bluuebunny/crossref_metadata_2025 huggingface dataset:
Filtration profile in isolated zone 1 and zone 3 dog lungs at constant high alveolar pressure
Authors: Gropper M. A. , Bhattacharya J. , Staub N. C.
Published: December 2017

We measured the rate of liquid filtration in isolated dog lung lobes inflated to a constant alveolar pressure of 25 cmH2O and with all open vessels filled with plasma. We measured lung weight gain at vascular pressures ranging from 5 to 40 cmH2O relative to pleural pressure. We confirmed that under zone 1 conditions the "arterial" and "venous" extra-alveolar segments have essentially the same filtration characteristics. Using the combined extra-alveolar vascular system, we determined when recruitment of filtration surface area occurred as we increased vascular pressure from 0 to 40 cmH2O. Based on an abrupt increase in filtration rate as vascular pressure approached the zone 1/3 boundary, we infer that a sudden recruitment of exchange surface area occurred at that point. Based on the slopes of the zone 1 and zone 3 filtration profiles, we conclude that extra-alveolar vascular segments contribute approximately 25% of total to filtration in the lung under zone 3 conditions, although the exact vessels filtering under zone 1 conditions have yet to be determined. Our analysis of the data supports the concept that there is a difference in the perimicrovascular pressure around alveolar and extra-alveolar vessels, which in part may account for the apparent high filtration fraction apportioned to extra-alveolar vessels.
Carbohydrate metabolism in human skeletal muscle during exercise is not regulated by G-1,6-P2
Authors: Katz A. , Sahlin K. , Henriksson J.
Published: December 2017

Glucose 1,6-bisphosphate (G-1,6-P2) is a potent activator of phosphofructokinase (PFK) and an inhibitor of hexokinase in vitro. It has been suggested that increases in G-1,6-P2 are a main means by which PFK can achieve significant catalytic function in vivo despite falling pH and that increases in G-1,6-P2 will inhibit hexokinase in vivo. The purpose of the present study was to determine whether contraction-induced changes in flux through PFK and hexokinase are associated with changes in G-1,6-P2 in skeletal muscle. Ten men performed bicycle exercise for 10 min at 40 and 75% of maximal O2 uptake (VO2max) and to fatigue [4.8 +/- 0.6 (SE) min] at 100% VO2max. Biopsies were obtained from the quadriceps femoris muscle at rest and after each work load and analyzed for G-1,6-P2. G-1,6-P2 averaged 111 +/- 13 mumol/kg dry wt at rest and 121 +/- 16, 123 +/- 15, and 123 +/- 11 mumol/kg dry wt after the low-, moderate-, and high-intensity exercise bouts, respectively (P less than 0.05 for all means vs. rest). Flux through PFK was estimated to increase exponentially as the exercise intensity increased and muscle pH decreased at the higher work loads, whereas flux through hexokinase was estimated to increase during exercise at 40 and 75% VO2max but decrease sharply at 100% VO2max. These data demonstrate that flux through neither PFK nor hexokinase is mediated by changes in G-1,6-P2 in human skeletal muscle during short-term dynamic exercise.
Thermoregulatory responses of middle-aged and young men during dry-heat acclimation
Authors: Pandolf K. B. , Cadarette B. S. , Sawka M. N. , Young A. J. , Francesconi R. P. , Gonzalez R. R.
Published: December 2017

Thermoregulatory responses during heat acclimation were compared between nine young (mean age 21.2 yr) and nine middle-aged men (mean age 46.4 yr) who were matched (P greater than 0.05) for body weight, surface area, surface area-to-weight ratio, percent body fat, and maximal aerobic power. After evaluation in a comfortable environment (22 degrees C, 50% relative humidity), the men were heat acclimated by treadmill walking (1.56 m/s, 5% grade) for two 50-min exercise bouts separated by 10 min of rest for 10 consecutive days in a hot dry (49 degrees C ambient temperature, 20% relative humidity) environment. During the first day of heat exposure performance time was 27 min longer (P less than 0.05) for the middle-aged men, whereas final rectal and skin temperatures and heart rate were lower, and final total body sweat loss was higher (P less than 0.05) compared with the young men. These thermoregulatory advantages for the middle-aged men persisted for the first few days of exercise-heat acclimation (P less than 0.05). After acclimation no thermoregulatory or performance time differences were observed between groups (P greater than 0.05). Sweating sensitivity, esophageal temperature at sweating onset, and the sweating onset time did not differ (P greater than 0.05) between groups either pre- or postacclimatization. Plasma osmolality and sodium concentration were slightly lower for the young men both pre- and postacclimatization; however, both groups had a similar percent change in plasma volume from rest to exercise during these tests.(ABSTRACT TRUNCATED AT 250 WORDS)
Ventilatory responses to increased blood flow and decreased lung volume in awake dogs
Authors: Chow E. , Cha E. J. , Yamashiro S. M.
Published: December 2017

