bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional diaphragmatic length and EMG activity during inspiratory pressure support and CPAP in awake sheep
Authors: Torres A. , Kacmarek R. M. , Kimball W. R. , Qvist J. , Stanek K. , Whyte R. , Zapol W. M.
Published: December 2017

We examined diaphragmatic mechanics in awake sheep during quiet breathing (QB) and the randomized application of 5, 10, and 15 cmH2O continuous positive airway pressure (CPAP), inspiratory pressure support (IPS), and equal combinations of IPS and CPAP (IPS/CPAP). We measured esophageal, gastric, and transdiaphragmatic (Pdi) pressures and regional length, shortening, and electromyogram (EMG) activity of both costal and crural diaphragmatic segments. Segmental resting length normalized to QB decreased during 15 cmH2O CPAP (costal, 19.2 +/- 3.3%; crural, 7.5 +/- 2.1%; P < 0.05) and during 15/15 cmH2O IPS/CPAP (costal 25.3 +/- 4.8%, crural 9.9 +/- 2.6%; P < 0.05). Only during 15 cmH2O IPS did costal shortening fraction increase (67% QB; P < 0.05). Compared with QB, during 15 cmH2O CPAP, end-tidal CO2 increased 6 Torr, regional EMG activity increased threefold, and Pdi increased 58%. During 15 cmH2O IPS these values decreased 3 Torr, threefold, and 44% respectively, but during IPS/CPAP they remained unchanged. Expiratory gastric pressure (Exp-Pga) reached 4.3 +/- 0.4 cmH2O at 15 cmH2O CPAP, but during IPS/CPAP Exp-Pga was less (maximum of 1.7 +/- 0.4 cmH2O) than at comparable CPAP (P < 0.05), despite the shorter diaphragmatic length. We conclude that: 1) IPS alters the actions of the diaphragm during CPAP, 2) Exp-Pga is poorly coupled to diaphragmatic end-expiratory length, and 3) both IPS and the release of Exp-Pga assist active diaphragmatic shortening.
Cerebral cortical evoked potentials elicited by cat intercostal muscle mechanoreceptors
Authors: Davenport P. W. , Shannon R. , Mercak A. , Reep R. L. , Lindsey B. G.
Published: December 2017

Intercostal muscle afferents discharge in response to changes in intercostal muscle mechanics and have spinal and brain stem projections. It was hypothesized that intercostal muscle mechanoreceptors also project to the sensorimotor cortex. In cats, the proximal muscle branch of an intercostal nerve was used for electrical stimulation. The mechanical stimulation was stretch of an isolated intercostal space. The sensorimotor cortex was mapped with a surface ball electrode. Primary cortical evoked potentials (CEP) were found in area 3a of the sensorimotor cortex with mechanical and electrical stimulation. The CEP was elicited with the smallest stretch amplitude used, 50 microns. The CEP response showed little increase beyond 300-microns stretch. The CEP elicited by 50-microns stretch suggests an initial cortical activation by intercostal muscle spindles. The minimal increase in CEP amplitude with stretch > 300 microns suggests that the CEP response is primarily due to muscle spindle recruitment. The increase in amplitude beyond this stretch may be due to recruitment of tendon organs. These results demonstrate a short-latency projection of intercostal muscle mechanoreceptors to the sensorimotor region of the cerebral cortex. This cortical activation may be involved in respiratory sensations and/or transcortical reflex responses to changes in respiratory muscle mechanics.
Calculation of venoarterial CO2 concentration difference
Authors: Giovannini I. , Chiarla C. , Boldrini G. , Castagneto M.
Published: December 2017

