bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep
Authors: Koos B. J. , Matsuda K. , Power G. G.
Published: December 2017

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.
Regional pulmonary blood flow during acute pulmonary edema: a PET study
Authors: Schuster D. P. , Haller J.
Published: December 2017

We used positron emission tomography to evaluate the effects of nitroprusside or prostacyclin (NP/Prost) on regional pulmonary blood flow (rPBF) in 21 dogs after oleic acid- (OA) induced acute pulmonary edema and compared the results with data from 11 dogs given OA only and 5 given meclofenamate after OA. After OA only, a progressive decrease in rPBF occurred in edematous gravity-dependent lung regions, but only in 6 of 11 dogs. In these six dogs, rPBF fell 41 +/- 12% compared with base line or with the other five dogs (3 +/- 19%) (P less than 0.05). In the NP/Prost group, the vasodilators failed to reverse any change in rPBF after OA but did prevent additional derecruitment until the drug infusion was stopped, after which rPBF to the edematous regions decreased further. In contrast, meclofenamate after OA temporally accelerated but did not quantitatively enhance rPBF reduction in edematous lung regions. Thus, in this model, vessels in edematous lung regions remain vasoreactive only until derecruited. We speculate that the mechanism of derecruitment involves an interaction between edema accumulation and vasoconstriction, in which the actual pattern of rPBF after lung injury represents a balance between mechanisms responsible for vascular derecruitment and vasodilation from prostacyclin production.
Mathematical modeling of heat and water transport in human respiratory tract
Authors: Daviskas E. , Gonda I. , Anderson S. D.
Published: December 2017

Excessive heat and water losses from the airways are stimuli to asthma. To study heat and water vapor transport in the human respiratory tract, a time-dependent model, based on a single differential equation with an analytical solution, was developed that could predict the intra-airway temperatures and water vapor contents. The key feature is the dependence of the temperature and water vapor along the respiratory tract as a function of the air residence time at each location. The model assumes disturbed laminar flow leading to enhanced transport mechanisms and wall temperature profiles modeled according to experimental data (E. R. McFadden, Jr., B. M. Pichurko, H. F. Bowman, E. Ingenito, S. Burns, N. Dowling, and J. Soloway. J. Appl. Physiol. 58: 564-570, 1985). It predicts that 1) the air equilibrates with the wall before it reaches body conditions (37 degrees C, 99.5% relative humidity); 2) conditioning of the inspired air involves several generations, with the number depending on the respiratory conditions; and 3) the walls of the upper airways are unsaturated, although it is difficult to judge at this state the depth of the respiratory tract affected.
Effect of artificial surfactant on pulmonary function in preterm and full-term lambs
Authors: Gladstone I. M. , Ray A. O. , Salafia C. M. , Perez-Fontan J. , Mercurio M. R. , Jacobs H. C.
Published: December 2017

We hypothesized that agents very different from surfactant may still support lung function. To test this hypothesis, we instilled FC-100, a fluorocarbon, and Tween 20, a detergent, which have higher minimum surface tensions and less hysteresis than surfactant, into 15 full-term and 14 preterm lambs. FC-100 and Tween 20 were as efficient as natural surfactant in improving gas exchange and compliance in preterm lambs with respiratory failure. Dynamic compliance correlated with the equilibrium surface tension of the alveolar wash in both full-term (P less than 0.02) and preterm (P less than 0.008) lambs. Functional residual capacity in full-term and preterm lambs was lower after treatment with the two test agents than with surfactant, findings consistent with qualitative histology. Oxygenation in full-term lambs correlated with mean lung volumes (P less than 0.003), suggesting that the hysteresis and/or low minimum surface tension of surfactant may improve mean lung volume, and hence oxygenation, by maintaining functional residual capacity. The effects of the test agents suggest that agents with biophysical properties different from surfactant may still aid lung expansion.
Lung overexpansion increases pulmonary microvascular protein permeability in young lambs
Authors: Carlton D. P. , Cummings J. J. , Scheerer R. G. , Poulain F. R. , Bland R. D.
Published: December 2017

To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (QL), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 +/- 1 cmH2O and a VT of 10 +/- 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 +/- 3 cmH2O and a VT of 48 +/- 4 ml/kg for 4-8 h. QL increased from 2.1 +/- 0.4 to 13.9 +/- 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 +/- 1 cmH2O and a VT of 23 +/- 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 +/- 1 cmH2O for 4-6 h without a change in VT. QL decreased on average from 2.8 +/- 0.6 to 1.9 +/- 0.3 ml/h (P = 0.08), and L/P was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular flow capacity of hindlimb skeletal muscles in spontaneously hypertensive rats
Authors: Sexton W. L. , Korthuis R. J. , Laughlin M. H.
Published: December 2017