The effect of decreased lung volume on ventilatory responses to arteriovenous fistula-induced increased cardiac output was studied in four chronic awake dogs. Lung volume decreases were imposed by application of continuous negative-pressure breathing of -10 cmH2O to the trachea. The animals were surgically prepared with chronic tracheostomy, indwelling carotid artery catheter, and bilateral arteriovenous femoral shunts. Control arteriovenous blood flow was 0.5 l/min, and test flow level was 2.0 l/min. Arterial blood CO2 tension (PaCO2) was continuously monitored using an indwelling Teflon membrane mass spectrometer catheter, and inhaled CO2 was given to maintain isocapnia throughout. Increased fistula flow alone led to a mean 52% increase in cardiac output (CO), whereas mean systemic arterial blood pressure (Psa) fell 4% (P less than 0.01). Negative-pressure breathing alone raised Psa by 3% (P less than 0.005) without a significant change in CO. Expired minute ventilation (VE) increased by 27% (P less than 0.005) from control in both of these conditions separately. Combined increased flow and negative pressure led to a 50% increase in CO and 56% increase in VE (P less than 0.0025) without any significant change in Psa. Effects of decreased lung volume and increased CO appeared to be additive with respect to ventilation and to occur under conditions of constant PaCO2 and Psa. Because both decreased lung volume and increased CO occur during normal exercise, these results suggest that mechanisms other than chemical regulation may play an important role in the control of breathing and contribute new insights into the isocapnic exercise hyperpnea phenomenon.
Measurements of metabolic rate in rats: a comparison of techniques
Authors: Musch T. I. , Bruno A. , Bradford G. E. , Vayonis A. , Moore R. L.
Published: December 2017

Two different open-circuit techniques of measuring metabolic rate were examined in rats at rest and during exercise. With one technique ambient air was drawn through a tightly fitting mask that was secured to the rat's head, whereas with the other technique the rat was placed into and ambient air was drawn through a Plexiglas box. Two series of experiments were performed. In series I, two groups were studied that consisted of rats that had received myocardial infarctions produced by coronary arterial ligations and rats that had received sham operations. In this series of experiments O2 uptake (VO2) and CO2 production (VCO2) were measured at rest, during four levels of submaximal exercise, and during maximal treadmill exercise in the same group of rats by use of both techniques in random order. VO2, VCO2, and the calculated respiratory exchange ratio (R) were similar at rest, during the highest level of submaximal exercise (20% grade, 37 m/min), and during maximal exercise; however, VO2 and VCO2 were significantly lower with the metabolic box technique compared with the mask technique during the three lowest work loads (5% grade, 19 m/min; 10% grade, 24 m/min; and 15% grade, 31 m/min). These differences appeared to be associated with a change in gait produced when the mask was worn. In series II, the arterial blood gas and acid-base responses to both submaximal and maximal exercise were measured using both techniques in a group of instrumented rats that had a catheter placed into the right carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of ischemia on VO2, tension, and vascular resistance in contracting canine skeletal muscle
Authors: Gorman M. W. , Barclay J. K. , Sparks H. V.
Published: December 2017

This study examined the changes in O2 consumption (VO2), vascular resistance, and tension development during skeletal muscle contractions at reduced flow. We tested the hypothesis that when VO2 is limited by O2 supply, the skeletal muscle vasculature is not maximally dilated because of the fall in contractile force that accompanies the decrease in O2 supply. During 30 min of ischemic contractions, tension fell by 45 +/- 4% and VO2 fell 54 +/- 1% from preischemic levels. The O2 cost per unit tension did not change compared with nonischemic muscles. After the initial flow reduction, flow fell an additional 16 +/- 3% over 30 min. Adenosine infusion after 30 min of ischemic contractions increased flow by 42 +/- 3% but increased VO2 by only 9.8 +/- 2.3% and had no effect on tension development. When perfusion pressure was returned to normal after 30 min of ischemic contractions, twitch tension did not begin to recover within 20 min but tetanic tension showed a small improvement. VO2, although increased, remained well below the preischemic level. These results suggest that because of the reduced tension during ischemic contractions, the O2 supply-to-consumption ratio is nearly normal, which could explain the presence of the vasodilator reserve. The defect in tension development is long lived, producing a "stunned" muscle in which excess O2 supply does not restore function or VO2 to normal.
Methylcholine-activated eccrine sweat gland density and output as a function of age
Authors: Kenney W. L. , Fowler S. R.
Published: December 2017

The purpose of this investigation was to examine eccrine sweat gland responsiveness to intradermal injections of methylcholine (MCh) across three age groups of men [young (Y) = 22-24; middle (M) = 33-40; older (O) = 58-67 yr old, n = 5 per group]. Subjects were matched with respect to maximum O2 consumption, body size, and body composition, and were thoroughly heat acclimated before participation. Randomly ordered concentrations of acetyl-beta-methylcholine chloride ranging from 0% (saline) to 0.1% (5 x 10(-3) M) were injected into the skin of the dorsal thigh in a thermoneutral environment, and activated sweat glands were photographed at 30-s intervals for the next 8 min. Density of MCh-activated glands was independent of both age and [MCh] (e.g., 2 min after injection of 5 x 10(-3) M [MCh]: Y = 45 +/- 7, M = 46 +/- 12, O = 42 +/- 5 glands/cm2). However, sweat gland output (SGO) per active gland was significantly lower for the O group and failed to increase with increasing [MCh] above 5 x 10(-4) M. When MCh (5 x 10(-3) M) was injected after 1 h of exercise in the heat, higher SGO's were elicited in each group; however, the SGO of the O group was again significantly lower than that of the Y group (91 +/- 11 vs. 39 +/- 4 ng/gland, P less than 0.02) with the M group intermediate (69 +/- 11 nl/gland; 2 min postinjection data).(ABSTRACT TRUNCATED AT 250 WORDS)
Increase in pulmonary capillary permeability in dogs exposed to 100% O2
Authors: Royer F. , Martin D. J. , Benchetrit G. , Grimbert F. A.
Published: December 2017

