the peripheral chemoreceptors. In this respect its action is similar to hypoxia. To investigate whether almitrine is hypoxia mimetic, we examined the effect of almitrine in nine fetal lambs of 120-130 days gestation. Five had lesions in the lateral pons that changed the fetal depressive response to hypoxia to one of stimulation. In the remaining four fetuses, the lesions did not bilaterally encompass the appropriate area of the pons; thus they still showed the normal fetal depressive response to hypoxia and so acted as controls. Almitrine (10 mg iv) caused a pronounced stimulation of breathing that lasted 406 +/- 26 min in all five fetuses with lesions that caused a stimulatory response to hypoxia. However, in the remaining four fetuses, in which the response to hypoxia was inhibitory, almitrine caused an inhibition of breathing that lasted 184 +/- 28 min. We conclude that the action of almitrine is like that of hypoxia and that, because it acts specifically on the chemoreceptors, it may prove to be a useful tool in the study of possible central chemoreceptor mechanisms.
Late response of the upper airway of the rat to inhaled antigen
Authors: Xu L. J. , Eidelman D. H. , Bates J. H. , Martin J. G.
Published: December 2017

We studied the magnitude and time course of changes in upper airway resistance (Ruaw) of actively sensitized Brown-Norway rats after aerosol challenge with ovalbumin (OA). Two weeks after sensitization, eight rats were challenged by inhalation of aerosolized OA through the nose. The airway responses of these rats 5-10 h after OA challenge were compared with those of seven animals challenged with saline. Seven of eight test rats had increased Ruaw, and six displayed discrete late responses (LR). Ruaw during expiration was highly alinear so analysis was confined to Ruaw during inspiration (Ruaw,I). The Ruaw,I averaged over 5 h was 1.262 +/- 0.09 (SE) cmH2O.ml-1.s, 2.6 times the value for saline-challenged animals (0.476 +/- 0.143 cmH2O.ml-1.s), and it reached a peak value of 3.454 +/- 0.45 cmH2O.ml-1.s. The time to the peak of the LR was 446 +/- 37.3 min. The duration of the LR in the upper airway was 146 +/- 34.9 min. At the time corresponding to the peak value of Ruaw,I, the lung elastance in the test rats was double the value preceding the peak. Lung elastance was unchanged in the control group. We conclude that inhalation of antigen through the upper airway of the sensitized rat results in a substantial increase in upper airway resistance and a distinct LR. The predominant site of the change in respiratory system resistance is in the upper airway.
Respiratory input impedance in anesthetized paralyzed patients
Authors: Navajas D. , Farre R. , Canet J. , Rotger M. , Sanchis J.
Published: December 2017

Respiratory impedance (Zrs) was measured between 0.25 and 32 Hz in seven anesthetized and paralyzed patients by applying forced oscillation of low amplitude at the inlet of the endotracheal tube. Effective respiratory resistance (Rrs; in cmH2O.l-1.s) fell sharply from 6.2 +/- 2.1 (SD) at 0.25 Hz to 2.3 +/- 0.6 at 2 Hz. From then on, Rrs decreased slightly with frequency down to 1.5 +/- 0.5 at 32 Hz. Respiratory reactance (Xrs; in cmH2O.l-1.s) was -22.2 +/- 5.9 at 0.25 Hz and reached zero at approximately 14 Hz and 2.3 +/- 0.8 at 32 Hz. Effective respiratory elastance (Ers = -2pi x frequency x Xrs; in cmH2O/1) was 34.8 +/- 9.2 at 0.25 Hz and increased markedly with frequency up to 44.2 +/- 8.6 at 2 Hz. We interpreted Zrs data in terms of a T network mechanical model. We represented the proximal branch by central airway resistance and inertance. The shunt pathway accounted for bronchial distensibility and alveolar gas compressibility. The distal branch included a Newtonian resistance component for tissues and peripheral airways and a viscoelastic component for tissues. When the viscoelastic component was represented by a Kelvin body as in the model of Bates et al. (J. Appl. Physiol. 61: 873-880, 1986), a good fit was obtained over the entire frequency range, and reasonable values of parameters were estimated. The strong frequency dependence of Rrs and Ers observed below 2 Hz in our anesthetized paralyzed patients could be mainly interpreted in terms of tissue viscoelasticity. Nevertheless, the high Ers we found with low volume excursions suggests that tissues also exhibit plasticlike properties.
Maximal exercise capacity and oxygen consumption of lambs with an aortopulmonary left-to-right shunt
Authors: Gratama J. W. , Meuzelaar J. J. , Dalinghaus M. , Koers J. H. , Werre A. J. , Zijlstra W. G. , Kuipers J. R.
Published: December 2017