Quantitative relationships in CO2 transport and exchange processes were combined for use as the basic components of an original mathematical model for the calculation of venoarterial blood CO2 concentration difference (v-aDCO2). This is calculated as the sum of the increment in CO2 concentration (CCO2) related to the increase in CO2 tension (delta P) from arterial to venous value at constant O2 saturation (delta CCO2/delta P) and of the increment in CO2 concentration related to the decrease in O2 saturation (delta S) from arterial to venous value at constant CO2 tension (delta CCO2/delta S). The newly developed relationships correlated well with the experimental data from which they were derived (r2 = 0.94–0.99). The results provided by the model compared remarkably well with the results of previously published measurements (r2 = 0.96–0.99). This new model allows one to overcome some of the limitations implicit in previously available methods and provides a useful tool for the assessment and monitoring of hemodynamic, metabolic, and O2-CO2 exchange patterns in whole body and regional vascular beds.
Comparison of the secretory response of the nasal mucosa to methacholine and histamine
Authors: Baroody F. M. , Wagenmann M. , Naclerio R. M.
Published: December 2017

To better understand the secretory response of the nasal mucosa, we must be able to accurately measure its physiological response. To this end, we developed a localized challenge technique using paper disks to stimulate the mucosa on one side and measure secretions from both sides to study both direct and reflex responses. Both methacholine and histamine induced a dose-dependent increase in secretion weights on the challenge side, whereas only histamine induced a contralateral reflex. Repeated stimulation with histamine, but not methacholine, resulted in tachyphylaxis. Pretreatment with atropine resulted in inhibition of the contralateral secretory response to histamine and the ipsilateral response to methacholine with only partial inhibition of the ipsilateral histamine response. Terfenadine pretreatment resulted in the complete inhibition of both the ipsilateral and contralateral responses to histamine with no effect on methacholine anduced secretions. Ipsilaterally applied lidocaine had no effect on the histamine response but, when applied contralaterally, partially inhibited that response. Topical diphenhydramine applied ipsilaterally led to significant inhibition of the ipsilateral and contralateral secretory responses to histamine but had no effect when applied contralaterally. We conclude that methacholine and histamine have different effects on the nasal mucosa. We speculate that methacholine stimulates glands directly, whereas histamine includes both direct and neurogenic stimulation.
Change in recruitment order of motor units in human parasternal intercostal muscles with sleep state
Authors: Whitelaw W. A. , Rimmer K. P. , Sun H. S.
Published: December 2017

Recruitment order of individual motor units in the early part of inspiration in parasternal intercostal muscles was observed in normal human subjects during wakefulness and non-rapid-eye-movement sleep. Electromyograms from bipolar fine wire intramuscular electrodes were recorded while the subjects lay supine in a sleep laboratory, and sleep stage was determined by polysomnography. From wakefulness to sleep there were numerous examples of shifts in order of recruitment among the low threshold units of early inspiration. There were corresponding shifts in the order of derecruitment of these units. Analysis of frequency of firing of units also suggested that the levels of excitatory input to one unit of a pair could be altered relative to the level of input of the other one. The data imply that there are at least minor differences in distribution of excitatory inputs from various sources among motoneurons of this muscle pool.
Oxygen cost of increasing tidal volume and diaphragm flattening in obstructive pulmonary disease
Authors: Pitcher W. D. , Cunningham H. S.
Published: December 2017

Hypercapnia is associated with a shallow breathing pattern in patients with severe chronic obstructive pulmonary disease (COPD). We sought to determine the oxygen cost of increasing tidal volume and to relate this to hypercapnia [arterial PCO2 (PaCO2) > or = 45 Torr] and diaphragm flattening. We studied 3 normal subjects and 12 patients with stable but comparably severe COPD (forced expired volume in 1 s 1.01 +/- 0.09 liters) who had baseline PaCO2 ranging from 36 to 56 Torr. Oxygen consumption was measured during the subject's native breathing pattern and then while tidal volume was increased by 20%; minute ventilation was held constant by proportionately slowing frequency. There was a significant oxygen cost of increasing tidal volume for hypercapnic patients (235 +/- 23 to 260 +/- 25 ml O2/min; P = 0.002); no significant oxygen cost was observed in normal or eucapnic patients. This oxygen cost was positively correlated to baseline PaCO2 (r2 = 0.88, P < 0.001) and degree of diaphragm flattening assessed from chest radiographs (r2 = 0.74, P < 0.05). Although others have shown that force generation is preserved during chronic hyperinflation (G. A. Farkas and C. Roussos. J. Appl. Physiol. 54: 1635–1640, 1983; T. Similowski et al. N. Engl. J. Med. 325: 917–923, 1991), we conclude that diaphragm flattening produces mechanical inefficiency that may contribute to limiting the effective operating range of the respiratory muscles during tidal breathing.
Strenuous endurance training increases lipolysis and triglyceride-fatty acid cycling at rest
Authors: Romijn J. A. , Klein S. , Coyle E. F. , Sidossis L. S. , Wolfe R. R.
Published: December 2017