Changes in pulmonary capillary filtration induced by hyperoxia were investigated in 15 dogs. After 12 h of normobaric hyperoxic exposure, animals were anesthetized and artificially ventilated with 100% O2. A pulmonary lymphatic vessel was cannulated, and lymph flow and protein content were measured together with pulmonary and systemic hemodynamics. An increase in pulmonary capillary filtration was found when compared with reference data (normoxic dogs in similar conditions) gathered from available literature: lymph flow increased from 21.8 +/- 13.4 to 125.2 +/- 131.6 microliter/min, and the lymph-to-plasma protein concentration ratio increased from 0.67 +/- 0.08 to 0.78 +/- 0.08. To characterize the mechanisms involved, left atrial pressure was increased in two stages (approximately 10 and approximately 25 mmHg). The results clearly indicated an increase in pulmonary capillary permeability as evidenced by a decrease of the minimal estimate of the protein reflection coefficient from 0.62 +/- 0.05 to 0.42 +/- 0.05.
Role of brain lactic acidosis in hypoxic depression of respiration
Authors: Neubauer J. A. , Simone A. , Edelman N. H.
Published: December 2017

The role of lactic acidosis of progressive brain hypoxia (PBH) as both a central chemoreceptor stimulant and a general respiratory depressant was assessed by preventing lactate formation both locally and globally with dichloroacetate (DCA). Phrenic nerve activity (PN) and ventral medullary pH (Vm pH) responses to PBH (1% CO-40% O2-balance N2) were determined in anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats while fraction of end-tidal CO2 (FETCO2) and mean arterial blood pressure (MABP) were maintained constant. Topical DCA near the central chemoreceptors prevented the progressive Vm acidosis of PBH and was associated with a slightly greater depression of PN for any given level of brain hypoxia [75 +/- 12% base-line mock cerebrospinal fluid compared with 63 +/- 11% base-line topical DCA at O2 content of arterial blood (CaO2) of 7.5 ml O2/dl]. Systemic DCA also prevented the progressive acidosis of PBH and significantly altered the profile of depression with PBH. Before DCA, PBH produced a progressive reduction in PN after reducing CaO2 by 20%. After DCA, PN was not significantly depressed until CaO2 was reduced to very low levels, whereupon there was a sharp decline in PN. Before DCA, reducing CaO2 to 6 ml O2/dl reduced PN by 41 +/- 16%, whereas after DCA there was no significant reduction in PN (4 +/- 5%). We conclude that 1) lactic acidosis near the central chemosensitive regions does produce a small stimulation of respiration during PBH but that 2) the overwhelming response to central lactic acidosis of PBH is respiratory depression.
Effect of amrinone on diaphragm blood flow
Authors: Bundy R. J. , Arnold J. S. , DiMarco A. F. , Hussein F. , Supinski G. S.
Published: December 2017

The purpose of the present study was to examine the effect of amrinone, a drug known to augment cardiac output and dilate peripheral vascular beds, on diaphragm blood flow. Studies were performed on 12 anesthetized mechanically ventilated dogs in which strips of left costal diaphragm were developed in situ. Strip blood flow was assessed with a drop counter attached to a catheter tied into the phrenic veins' draining strips. Strip tension was measured with an isometric force transducer. Amrinone was administered as an intravenous bolus of 2 mg/kg followed by a continuous infusion of 25 micrograms.kg-1.min-1. Amrinone increased cardiac output and resting diaphragm blood flow [from 1.8 +/- 0.1 to 3.2 +/- 3 (SE) l/min and from 13 +/- 2 to 29 +/- 6 (SE) ml.100 g-1.min-1, respectively, P less than 0.001 for both comparisons]. Amrinone also increased blood flow during periods of rhythmic contraction (tension time indexes of 0.1-0.4, P less than 0.05 for comparisons of flow with and without amrinone at each tension time index) and increased the magnitude of the postcontraction hyperemia (P less than 0.02 for comparisons of hyperemic flow with and without amrinone at tension time indexes of 0.3 and 0.4). Graded occlusion of the inferior vena cava produced reductions in arterial pressure, cardiac output, and diaphragm blood flow both before and after amrinone. Both cardiac output and diaphragm blood flow were greater after amrinone, however, at all levels of blood pressure examined. These findings indicate that amrinone can override diaphragm vasoregulatory systems and augment diaphragm blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Ventilatory and diaphragmatic EMG responses to negative-pressure ventilation in airflow obstruction
Authors: Rodenstein D. O. , Stanescu D. C. , Cuttita G. , Liistro G. , Veriter C.
Published: December 2017

To assess the responses of patients with chronic obstructive lung disease (COLD) to negative-pressure ventilation (NPV), we studied eight naive patients with moderate to severe COLD before (control) and during NPV with "low" (-10-cmH2O) and "high" (-30-cmH2O) pressure swings in a Drinker tank respirator. Tidal volume (VT) and minute ventilation (VE) were recorded from a Respitrace and diaphragmatic electromyogram (DEMG) from a bipolar esophageal electrode. During short, 5-min runs of "low" and "high" NPV, VT did not change and VE increased in a borderline significant way at -30-cmH2O NPV. Peak integrated DEMG amplitude did not change with respect to control during short runs of NPV. However, when NPV was maintained for 20-60 min, a significant (though small, 20%) decrease in peak DEMG amplitude was observed with respect to control. By contrast, in a ninth patient habituated to NPV, the decrease in peak DEMG amplitude during a 5-min run of NPV was 60%. Significant increases in arterial PO2 (at -10- and -30-cmH2O NPV) and decreases in arterial PCO2 (at -30-cmH2O NPV) were found during NPV for the whole group of patients. One-to-one phase locking between the respirator and patients was the most common pattern of entrainment observed. However, 1:1 phase locking did not preclude the presence of dissociation between the two pacemakers. We conclude that short runs of NPV in naive patients do not result in changes in DEMG, as opposed to immediate and nearly complete cessation of inspiratory activity in trained patients.
Ventilation-perfusion relationships during induced normovolemic polycythemia in dogs
Authors: Balgos A. A. , Willford D. C. , West J. B.
Published: December 2017