We determined maximal exercise capacity and measured hemodynamics in 10 6-wk-old lambs with an aortopulmonary left-to-right shunt [S, 57 +/- 11%, (SD)] and in 9 control lambs (C) during a graded treadmill test 8 days after surgery. Maximal exercise capacity (3.7 +/- 0.2 km/h and 10 +/- 5% inclination vs. 4.0 +/- 0.9 km/h and 15 +/- 0% inclination, P less than 0.02) and peak oxygen consumption (25 +/- 7 vs. 34 +/- 8 ml O2.min-1.kg-1, P less than 0.02) were both lower in the shunt than in the control lambs. This was due to a lower maximal systemic blood flow in the shunt lambs (271 +/- 38 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.01). Despite their high maximal left ventricular output, which was higher than in the control lambs (448 +/- 87 vs. 359 +/- 71 ml.min-1.kg-1, P less than 0.05), the left-to-right shunt could not be compensated for during maximal exercise because of a decreased reserve in heart rate (S: 183 +/- 22 to 277 +/- 38 beats/min; C: 136 +/- 25 to 287 +/- 29 beats/min) and in left ventricular stroke volume (S: 1.8 +/- 0.3 to 1.6 +/- 0.4 ml/kg; C: 1.0 +/- 0.3 to 1.3 +/- 0.2 ml/kg). We conclude that exercise capacity of shunt lambs is lower than that of control lambs, despite a good left ventricular performance, because a part of the reserves for increasing the left ventricular output is already utilized at rest.
Fluid balance in sheep lungs before and after extracorporeal perfusion
Authors: Roselli R. J. , Parker R. E. , Riddle W. R. , Pou N. A.
Published: December 2017

Lung fluid balance was studied in sheep under the following conditions: 1) unanesthetized, standing in a metabolic cage; 2) anesthetized, in a supine position; 3) 1 h after extracorporeal perfusion; and 4) either 4-6 h after extracorporeal perfusion (i.e., control experiments) or 1.5 h after left atrial pressure was increased by 15 cmH2O. Lung lymph flow rate (QL), plasma and lymph concentrations for nine protein fractions, urea permeability-surface area product (PS), urea effective diffusivity (D1/2S), and extravascular lung water (VE) were measured under each condition. Bloodless wet and dry lung weights were measured at the end of each experiment. QL increased and lymph-to-plasma concentration ratio for total proteins (L/P) decreased after the sheep were anesthetized and placed in a supine position. This possibly resulted from an increase in microvascular pressure induced by anesthesia and/or reorientation of the lungs. PS, D1/2S, and VE decreased, indicating a decrease in perfused surface area associated with a decreased cardiac output or alteration in lung orientation. After 90 min of extracorporeal perfusion, no significant differences were found in QL, PS, and D1/2S compared with those measured during the anesthetized period. No changes in PS or D1/2S could be detected after an average of 4.2 h of extracorporeal perfusion. The average bloodless wet-to-dry lung weight ratio [(W-D)/D] was 3.77 +/- 0.12, well within the range for normal sheep lungs. An increase in venous pressure of 15 cmH2O produced a response similar to that observed in the unanesthetized sheep lung lymph preparation: QL increased, L/P decreased, PS and D1/2S did not increase, and VE and (W-D)/D increased slightly.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary pressure-flow relationships in the fetal lamb during in utero ventilation
Authors: Reid D. L. , Thornburg K. L.
Published: December 2017

