bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute and chronic respiratory effects of sulfur mustard intoxication in guinea pig
Authors: Calvet J. H. , Jarreau P. H. , Levame M. , D′Ortho M. P. , Lorino H. , Harf A. , Macquin-Mavier I.
Published: December 2017

Sulfur mustard (SM) has been used as a vesicant chemical warfare agent. To investigate the respiratory damages it causes, we studied the effects on guinea pigs of an intratracheal injection of 0.3 mg/kg of SM 5 h and 14 days after injection. Five hours after SM intoxication, respiratory system resistance and microvascular permeability were increased. These alterations were not prevented by pretreatment with 50 mg/kg sc of capsaicin 2 wk before SM intoxication. Histological studies showed columnar cell shedding all along the tracheal epithelium, bronchoconstriction, and peribronchial edema. Fourteen days after SM intoxication, guinea pigs demonstrated airway hyperreactivity to aerosolized substance P and histamine. Pretreatment with phosphoramidon caused a further increase in airway responsiveness to substance P. Neutral endopeptidase activity in the tracheal epithelium was decreased by twofold in SM-intoxicated guinea pigs. At this stage, the tracheal epithelium was disorganized and atrophic. These results demonstrate that in guinea pigs SM intoxication induces severe lesions to the tracheal epithelium, which might account for the airway hyperresponsiveness observed 14 days after intoxication.
Dynamic moduli of rabbit lung tissue and pigeon ligamentum propatagiale undergoing uniaxial cyclic loading
Authors: Mijailovich S. M. , Stamenovic D. , Brown R. , Leith D. E. , Fredberg J. J.
Published: December 2017

In fibrous connective tissue networks, mechanical loads may be transferred from one fiber to the next by friction between slipping fibers (J. Appl. Physiol. 74: 665–681, 1993). Here we tested that hypothesis; it predicts that elastance of fibrous networks increases with increasing frequency, decreases with increasing strain amplitude (delta epsilon), and decreases with tissue swelling by solvent. Similarly, it predicts that hysteresivity (eta) decreases with increasing frequency, increases with increasing delta epsilon, decreases with tissue swelling, and, importantly, exceeds that of isolated fibrous constituents of the matrix. Elastance and eta of two structurally dissimilar connective tissues were measured, the rabbit lung parenchymal strip (a loose collagenous tissue) and the pigeon ligamentum propatagiale (an elastin-rich tissue). Experiments covered the frequency range 0.03125-3.125 Hz. Elastance of lung parenchyma was substantially lower than that of propatagial ligament, increased linearly with the logarithm of frequency, and decreased with delta epsilon; that of ligamentum propatagiale was insensitive to both frequency and delta epsilon. eta of lung parenchyma decreased moderately with increasing frequency and assumed values of approximately 0.1, but eta of ligamentum propatagiale was frequency and delta epsilon invariant and assumed values an order of magnitude smaller. These tissues also showed disparate mechanical responses when exposed to hypertonic bath solutions. Although there were some quantitative differences between predictions and experimental observations, the dynamic behavior of lung parenchyma was generally consistent with that of a network in which load is transferred from one fiber to the next by the agency of friction acting at slipping interface surfaces.
Glucocorticoids in metabolic control during exercise: alanine metabolism
Authors: Viru A. , Litvinova L. , Viru M. , Smirnova T.
Published: December 2017

To evaluate glucocorticoid participation in the control of alanine metabolism during exercise, experiments were performed on adrenalectomized and normal male rats. The adrenal insufficiency prevented the rises induced by 3 h of swimming in alanine levels of blood plasma, red portion of quadriceps, and liver. In normal rats, the rise in alanine content by 65% in blood, 50% in fast-twitch oxidative fibers, and 93% in liver was associated with increased activity of alanine aminotransferase in fast-twitch oxidative-glycolytic fibers (by 23%). In adrenalectomized rats, enzyme activity during exercise did not change in muscles and decreased in hepatic tissue (by 25%). The dependence of exercise-induced changes in alanine aminotransferase activity on glucocorticoids was confirmed by an increased enzyme activity (by 53%) in exercised adrenalectomized rats treated with 125 micrograms corticosterone. In normal rats, training prevented both the rise of blood corticosterone and the activation of hepatic alanine aminotransferase during exercise. The results support the view that the stimulation of the glucose-alanine cycle by glucocorticoids promotes alanine supply and utilization in liver during exercise. In adrenalectomized rats, hepatic arginase activity was decreased during exercise and no elevation of urea levels was found in blood, liver, or skeletal muscles. Consequently, the use of products of the deamination of alanine (and other amino acids) for urea formation also depends on glucocorticoids.
Humoral pulmonary vasoregulation in conscious dogs after left lung autotransplantation
Authors: Desai P. M. , Nishiwaki K. , Stuart R. S. , Nyhan D. P. , Murray P. A.
Published: December 2017