Previous studies on normal subjects and patients with polycythemia have given conflicting results of the effect of polycythemia on pulmonary gas exchange. We studied acutely induced normovolemic polycythemia in the dog and measured arterial blood gases and ventilation-perfusion (VA/Q) relationships using the multiple inert gas elimination technique. The mean base-line hematocrit of 43 +/- 5% was increased to 57 +/- 4 and 68 +/- 8%, respectively, after two exchange transfusions of packed erythrocytes. Subsequent plasma exchange transfusions returned the mean hematocrit to 44 +/- 4%. Polycythemia caused no significant arterial hypoxemia; indeed there was a slight improvement in the alveolar-arterial PO2 difference. The multiple inert gas elimination measurements showed no increase in VA/Q inhomogeneity with no increase in log SD ventilation (V) or log SD blood flow (Q). There was a shift of mean V and mean Q to high VA/Q areas because of a decrease in cardiac output, presumably caused by increased blood viscosity. This study showed no deleterious effects on pulmonary gas exchange within the hematocrit range of 36-76%.
Carotid chemoreceptor activity during acute and sustained hypoxia in goats
Authors: Nielsen A. M. , Bisgard G. E. , Vidruk E. H.
Published: December 2017

The role of carotid body chemoreceptors in ventilatory acclimatization to hypoxia, i.e., the progressive, time-dependent increase in ventilation during the first several hours or days of hypoxic exposure, is not well understood. The purpose of this investigation was to characterize the effects of acute and prolonged (up to 4 h) hypoxia on carotid body chemoreceptor discharge frequency in anesthetized goats. The goat was chosen for study because of its well-documented and rapid acclimatization to hypoxia. The response of the goat carotid body to acute progressive isocapnic hypoxia was similar to other species, i.e., a hyperbolic increase in discharge as arterial PO2 (PaO2) decreased. The response of 35 single chemoreceptor fibers to an isocapnic [arterial PCO2 (PaCO2) 38-40 Torr)] decrease in PaO2 of from 100 +/- 1.7 to 40.7 +/- 0.5 (SE) Torr was an increase in mean discharge frequency from 1.7 +/- 0.2 to 5.8 +/- 0.4 impulses. During sustained isocapnic steady-state hypoxia (PaO2 39.8 +/- 0.5 Torr, PaCO2, 38.4 +/- 0.4 Torr) chemoreceptor afferent discharge frequency remained constant for the first hour of hypoxic exposure. Thereafter, single-fiber chemoreceptor afferents exhibited a progressive, time-related increase in discharge (1.3 +/- 0.2 impulses.s-1.h-1, P less than 0.01) during sustained hypoxia of up to 4-h duration. These data suggest that increased carotid chemoreceptor activity contributes to ventilatory acclimatization to hypoxia.
Comparison of particle clearance and macrophage phagosomal motion in liver and lungs of rats
Authors: Weinstock S. B. , Brain J. D.
Published: December 2017

Magnetic particles and magnetometry were used to noninvasively measure motion of particle-containing organelles in macrophages as well as to monitor the disappearance of particles from tissues. We compared these parameters in the liver (where macrophages are attached to the endothelium) and in the lungs (where macrophages were mobile on epithelial surfaces). Submicrometric magnetic particles were injected intravenously (1.5 mg/kg) into rats; 94% was taken up by the liver. Rats were also instilled intratracheally (1.0 mg/kg) with the same particles. Ultrastructural analyses showed that almost all particles were ingested by macrophages in both organs. Periodically, the retained particles were magnetized and aligned with an external magnet. After the magnet was removed, the decay of the resulting remanent field (relaxation) was followed for 25 min. Relaxation parameters (t1/2 and lambda 0) in the liver were constant from 30 min to 30 days after particle administration, but relaxation in lungs showed a time-dependent increase during the 1st day due to the slower rate of particle phagocytosis. Relaxation in both organs primarily reflects the motion of particle-containing organelles as they are rotated by the cytoskeleton. Relaxation in the lungs may also reflect cell translocation or even changes in alveolar shape. Clearance of particles from the lungs or liver was measured by following B0 (initial magnetic field strength). After correction for growth, the clearance t1/2 was 17.7 and 27.3 days for the lungs and liver, respectively. Bulk transport of particles is probably a more important clearance mechanism in the lungs than in the liver.
Phosphate supplementation, cardiovascular function, and exercise performance in humans
Authors: Bredle D. L. , Stager J. M. , Brechue W. F. , Farber M. O.
Published: December 2017

The use of oral phosphate (Pi) supplements to improve muscular work performance has long been proposed without substantiating data. In a double-blind, crossover experiment 11 male runners ingested calcium Pi (176 mmol/day) or placebo for 4 days. On the 3rd treatment day, subjects ran an incremental maximal aerobic capacity test (VO2 max) on a treadmill, and on the 4th day a treadmill run to exhaustion at approximately 70% VO2max. By the 4th day of Pi loading, plasma Pi was significantly higher than control (P less than 0.05); however, erythrocyte Pi, 2,3-diphosphoglycerate, and O2 half-saturation pressure of hemoglobin (P50) were not elevated. VO2 max was not changed by the treatments (mean 62.9, 64.2, 64.9 ml.kg-1.min-1 for control, Pi, and placebo bouts, respectively) nor was submaximal run time to exhaustion (61.6 min for Pi, 65.5 min for placebo). Stroke volume at steady-state VO2 was decreased with Pi (P less than 0.05), whereas cardiac output tended (P = 0.07) to be lower. Greater arteriovenous O2 difference (P less than 0.05) with Pi suggested a peripheral effect that increased O2 extraction. We concluded that in healthy individuals Pi loading produced no improvement in work tolerance or aerobic capacity but did alter some aspects of cardiovascular function.
Platelet-activating factor antagonists increase vascular reactivity in perfused rat lungs
Authors: Haynes J. , Chang S. W. , Morris K. G. , Voelkel N. F.
Published: December 2017