Pressure-flow relationships in the ventilated lung have not been previously determined in undelivered fetal sheep. Therefore we studied 11 late-gestation chronically prepared fetal sheep during positive-pressure ventilation with different gas mixtures to determine the roles of mechanical distension and blood gas tensions on pressure-flow relationships in the lung. Ventilation with 3% O2-7% CO2 produced a substantial fall in pulmonary vascular resistance even though arterial blood gases were not changed. Increases in pulmonary arterial PO2 during ventilation were associated with falls in pulmonary vascular resistance beyond that measured during mechanical distension. Decreases in pulmonary arterial PCO2 and associated increases in pH were also associated with falls in pulmonary vascular resistance. Pulmonary blood flow ceased at a pulmonary arterial pressure that exceeded left atrial pressure, indicating that left atrial pressure does not represent the true downstream component of driving pressure through the pulmonary vascular bed. The slope of the driving pressure-flow relationship in the normal mature fetal lamb was therefore different from the ratio of pulmonary arterial pressure to pulmonary arterial flow. We conclude that mechanical ventilation, increased PO2 and decreased PCO2, and/or increased pH has an important influence on the fall in pulmonary vascular resistance elicited by positive pressure in utero ventilation of the fetal lamb and that the downstream driving pressure for pulmonary blood flow exceeds left atrial pressure.
Impedance measurement during air and He-O2 breathing before and after salbutamol in normal subjects
Authors: Wouters E. F.
Published: December 2017

Total respiratory resistance and reactance from 4 to 52 Hz were determined by the method of forced pseudorandom noise oscillation in 20 normal male subjects before and after inhalation of 0.200 mg salbutamol (albuterol) and before and after the subjects were equilibrated with 80% He-20% O2. During air breathing, there was a statistically significant decrease of resistance values at lower frequencies after inhalation of salbutamol. When the subject was equilibrated with 80% He-20% O2, total respiratory resistance markedly decreased at all frequencies, and a negative frequency dependence of resistance was observed between 8 and 20 Hz. Resistance values further decreased during He-O2 breathing after inhalation of salbutamol. After inhalation of salbutamol, reactance values increased during air and He-O2 breathing. The density-dependent decrease of the real part of impedance can be explained by a decrease of turbulence in the larger airways. The bronchodilating effect of salbutamol was not influenced by a change in the physical properties of the inhaled gas. During He-O2 breathing, reactance values significantly decreased, resulting in an increase of resonant frequency due to a decrease of inductive reactance. It is concluded that an increase in the capacitance of the respiratory system must be supposed to explain the increase in reactance values after inhalation of the beta-adrenergic agonist salbutamol.
High-frequency characteristics of respiratory mechanics determined by flow interruption
Authors: Romero P. V. , Sato J. , Shardonofsky F. , Bates J. H.
Published: December 2017

When flow at the airway opening is suddenly interrupted, the pressure measured just behind the point of interruption generally exhibits certain characteristic features, including some rapid and highly damped oscillations immediately after the interruption. It has previously been assumed that these oscillations reflect ringing of central airways gas. In the present study we investigated this hypothesis by performing flow interruptions during relaxed expiration in normal, tracheostomized, anesthetized, paralyzed dogs while the lungs were filled with four different gas mixtures having widely varying physical properties. We found that the power spectrum of the oscillations exhibited two peaks. The larger peak was centered about a frequency that varied approximately linearly with the inverse of the square root of the gas density. The other peak was smaller and was located at approximately 70 Hz with all gas mixtures. The area under the power spectrum of the ringing varied approximately linearly with the density of the gas mixture. These results indicate that the larger peak in the power spectrum reflects the quarter-wave resonance of the gas in the airways, whereas the smaller peak reflects a tissue resonance.
Proton magnetic resonance of exercise-induced water changes in gastrocnemius muscle
Authors: Fotedar L. K. , Slopis J. M. , Narayana P. A. , Fenstermacher M. J. , Pivarnik J. , Butler I. J.
Published: December 2017

Exercise-induced water concentration changes have been determined in the medial gastrocnemius muscle noninvasively with image-guided in vivo proton magnetic resonance spectroscopy (MRS). These measurements were performed on seven normal male volunteers during and after isometric and ischemic-isometric exercise at 5, 10, and 20% maximum voluntary contraction (MVC). The observed water flux changes during different phases of exercise have been interpreted in terms of fluid transfer between the vasculature and exercising muscle. Good correlation between individual MVC and changes in water fluxes and the decay of water content was observed after 20% MVC exercise level. MRS results have been found to be consistent with those reported in the literature based on invasive biopsy techniques.
Protein metabolism in rat tibialis anterior muscle after stimulated chronic eccentric exercise
Authors: Wong T. S. , Booth F. W.
Published: December 2017