We investigated the roles of cyclooxygenase metabolites, arginine vasopressin (AVP) and angiotensin II (ANG II), as mediators of the chronic increase in pulmonary vascular resistance associated with left lung autotransplantation (LLA) in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q) plots were generated in conscious dogs 2- to 5-wk post-LLA and in sham-operated control conscious dogs. LLA resulted in a marked shift (P < 0.01) in the LP-Q relationship as reflected by an approximate doubling of the pulmonary vascular pressure gradient at each common value of left pulmonary blood flow compared with the control group. Cyclooxygenase pathway inhibition (indomethacin) and AVP V1-receptor block had no effect on the LP-Q relationship post-LLA. Angiotensin-converting enzyme inhibition (captopril) also failed to reverse the increase in pulmonary vascular resistance post-LLA. Because captopril has the dual effect of inhibiting the production of ANG II and the degradation of bradykinin, additional studies utilizing a selective ANG II receptor antagonist were performed. ANG II receptor block (saralasin) significantly altered the LP-Q relationship post-LLA to cause active pulmonary vasodilation (P < 0.01). Thus, the chronic increase in pulmonary vascular resistance post-LLA is not mediated by metabolites of the cyclooxygenase pathway or AVP V1-receptor activation. A significant component of the increase in pulmonary vascular resistance resulting from LLA is mediated by ANG II. The differential responses to captopril and saralasin may imply a pulmonary vasoregulatory role for bradykinin post-LLA.
Dynamical assessment of physiological systems and states using recurrence plot strategies
Authors: Webber C. L. , Zbilut J. P.
Published: December 2017

Physiological systems are best characterized as complex dynamical processes that are continuously subjected to and updated by nonlinear feedforward and feedback inputs. System outputs usually exhibit wide varieties of behaviors due to dynamical interactions between system components, external noise perturbations, and physiological state changes. Complicated interactions occur at a variety of hierarchial levels and involve a number of interacting variables, many of which are unavailable for experimental measurement. In this paper we illustrate how recurrence plots can take single physiological measurements, project them into multidimensional space by embedding procedures, and identify time correlations (recurrences) that are not apparent in the one-dimensional time series. We extend the original description of recurrence plots by computing an array of specific recurrence variables that quantify the deterministic structure and complexity of the plot. We then demonstrate how physiological states can be assessed by making repeated recurrence plot calculations within a window sliding down any physiological dynamic. Unlike other predominant time series techniques, recurrence plot analyses are not limited by data stationarity and size constraints. Pertinent physiological examples from respiratory and skeletal motor systems illustrate the utility of recurrence plots in the diagnosis of nonlinear systems. The methodology is fully applicable to any rhythmical system, whether it be mechanical, electrical, neural, hormonal, chemical, or even spacial.
Suitability of 2-deoxyglucose for in vitro measurement of glucose transport activity in skeletal muscle
Authors: Hansen P. A. , Gulve E. A. , Holloszy J. O.
Published: December 2017

The purpose of this study was to evaluate the suitability of the glucose analogue 2-deoxyglucose (2-DG) for measurement of glucose transport activity in rat skeletal muscles in vitro when transport rates are high. The goal was to determine whether glucose phosphorylation rather than transport becomes limiting under experimental conditions normally employed in muscle incubation experiments. The rate of 2-DG uptake assayed in the presence of 8 mM 2-DG and a maximally effective concentration of insulin remained linear for > or = 60 min in the split soleus and 120 min in the epitrochlearis. Hexokinase activity assayed in skeletal muscle homogenates was not inhibited appreciably by 2-deoxyglucose 6-phosphate (2-DG-6-P) concentrations in the range of those achieved intracellularly during the linear phase of 2-DG uptake (i.e., 2-DG-6-P below approximately 30 mM). During this linear phase of 2-DG uptake, total intracellular 2-DG concentrations did not exceed 30 mM. The combined effects of contractions plus a maximally effective concentration of insulin on glucose transport activity measured at a near-saturating concentration of 2-DG were additive in the epitrochlearis and the soleus. Our results indicate that, under the conditions employed in our isolated muscle preparations, 2-DG uptake accurately reflects glucose transport activity and that 2-DG is the most appropriate glucose analogue for measurement of glucose transport activity when transport rates are high.
Catecholamine and blood lactate responses to incremental rowing and running exercise
Authors: Weltman A. , Wood C. M. , Womack C. J. , Davis S. E. , Blumer J. L. , Alvarez J. , Sauer K. , Gaesser G. A.
Published: December 2017

Ten collegiate rowers performed discontinuous incremental exercise to their tolerable limit on two occasions: once on a rowing ergometer and once on a treadmill. Ventilation and pulmonary gas exchange were monitored continuously, and blood was sampled from a venous catheter located in the back of the hand or forearm for determination of blood lactate ([La]) and plasma epinephrine ([Epi]) and norepinephrine ([NE]) concentrations. Thresholds for lactate (LT), epinephrine (Epi-T), and norepinephrine (NE-T) were determined for each subject under each condition and defined as breakpoints when plotted as a function of O2 uptake (VO2). For running, LT (3.76 +/- 0.18 l/min) was lower (P < 0.05) than Epi-T (4.35 +/- 0.14 l/min) and NE-T (4.04 +/- 0.19 l/min). For rowing, LT (3.35 +/- 0.16 l/min) was lower (P < 0.05) than Epi-T (3.72 +/- 0.22 l/min) and NE-T (3.70 +/- 0.18 l/min) and was lower (P < 0.05) than LT for running. Within each mode of exercise, Epi-T and NE-T did not differ. Because LT occurred at a significantly lower VO2 than either Epi-T or NE-T, we conclude that catecholamine thresholds, per se, were not the cause of LT. However, for both modes of exercise LT occurred at a plasma [Epi] of approximately 200–250 pg/ml (rowing, 221 +/- 48 pg/ml; running, 245 +/- 45 pg/ml); these concentrations are consistent with the plasma [Epi] reported necessary for eliciting increments in blood [La] during Epi infusion at rest. Plasma [NE] at LT differed significantly between modes (rowing, 820 +/- 127 pg/ml; running, 1,712 +/- 217 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Canine hindlimb blood flow and O2 uptake after inhibition of EDRF/NO synthesis
Authors: King C. E. , Melinyshyn M. J. , Mewburn J. D. , Curtis S. E. , Winn M. J. , Cain S. M. , Chapler C. K.
Published: December 2017

The nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used to determine whether the decrease in canine hindlimb blood flow (QL) with NOS inhibition would limit skeletal muscle O2 uptake (VO2). Arterial inflow and venous outflow from the hindlimb were isolated, and the paw was excluded from the circulation. Pump perfusion from the right femoral artery kept the hindlimb perfusion pressure near the auto-perfused level. Six anesthetized dogs received L-NAME (20 mg/kg i.v.), whereas another group of five dogs received the stereospecific enantiomer N omega-nitro-D-arginine methyl ester (D-NAME 20 mg/kg i.v.). Efficacy of NOS inhibition was tested with intra-arterial boluses of acetylcholine. QL was measured continuously, and whole body and hindlimb VO2 were measured 60 and 120 min after L-NAME or D-NAME. Whole body VO2 remained at control levels, but cardiac output decreased from 117 +/- 17 to 57 +/- 7 ml.kg-1.min-1 60 min after L-NAME (P < 0.05) and remained at that level for the duration of the experiment. Cardiac output was significantly higher in the D-NAME group than in the L-NAME group at 60 min. After L-NAME, QL fell 24% but VO2 increased from 5.2 +/- 0.4 to 7.4 +/- 0.6 ml.kg-1.min-1 (P < 0.05). No change in QL or VO2 occurred after D-NAME. NOS inhibition did not limit hindlimb VO2, despite decreases in blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Exercise-induced changes in plasma catecholamines and neuropeptide Y: relation to age and sampling times
Authors: Jensen E. W. , Espersen K. , Kanstrup I. L. , Christensen N. J.
Published: December 2017

Plasma norepinephrine (NE), epinephrine (E), and neuropeptide Y (NPY) were evaluated in seven young (median age 29 yr, range 21–31) and seven elderly (median age 61 yr, range 51–72) healthy subjects. They were all nonsmokers and had never smoked. Basal values and the initial increase in plasma NE and E during exercise at 75% of maximal work load were identical in the two groups. After 5 min of exercise at this load, plasma NE and E remained constant in the elderly but were still increasing in the young subjects. Plasma NE and E increased to significantly higher values after 15 min in the young subjects: 1.68 +/- 0.18 vs. 0.92 +/- 0.11 ng/ml (NE) and 0.136 +/- 0.012 vs. 0.061 +/- 0.013 ng/ml (E). Basal plasma NPY was highest at rest and increased only during exercise in the young subjects. Our results demonstrate that in nonsmokers aging is not associated with increased plasma NE levels. The blood pressure response to exercise was the same in both groups, suggesting that the increase in the sympathetic activity was adequate in the elderly. Alternatively, the higher increase in sympathetic activity in the young subjects may be attributed to their higher work capacity.
Inhaled nitric oxide partially reverses hypoxic pulmonary vasoconstriction in the dog
Authors: Romand J. A. , Pinsky M. R. , Firestone L. , Zar H. A. , Lancaster J. R.
Published: December 2017

Nitric oxide (NO) inhaled during a hypoxia-induced increase in pulmonary vasomotor tone decreases pulmonary arterial pressure (Ppa). We conducted this study to better characterize the hemodynamic effects induced by NO inhalation during hypoxic pulmonary vasoconstriction in 11 anesthetized ventilated dogs. Arterial and venous systemic and pulmonary pressures and aortic flow probe-derived cardiac output were recorded, and nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) were measured. The effects of 5 min of NO inhalation at 0, 17, 28, 47, and 0 ppm during hyperoxia (inspiratory fraction of O2 = 0.5) and hypoxia (inspiratory fraction of O2 = 0.16) were observed. NO inhalation has no measurable effects during hyperoxia. Hypoxia induced an increase in Ppa that reached plateau levels after 5 min. Exposure to 28 and 47 ppm NO induced an immediate (< 30 s) decrease in Ppa and calculated pulmonary vascular resistance (P < 0.05 each) but did not return either to baseline hyperoxic values. Increasing the concentration of NO to 74 and 145 ppm in two dogs during hypoxia did not induce any further decreases in Ppa. Reversing hypoxia while NO remained at 47 ppm further decreased Ppa and pulmonary vascular resistance to baseline values. NO inhalation did not induce decreases in systemic arterial pressure. MetHb remained low, and NO-Hb was unmeasurable. We concluded that NO inhalation only partially reversed hypoxia-induced increases in pulmonary vasomotor tone in this canine model. These effects are immediate and selective to the pulmonary circulation.
Distribution function of transit times in the human pulmonary circulation
Authors: Lewis M. L. , De Caterina R. , Giuntini C.
Published: December 2017