Total and regional skeletal muscle flows (radiolabeled microspheres) were determined in isolated maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and age-matched (11-12 mo) normotensive Wistar-Kyoto rats (WKY) to assess the vascular flow capacity of the skeletal muscle vascular beds. Vascular flow capacity was estimated by measuring total hindquarters and regional muscle blood flows (under conditions of maximal vasodilation with papaverine or papaverine plus isoproterenol) over a wide range of perfusion pressures in WKY and SHR. Capillary exchange capacity was estimated by determining the capillary filtration coefficient. Isogravimetric capillary pressures and segmental vascular resistances were determined in each hindquarter. Isogravimetric flows and capillary pressures were not different between WKY and SHR. However, total and precapillary vascular resistances were significantly elevated in SHR, and postcapillary resistances were not different compared with WKY. Maximal capillary filtration coefficient values for the SHR group averaged 20% lower than WKY values, suggesting that hypertension was associated with a reduction in the microvascular surface area available for fluid exchange and, therefore, the capillary exchange capacity. Over the perfusion pressures studied, total hindquarters flows averaged 60% lower in SHR than in WKY. Flows to individual skeletal muscles averaged 76% lower in SHR than in WKY regardless of the muscle fiber type. Thus, modifications exist in the hindlimb skeletal muscle vasculature of SHR that reduces the capillary exchange capacity and limit the capacity of deliver flow at a given perfusion pressure gradient.
Enzyme profiles of single muscle fibers never exposed to normal neuromuscular activity
Authors: Hoffmann S. J. , Roy R. R. , Blanco C. E. , Edgerton V. R.
Published: December 2017

Do muscle fiber properties commonly associated with fiber types in adult animals and the population distribution of these properties require normal activation patterns to develop? To address this issue, the activity of an oxidative [succinic dehydrogenase (SDH)] and a glycolytic [alpha-glycerophosphate dehydrogenase (GPD)] marker enzyme, the characteristics of myosin adenosinetriphosphatase (myosin ATPase, alkaline preincubation), and the cross-sectional area of single fibers were studied. The soleus and medial gastrocnemius of normal adult cats were compared with cats that 6 mo earlier had been spinally transected at T12-T13 at 2 wk of age. In control cats, SDH activity was higher in dark than light ATPase fibers in the soleus and higher in light than dark ATPase fibers in the medial gastrocnemius. After transection, SDH activity was similar to control in both muscles. GPD activity appeared to be elevated in some fibers in each fiber type in both muscles after transection. The cross-sectional areas most affected by spinal transection were light ATPase fibers of the soleus and dark ATPase fibers of the medial gastrocnemius, the predominant fiber type in each muscle. These data demonstrate that although the muscle fibers of cats spinalized at 2 wk of age presumably were never exposed to normal levels of activation, the activity of an oxidative marker enzyme was maintained or elevated 6 mo after spinal transection. Furthermore, although the absolute enzyme activities in some fibers were elevated by transection, three functional protein systems commonly associated with fiber types, i.e., hydrolysis of ATP by myosin ATPase and glycolytic (GPD) and oxidative (SHD) metabolism, developed in a coordinated manner typical of normal adult muscles.
Metabolic effects of training in humans: a 31P-MRS study
Authors: Kent-Braun J. A. , McCully K. K. , Chance B.
Published: December 2017

The purpose of this study was to determine the feasibility of measuring with 31P nuclear magnetic resonance the effects of an endurance training program on the high-energy phosphate metabolism of exercising human skeletal muscle. The system used included a 1.9-T 30-cm-bore Oxford Systems superconducting magnet, a PhosphoEnergetics spectrometer, and a modified Cybex isokinetic ergometer. Seven healthy human volunteers exercised their wrist flexor muscles 20 min/day 5 days/wk for 8 wk. Testing before and after the training period consisted of a performance test to measure muscle functional capacity and a ramp test to measure the work-energy cost relationship of the exercising muscles. The results indicate that the subjects had a significant increase in their work output on the 10-min performance test after training. They also exhibited an increase in the work-energy cost relationship on the ramp test as indicated by a decrease in peak Pi-to-phosphocreatine ratio and an increase in pH at the same relative power output after training. These results indicate that 1) the training program was sufficient to elicit a training effect and 2) this effect was observed with 31P nuclear magnetic resonance as an increased potential for oxidative metabolism, particularly at the high exercise levels.
Comparison of phenylephrine bolus and infusion methods in baroreflex measurements
Authors: Sullebarger J. T. , Liang C. S. , Woolf P. D. , Willick A. E. , Richeson J. F.
Published: December 2017

Phenylephrine (PE) bolus and infusion methods have both been used to measure baroreflex sensitivity in humans. To determine whether the two methods produce the same values of baroreceptor sensitivity, we administered intravenous PE by both bolus injection and graded infusion methods to 17 normal subjects. Baroreflex sensitivity was determined from the slope of the linear relationship between the cardiac cycle length (R-R interval) and systolic arterial pressure. Both methods produced similar peak increases in arterial pressure and reproducible results of baroreflex sensitivity in the same subjects, but baroreflex slopes measured by the infusion method (9.9 +/- 0.7 ms/mmHg) were significantly lower than those measured by the bolus method (22.5 +/- 1.8 ms/mmHg, P less than 0.0001). Pretreatment with atropine abolished the heart rate response to PE given by both methods, whereas plasma catecholamines were affected by neither method of PE administration. Naloxone pretreatment exaggerated the pressor response to PE and increased plasma beta-endorphin response to PE infusion but had no effect on baroreflex sensitivity. Thus our results indicate that 1) activation of the baroreflex by the PE bolus and infusion methods, although reproducible, is not equivalent, 2) baroreflex-induced heart rate response to a gradual increase in pressure is less than that seen with a rapid rise, 3) in both methods, heart rate response is mediated by the vagus nerves, and 4) neither the sympathetic nervous system nor the endogenous opiate system has a significant role in mediating the baroreflex control of heart rate to a hypertensive stimulus in normal subjects.
Distribution of muscle fiber types and EMG activity in cat intercostal muscles
Authors: Greer J. J. , Martin T. P.
Published: December 2017