In another study (J. Appl. Physiol. 69: 1709-1717, 1990) we reported that gastrocnemius (GAST) muscle enlargement failed to occur after 10 wk of 192 contractions performed every 3rd or 4th day. This result was surprising because increased protein synthesis rates were determined after an initial acute exercise bout with the same paradigms. In the same set of animals, tibialis anterior (TA) muscles were enlarged 16-30% compared with sedentary control muscles after the same chronic training regimen. This indicated that the regulation of protein expression may be different between the GAST and TA muscles. The present experiment attempted to define and explain these differences by comparing changes in various indexes of protein metabolism in TA with the same parameters determined in the accompanying study for the GAST. As in the GAST, results showed that TA protein synthesis rates are increased by acute exercise and principally regulated by translational and possibly posttranslational mechanisms. The differential response in muscle mass between the GAST and TA muscles after training may be due, in part, to greater relative resistances imposed on the TA than on the GAST that result in a more-prolonged effect on protein synthesis rates, with lower numbers of stimulated contractions required to stimulate increases in protein synthesis. Data also revealed that although as little as 1 min of total contractile duration (24 repetitions) increased TA protein synthesis rate by 30%, 8 min of total contractile duration (192 repetitions) further increased TA protein synthesis rates to only 45% above control.
Positive adaptations to weight-lifting training in the elderly
Authors: Brown A. B. , McCartney N. , Sale D. G.
Published: December 2017

Maximal weight-lifting performance, isometric strength, isokinetic torque, whole muscle and individual fiber cross-sectional areas, and muscle evoked contractile properties were assessed in 14 elderly males before and after 12 wk of weight-lifting training. Dynamic elbow flexion training of one arm resulted in a significant 48% mean increase in the maximal load that could be lifted once (1 RM) and a smaller improvement in isokinetic torque (8.8%) but no change in isometric strength. In the contralateral control arm, 1 RM and isokinetic torque increased by 12.7 and 6.5%, respectively, but isometric strength did not change. The interpolated twitch technique confirmed complete motor unit activation during a maximal isometric contraction of the elbow flexors before and after the training. Bilateral leg press training effected mean increases of 17 and 23% in isokinetic torque and dynamic lifting capacity, respectively. The mean maximal cross-sectional area of the elbow flexors (biceps brachii and brachialis) increased by 17.4% in the trained arm but did not change the control arm. The increase in the mean area of type II fibers in the biceps brachii muscle in the trained arm (30.2%) was greater than the corresponding change in the control arm (10.7%, P less than 0.05). The most significant change in the evoked contractile properties of the trained elbow flexors was the increase in twitch half-relaxation time. It is concluded that older individuals retain the potential for significant increases in strength performance and upper limb muscle hypertrophy in response to overload training.
Atelectasis affects the rate of arterial desaturation during obstructive apnea
Authors: Fletcher E. C. , Goodnight S. , Miller T. , Luckett R. A. , Rosborough J. , Munafo D. , Muniz S.
Published: December 2017

Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed.
Evaluation of animal models for the study of exercise-induced muscle enlargement
Authors: Timson B. F.
Published: December 2017

Skeletal muscle is known to enlarge in response to high-resistance training programs in humans. Study of the cellular mechanisms of muscle enlargement and the adaptations of muscle to strength-training programs has been difficult because of the need to analyze entire muscles. This precludes the use of human subjects in many experiments of this nature. Several animal models have been developed for the study of muscle enlargement; these models basically fall into three categories: 1) stretch hypertrophy, 2) compensatory hypertrophy, and 3) exercise-induced hypertrophy. This review attempts to analyze these models as models of muscle enlargement produced by strength training in humans. Three areas must be considered when evaluating animal models of human muscle enlargement produced by strength training: 1) response topography, 2) magnitude of enlargement, and 3) muscle fiber adaptations produced as a result of the enlargement. Based on these considerations, it is concluded that none of the animal models currently in use truly represents the human strength-training situation under all conditions. All three models, however, provide valuable information about the plasticity of skeletal muscle in response to a broad spectrum of muscle enlargement.
Cold-induced changes in breathing pattern as a strategy to reduce respiratory heat loss
Authors: Diesel D. A. , Tucker A. , Robertshaw D.
Published: December 2017