Basal whole body lipid kinetics were evaluated in nine endurance-trained cyclists and 10 untrained healthy controls. The rate of appearance (Ra) of glycerol (an index of whole body lipolysis), the Ra of palmitate (an index of fatty acid release), and the rate of triglyceride-fatty acid cycling (reesterification of fatty acids released during lipolysis) were determined by infusing [2H5]glycerol and [2H2]palmitate in conjunction with indirect calorimetry. All subjects were studied while they were at rest after fasting overnight. Glycerol Ra and free fatty acid Ra in the athletes (7.33 +/- 0.68 and 14.88 +/- 1.35 mumol.kg-1 x min-1, respectively) were two- to threefold higher than the values in untrained control subjects (2.53 +/- 0.15 and 7.64 +/- 0.92 mumol.kg-1 x min-1, respectively; P < 0.02). The total rate of triglyceride-fatty acid cycling was approximately four-fold higher in the athletes (16.86 +/- 2.07 mumol.kg-1 x min-1) than in the control subjects (3.91 +/- 0.36 mumol.kg-1 x min-1). Plasma concentrations of insulin and catecholamines, hormones that regulate whole body lipid kinetics, were the same in both groups. We conclude that resting basal lipid kinetics are markedly increased in athletes involved in strenuous endurance training and that this enhances the potential for increasing fatty acid oxidation rapidly at the onset of exercise.
Cardiopulmonary responses to chronic hypoxia in transgenic mice that overexpress ANP
Authors: Klinger J. R. , Petit R. D. , Curtin L. A. , Warburton R. R. , Wrenn D. S. , Steinhelper M. E. , Field L. J. , Hill N. S.
Published: December 2017

Elevated plasma atrial natriuretic peptide (ANP) levels have been shown to blunt pulmonary hemodynamic responses to chronic hypoxia, but whether elevated circulating ANP levels negatively feedback on cardiac expression of the ANP gene is unknown. Using a recently developed strain of transgenic mouse (TTR-ANF) that expresses a transthyretin promoter-ANP fusion gene in the liver, we studied the effect of chronically elevated plasma ANP levels on cardiac hypertrophic and pulmonary hemodynamic responses and expression of the endogenous cardiac ANP gene during chronic hypoxia. Plasma ANP levels were 10-fold higher in TTR-ANF mice than in their non-transgenic littermates. After 3 wk of hypobaric hypoxia (0.5 atm), right ventricular hypertrophy and pulmonary hypertension had developed in both groups of mice, but TTR-ANF mice had lower right ventricle-to-left ventricle plus septum weight ratios (0.39 +/- 0.01 vs. 0.45 +/- 0.02), right ventricular systolic pressures (25 +/- 2 vs. 29 +/- 2 mmHg), and lung dry weight-to-body weight ratios (0.48 +/- 0.03 vs. 0.57 +/- 0.01 mg/g) and less muscularization of peripheral pulmonary vessels (8.3 +/- 1.4 vs. 17.4 +/- 2.5%) than nontransgenic controls. Right atrial and ventricular steady-state ANP mRNA levels were the same in both groups of mice under normoxic and hypoxic conditions despite much higher plasma ANP levels and less pulmonary hypertension in TTR-ANF mice. We conclude that chronically elevated plasma ANP levels attenuate the development of hypoxic pulmonary hypertension in mice but do not suppress cardiac expression of the endogenous ANP gene under normoxic conditions nor blunt the upregulation of right ventricular ANP expression during chronic hypoxia.
Isotopic estimation of CO2 production during exercise before and after endurance training
Authors: Coggan A. R. , Habash D. L. , Mendenhall L. A. , Swanson S. C. , Kien C. L.
Published: December 2017