The electromyogram (EMG) activity and histochemical properties of intercostal muscles in the anesthetized cat were studied. The parasternal muscles were consistently active during inspiration. The external intercostals in the rostral spaces and the ventral portions of the midthoracic spaces were also recruited during inspiration. The remaining external intercostals were typically silent, regardless of the level of respiratory drive. The internal intercostal muscles located in the caudal spaces were occasionally recruited during expiration. There was a clear correlation between recruitment patterns of the intercostals and the histochemically defined fiber type properties of the muscles. Intercostal muscles that were routinely recruited during inspiration had a significantly higher proportion of slow-oxidative muscle fibers.
Upper airway resistance and geniohyoid muscle activity in normal men during wakefulness and sleep
Authors: Wiegand D. A. , Latz B. , Zwillich C. W. , Wiegand L.
Published: December 2017

Sleep-related reduction in geniohyoid muscular support may lead to increased airway resistance in normal subjects. To test this hypothesis, we studied seven normal men throughout a single night of sleep. We recorded inspiratory supraglottic airway resistance, geniohyoid muscle electromyographic (EMGgh) activity, sleep staging, and ventilatory parameters in these subjects during supine nasal breathing. Mean inspiratory upper airway resistance was significantly (P less than 0.01) increased in these subjects during all stages of sleep compared with wakefulness, reaching highest levels during non-rapid-eye-movement (NREM) sleep [awake 2.5 +/- 0.6 (SE) cmH2O.l-1.s, stage 2 NREM sleep 24.1 +/- 11.1, stage 3/4 NREM sleep 30.2 +/- 12.3, rapid-eye-movement (REM) sleep 13.0 +/- 6.7]. Breath-by-breath linear correlation analyses of upper airway resistance and time-averaged EMGgh amplitude demonstrated a significant (P less than 0.05) negative correlation (r = -0.44 to -0.55) between these parameters in five of seven subjects when data from all states (wakefulness and sleep) were combined. However, we found no clear relationship between normalized upper airway resistance and EMGgh activity during individual states (wakefulness, stage 2 NREM sleep, stage 3/4 NREM sleep, and REM sleep) when data from all subjects were combined. The timing of EMGgh onset relative to the onset of inspiratory airflow did not change significantly during wakefulness, NREM sleep, and REM sleep. Inspiratory augmentation of geniohyoid activity generally preceded the start of inspiratory airflow. The time from onset of inspiratory airflow to peak inspiratory EMGgh activity was significantly increased during sleep compared with wakefulness (awake 0.81 +/- 0.04 s, NREM sleep 1.01 +/- 0.04, REM sleep 1.04 +/- 0.05; P less than 0.05). These data indicate that sleep-related changes in geniohyoid muscle activity may influence upper airway resistance in some subjects. However, the relationship between geniohyoid muscle activity and upper airway resistance was complex and varied among subjects, suggesting that other factors must also be considered to explain sleep influences on upper airway patency.
Prostacyclin production with serotonin, increased flow, or elevated venous pressure in dog lung
Authors: el-Kashef H. A. , Hofman W. F. , Ehrhart I. C.
Published: December 2017

The lung may release prostacyclin (PGI2) in response to humoral or mechanical stimuli. We measured 6 keto-PGF1 alpha as an index of PGI2 production during serotonin (5-HT) infusion, elevated venous pressure (Pv), or increased blood flow (Q) in the isolated canine lower left lung lobe (LLL). Lobar vascular resistance (LVR) was partitioned into arterial (Ra), middle (Rm), and venous (Rv) components by arterial and venous occlusions. The infusion of 55-210 micrograms/min 5-HT (n = 9) was associated with concomitant increases in PGI2 production and dose-related increases in pulmonary arterial pressure (Pa) and LVR. 5-HT increased Ra at each infusion rate, whereas Rm was not changed and Rv was increased only at the highest infusion rate. When Pa was increased by stepwise elevations in Pv from 3.7 to 19.1 cmH2O (n = 8) or by increases in Q from 250 to 507 ml/min (n = 5) to match the Pa increase observed during 5-HT infusion, PGI2 production was not altered. Increases in Pv reduced LVR largely by decreasing Ra, whereas increases in Q reduced LVR without changing Ra, Rm, or Rv. Infusion of 5-HT when Pa was held constant by reduction in blood flow (n = 6) did not increase PGI2. Thus infusion of 5-HT at a normal blood flow rate increased PGI2 formation in the isolated blood-perfused dog lung lobe. The results also suggest that sustained mechanical effects related to increased venous pressure or elevated blood flow are not associated with a sustained elevation of PGI2 formation.
Training increases muscle blood flow in rats with peripheral arterial insufficiency
Authors: Yang H. T. , Dinn R. F. , Terjung R. L.
Published: December 2017