The distribution function of pulmonary transit times (fPTT) defines contact time between blood and vascular bed, which affects gas exchange and endothelial metabolic functions. This study was undertaken to assess effects of abnormal pulmonary inflow (PPA) and outflow pressures (PLA) on fPTT. Three groups were studied: five patients with elevated PLA and passive pulmonary hypertension (LVD-Ab), eight with normal PLA (LVD-Nl), and six with pulmonary disease and various levels of PPA (PD). Empirical complex exponential functions were convoluted on right and left ventricular indicator-dilution curves to derive fPTT; mean transit time (Mo1), standard deviation (Sm2), and cube root of the third moment about Mo1 (Sm3) were calculated by standard equations. A single linear regression of Sm3 and Sm2 on Mo1 was observed for all patients, regardless of disease process. Inverse relations between Mo1, Sm2, and Sm3 and blood flow were highly significant, but dispersion volumes (DV = Mo1 x flow) were higher in patients with elevated PPA. Significant linear regressions of fPTT parameters on PPA, derived in LVD-Nl and LVD-Ab patients, failed to predict Mo1, Sm2, and Sm3 for the PD group, whereas linear regressions on PLA accurately predicted Mo1, Sm2, and Sm3 in the PD group. Relations between fPTT parameters and PLA were equally well fit by exponential equations in all 19 patients, consistent with an asymptotic pressure-volume relation of distensible vessels. Microvascular pressure (PMV), combining PPA and PLA, was not a better predictor of fPTT parameters in LVD-NL and LVD-Ab patients but provided a slightly closer estimate of relative dispersion and skewness in PD patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Regurgitant volume in aortic regurgitation from a parameter estimation procedure
Authors: Slordahl S. A. , Kuecherer H. F. , Solbakken J. E. , Piene H. , Angelsen B. A. , Schiller N. B.
Published: December 2017

The regurgitant volume and regurgitant orifice area as well as total peripheral resistance and arterial compliance were estimated in a cardiovascular hydromechanical simulator and in 10 patients with aortic regurgitation. A parameter estimation procedure based on a simple model of the cardiovascular system, Doppler measurements of the regurgitant jet, aortic systolic flow, and systolic and diastolic blood pressures was used. In the cardiovascular simulator the estimated regurgitant orifice area was compared with the size of a hole in the disk of a mechanical aortic valve. In the patients the regurgitant fraction was compared with semiquantitative grading from echocardiography routinely performed in our laboratory. In the hydromechanical simulator, the estimated regurgitant orifice area of 26.5 +/- 3.5 (SD) mm2 (n = 9) was not different from the true value of 24 mm2. In the patients there was a fair relationship between the estimated regurgitant fraction and the semiquantitative grading. The estimated regurgitant orifice areas varied between 1.6 and 31.2 mm2. The estimated mean values of total peripheral resistance and arterial compliance were 1.67 +/- 0.55 mmHg.s.ml-1 and 1.30 +/- 0.42 ml/mmHg, respectively.
Differential effects of voluntary and involuntary activation on contractile characteristics of two human muscles
Authors: Laframboise J. , Cafarelli E.
Published: December 2017

To compare the maximal rate of rise of torque (MRRT) of quadriceps femoris and adductor pollicis during voluntary and involuntary contractions, subjects performed voluntary isometric contractions as rapidly as possible over the full range of force-producing capacity. Involuntary contractions were evoked with single shocks and with trains of 10 pulses at 100 Hz at increasing voltages applied directly to the femoral and ulnar nerves. There were linear relationships between MRRT and absolute torque in both muscles during involuntary and voluntary contractions. At the same absolute torque, quadriceps femoris had a higher MRRT than adductor pollicis when both were voluntarily activated (P < 0.05). However, there was no difference in MRRT between these muscles during stimulated contractions. Compared with involuntary tetanic contractions, MRRT during voluntary contractions was the same in quadriceps femoris and was less in adductor pollicis (P < 0.05). These observations suggest that in activating some muscles, such as adductor pollicis, the central nervous system may adopt the strategy of a more gradual excitation to make the contractions more task appropriate.
Transmission of pressure across the chest wall during the rapid thoracic compression technique in infants
Authors: Stick S. , Turner D. , LeSouef P.
Published: December 2017

During the rapid thoracic compression maneuver in infants, the transmission of pressure from compression jacket to pleural space and airway is less at functional residual capacity than at end inspiration. To examine whether reduced pressure transmission at functional residual capacity vs. higher lung volumes is explained by passive characteristics of the chest wall rather than by respiratory muscle activity, we assessed the pressure transmitted across the chest wall in nine anesthetized infants and young children after muscle relaxation. We measured esophageal and airway occlusion pressure during chest compressions at different lung volumes determined by varying distending pressure. In six subjects studied under static conditions, there was an approximately linear relationship between distending pressure and the proportion of pressure transmitted to the airway and esophagus from the compression jacket. The mean r2 value (95% confidence interval) was 0.80 (0.09) for pressure transmission to the airway and 0.85 (0.04) for pressure transmission to the esophagus. This relationship between lung volume and pressure transmission observed under static conditions was also demonstrated dynamically. Thus the reduced transmission of pressure from compression jacket to airway and pleural space at low lung volumes occurs independently of respiratory muscle activity.
Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise
Authors: Stringer W. , Wasserman K. , Casaburi R. , Porszasz J. , Maehara K. , French W.
Published: December 2017

The slow rise in O2 uptake (VO2), which has been shown to be linearly correlated with the increase in lactate concentration during heavy constant work rate exercise, led us to investigate the role of H+ from lactic acid in facilitating oxyhemoglobin (O2Hb) dissociation. We measured femoral venous PO2, O2Hb saturation, pH, PCO2, lactate, and standard HCO3- during increasing work rate and two constant work rate cycle ergometer exercise tests [below and above the lactic acidosis threshold (LAT)] in two groups of five healthy subjects. Mean end-exercise femoral vein blood and VO2 values for the below- and above-LAT square waves and the increasing work rate protocol were, respectively, PO2 of 19.8 +/- 2.1 (SD), 18.8 +/- 4.7, and 19.8 +/- 3.3 Torr; O2 saturation of 22.5 +/- 4.1, 13.8 +/- 4.2, and 18.5 +/- 6.3%; pH of 7.26 +/- 0.01, 7.02 +/- 0.11, and 7.09 +/- 0.07; lactate of 1.9 +/- 0.9, 11.0 +/- 3.8, and 8.3 +/- 2.9 mmol/l; and VO2 of 1.77 +/- 0.24, 3.36 +/- 0.4, and 3.91 +/- 0.68 l/min. End-exercise femoral vein PO2 did not differ statistically for the three protocols, whereas O2Hb saturation continued to decrease for work rates above LAT. We conclude that decreasing capillary PO2 accounted for most of the O2Hb dissociation during below-LAT exercise and that acidification of muscle capillary blood due to lactic acidosis accounted for virtually all of the O2Hb dissociation above LAT.
Isometric relaxation of isolated diaphragm muscle: influence of load, length, time, and stimulation
Authors: Coirault C. , Chemla D. , Pery-Man N. , Suard I. , Salmeron S. , Lecarpentier Y.
Published: December 2017