Thermoregulatory benefits of cold-induced changes in breathing pattern and mechanism(s) by which cold induces hypoventilation were investigated using male Holstein calves (1-3 mo old). Effects of ambient temperatures (Ta) between 4 and 18 degrees C on ventilatory parameters and respiratory heat loss (RHL) were determined in four calves. As Ta decreased, respiratory frequency decreased 29%, tidal volume increased 35%, total ventilation and RHL did not change, and the percentage of metabolic rate attributed to RHL decreased 26%. Total ventilation was stimulated by increasing inspired CO2 in six calves (Ta 4-6 degrees C), and a positive relationship existed between respiratory frequency and expired air temperature. Therefore, cold-exposed calves conserve respiratory heat by decreasing expired air temperature and dead space ventilation. Compared with thermoneutral exposure (16-18 degrees C), hypoventilation was induced by airway cold exposure (4-6 degrees C) alone and by exposing the body but not the airways to cold. Blocking nasal thermoreceptors with topical lidocaine during airway cold exposure prevented the ventilatory response but did not lower hypothalamic temperature. Hypothalamic cooling (Ta 16-18 degrees C) did not produce a ventilatory response. Thus, airway temperature but not hypothalamic temperature appears to control ventilation in cold-exposed calves.
Changes in lung mechanics and reactivity with age after viral bronchiolitis in beagle puppies
Authors: Quan S. F. , Lemen R. J. , Witten M. L. , Sherrill D. L. , Grad R. , Sobonya R. E. , Ray C. G.
Published: December 2017

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.
Mechanisms of extracellular hydrogen peroxide clearance by alveolar type II pneumocytes
Authors: Engstrom P. C. , Easterling L. , Baker R. R. , Matalon S.
Published: December 2017

This study quantified the ability of freshly isolated alveolar type II (ATII) pneumocytes to reduce extracellularly produced hydrogen peroxide (H2O2) and identify the mechanisms involved. ATII cells were isolated to high purity (greater than 85%) from rabbit lungs by enzymatic digestion and Percoll centrifugation and suspended in Eagle's minimum essential medium (MEM). They were then coincubated with either 500 microM xanthine and 10 mU/ml xanthine oxidase (XO; pH 7.4; 25 degrees C) or 300 microM H2O2. The extracellular H2O2 concentration [H2O2] was measured in the following conditions over a 60-min period: 1) MEM alone, 2) untreated (control), 3) 3-amino-1,2,4-triazole (ATZ)-treated, or 4) 1-chloro-2,4-dinitrobenzene-treated ATII cells. Addition of xanthine and XO to MEM alone resulted in a time-dependent increase in [H2O2], reaching a plateau value of approximately 300 microM after 45 min. In the presence of control ATII cells (1 x 10(6) cells/ml), [H2O2] remained at control levels. When coincubated with 300 microM H2O2, ATII cells cleared H2O2 at a higher rate than an equivalent amount of free catalase. Incubation with ATZ decreased ATII cell catalase activity by 89% and significantly impaired their ability to clear H2O2 (half-life = 18.1 +/- 2.7 vs. 1.3 +/- 0.1 min, P less than 0.01). ATZ-treated cells were more susceptible to oxidant injury, as shown by their decreased ability to exclude trypan blue after 60 min of H2O2 exposure. On the other hand, glutathione-depleted cells scavenged H2O2 at the same rate as controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Cystic fibrosis, vasoactive intestinal polypeptide, and active cutaneous vasodilation
Authors: Savage M. V. , Brengelmann G. L. , Buchan A. M. , Freund P. R.
Published: December 2017

The transmitter substance for the active cutaneous vasodilation that accompanies sweating during hyperthermia in humans is unknown. Hokfelt et al. (Nature Lond. 284: 515-521, 180) hypothesized that it is vasoactive intestinal polypeptide (VIP) that is cotransmitted with acetylcholine. Heinz-Erian et al. (Science Wash. DC 229: 1407-1408, 1985) reported that VIP innervation is sparse in the skin of persons with cystic fibrosis (CF). A corresponding attenuation of active vasodilation in these subjects would be evidence that VIP is involved in this effector mechanism of human thermor-regulation. Immunocytochemical analysis of skin biopsies from four men with CF confirmed that VIP innervation was sparse. We also analyzed immunoreactivity for calcitonin gene-related peptide (CGRP; normal), substance P (normal), and neuropeptide Y (low). VIP-immunoreactive Merkel cells were abnormal. Despite sparse VIP-immunoreactive innervation, our CF subjects' cutaneous vascular responses to hyperthermia were normal. Because VIP was not completely absent, this evidence is insufficient to rule out VIP as the vasodilator transmitter. However, the CGRP and substance P innervation we observed could mean that release of one or both of these peptides was the mechanism of the fully developed active cutaneous vasodilation.
Model simulations of gas mixing and ventilation distribution in the human lung
Authors: Verbanck S. , Paiva M.
Published: December 2017