This study investigated the effect of physical training on muscle blood flow (BF) in rats with peripheral arterial insufficiency during treadmill running. Bilateral stenosis of the femoral artery of adult rats (300-350 g) was performed to reduce exercise hyperemia in the hindlimb but not limit resting muscle BF. Rats were divided into normal sedentary, acute stenosed (stenosed 3 days before the experiment), stenosed sedentary (limited to cage activity), and stenosed trained (run on a treadmill by a progressively intense program, up to 50-60 min/day, 5 days/wk for 6-8 wk). Hindlimb BF was determined with 85Sr- and 141Ce-labeled microspheres at a low (20 m/min) and high treadmill speed (30-40 m/min depending on ability). Maximal hindlimb BF was reduced to approximately 50% normal in the acute stenosed group. Total hindlimb BF (81 +/- 5 ml.min-1.100 g-1) did not change in stenosed sedentary animals with 6-8 wk of cage activity, but a redistribution of BF occurred within the hindlimb. Two factors contributed to a higher BF to the distal limb muscle of the trained animals. A redistribution BF within the hindlimb occurred in stenosed trained animals; distal limb BF increased to approximately 80% (P less than 0.001) of the proximal tissue. In addition, an increase in total hindlimb BF with training indicates that collateral BF has been enhanced (P less than 0.025). The associated increase in oxygen delivery to the relatively ischemic muscle probably contributed to the markedly improved exercise tolerance evident in the trained animals.
Plasma fibronectin levels during cardiopulmonary bypass
Authors: Charash W. E. , Foster E. D. , Saba T. M. , Dayton C. , Cho E.
Published: December 2017

Plasma fibronectin, also called cold-insoluble globulin, is a cryoprecipitable glycoprotein with both opsonic and adhesive activities. It binds to collagen, actin, and heparin and can form soluble as well as cryoprecipitable complexes in the cold. Fibronectin augments particulate phagocytosis by the reticuloendothelial system and can influence lung vascular permeability. Plasma fibronectin deficiency is temporally associated with respiratory failure in septic surgical, trauma, and burn patients. We measured plasma fibronectin and albumin levels in nine adults undergoing elective cardiopulmonary bypass to determine whether dilution alone could account for the changes in plasma fibronectin. Plasma fibronectin concentration decreased 17% with the surgical trauma of opening of the chest and placement of the vascular cannulas. On heparinization and initiation of cardiopulmonary bypass, plasma fibronectin fell an additional 48% (P less than 0.001), whereas albumin concentration (corrected for albumin in the pump prime) fell only 25% (P less than 0.001), emphasizing that dilution was not the only mechanism contributing to the decline in plasma fibronectin. Fibronectin levels began to increase after discontinuation of cardiopulmonary bypass and in association with diuresis, but unexpectedly they remained subnormal until 4 days postoperation. Thus the decline in fibronectin concentration with cardiopulmonary bypass may be due to dilution as well as opsonic consumption and possible complexing with heparin in the cold.
Temperature dependence of rat diaphragm muscle contractility and fatigue
Authors: Prezant D. J. , Richner B. , Valentine D. E. , Aldrich T. K. , Fishman C. L. , Nagashima H. , Chaudhry I. , Cahill J.
Published: December 2017

The diaphragm is a skeletal muscle of mixed fiber type that is unique in its requirement to maintain contractile function and fatigue resistance across a wide range of temperatures to sustain alveolar ventilation under conditions of hypo- or hyperthermia. The direct effect of temperature (15-41 degrees C) on rat diaphragm isometric contractility and fatigue was determined in vitro. As temperature decreased from 37 to 15 degrees C, contraction and relaxation times increased, and there was a left shift of the diaphragm's force-frequency curve, with decreased contractility at 41 and 15 degrees C. Fatigue was induced by 10 min of stimulation with 30 trains/min of 5 Hz at a train duration of 900 ms. Compared with 37 degrees C, fatigue resistance was enhanced at 25 degrees C, but no difference in fatigue indexes was evident at extreme hypothermia (15 degrees C) or hyperthermia (41 degrees C). Only when the fatigue program was adjusted to account for hypothermia-induced increases in tension-time indexes was fatigue resistance evident at 15 degrees C. These findings indicate that despite the diaphragm's unique location as a core structure, necessitating exposure to in vivo temperatures higher than found in limb muscle, the temperature dependence of rat diaphragm muscle contractility and fatigue is similar to that reported for limb muscle of mixed fiber type.
Potassium as a respiratory signal in humans
Authors: Newstead C. G. , Donaldson G. C. , Sneyd J. R.
Published: December 2017

Six renal transplant recipients underwent a series of incremental exercise experiments. Minute ventilation (VE), carbon dioxide production rate (VCO2), and arterial blood chemistry were measured at rest and while subjects exercised on a stationary bicycle. Four of the subjects performed a similar experiment while exercising on a static rowing machine. Within each subject, arterial potassium concentration ([K+]a) was linearly related to VCO2 and VE during exercise. The slope of the relationship between [K+]a and VCO2 was similar in the cycling and rowing experiments. This implies that the absorption of potassium by resting muscle does not significantly limit the arterial hyperkalemia seen during exercise. When VE, VCO2, and [K+]a were measured 1 and 5 min after the end of cycling there was no correlation, whereas VE continued to be closely correlated with VCO2. The relationship demonstrated between change in [K+]a and VCO2 in these experiments is compatible with change of [K+]a acting as a respiratory signal during exercise but not during recovery from exercise in humans.
Immunomodulations induced in rats by exercise on a treadmill
Authors: Ferry A. , Weill B. L. , Rieu M.
Published: December 2017