Endurance training reduces the rate of CO2 release (i.e., VCO2) during submaximal exercise, which has been interpreted to indicate a reduction in carbohydrate oxidation. However, decreased ventilation, decreased buffering of lactate, and/or increased fixation of CO2 could also account for a lower VCO2 after training. We therefore used a primed continuous infusion of NaH13CO3 to determine the whole body rate of appearance of CO2 (RaCO2) in seven men during 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake (VO2peak) before and after endurance training. RaCO2 is independent of the above-described factors affecting VCO2 but may overestimate net CO2 production due to pyruvate carboxylation and subsequent isotopic exchange in the tricarboxylic acid cycle. Training consisted of cycling at 75–100% VO2peak for 45–90 min/day, 6 days/wk, for 12 wk and increased VO2peak by 28% (P < 0.001). VCO2 during submaximal exercise was reduced from 86.8 +/- 3.7 to 76.2 +/- 4.2 mmol/min, whereas RaCO2 fell from 88.9 +/- 4.0 to 76.4 +/- 4.4 mmol/min (both P < 0.001). VCO2 and RaCO2 were highly correlated in the untrained (r = 0.98, P < 0.001) and trained (r = 0.99, P < 0.001) states, as were individual changes in VCO2 and RaCO2 with training (r = 0.88, P < 0.01). These results support the hypothesis that endurance training decreases CO2 production during exercise. The magnitude and direction of this change cannot be explained by reported training-induced alterations in amino acid oxidation, indicating that it must be the result of a decrease in carbohydrate oxidation and an increase in fat oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of reduced hemoglobin concentration on leg oxygen uptake during maximal exercise in humans
Authors: Schaffartzik W. , Barton E. D. , Poole D. C. , Tsukimoto K. , Hogan M. C. , Bebout D. E. , Wagner P. D.
Published: December 2017

Maximum oxygen uptake (VO2max) is affected by hemoglobin concentration ([Hb]). Whether this is simply due to altered convection of O2 into the muscle microcirculation or also to [Hb]-dependent diffusive transport of O2 out of the muscle capillary is unknown in humans. To examine this, seven healthy volunteers performed four maximal cycle exercise bouts at sea level immediately after 8 wk at altitude (3,801 m, barometric pressure 485 Torr), a sojourn designed to increase [Hb]. The first two bouts were at ambient [Hb] of 15.9 +/- 0.7 g/100 ml breathing 21 or 12% O2 in random order. [Hb] was then decreased to a prealtitude level of 13.8 +/- 0.6 g/100 ml by venesection and isovolemic replacement with 5% albumin in 0.9% saline, and the exercise bouts were repeated. At whole body VO2max, PO2, PCO2, pH, and O2 saturation were measured in radial arterial and femoral venous blood. Femoral venous thermodilution blood flow was determined for calculation of leg VO2. Mean muscle capillary PO2 and muscle diffusing capacity (DO2) were computed by Bohr integration between measured arterial and femoral venous PO2. Averaged over both fractional concentrations of inspired O2, leg VO2 at maximum decreased by 17.7 +/- 4.3% as [Hb] was lowered while leg O2 delivery decreased by 17.5 +/- 2.6% and DO2 decreased by 10.7 +/- 2.7% (all P < 0.05). The relative contributions of decreases in leg O2 delivery and DO2 to the decrease in VO2max were computed to be 64 and 36%, respectively. These findings suggest that [Hb] is an important determinant of O2 diffusion rates into working muscle in humans. Possible mechanisms include 1) dependence of DO2 on intracapillary red blood cell spacing, 2) changes in the total rate of dissociation of O2 from [Hb], and 3) increased red blood cell flow heterogeneity as [Hb] is reduced.
Antioxidant status and indexes of oxidative stress during consecutive days of exercise
Authors: Viguie C. A. , Frei B. , Shigenaga M. K. , Ames B. N. , Packer L. , Brooks G. A.
Published: December 2017