A new lung model that incorporates intra-acinar diffusion- and convection-dependent inhomogeneities (DCDI) and interregional and intraregional convection-dependent inhomogeneities (CDI) is described. The model is divided into two regions, each containing two subunits. Each of the four subunits in the model consists of a multi-branch-point structure, based on the anatomic data from Haefeli-Bleuer and Weibel (Anat. Record 220: 401-414, 1988). The subunit turnover (TO), i.e., the ratio of subunit tidal to resting volume, and the flow sequences (FS) between the subunits are used as model parameters. The model simulates the normalized alveolar slope (Sn), Fowler and Bohr dead space (VDF and VDB), and alveolar mixing efficiency (AME) as a function of breath number (n) during a multiple-breath N2 washout (MBNW). For the first breath of the MBNW, these indexes are poorly sensitive to the TO distribution or FS between the subunits. However, as the washout proceeds, the n dependence of both Sn and VDB becomes markedly distinct for simulations with different TO and FS. VDF increases only slightly with n during the MBNW for a large range of TO and FS combinations, and AME is independent of FS. Comparison of published experimental observations with model simulations gave a consistent picture of ventilation maldistribution in the human lung. MBNW simulations in conditions of weightlessness, which will be performed shortly in Spacelab, suggest that it will be possible to evaluate quantitatively the intraregional elastic inhomogeneities in the human lung.
Cholinergic stimulation of the pons depresses respiration in decerebrate cats
Authors: Kimura H. , Kubin L. , Davies R. O. , Pack A. I.
Published: December 2017

The injection of carbachol into the pontine tegmentum of decerebrate cats evokes a postural motor atonia that has many of the characteristics of the atonia of natural rapid-eye-movement (REM) sleep (Morales et al. J. Neurophysiol. 57: 1118-1129, 1987). We have used the carbachol-injected decerebrate cat to study the changes in respiratory neuronal activity that accompany the atonia. The activities of representative respiratory motor nerves--phrenic, intercostal, and hypoglossal--and that of a motor branch of C4 were recorded in decerebrate, vagotomized, paralyzed, and artificially ventilated cats. After the microinjection of carbachol, there was a profound suppression of activity in all the nerves and a decrease in respiratory rate. This was a consistent stereotyped response in which the magnitude of the suppression of respiratory-related activity was phrenic (to approximately 65% of control) less than inspiratory intercostal (approximately 50%) less than hypoglossal (approximately 10%) less than expiratory intercostal (approximately 5%). The decrease in respiratory rate (to approximately 70% of control) was caused by a prolongation of both inspiratory and expiratory durations. Complete reversal of the carbachol effect was elicited by the microinjection of atropine into the same site as the carbachol injection. This allowed us to produce a second episode of atonia by the injection of carbachol into the contralateral pons. Thus we have demonstrated the existence of neural pathways originating in the cholinoceptive cells of the pons that have the potential to powerfully and differentially depress various respiratory motoneuronal pools and to reduce the respiratory rate. These pathways are likely to be activated along with the atonia of REM sleep.
Hepatic oxygen and lactate extraction during stagnant hypoxia
Authors: Samsel R. W. , Cherqui D. , Pietrabissa A. , Sanders W. M. , Roncella M. , Emond J. C. , Schumacker P. T.
Published: December 2017

As O2 delivery falls, tissues must extract increasing amounts of O2 from blood to maintain a normal O2 consumption. Below a critical delivery threshold, increases in O2 extraction cannot compensate for the falling delivery, and O2 uptake falls in a supply-dependent fashion. Numerous studies have identified a critical delivery in whole animals, but the regional contributions to the critical O2 delivery are less fully understood. In the present study, we explored the limits of O2 extraction in the isolated liver, seeking to determine 1) the normal relationship between O2 consumption and delivery in the liver and 2) the relationship of hepatic lactate extraction to the drop in hepatic O2 consumption at low O2 deliveries. To answer these questions, using support dogs as a source for oxygenated metabolically stable blood, we studied eight pump-perfused canine livers. By lowering the blood flow in a model of stagnant hypoxia, we explored the relationship between O2 consumption and delivery over the entire physiological range of O2 delivery. The critical O2 delivery was 28 +/- 5 (SD) ml.kg-1.min-1; the livers extracted 68 +/- 9% of the delivered O2 before reaching supply dependence. This suggests that the liver has an O2 extraction capacity quite similar to the body as a whole and not different from other tissues that have been isolated. At high blood flows, the livers extracted approximately 10% of the lactate delivered by the blood, but the arteriovenous lactate differences were small. At low blood flows, however, the livers changed from lactate consumption to production. The O2 delivery coinciding with the dropoff in lactate extraction did not differ significantly from the critical O2 delivery. We conclude that reductions in lactate uptake by the liver do not precede the transition to O2 supply dependence.
Abnormal oxidative metabolism and O2 transport in muscle phosphofructokinase deficiency
Authors: Lewis S. F. , Vora S. , Haller R. G.
Published: December 2017