Various regimens of treadmill exercise (0% slope) were used with rats: 60 min at 15 m/min (T-15), 180 min at 10 m/min (T-10), and 60 min/day at 15 m/min for 6 consecutive days (T-15-6). Exercise resulted in 1) decreases in the absolute number of mononuclear spleen cells in T-10 rats, 2) significant increases in in vitro splenic T-cell blastogenesis in response to phytohemagglutinin in T-10 rats, and 3) significant decreases in T-cell blastogenesis in T-15-6 rats. T-15-6 rats were given aminoglutethimide per os before exercise sessions to study the role of corticosteroids in the alteration of splenic T-cell blastogenesis. Aminoglutethimide significantly increased the T-cell blastogenesis in these T-15-6 rats compared with those not given aminoglutethimide, whereas it had no effect on immune parameters of sedentary rats. These results show that immunomodulations in the rat depend on the treadmill exercise regimen employed. If the mechanisms of the immunomodulation induced by isolated exercise of long duration are not elucidated, these data suggest that corticosteroids are involved in the alteration in T-cell blastogenesis induced by chronic muscular exercise.
Substrate utilization during acute exercise in obese Zucker rats
Authors: Torgan C. E. , Brozinick J. T. , Willems M. E. , Ivy J. L.
Published: December 2017

The purpose of the present study was to compare the carbohydrate use of insulin-resistant obese Zucker rats with that of their lean littermates during steady-state exercise. Obese and lean rats were randomly assigned to a sedentary group or to a run group in which rats ran at 72-73% of their maximal O2 consumption, with the duration of exercise set to require an energy expenditure of 2.1-2.2 kcal. During the run the respiratory exchange ratio was significantly higher in the obese than in the lean rats [0.94 +/- 0.01 (SE) and 0.86 +/- 0.01, respectively], which indicate that the obese rats required 54% more carbohydrate than the lean rats. Total muscle glycogen utilization in the soleus, plantaris, and red and white gastrocnemius was not different between groups. Obese rats had total liver glycogen values five times greater than those of lean rats (833.38 +/- 101.4 and 152.8 +/- 37.5 mg, respectively) and utilized twice as much liver glycogen as their lean littermates (193.5 and 90.4 mg, respectively). The obese rats exhibited higher blood glucose and insulin concentrations than the lean rats during the run. These findings indicate that, despite their characteristic insulin resistance, the obese Zucker rats had a greater dependency on carbohydrate as a substrate during exercise than their lean littermates and that the major source of this carbohydrate was liver glycogen.
Effect of norepinephrine on diaphragm contractility and blood flow
Authors: Supinski G. S. , DiMarco A. F. , Gonzalez J. , Altose M. D.
Published: December 2017

Recent studies have shown that diaphragm fatigue can be reversed by mechanical augmentation of phrenic arterial flow. The purpose of the present experiment was to determine whether it was possible to pharmacologically augment diaphragm blood flow and reverse fatigue by the administration of norepinephrine. Four groups of studies were performed, all employing our previously described in situ isometric canine diaphragm strip preparation (Supinski et al., J. Appl. Physiol. 60: 1789-1796, 1986). Group I studies examined the effects of norepinephrine on the contractility of the nonfatigued diaphragm in normotensive dogs, group II studies examined the effects of this drug on the contractility of the fatigued diaphragm in normotensive animals, and group III studies examined the effect of this drug on the contractility of the fatigued diaphragm in hypotensive animals. Group IV studies examined the effect of norepinephrine in normotensive animals in which the phrenic artery was cannulated and pump perfused at constant flow. Fatigue was induced in group II, III, and IV studies by rhythmically stimulating the diaphragm via intramuscular electrodes. Norepinephrine had no effect on the contractility of the nonfatigued diaphragm (group I). In normotensive (group II) and hypotensive animals (group III), norepinephrine elicited dramatic increases in arterial blood pressure and phrenic arterial flow and produced a significant upshift in the force-frequency curve of the fatigued diaphragm. However, when phrenic flow was held constant (group IV experiments), norepinephrine failed to augment the contractility of the fatigued diaphragm. These results indicate that 1) norepinephrine can increase phrenic blood flow and augment the contractility of the fatigued diaphragm in both normotensive and hypotensive conditions and 2) this effect of norepinephrine to partially reverse fatigue is secondary to its action to augment diaphragmatic blood flow.
Decreased thermal conductance during the luteal phase of the menstrual cycle in women
Authors: Frascarolo P. , Schutz Y. , Jequier E.
Published: December 2017