Platelet-activating factor (PAF) administered to the pulmonary circulation in low dose (nanogram) has vasodilatory properties. Therefore, we investigated whether endogenous PAF plays a role in the control of tone in the pulmonary circulation. The PAF receptor antagonists, SRI 63-441 (2.6 X 10(-4) M) and L659,989 (1 X 10(-5) M), were the major investigative tools. In isolated perfused rat lungs, both agents caused a persistent increase in base-line perfusion pressure (Ppa), potentiated angiotensin II (ANG II) vasoconstriction, and potentiated hypoxic vasoconstriction (HPV). This potentiation of ANG II and HPV was found to be independent of circulating blood elements. Vasodilation in the presence of PAF blockade was also impaired. The combination of cyclooxygenase inhibition and PAF receptor blockade had an additive effect on ANG II vasoconstriction but did not cause more potentiation of HPV than achieved with PAF antagonism alone. In vivo, SRI 63-441 (10 mg/kg) caused only a transient increase in base-line Ppa without altering ANG II and hypoxic vasoconstriction. These findings support a vasodilatory role for endogenous PAF in the pulmonary circulation.
Pirenzepine prevents diethyl pyrocarbonate inhibition of central CO2 sensitivity
Authors: Nattie E. E. , Mills J. W. , Ou L. C.
Published: December 2017

Application by pledget of the M1-antimuscarinic receptor agent pirenzepine (40 mM) to the rostral chemosensitive areas of the ventrolateral medulla in anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated cats inhibited the slope of the integrated phrenic response to CO2 by 32.5% (P less than 0.03) and the maximum value by 21.1% (P less than 0.01). Similar application of the imidazole-histidine blocking agent diethyl pyrocarbonate (DEPC) decreased the slope by 40.3% (P less than 0.01) and the maximum value by 29.3% (P less than 0.05). Both responses confirm previous results. DEPC treatment decreased the effectiveness of subsequent pirenzepine application such that although slope and maximum were further decreased, the values were not significantly different from those after DEPC. Pirenzepine treatment prevented any subsequent DEPC inhibitory effect. The results raise the possibility that the inhibitory effects of DEPC on CO2 chemosensitivity are via muscarinic receptors and that muscarinic receptor involvement in CO2 chemosensitivity requires the presence of imidazole-histidine. Analysis by scintillation counting of successive 100-micron sections of medulla after rostral area application of [3H]pirenzepine indicated that the pirenzepine and DEPC effects are most probably within 2.0 mm of the ventral surface as measured from the midline, well away from the dorsal and ventral respiratory group neurons.
Gain of the ventilatory exercise stimulus: definition and meaning
Authors: Bennett F. M. , Fordyce W. E.
Published: December 2017

The ratio G = delta VE/delta VCO2 where delta VA is change in ventilation and delta VCO2 is change in CO2 production, is often used to quantitate the ventilatory response to exercise and is the overall system gain (G). However, the actual variable of interest often is the gain for the exercise stimulus (GEX). Exercise stimulus refers to a stimulus or group of stimuli other than the mean levels of arterial PO2 (PaCO2), PCO2 (PaCO2), and pH (pHa) that act to increase ventilation during exercise. GEX will be equal to G only if the response to exercise is precisely isocapnic, normoxic, and without metabolic acidosis. A mathematical model was used to examine the relationship between G and GEX when 1) the response to exercise is not strictly isocapnic and 2) when the resting PaCO2 is shifted away from its normal value. It was found that 1) when the exercise response was not strictly isocapnic, G was a poor estimate of GEX and 2) when resting PaCO2 was changed while GEX wa assumed to remain constant, G was a function of the resting PaCO2. However, this dependence of G on resting PaCO2 is a system property that was caused by the nonlinear properties of the gas exchange processes and was not a fundamental property of the controller. It is concluded that G may not always be a good estimate of GEX and may lead to incorrect conclusions concerning the nature of the exercise stimulus.
Ventilation inhomogeneity during controlled ventilation. Which index should be used?
Authors: Larsson A. , Jonmarker C. , Werner O.
Published: December 2017

Six indexes for diagnosing uneven ventilation by tracer gas washout were studied. The indexes were lung clearance index, mixing ratio, Becklake index, multiple-breath alveolar mixing inefficiency, moment ratio, and pulmonary clearance delay, all of which increase with impaired pulmonary gas mixing. In model lung tests, indexes that compared the actual washout curve with a calculated ideal curve (mixing ratio, multiple-breath alveolar mixing inefficiency, and pulmonary clearance delay) were unaffected by changes in tidal volume and series dead space, whereas the others varied markedly. In both spontaneously breathing and mechanically ventilated patients all indexes showed a significant difference between smokers and nonsmokers (P less than 0.002), but the indexes were somewhat different in their assessment of different ventilatory patterns. However, the mean value for all indexes, with the exception of mixing ratio, was smallest with a fast insufflation followed by an end-inspiratory pause. Any of the indexes may be useful if its limitations are recognized, but mixing ratio, multiple-breath alveolar mixing inefficiency, and pulmonary clearance delay seem preferable, because they are not affected by changes in tidal volume and dead space fraction.
Dimethylthiourea does not ameliorate reperfusion lung injury in dogs or rabbits
Authors: Bishop M. J. , Chi E. Y. , Su M. , Cheney F. W.
Published: December 2017