Humans who lack availability of carbohydrate fuels may provide important models for the study of physiological control mechanisms. We compared seven patients who had unavailability of muscle glycogen and blood glucose as oxidative fuels due to muscle phosphofructokinase deficiency (PFKD) with five patients who had a selective defect in long-chain fatty acid oxidation due to carnitine palmitoyltransferase deficiency (CPTD) and with six healthy subjects. Peak cycle exercise work rate, peak O2 uptake (Vo2), and arteriovenous O2 difference were markedly lower (P less than 0.001) for PFKD patients (23 +/- 6 W, 14 +/- 2 ml.min-1.kg-1, and 7.1 +/- 0.5 ml/dl, respectively) than for CPTD patients (142 +/- 33 W, 31 +/- 4 ml.min-1.kg-1, and 15.0 +/- 0.8 ml/dl, respectively) or healthy subjects (171 +/- 17 W, 36 +/- 1 ml.min-1.kg-1, and 16.4 +/- 0.7 ml/dl, respectively). Peak cardiac output (Q) was similar (P less than 0.05) in all three groups, but the slope of increase in Q (l/min) on Vo2 (l/min) from rest to exercise (delta Q/ delta Vo2) was more than twofold greater (P less than 0.001) for PFKD patients (11.2 +/- 1.2) than for CPTD patients (4.6 +/- 0.6) and healthy subjects (4.6 +/- 0.2). Increasing availability of blood-borne oxidative substrates capable of metabolically bypassing the defect at phosphofructokinase (by fasting plus prolonged moderate exercise to increase plasma free fatty acids or by iv lactate infusion) increased peak work rate, Vo2, and arteriovenous O2 difference, lacked consistent effect on peak Q, and normalized delta Q/ delta Vo2 in PFKD patients. The results extend our previous observations in patients with a block in muscle glycogen but not blood glucose oxidation due to phosphorylase deficiency and imply that specific unavailability of muscle glycogen as an oxidizable fuel is primarily responsible for abnormal muscle oxidative metabolism and associated exercise intolerance and exaggerated delta Q/ delta Vo2 in muscle PFKD. The findings also endorse the concept that factors closely linked with muscle oxidative phosphorylation participate in regulating delta Q/ delta Vo2, likely via activation of metabolically sensitive muscle afferents.
Evidence for hypoxic depression of CO2-ventilation response in carotid body-resected humans
Authors: Honda Y. , Hashizume I.
Published: December 2017

Steady-state CO2-ventilation response curves with hyperoxia (end-tidal PO2 greater than 200 Torr) and mild hypoxia (end-tidal PO2 approximately equal to 60 Torr) were compared in five carotid body-resected (BR) patients and five control patients. The data were analyzed by fitting a linear equation, V = S(PETCO2-B), where V is minute ventilation S is the response curve slope. PETCO2 is end-tidal PCO2, and B is the response curve threshold. S slightly increased from hyperoxia to hypoxia in both BR and control groups. On the other hand, B moderately increased with hypoxia in BR patients, whereas it slightly decreased in controls. These changes were all not significant. However, in accordance with the change in B, the response curve to hypoxia at V of 10 1/min was significantly shifted in opposite directions in the two groups, i.e., rightward and leftward shift in BR and control groups, respectively. Thus the average magnitude of V calculated at PETCO2 of 40 Torr in hypoxia was significantly lower in BR patients than in controls (P less than 0.01). We conclude that this hypoxic depression of the CO2-ventilation response found in BR patients may have resulted, at least in part, from modulation of the brain stem neural mechanisms that were elicited by loss of afferent discharges from the carotid body.
Criteria for analysis of arterial and venous occlusion
Authors: Hakim T. S.
Published: December 2017