To study the influence of the menstrual cycle on whole body thermal balance and on thermoregulatory mechanisms, metabolic heat production (M) was measured by indirect calorimetry and total heat losses (H) were measured by direct calorimetry in nine women during the follicular (F) and the luteal (L) phases of the menstrual cycle. The subjects were studied while exposed for 90 min to neutral environmental conditions (ambient temperature 28 degrees C, relative humidity 40%) in a direct calorimeter. The values of M and H were not modified by the phase of the menstrual cycle. Furthermore, in both phases the subjects were in thermal equilibrium because M was similar to H (69.7 +/- 1.8 and 72.1 +/- 1.8 W in F and 70.4 +/- 1.9 and 71.4 +/- 1.7 W in L phases, respectively). Tympanic temperature (Tty) was 0.24 +/- 0.07 degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. Calculated skin thermal conductance (Ksk) was lower in the L (17.9 +/- 0.6 W.m-2.degrees C-1) than in the F phase (20.1 +/- 1.1 W.m-2.degrees C-1; P less than 0.05). Calculated skin blood flow (Fsk) was also lower in the L (0.101 +/- 0.008 l.min-1.m-2) than in the F phase (0.131 +/- 0.015 l.min-1.m-2; P less than 0.05). Differences in Tty, Ksk, and Fsk were not correlated with changes in plasma progesterone concentration. It is concluded that, during the L phase, a decreased thermal conductance in women exposed to a neutral environment allows the maintenance of a higher internal temperature.
Impairment of left ventricular function during maximal isometric dead lifting
Authors: Vitcenda M. , Hanson P. , Folts J. , Besozzi M.
Published: December 2017

High-intensity short-duration lifting is frequently performed by athletes and laborers. Little is known about the magnitude and pattern of blood pressure response and resultant effects on left ventricular (LV) function during this form of intense isometric exercise. We monitored brachial intra-arterial pressure and LV ejection fraction (LVEF) during upright isometric dead lifting performed on a force platform. Fourteen healthy male subjects (age 27 yr) maintained maximal sustained isometric dead lift (140 +/- 34 kg) for 32 s. LVEF was measured by 99mTc first-pass radionuclide ventriculography. Mean arterial pressure increased from 107 +/- 15 mmHg at rest to a peak of 174 +/- 28 mmHg and fell precipitously to 88 +/- 13 mmHg within 10 s after release of the dead lift. LVEF decreased from 63 +/- 8 to 51 +/- 14% (P less than 0.02) in seven subjects with technically acceptable ventriculograms. We conclude that maximal upright isometric dead-lift exercise produces a marked increase in arterial pressure and corresponding LV afterload that is associated with a transient reduction in LVEF in normal men.
Effect of metoclopramide on angiotensins, aldosterone, and atrial peptide during hypoxia
Authors: Vonmoos S. , Nussberger J. , Waeber B. , Biollaz J. , Brunner H. R. , Leuenberger P.
Published: December 2017

The coupling of aldosterone with renin is altered during acute hypoxemia. We measured the various components of the renin-angiotensin system and the plasma levels of immunoreactive atrial natriuretic factor (iANF) during room air and hypoxic gas-mixture breathing before and after administration of metoclopramide, a competitive antagonist of dopamine. Seven resting volunteers were studied 1 wk apart under room air and hypoxic conditions (inspired O2 fraction 0.12). During hypoxemia, the release of aldosterone induced by metoclopramide was significantly smaller. This change was associated with a slight increase in iANF and with a decrease in plasma angiotensin II levels, without any change in immunoreactive blood angiotensin I concentrations. Plasma electrolytes and blood acid-base status did not show relevant changes, nor did blood pressure and heart rate. We conclude that the decreased aldosterone concentrations seen under hypoxemia are related to decreased angiotensin II levels. Other influences, such as elevated ANF, may also mediate this effect.
Persistence of enhanced aerosol deposition in the lung after recovery from carbachol-induced airway obstruction
Authors: Kim C. S. , Garcia L. , Eldridge M. A. , Wanner A.
Published: December 2017

Time course recovery from induced airway obstruction by carbachol infusion (CI; 0.2 microgram.kg-1.min-1 for 40 min), carbachol aerosol (CA; 10 breaths of 2% solution), and histamine aerosol (HA; 25-50 breaths of 5% solution) challenge was investigated in conscious sheep (n = 6 each). Total lung aerosol deposition and airway caliber as assessed by pulmonary airflow resistance (RL) were measured every 20-30 min up to 4 h after the challenges. Aerosol deposition was measured by monitoring aerosol concentration continuously with a laser aerosol photometer while the sheep rebreathed 1.0-micron-diam inert oil droplets delivered by a 0.25-liter bag-in-box system driven by a respiratory pump at a breathing frequency of 30 breaths/min. Total accumulated deposition at the fifth breath (AD5) as percentage of the initial aerosol concentration was determined and used as an aerosol deposition index. Percent changes in AD5 from baseline were compared with corresponding changes in RL. Both RL and AD5 increased after Cl, CA, and HA: 192-477% for RL and 23-44% for AD5 (P less than 0.05). Mean RL return to baseline values 1 h after CI and HA and 2 h after CA. Mean AD5 returned to baseline at 1 h post-HA. In contrast, mean AD5 remained elevated for 2-4 h after CI and CA (P less than 0.05), and the increased AD5 could not be reversed by a bronchodilator aerosol. The persistence of enhanced aerosol deposition long after the return of RL to baseline suggests that complete recovery of airway conditions after CI and CA takes much longer than predicted by RL.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative relationships between left ventricular ejection and wall thickening and geometry
Authors: Dumesnil J. G. , Shoucri R. M.
Published: December 2017