We previously demonstrated that in vivo reperfusion of a dog lung after 48 h of pulmonary arterial (PA) ischemia results in pulmonary edema with a significant infiltrate of polymorphonuclear leukocytes. We hypothesized that the injury resulted from production of hydroxyl radical by activated neutrophils. In the current study, we attempted to prevent the injury in both dogs and rabbits with dimethylthiourea (DMTU), a scavenger of hydroxyl radical. After 48 h of left PA occlusion in 18 dogs, DMTU was administered to 9 animals and 9 were not treated. The occlusion was then released, and the dogs were killed 4 h later. Reperfusion resulted in a drop in leukocyte count and left lung edema, but there was no difference between treated and untreated animals. The wet-to-dry ratios of the lungs in the treated group were 5.76 +/- 0.44 (SE) on the reperfused left side and 4.50 +/- 0.06 (P less than 0.05) on the right side. In the untreated groups the comparable ratios were 5.73 +/- 0.31 and 4.92 +/- 0.10 (P less than 0.05 for right vs. left). Histological examination revealed significant differences between the right and left lungs in the extent of intra-alveolar granulocytes and macrophages but did not reveal differences between the treated and untreated animals. To ensure that neither the model nor the lack of response to DMTU was species specific, we then developed a rabbit model of reperfusion edema.(ABSTRACT TRUNCATED AT 250 WORDS)
Propelling efficiency of front-crawl swimming
Authors: Toussaint H. M. , Beelen A. , Rodenburg A. , Sargeant A. J. , de Groot G. , Hollander A. P. , van Ingen Schenau G. J.
Published: December 2017

In this study the propelling efficiency (ep) of front-crawl swimming, by use of the arms only, was calculated in four subjects. This is the ratio of the power used to overcome drag (Pd) to the total mechanical power (Po) produced including power wasted in changing the kinetic energy of masses of water (Pk). By the use of an extended version of the system to measure active drag (MAD system), Pd was measured directly. Simultaneous measurement of O2 uptake (VO2) enabled the establishment of the relationship between the rate of the energy expenditure (PVO2) and Po (since when swimming on the MAD system Po = Pd). These individual relationships describing the mechanical efficiency (8-12%) were then used to estimate Po in free swimming from measurements of VO2. Because Pd was directly measured at each velocity studied by use of the MAD system, ep could be calculated according to the equation ep = Pd/(Pd + Pk) = Pd/Po. For the four top class swimmers studied, ep was found to range from 46 to 77%. Total efficiency, defined as the product of mechanical and propelling efficiency, ranged from 5 to 8%.
Propranolol and serotonin removal in lung injury
Authors: Merker M. P. , Gillis C. N.
Published: December 2017

Indicator dilution technique was used to study effects of reduced vascular volume or acute injury on removal of low doses of [3H]propranolol and [14C]serotonin (5-hydroxytryptamine, 5-HT) by perfused rabbit lung. Glass-bead (500 micron) embolization doubled pulmonary arterial pressure (Ppa) at flow rates of 20, 50, and 100 ml/min, decreased volume of distribution by approximately 50%, and increased pulmonary vascular resistance by at least 60%. Before embolization, (flow rate 20 ml/min) removal of [3H]propranolol and [14C] 5-HT was 89 +/- 2 and 75 +/- 5%, respectively, and was unaltered by changes in flow rate. However, after embolization, [3H]propranolol and [14C]5-HT removal decreased in a flow-dependent manner, reaching 28 +/- 4 and 1 +/- 3% (P less than 0.05), respectively, at a flow rate of 100 ml/min. When phorbol myristate acetate (PMA, 200 nM) was perfused (50 ml/min) through the lungs for 15 min, Ppa increased from 13 +/- 1 to 25 +/- 2 cmH2O (P less than 0.05), whereas [3H]propranolol removal decreased from 92 +/- 1 to 75 +/- 5% (P less than 0.05) and [14C]5-HT removal decreased from 73 +/- 3 to 46 +/- 8% (P less than 0.05). The PMA also caused vasoconstriction, which could be partially blocked by adding papaverine (500 microM) to the perfusion medium. Under the latter conditions, Ppa increased to 19 +/- 1 cmH2O and [3H]propranolol removal was unaffected. However, the combination of PMA and papaverine reduced [14C]5-HT removal from 64 +/- 4 to 19 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory enthalpy changes in mine rescue workers exercising under heat stress
Authors: Leigh J. , Griffits R. K. , Ellis C. G.
Published: December 2017

Respiratory enthalpy change, rectal temperature, and heart rate of mine rescue workers exercising at a metabolic energy production rate of 4 met (1 met-58.15 W.m-2) in a 40 degrees C saturated environment, wearing closed-circuit breathing apparatus, were continuously measured in 10 volunteer subjects. The effects of using liquid O2 and compressed O2 apparatus were compared in each subject. Evaporative heat exchange was much greater with the liquid O2 type of apparatus, causing a significantly lower rate of rise of rectal temperature and heart rate. Convective heat exchange was negligible. Mean values for evaporative heat loss (maximum) were 61 +/- 16 (SD) W with liquid O2 and 20 +/- 18 W with compressed O2 (P less than 0.0001, 2-sided t test). Mean values for rectal temperature (rate of increase) were 0.022 +/- 0.009 (SD) degrees C.min-1 for liquid O2 and 0.036 +/- 0.015 degrees C.min-1 for compressed O2 (P less than 0.005, 2-sided paired t test). Mean values for heart rate (rate of increase) were 2.64 +/- 0.74 (SD) min-2 for liquid O2 and 3.27 +/- 0.89 min-2 for compressed O2 (P less than 0.02, 2-sided paired t test). This study quantifies, for the first time, the respiratory enthalpy change in exercising heat-stressed mine rescue workers and shows, from a physiological point of view, that the liquid O2 apparatus is clearly superior to the compressed O2 apparatus.
H2O2 and cGMP may function as an O2 sensor in the pulmonary artery
Authors: Burke-Wolin T. , Wolin M. S.
Published: December 2017