Determinants of the isometric relaxation rate were investigated in isolated rat diaphragm (n = 30). We tested the hypothesis that these determinants could include loading conditions, namely preload and afterload; abrupt changes in load during the contraction phase; stimulation conditions; and time. Two relaxation sequences were studied. When isometric relaxation occurred at initial muscle length (isotonic-isometric sequence), an increase in total load (P) accelerated the negative peak rate of tension decline (-dP/dtmax). Variations in initial length, stimulation, and onset of relaxation did not modify the -dP/dtmax vs. afterload relationship. When isometric relaxation was analyzed after -dP/dtmax, for a given afterload level the instantaneous rate of tension decline (-dP/dt) was a unique function of instantaneous tension, regardless of previous loading conditions, stimulation mode, or time. When the isometric relaxation occurred at end-shortening muscle length (isometric-isotonic sequence), the -dP/dtmax vs. P relationship was flat. The rate of tension decay, as attested by either -dP/dtmax or instantaneous -dP/dt vs. instantaneous tension phase plane, differed markedly depending on stimulation conditions. Thus the regulation of isometric relaxation rate differed according to the relaxation sequence. In muscle isometrically relaxing at initial muscle length, peak isometric relaxation rate was mainly determined by afterload. Conversely, in muscle isometrically relaxing at end-shortening length, isometric relaxation rate was highly dependent on the level of activation and was independent of preload and afterload.
Effect of ambient temperature during 1st day of life on thermoregulation in lambs delivered by cesarean section
Authors: Clarke L. , Darby C. J. , Lomax M. A. , Symonds M. E.
Published: December 2017

We examined the effect of delivering near-term twin lambs by cesarean section into a warm (30 degrees C) or cool (15 degrees C) ambient temperature on the control of thermoregulation. Heat production was measured 20–30 h after birth during non-rapid-eye-movement sleep at 29 and 14 degrees C. At 29 degrees C there was no difference in heat production between groups, but at 14 degrees C cool-delivered (CD) lambs exhibited a 62% greater metabolic response. Irrespective of delivery temperature, 15 of the 18 lambs used shivering thermogenesis during cold exposure, indicating a reduction in the ability to use nonshivering thermogenesis in brown adipose tissue (BAT). Mean plasma concentrations of thyroxine and triiodothyronine were 35 and 45% greater, respectively, in CD lambs than in warm-delivered lambs. The level of guanosine 5′-diphosphate binding in BAT was lower than in normally delivered lambs and was not different between CD and warm-delivered lambs. Cesarean section delivery prevents the rise in BAT thermogenic activity, which results in an increased reliance on shivering thermogenesis to maintain colonic temperature. Under these conditions, delivery into a cool environment increases the plasma concentration of thyroid hormones, which benefits the neonate by enabling a greater thermogenic response via shivering.
Combined effects of age and exercise on thromboxane B2 and platelet activation
Authors: Todd M. K. , Goldfarb A. H. , Kauffman R. D. , Burleson C.
Published: December 2017

Nine healthy young (27.8 +/- 0.8 yr old, YM) and nine healthy older men (55.4 +/- 1.3 yr old, OM) ran on a treadmill at 70–75% of maximal O2 consumption for 30 min to determine the combined effects of age and acute exercise on plasma thromboxane B2 (TxB2) and beta-thromboglobulin (beta-TG). Blood samples (10 ml) were collected in tubes containing 0.5 ml of 4.5 mM EDTA, 30 mM acetylsalicylic acid, and 1 microM prostaglandin E1 after 15 min of rest, immediately after exercise, and at 30 min of recovery. Concentrations of TxB2 and beta-TG were determined by radioimmunoassay. Samples were adjusted for hemoconcentration and changes in platelet count not accounted for by plasma volume shifts. Data were analyzed with repeated-measures analysis of variance and Tukey's post hoc technique. Resting TxB2 was 53.3 +/- 9.6 and 79.0 +/- 18.2 pg/ml for the YM and OM, respectively. beta-TG at rest was 152.5 +/- 13.9 and 114.0 +/- 10.9 ng/ml for the YM and OM, respectively. No significant age group or exercise-induced differences for TxB2 or beta-TG were found immediately after exercise. TxB2 in the OM (101.7 +/- 16.4 pg/ml) 30 min after exercise was significantly (P = 0.05) higher than that in the YM (54.4 +/- 6.2 pg/ml). beta-TG values 30 min after exercise were not significantly different: 183.3 +/- 26.9 and 169.9 +/- 17.0 ng/ml in the OM and YM, respectively. These data suggest that OM may experience greater increases in TxB2 than YM 30 min after exercise and may be more predisposed to platelet activation.
Body fluid balance in dehydrated healthy older men: thirst and renal osmoregulation
Authors: Mack G. W. , Weseman C. A. , Langhans G. W. , Scherzer H. , Gillen C. M. , Nadel E. R.
Published: December 2017