The quantitative relationships that exist between left ventricular (LV) wall shortening, wall thickening, and geometry during LV ejection are not well defined. We used a mathematical model to measure these parameters in 40 patients with various LV geometries studied by echocardiography. As opposed to wall shortening, the percent contribution of wall thickening to LV ejection (% delta Vh) was 25 +/- 2% in normal subjects; in all the patients, it varied from 18 to 45% and was inversely correlated (r = 0.94) to the midwall radius-to-wall thickness ratio (R/h) of the ventricle at end diastole. On the other hand, the ratio of the quantity of blood ejected per unit of LV wall volume magnitude of delta V/V omega magnitude of varied from 0.20 to 1.20 (normal subjects 0.83 +/- 0.11) and was directly correlated (r = 0.94) to R/h; using independent data in the literature, we also found a similar relationship (r = 0.80) between the ratio of quantity of blood ejected per unit of LV mass (magnitude of delta V/M omega magnitude of) and R/h. Patients with presumably abnormal myocardial function did not satisfy the relationship between magnitude of delta V/V omega magnitude of or magnitude of delta V/M omega magnitude of and R/h.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium channel blockers modulate airway constriction in the canine lung periphery
Authors: Lindeman K. S. , Hirshman C. A. , Freed A. N.
Published: December 2017

We studied the effect of two voltage-sensitive calcium channel blockers on Na2EDTA-induced bronchoconstriction in the canine lung periphery. A wedged bronchoscope technique was used to measure collateral system resistance before and after challenges with aerosolized Na2EDTA, hypocapnia, aerosolized acetylcholine, and increased flow of dry air in anesthetized mongrel dogs. Nifedipine, a dihydropyridine calcium channel blocker, reduced hypocapnia-induced bronchoconstriction by 88 +/- 6% (SE) but did not alter Na2EDTA-induced constriction. Verapamil, a phenylalkylamine calcium channel blocker, attenuated hypocapnia- and Na2EDTA-induced bronchoconstriction by 69 +/- 6 and 44 +/- 7%, respectively, but did not significantly alter responses to either acetylcholine or dry air challenge. We conclude that calcium influx through voltage-sensitive calcium channels, perhaps of the T subtype, has a limited role in the initiation of Na2EDTA-induced bronchoconstriction in the canine lung periphery.
Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength
Authors: Cuneo R. C. , Salomon F. , Wiles C. M. , Hesp R. , Sonksen P. H.
Published: December 2017

The effect of recombinant DNA human growth hormone (rhGH) treatment in adults with growth hormone (GH) deficiency was studied in 24 patients in a double-blind placebo-controlled trial. The dose was 0.07 U/kg body wt daily. After 6 mo of treatment, significant increases were noted in the rhGH group for total cross-sectional area of thigh muscle (+11.2 +/- 3.1 vs. -0.5 +/- 3.0 cm2; P = 0.015 vs. placebo) and quadriceps muscle (+4.1 +/- 0.8 vs. +0.4 +/- 1.2 cm2; P = 0.031) measured by computerized tomography. Strong correlations were noted between lean body mass (measured as total body potassium) and total thigh muscle area in normal and GH-deficient adults both before and after rhGH treatment. Strength of hip flexors (+1.25 +/- 0.27 vs. +0.25 +/- 0.12 z-scores; P = 0.004) and limb girdle muscles increased (P = 0.02) in the rhGH group. We conclude that 1) rhGH increases lean tissue and skeletal muscle mass in adults with human GH deficiency, 2) this suggests a role for GH in the regulation of body composition of adult humans, 3) the increase in strength of limb girdle muscles after rhGH treatment suggests that adults with GH deficiency may have a proximal myopathy, and 4) the failure to demonstrate an increase in strength in other muscle groups may require the study of larger numbers of patients.
Effect of hemoglobin concentration on maximal O2 uptake in canine gastrocnemius muscle in situ
Authors: Hogan M. C. , Bebout D. E. , Wagner P. D.
Published: December 2017

O2 delivery to maximally working muscle was decreased by altering hemoglobin (Hb) concentration and arterial PO2 (PaO2) to investigate whether the reductions in maximal O2 uptake (VO2max) that occur with lowered [Hb] are in part related to changes in the effective muscle O2 diffusing capacity (DmO2). Two sets of experiments were conducted. In the initial set (n = 8), three levels of Hb [5.8 +/- 0.3, 9.4 +/- 0.1, and 14.4 +/- 0.6 (SE) g/100 ml] in the blood were used in random order to pump perfuse, at equal muscle blood flows and PaO2, maximally working isolated dog gastrocnemius muscle. VO2max declined with decreasing [Hb], but the relationship between VO2max and both the effluent venous PO2 (PvO2) and the calculated mean capillary PO2 (PcO2) was not linear through the origin and, therefore, not compatible with a single value of DmO2 (as calculated by Bohr integration using a model based on Fick's law of diffusion). To clarify these results, a second set of experiments (n = 6) was conducted in which two levels of Hb (14.0 +/- 0.6 and 6.9 +/- 0.6 g/100 ml) were each combined with two levels of oxygenation (PaO2 79 +/- 8 and 29 +/- 2 Torr) and applied in random sequence to again pump perfuse maximally working dog gastrocnemius muscle at constant blood flow. In these experiments, the relationship between VO2max and both PvO2 and calculated PcO2 for each [Hb] was consistent with a constant estimate of DmO2 as PaO2 was reduced, but the calculated DmO2 for the lower [Hb] was 33% less than that at the higher [Hb] (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Oxygen transport during steady-state submaximal exercise in chronic hypoxia
Authors: Wolfel E. E. , Groves B. M. , Brooks G. A. , Butterfield G. E. , Mazzeo R. S. , Moore L. G. , Sutton J. R. , Bender P. R. , Dahms T. E. , McCullough R. E. , et al.
Published: December 2017