The effects of O2 tension on force in precontracted isolated pulmonary arterial smooth muscle from calf lungs was characterized to investigate the mechanism of O2 tension sensing. These arteries display a decrease in force with increasing O2 tension that is antagonized via inhibition of soluble guanylate cyclase activation by 10 microM methylene blue or inactivation of catalase by pretreatment with 50 mM 3-amino-1,2,4-triazole for 30 min. O2 tension-dependent relaxation is associated with an increase in intracellular H2O2 metabolism through catalase (detected as the peroxide-dependent inactivation of tissue catalase activity by aminotriazole) and cyclic guanosine 5'-monophosphate (cGMP), known mediators of relaxation in calf pulmonary arteries. Thus a recently reconstructed mechanism of activation of soluble guanylate cyclase involving the metabolism of H2O2 by catalase appears to function as an O2 tension sensor in pulmonary arteries.
Medical collateral ligament healing subsequent to different treatment regimens
Authors: Gomez M. A. , Woo S. L. , Inoue M. , Amiel D. , Harwood F. L. , Kitabayashi L.
Published: December 2017

The response of transected canine medical collateral ligaments (MCL) to clinical treatment regimens was investigated. These regimens included no surgical repair with no immobilization and surgical repair with various periods of immobilization. The biomechanical, biochemical, and histological properties of the healing MCL were examined 6 and 12 wk postoperatively. At 6 wk, all healing MCLs had increased cellularity with decreased levels of total collagen and increased amounts of reducible Schiff base cross-links and type III collagen. Biomechanically, the varus-valgus (V-V) knee laxity was significantly increased, and no group achieved normal structural or mechanical properties. At 12 wk the histological appearance of the MCL became more normal but still had increased cellularity. Biochemically, the total collagen levels in experimental MCLs were not statistically different from the controls, but these MCLs still had high amounts of type III collagen and an even higher number of reducible cross-links. From knees in which the MCL was not treated, the V-V knee laxity and the ultimate loads of the femur-MCL-tibia complex achieved normal values. However, the stress-strain properties for these MCLs and those treated with repair and immobilization did not completely recover.
Lipolytic response of fat cells to catecholamines in sedentary and exercise-trained women
Authors: Riviere D. , Crampes F. , Beauville M. , Garrigues M.
Published: December 2017

It has been shown that adipose tissue lipolytic activity is increased in endurance-trained subjects. In women, adipose tissue is extensive and it was thought interesting to confirm that endurance training increases the capacity of female adipose tissue to mobilize lipids, and moreover to more fully understand the mechanisms involved. So, biopsies of fat were obtained from the periumbilical region of 13 trained female runners (T) and 17 sedentary women (S) and the in vitro response to catecholamines of the collagenase-isolated fat cells was studied. Glycerol release, chosen as adipocyte lipolysis indicator, was measured by bioluminescence for various epinephrine and norepinephrine concentrations. In both groups, these substances provoked an increase in lipolysis, but the response was significantly higher in T. In both groups, isoproterenol increased the lipolytic activity above basal concentrations at 10(-8) M and above. Lipolytic activity in T was significantly higher (P less than 0.01) than the S control at 10(-7) M and above. Epinephrine plus propranolol decreased lipolysis in both groups, but at 10(-5) M, lipolytic activity was significantly lower in S than in T (P less than 0.05). It is concluded that in female subjects, endurance training increases the sensitivity of subcutaneous abdominal adipose tissue to the lipolytic action of catecholamines; this effect seems to be related both to a decreased efficiency of the alpha 2-adrenergic pathway and to an increased efficiency of the beta-adrenergic pathway. This latter effect seems to take place at a step beyond the receptor-adenylate cyclase system in the lipolytic cascade.
Differential timing of respiratory muscles in response to chemical stimuli in awake dogs
Authors: Smith C. A. , Ainsworth D. M. , Henderson K. S. , Dempsey J. A.
Published: December 2017

We assessed changes in respiratory muscle timing in response to hyperpnea and shortened inspiratory and expiratory times caused by chemoreceptor stimuli in six awake dogs. Durations of postinspiratory inspiratory activity of costal and crural diaphragm (PIIA), the delay in diaphragm electromyogram (EMG) after the initiation of inspiratory airflow, postexpiratory expiratory activity of the transversus abdominis (PEEA), and the delay of abdominal expiratory muscle activity after the initiation of expiratory airflow were measured. In control, four out of six dogs showed PIIA [8–10% of expiratory time (TE)]; all showed delay of diaphragm [19% of inspiratory time (TI)], delay of abdominal muscle activation (21% of TE), and PEEA (24% of TI). Hypercapnia decreased PIIA (4–9% of TE), maintained diaphragm delay at near control values (23% of TI), increased PEEA (36% of TI), eliminated delay of abdominal muscle activation (4% of TE), and decreased end-expiratory lung volume (EELV). Hypocapnic hypoxia increased PIIA (24–25% of TE), eliminated diaphragm delay (3% of TI), eliminated PEEA (3% of TI), reduced delay of abdominal muscle activation (14% of TE), and increased EELV. Most of these effects of hypoxic hypocapnia vs. hypercapnia on the within-breath EMG timing parameters corresponded to differences in the magnitude of expiratory muscle activation. These changes exerted significant influences on flow rates and EELV.
Tumor-promoting phorbol esters inhibit monocyte adherence to endothelial cells
Authors: Kamp D. W. , Bauer K. D. , Rubin D. B. , Dunn M. M.
Published: December 2017