To provide a better understanding of analysis of arterial (AO) and venous occlusion (VO) tracings, using a constant and nonpulsatile perfusion pressure system, we set up an isolated in situ dog lobe preparation perfused with autologous blood. Four signals were recorded: arterial pressure, arterial inflow rate, venous pressure, and venous outflow rate. The four signals were recorded into the memory of a computer. When flow into the lobe was abruptly stopped (AO), flow out of the lung continued unchanged for approximately 150 ms and then decreased slowly to zero. Likewise, when flow out of the lung was abruptly stopped (VO), the flow into the lung continued unchanged for approximately 130 ms and then decreased slowly to zero. A monoexponential curve was fitted to different stretches of data between 0.1 and 5 s postocclusion and extrapolated to the instant of occlusion (defined here as the instant when flow at the site of occlusion becomes zero). The results indicate that 1) the first 150 ms postocclusion should be avoided because of the oscillatory artifacts generated by the occlusion maneuver, 2) use of a long segment of postocclusion data (5 s) tends to underestimate the middle pressure gradient and overestimate the arterial and venous pressure gradients, and 3) the changes in segmental vascular resistance under different experimental conditions were found to be unaffected by the criteria of analysis. Analysis of the postocclusion (AO and VO) tracings was found to be most compatible with the double-occlusion capillary pressure by fitting a stretch of data between 0.2 and 2.5 s postocclusion and extrapolating back to the instant when flow becomes zero at the site of occlusion but no earlier.
Physiological basis for resonant frequencies in respiratory system impedances in dogs
Authors: Jackson A. C. , Lutchen K. R.
Published: December 2017

The lumped six-element model of the respiratory system proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956) has often been used to analyze respiratory system impedance (Zrs) data. This model predicts a resonance (relative minimum in Zrs) at fr between 6 and 10 Hz and an antiresonance (relative maximum in Zrs) at far at higher frequencies (greater than 64 Hz). The far is due to the lumped tissue inertance (Iti) and the alveolar gas compression compliance (Cg). An fr and far have been recently reported in humans, but the far was shown to be not related to Iti and Cg, but instead it is the first acoustic antiresonance of the airways due to their axial dimensions). Zrs data to frequencies high enough to include the far have not been reported in dogs. In this study, we measured Zrs in dogs for frequencies between 5 and 320 Hz and found an fr at 7.5 +/- 1.6 Hz and two far at 97 +/- 13 and 231 +/- 27 Hz (far,1 and far,2, respectively). When breathing 80% He-20% O2, the fr shifted to 14 +/- 2 Hz, far,1 did not change (98 +/- 9 Hz), and far,2 increased to greater than 320 Hz. The behavior of fr and far,1 is consistent with the structure-function implied by the six-element model. However, the presence of an far,2 is not consistent with this model, because it is the airway acoustic antiresonance not represented in the model. These results indicate that, for frequencies that include the fr and far,1, the six-element model can be used to analyze Zrs data and reliable estimates of the model's parameters can be extracted by fitting the model to the data. However, more complex models must be used to analyze Zrs data that include far,2.
Comparison of muscle sympathetic responses to hemorrhage and lower body negative pressure in humans
Authors: Rea R. F. , Hamdan M. , Clary M. P. , Randels M. J. , Dayton P. J. , Strauss R. G.
Published: December 2017

We compared changes in muscle sympathetic nerve activity (SNA) during graded lower body negative pressure (LBNP) and 450 ml of hemorrhage in nine healthy volunteers. During LBNP, central venous pressure (CVP) decreased from 6.1 +/- 0.4 to 4.5 +/- 0.5 (LBNP -5 mmHg), 3.4 +/- 0.6 (LBNP -10 mmHg), and 2.3 +/- 0.6 mmHg (LBNP -15 mmHg), and there were progressive increases in SNA at each level of LBNP. The slope relating percent change in SNA to change in CVP during LBNP (mean +/- SE) was 27 +/- 11%/mmHg. Hemorrhage of 450 ml at a mean rate of 71 +/- 5 ml/min decreased CVP from 6.1 +/- 0.5 to 3.7 +/- 0.5 mmHg and increased SNA by 47 +/- 11%. The increase in SNA during hemorrhage was not significantly different from the increase in SNA predicted by the slope relating percent change in SNA to change in CVP during LBNP. These data show that nonhypotensive hemorrhage causes sympathoexcitation and that sympathetic responses to LBNP and nonhypotensive hemorrhage are similar in humans.