We examined osmotic control of thirst and free water clearance in healthy older (65+, n = 10) and younger (Y, n = 6) subjects during a 3-h rehydration period after an approximately 2.4% decrease in body weight. Plasma volume (PV), plasma osmolality (Posm), renal function, and thirst were measured before and after dehydration and during rehydration. In 65+, baseline PV was lower (43.1 +/- 1.6 vs. 48.1 +/- 2.5 ml/kg), Posm was higher (287 +/- 1 vs. 281 +/- 2 mosmol/kgH2O), and perceived thirst was lower than in Y. During dehydration, the osmotic threshold for increased thirst was shifted to a higher Posm in 65+. Total fluid intake was greater in Y than in 65+ (16.6 +/- 4.1 vs. 8.9 +/- 2.0 ml/kg); however, the relation between thirst and the rate of fluid intake was identical. Thus the blunted rehydration in 65+ is related to a lower overall sensation of thirst. The stimulus-response characteristics of osmotic control of free water clearance was similar in 65+ and Y; however, 65+ operated around a higher Posm and on a less-steep portion of the stimulus-response curve. These data support the hypothesis that the hyperosmotic hypovolemic state of healthy older individuals is not a result of a simple water deficit but represents a shift in the operating point for control of body fluid volume and composition.
Reproducibility of the vascular response to heating in human skin
Authors: Savage M. V. , Brengelmann G. L.
Published: December 2017

Blood flow in human skin increases enormously in response to direct heating. If local skin temperature is held above 42 degrees C, blood flow eventually stabilizes at a level beyond which other influences, barring change in blood pressure, can produce no further increase. If this maximal level is a reproducible characteristic of an individual's cutaneous vasculature, it could be useful in comparing individuals; for example, in their response to hyperthermia. Our experiments were carried out to discover whether the maximal response of the vasculature of the skin of the forearm can be reproduced within reasonable limits and, also, to clarify the time course of the response. We used water sprayed over the surface of the forearms of 10 subjects to hold skin temperature above 42 degrees C for 60 min. During the last 10 min of heating, forearm blood flow (via venous occlusion plethysmography) was stable, at a level ranging from 16 to 38 ml.min-1.100 ml-1. This level, normalized to a blood pressure of 100 mmHg, was reproduced in a given individual on four or five occasions, with an average coefficient of variation of 10%. The response was 77 +/- 11% (SD) complete after 20 min of heating. Elapsed time at 90% of the final value was 35 +/- 9 (SD) min. We conclude that the maximal forearm blood flow response to local heating is a reproducible characteristic of the cutaneous vasculature with potential utility in the scaling of responses between and within individuals.
Hemodynamic effects and metabolic fate of inhaled nitric oxide in hypoxic piglets
Authors: Jacob T. D. , Nakayama D. K. , Seki I. , Exler R. , Lancaster J. R. , Sweetland M. A. , Yousem S. , Simmons R. L. , Billiar T. R. , Peitzman A. B. , et al.
Published: December 2017

We describe the hemodynamic effects and metabolic fate of inhaled NO gas in 12 anesthetized piglets. Pulmonary and systemic hemodynamic responses to incremental [NO] (5–80 ppm) were tested during ventilation with high- [0.30 inspired O2 fraction (FIO2)] and low-O2 (0.10 FIO2) mixtures. In six animals, inhalation of 40 ppm NO was maintained over 6 h to test effects of prolonged exposure (0.30 FIO2). In the other six animals, pulmonary hypertension was induced by hypoxic ventilation (0.10 FIO2) and responses to NO were tested. Inhaled low [NO] partially reversed pulmonary hypertension induced by alveolar hypoxia; mean pulmonary arterial pressure decreased from 31.4 +/- 2.3 mmHg during hypoxia to 18.2 +/- 1.2 mmHg during 5 ppm NO. Mean pulmonary arterial pressure at 0.10 FIO2 did not fall further at higher [NO] (10–40 ppm) and never reached control levels. Pulmonary vascular resistance increased with institution of hypoxic ventilation and fell with subsequent administration of NO, ultimately reaching control levels. Inhaled NO did not affect systemic vascular resistance. Plasma levels of NO2- + NO3- and methemoglobin (MetHb) levels increased with increasing [NO]. Over 6 h of NO administration during high-O2 ventilation, MetHb equilibrated at subtoxic levels while NO2- + NO3- increased. Nitrosylhemoglobin, analyzed by electron paramagnetic resonance spectrophotometry was not detected in blood at any time. At the relatively low concentrations (5–80 ppm) that are effective in relieving experimental pulmonary hypertension induced by alveolar hypoxia, inhaled NO gas causes accumulation of NO2- + NO3- in plasma and a small increase in MetHb but no detectable nitrosylhemoglobin.
A simplified method for endotracheal intubation in the rat
Authors: Weksler B. , Ng B. , Lenert J. , Burt M.
Published: December 2017