Monocyte adherence to endothelial cells (EC) is an important event in the development of a monocytic inflammatory response, yet the effects of inflammatory mediators on monocyte adherence to EC are not well described. We compared the effects of phorbol esters known to activate protein kinase C, including phorbol myristate acetate (PMA) and phorbol 12,13-dibutyrate (PDA), on monocyte adherence to bovine aortic EC. Human monocytes (purity 90 +/- 1% SE) were isolated by centrifugal elutriation to obtain monocytes not previously exposed to a surface. Kinetic studies revealed that 51Cr-labeled monocyte adherence to EC reached a plateau after a 45-min incubation. Concentrations of PMA between 10 and 1,000 ng/ml significantly decreased monocyte adherence to EC (26 +/- 10 and 35 +/- 8% decrease compared with control, respectively). Concentrations of PDA of 100 and 1,000 ng/ml had a similar inhibitory effect. In contrast, the chemotactic stimulus, zymosan-activated serum, significantly increased monocyte adherence (40 +/- 14% increase compared with control). Thus inflammatory stimuli have different effects on the adhesive interaction of monocytes to EC. This may provide a mechanism to selectively modulate monocyte egress from the circulation into extravascular inflammatory sites.
Reflex effect of esophageal distension on respiratory muscle activity and pressure
Authors: Oliven A. , Haxhiu M. , Kelsen S. G.
Published: December 2017

The electrical activity of the respiratory skeletal muscles is altered in response to reflexes originating in the gastrointestinal tract. The present study evaluated the reflex effects of esophageal distension (ED) on the distribution of motor activity to both inspiratory and expiratory muscles of the rib cage and abdomen and the resultant changes in thoracic and abdominal pressure during breathing. Studies were performed in 21 anesthetized spontaneously breathing dogs. ED was produced by inflating a balloon in the distal esophagus. ED decreased the activity of the costal and crural diaphragm and external intercostals and abolished all preexisting electrical activity in the expiratory muscles of the abdominal wall. On the other hand, ED increased the activity of the parasternal intercostals and expiratory muscles located in the rib cage (i.e., triangularis sterni and internal intercostal). All effects of ED were graded, with increasing distension exerting greater effects, and were eliminated by vagotomy. The effect of increases in chemical drive and lung inflation reflex activity on the response to ED was examined by performing ED while animals breathed either 6.5% CO2 or against graded levels of positive end-expiratory pressure (PEEP), respectively. Changes in respiratory muscle electrical activity induced by ED were similar (during 6.5% CO2 and PEEP) to those observed under control conditions. We conclude that activation of mechanoreceptors in the esophagus reflexly alters the distribution of motor activity to the respiratory muscles, inhibiting the muscles surrounding the abdominal cavity and augmenting the parasternals and expiratory muscles of the chest wall.
Diaphragm metabolism during supramaximal phrenic nerve stimulation
Authors: Pope A. , Scharf S. M. , Brown R.
Published: December 2017

The metabolic changes accompanying diaphragm fatigue caused by supramaximal stimulation of the phrenic nerves are incompletely described. In particular, we wished to determine whether the occurrence of anaerobic metabolism correlated with fatigue as defined by decline in force generation. In 10 anesthetized mechanically ventilated mongrel dogs we measured arterial pressure, transdiaphragmatic pressure (Pdi), phrenic arterial flow (Qdi-Doppler flow probe), arterial and phrenic venous blood gases, and lactate levels. From these we derived indexes of diaphragm O2 consumption (VO2) and lactate production. Bilateral phrenic nerve pacing was carried out (50 Hz, duty cycle 0.4, 24 contractions/min) for two 15-min pacing periods separated by a 45-min rest period. Over each pacing period Pdi decreased from approximately 16 to approximately 10 cmH2O (P less than 0.01, no significant difference between periods). Initially, during pacing, Qdi and VO2 each increased fivefold over prepacing base line. Qdi remained elevated at this level whereas VO2 decreased over the pacing period by approximately 25%. Hence, the change in VO2 over the pacing period was due primarily to changes in O2 extraction. During the first pacing period lactate production was observed early and declined throughout the pacing period. No lactate production was observed during the second pacing period, although Pdi, VO2, and Qdi responses were the same for both pacing periods. Phrenic venous PO2 remained greater than 30 Torr throughout both pacing periods.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of indomethacin on allergen-induced asthmatic responses
Authors: Kirby J. G. , Hargreave F. E. , Cockcroft D. W. , O'Byrne P. M.
Published: December 2017

Previous studies have suggested that inhibition of the cyclooxygenase pathway of arachidonic acid metabolism may suppress the late asthmatic responses to inhaled allergen. Both human and animal studies have suggested that prostanoids may also be involved in increases in airway responsiveness after ozone and allergen. We studied seven atopic subjects, who had a dual asthmatic response to inhaled allergen, during a control period and then after pretreatment with indomethacin (50 mg) or placebo twice daily for 2 days, administered in a randomized, double-blind manner. Indomethacin had no significant effect on the base-line airway responsiveness to histamine (P = 0.22) or the allergen-induced early or late asthmatic response (P = 0.49). However, indomethacin inhibited the increase in airway responsiveness (express as histamine PC20) after allergen inhalation. The log difference in preallergen to postallergen histamine PC20 was 0.49 +/- 0.08 (SE) during the control period, 0.46 +/- 0.08 (SE) after placebo (P = 0.81), and 0.22 +/- 0.10 (SE) after indomethacin (P = 0.02). Although indomethacin is useful for examining the role of cyclooxygenase products in asthmatic responses, it should not be considered in the treatment of asthma. We conclude that cyclooxygenase products are not significant mediators of allergen-induced early or late asthmatic responses but are involved in the pathogenesis of airway hyperresponsiveness after allergen inhalation.