Arterial O2 delivery during short-term submaximal exercise falls on arrival at high altitude but thereafter remains constant. As arterial O2 content increases with acclimatization, blood flow falls. We evaluated several factors that could influence O2 delivery during more prolonged submaximal exercise after acclimatization at 4,300 m. Seven men (23 +/- 2 yr) performed 45 min of steady-state submaximal exercise at sea level (barometric pressure 751 Torr), on acute ascent to 4,300 m (barometric pressure 463 Torr), and after 21 days of residence at altitude. The O2 uptake (VO2) was constant during exercise, 51 +/- 1% of maximal VO2 at sea level, and 65 +/- 2% VO2 at 4,300 m. After acclimatization, exercise cardiac output decreased 25 +/- 3% compared with arrival and leg blood flow decreased 18 +/- 3% (P less than 0.05), with no change in the percentage of cardiac output to the leg. Hemoglobin concentration and arterial O2 saturation increased, but total body and leg O2 delivery remained unchanged. After acclimatization, a reduction in plasma volume was offset by an increase in erythrocyte volume, and total blood volume did not change. Mean systemic arterial pressure, systemic vascular resistance, and leg vascular resistance were all greater after acclimatization (P less than 0.05). Mean plasma norepinephrine levels also increased during exercise in a parallel fashion with increased vascular resistance. Thus we conclude that both total body and leg O2 delivery decrease after arrival at 4,300 m and remain unchanged with acclimatization as a result of a parallel fall in both cardiac output and leg blood flow and an increase in arterial O2 content.(ABSTRACT TRUNCATED AT 250 WORDS)
Ventilation in newborn rats after gestation at simulated high altitude
Authors: Gleed R. D. , Mortola J. P.
Published: December 2017

Pregnant rats were kept at a simulated altitude of 4,500 m (PO2 91 Torr) for the whole of gestation and returned to sea level 1 day after giving birth. During pregnancy, body weight gain and food intake were approximately 30% less than in controls at sea level. Measurements were made on the 1-day-old (HYPO) pups after a few hours at sea level. In normoxia, ventilation (VE) measured by flow plethysmography was more (+17%) and O2 consumption (VO2) measured by a manometric method was less (-19%) than in control (CONT) pups; in HYPO pups VE/VO2 was 44% greater than in CONT pups. In acute hyperoxia, VE/VO2 of HYPO and CONT pups decreased by a similar amount (15-20%), indicating some limitation in O2 availability for both groups of pups in normoxia. However, VE/VO2 of HYPO pups, even in hyperoxia, remained above (+34%) that of CONT pups. HYPO pups weighed slightly less than CONT pups, their lungs were hypoplastic, and their hearts were a larger fraction of body weight. An additional group of female rats was acclimatized (8 days) to high altitude before insemination. During pregnancy, body weight gain and food intake of these females were similar to those of pregnant rats at sea level. Measurements on the 1-day-old pups of this group were similar to those of HYPO pups. We conclude that newborn rats born after hypoxic gestation present metabolic adaptation (low VO2) and acclimatization (high VE/VO2), possibly because of hypoxemia. Maternal acclimatization before insemination substantially alters maternal growth in hypoxia but does not affect neonatal outcome.
Tachykinin recovery during postmortem bronchoconstriction in guinea pig lungs
Authors: Martins M. A. , Shore S. A. , Drazen J. M.
Published: December 2017

We examined the role of substance P (SP) and neurokinin A (NKA) in the postmortem bronchoconstriction in guinea pig lungs using isolated lungs superfused via the trachea. Airway opening pressure (Pao) during superfusion was monitored and the superfusate collected for analysis of SP- and NKA-like immunoreactivities (SP-LI and NKA-LI, respectively). Peak Pao (39.0 +/- 3.9 cmH2O) was reached 10 min after starting superfusion; Pao decreased slowly thereafter, reaching only 9.9 +/- 2.2% of the peak value 2 h after starting superfusion (P less than 0.005); 12.6 +/- 2.6 and 34.0 +/- 9.7 fmol of SP-LI and NKA-LI, respectively, were found in the fraction corresponding to 10-20 min of superfusion. Recovered immunoreactivities decreased to 5.2 +/- 0.3 and 9.3 +/- 1.8 fmol of SP-LI and NKA-LI, respectively, in the fraction corresponding to 110-120 min of superfusion (P less than 0.05). Inhibition of neutral endopeptidase with thiorphan resulted in significantly greater increases in Pao (P less than 0.005) and augmentation of the recovery of SP-LI and NKA-LI (P less than 0.05 and P less than 0.001, respectively). Capsaicin treatment of animals 7-10 days before the removal of their lungs abolished the increase in Pao during superfusion and resulted in a significant decrease in the amount of SP-LI and NKA-LI recovered. Our data confirm that tachykinin release occurs during postmortem bronchoconstriction in guinea pig lungs and, furthermore, that tachykinin degradation by NEP modulates the intensity of this response.