Endotracheal intubation in small laboratory animals is often necessary for survival experiments. Methods of airway control have included tracheostomy, blind intubation, and intubation under direct vision. Most of these methods are unsatisfactory and associated with high failure and complication rate. We developed an easy method of endotracheal intubation in the rat that requires simple material that is easily available to any research facility. The animals were anesthetized with pentobarbital sodium, the tongue was pulled out, and an otoscope was introduced into the oropharynx. By direct vision, a guide wire was inserted into the trachea and a 16-gauge intravenous catheter was glided over the wire. The first group of 70 rats underwent left thoracotomy with endotracheal intubation and mechanical ventilation at our laboratory as part of a study on isolated lung perfusion. The second group of five rats was anesthetized with pentobarbital, and a left carotid catheter and an endotracheal tube were inserted. Animals were ventilated with 100% O2. Arterial blood gases were sampled before intubation, 30 min after ventilation, and 60 min after extubation. In the first group, 94.3% (66 of 70) of the animals survived surgery and mortality was not directly related to the intubation and/or ventilation. All five animals of the second group survived the procedure to be extubated. Arterial PO2 before intubation, 30 min after intubation and ventilation, and 60 min after extubation was 77.1 +/- 8.5, 465.0 +/- 55.6, and 98.9 +/- 12.8 Torr, respectively. PCO2 at the same time points was 42.5 +/- 10.1, 35.1 +/- 6.3, and 32.7 +/- 6.5 Torr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary dead space and airway dimensions in dogs at different levels of lung inflation
Authors: Schulz A. , Schulz H. , Heilmann P. , Brand P. , Heyder J.
Published: December 2017

The quasi-stationary front that separates inspired gas from mixed alveolar gas is largely determined by the balance between diffusive and convective forces of gas transport. To investigate parameters influencing this balance, a study was performed on eight anesthetized ventilated beagle dogs. Measurements were made of the volume of pulmonary dead space corresponding to four end-inspiratory lung volumes. Aerosol recovery techniques were used to determine airway sizes at lung depths corresponding to those respective dead space volumes as well as at fixed volumetric depths between 70 and 250 ml. Mean dead space volumes as measured by a single inhalation of He (and SF6) were 112 +/- 15 (SD) ml (127 +/- 15 ml), 120 +/- 18 ml (137 +/- 20 ml), 127 +/- 18 ml (145 +/- 20 ml), and 133 +/- 19 ml (155 +/- 21 ml) at end-inspiratory lung volumes of 64, 71, 79, and 86%, respectively, of total lung capacity. At fixed lung depths the airway diameters increased with higher levels of lung inflation. However, airway diameters “at the end of the dead space” did not change significantly. They were approximately 0.5 mm for SF6 dead space and approximately 0.75 mm for He dead space. These findings support the theoretical prediction that the position of the diffusion front during breathing is strongly dependent on airway geometry and much less dependent on parameters of the breathing maneuver.
Energy balance in endurance-trained female cyclists and untrained controls
Authors: Horton T. J. , Drougas H. J. , Sharp T. A. , Martinez L. R. , Reed G. W. , Hill J. O.
Published: December 2017

Reports of low energy intakes in trained female athletes imply they have an increased energetic efficiency. To address this question, we determined how energy balance was achieved in endurance-trained females cyclists and lean controls (n=5 in each group). Daily energy expenditure was measured by using standardized physical activity protocols in a whole room calorimeter on two separate occasions: a cycling day and a noncycling day. Energy intake for weight maintenance was determined by a period of controlled feeding 5 days before and the day of each energy expenditure measurement. Energy balance was achieved in the cyclists on the cycling day while they consumed 2,900–3,000 kcal (their usual condition) and in controls on the noncycling day while they consumed 2,100–2,200 kcal (their usual condition). Total daily energy expenditure was not significantly different between the cyclists and controls on the noncycling day with both groups performing similar levels of activity. On the cycling day, daily energy expenditure was significantly greater in the cyclists vs. controls (P<0.03) as a result of their greater amount of cycling activity. Components of daily energy expenditure, i.e., resting metabolic rate and thermic effect of food and activity (noncycling), were not significantly different between groups. Overall, we found no significant increase in the energetic efficiency of endurance-trained female cyclists compared with controls.
Relationship between fat-free mass and urinary excretion of creatinine and 3-methylhistidine in adult humans
Authors: Virgili F. , Maiani G. , Zahoor Z. H. , Ciarapica D. , Raguzzini A. , Ferro-Luzzi A.
Published: December 2017

The urinary excretion of endogenous creatinine (CRTN) and 3-methylhistidine (3-MH) has been proposed as a predictor of fat-free mass (FFM) in healthy subjects. In this study, we report the relationship between FFM, estimated by densitometry plus deuterium dilution, and daily urinary excretion of CRTN and 3-MH in a sample of 20 healthy adult subjects of both sexes. 3-MH and CRTN were measured in 2 days of urine collection, which followed 4 days of meat-free diet. Meat-free diet was maintained throughout the period of urine collection. The mean of 2 days of excretion of 3-MH was 237.7 +/- 87.3 (SD) and 138.9 +/- 31.2 mumol/day in men and women, respectively. The mean CRTN excretion was 1.51 +/- 0.22 and 0.98 +/- 0.15 g/day in men and women, respectively. CRTN excretion was found well associated with FFM (R2 = 0.89; P < 0.0001), whereas 3-MH was lightly associated with FFM (R2 = 0.33; P < 0.01). Residuals from the regression of 3-MH vs. FFM were found to be correlated with CRTN excretion and FFM (R2 = 0.57 and 0.67, respectively), suggesting that muscularity and the absolute amount of lean mass are relevant for the error in predicting FFM from 3-MH excretion. Data confirm that urinary CRTN excretion can be an expedient indirect method for evaluating body composition in healthy adult subjects. Data also suggest that the relationship between 3-MH and FFM is complex, limiting the possibility of predicting body composition from the excretion of this metabolite.
Heterogeneous microvascular coronary vasodilation by adenosine and nitroglycerin in dogs
Authors: Habazettl H. , Vollmar B. , Christ M. , Baier H. , Conzen P. F. , Peter K.
Published: December 2017

We investigated the effects of adenosine and nitroglycerin (NTG) on coronary microvessel diameters (intravital fluorescence microscopy) and coronary perfusion (radioactive microspheres). Measurements were performed during baseline conditions (intravenous piritramid) and during controlled hypotension (mean arterial pressure approximately 60 mmHg) induced by halothane, adenosine, and NTG. Coronary vascular resistance (CVR) remained unchanged during halothane (-7%) but decreased during adenosine (-76%) and NTG (-29%). Coronary arteriolar diameters increased during all experimental steps. In the smallest vessels (20–40 microns), diameters increased by 14, 43, and 42% during halothane-, adenosine-, and NTG-induced hypotension, respectively. Diameter increases were less pronounced in larger vessels. The uniform action of adenosine and NTG in 20- to 500-microns arterial vessels is in contrast to the pronounced differences in reduction of CVR. Preferential dilation of arterioles < 20 microns or recruitment of coronary microvessels by adenosine might account for the more pronounced decrease of CVR during adenosine. Intracoronary application of adenosine (0.8 mg.kg-1.h-1) and NTG (1, 5, and 25 micrograms.kg-1.h-1) equally caused near-maximum dilation of coronary arterioles > 100 microns. However, NTG dilation of arterioles < 100 microns was dose dependent and exceeded large-vessel dilation only with the highest concentration of NTG.
Adverse effects of strenuous exercise: a densitometric and histomorphometric study in the rat
Authors: Bourrin S. , Genty C. , Palle S. , Gharib C. , Alexandre C.
Published: December 2017

To investigate the manner in which cancellous bone in different skeletal sites and within a bone site adapts to strenuous training, 5-wk-old male rats were subjected to intensive treadmill running [80% of maximal O2 consumption (VO2max)] for 11 wk. VO2max, tibia length, and bone mineral density were measured. Histomorphometric analysis was performed in the epiphysis, primary spongiosa (1 zero sp) and secondary spongiosa (2 zero sp) of the contralateral proximal tibia, and the 2 zero sp of thoracic and lumbar vertebrae. VO2max was increased by 39%. No changes were observed in vertebrae. Tibia length, 1 zero sp bone volume, and number of trabeculae were significantly decreased, indicating a retarded longitudinal bone growth. Bone mineral density in the proximal tibia was significantly decreased. In the epiphysis, a trabecular thinning and an increase of trabecular number were shown. In the 2 zero sp, bone volume and number of trabeculae were significantly decreased. The increased total eroded surfaces could indicate an early but transient increase in bone resorption activity. Osteoid thickness was reduced, whereas osteoclast number and osteoid surfaces were unchanged, suggesting that the observed bone loss was mostly due to an impaired osteoblastic activity. In conclusion, 1) strenuous training in young rats reduces longitudinal bone growth and induces bone loss, 2) the cancellous bone adaptation is site specific, and 3) the bone loss is mainly due to decreased osteoblastic activity rather than a global adaptation of bone remodeling.
Influences of parenchymal tethering on the reopening of closed pulmonary airways
Authors: Yap D. Y. , Liebkemann W. D. , Solway J. , Gaver D. P.
Published: December 2017

We investigated the influence of parenchymal tethering on the reopening of collapsed pulmonary airways. Reopening experiments were performed with freshly excised canine lobes placed in a vacuum chamber with pleural pressure (Ppl) set by vacuum pressure. Noncartilaginous 2- to 3-mm airways were collapsed by suction and remained collapsed on subsequent atmospheric pressure equalization. The airway was reopened by constant-flow insufflation, and peak pressure (Ppeak) needed to reopen the collapsed airway was measured. Yield pressure needed to begin axial meniscus motion decreased markedly at Ppl = -7.5 cmH2O, indicating a possible change in airway-meniscus configuration from compliant collapse to meniscus occlusion, thus promoting onset of reopening. Two distinct types of reopening behavior were observed: unstable low-frequency fluttering phenomenon characteristic of small magnitudes of Ppl in which airway tended to recollapse after being reopened and stable reopening phenomena at larger magnitudes of Ppl in which airway remained patent after it was reopened. Stable reopening was always observed at Ppl < or = -7.0 cmH2O. Effective transmural pressure (=Ppeak - Ppl) required to reopen airway and subsequent postreopening airway pressure, reflecting airway and collateral resistance, decreased with increasing magnitudes of Ppl due to increased influence of parenchymal tethering. However, at Ppl < -8.0 cmH2O, an increase in lung volume did not result in a reduction of effective transmural pressure, possibly indicating full airway distension and influence of airway wall hoop stress.
Decreased femoral arterial flow during simulated microgravity in the rat
Authors: Roer R. D. , Dillaman R. M.
Published: December 2017

To determine whether the blood supply to the hindlimbs of rats is altered by the tail-suspension model of weightlessness, rats were chronically instrumented for the measurement of femoral artery flow. Ultrasonic transit-time flow probes were implanted into 8-wk-old Wistar-Furth rats under ketamine-xylazine anesthesia, and, after 24 h of recovery, flow was measured in the normal ambulatory posture. Next, rats were suspended and flow was measured immediately and then daily over the next 4–7 days. Rats were subsequently returned to normal posture, and flow was monitored daily for 1–3 days. Mean arterial flow decreased immediately on the rats being suspended and continued to decrease until a new steady state of approximately 60% of control values was attained at 5 days. On the rats returning to normal posture, flow increased to levels observed before suspension. Quantile-quantile plots of blood flow data revealed a decrease in flow during both systole and diastole. The observed decrease in hindlimb blood flow during suspension suggests a possible role in the etiology of muscular atrophy and bone loss in microgravity.