We tested whether consecutive days of prolonged submaximal exercise would result in oxidant stress sufficient to alter blood antioxidant profiles, progressively change and exhaust blood and plasma antioxidants, and damage RNA. Eleven moderately trained males (24.3 +/- 1.1 yr) exercised 90 min at 65% peak O2 uptake on a cycle ergometer for 3 consecutive days. During day 1 exercise, blood reduced glutathione (GSH) declined 55 +/- 10% and oxidized glutathione (GSSG) increased 28 +/- 7% within 15 min. Total blood glutathione did not significantly change during exercise. GSH levels returned to baseline after 15 min of recovery. On day 3, preexercise GSH and GSSG levels were not significantly different from day 1 preexercise values; essentially similar results were obtained during exercise and recovery. During day 1 exercise, plasma total ascorbate (ascorbate + dehydroascorbate) increased from 53.8 +/- 9.3 to 59.0 +/- 11.3 microM, and percent reduced ascorbate increased from 77.6 +/- 9.3 to 87.3 +/- 9.7%. During day 3 exercise, plasma ascorbate changes were similar to those on day 1. Plasma vitamin E did not change due to exercise on either day 1 or 3. RNA adducts, urinary 8-hydroxyguanosine, did not change significantly due to exercise. Observed increases in GSH oxidation indicate the presence of oxidant stress during prolonged submaximal exercise. Similar redox changes on consecutive days of exercise, with recovery to preexercise values within 15 min, indicate no evidence of persistent or cumulative exercise effects on blood glutathione redox status.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of exercise intensity and duration on norepinephrine spillover and clearance in humans
Authors: Leuenberger U. , Sinoway L. , Gubin S. , Gaul L. , Davis D. , Zelis R.
Published: December 2017

During dynamic exercise, blood flow to exercising muscle is closely matched to metabolic demands. This is made possible by metabolic vasodilation, vasoconstriction in inactive vascular beds, and a rise in cardiac output. The sympathetic nervous system plays an important role in regulating this exercise response. In this study, we used steady-state infusions of tritiated norepinephrine ([3H]NE) to determine the magnitude and time course of the arterial NE spillover response to sustained upright bicycle exercise at low (n = 11) and moderate-to-high (n = 14) exercise intensity (25 and 65% of maximum work load, respectively) in normal young subjects. In addition, we sought to examine whether exercise was associated with a change in NE clearance. During 30 min of low-level exercise, arterial NE spillover increased from 1.45 +/- 0.13 to 3.14 +/- 0.30 nmol.min-1 x m-2 (P < 0.01) and appeared to plateau at 20–30 min of exercise; NE clearance remained unchanged. During 20 min of moderate-to-high-intensity exercise, we found a substantial and progressive rise of arterial NE spillover from 2.15 +/- 0.27 to 13.52 +/- 1.62 nmol.min-1 x m-2 (P < 0.01). NE clearance decreased from 0.91 +/- 0.05 to 0.80 +/- 0.05 l.min-1 x m-2 (P < 0.05). These data suggest that, during dynamic exercise, sympathetic nervous system activity is related to exercise intensity, and there appears to be an interaction between the effects of exercise intensity and duration on NE spillover. In addition, at moderate-to-high exercise intensity, a small decrease of NE clearance contributes to the rise in plasma NE.
Influence of the timing of fluid ingestion on temperature regulation during exercise
Authors: Montain S. J. , Coyle E. F.
Published: December 2017

The purpose of this investigation was to determine whether the timing of fluid ingestion affects thermoregulation during exercise-heat stress. On four occasions, seven endurance-trained cyclists [age 25 +/- 2 (SE) yr, body weight 70.5 +/- 3.3 kg, maximal O2 uptake (VO2max) 4.69 +/- 0.11 l/min] performed 140 min of cycle ergometer exercise at 62–66% of VO2max in a hot environment (33 degrees C dry bulb, 51% relative humidity, wind speed 2.5 m/s). The subjects drank 1,173 +/- 44 ml of a carbohydrate-electrolyte beverage after 0 min (D0), 40 min (D40), or 80 min (D80) of exercise or consumed the same total volume in small aliquots throughout exercise (DT). The exercise-heat stress resulted in calculated sweating rates of approximately 1,200 ml/h and a body weight loss of 2.9 +/- 0.1% after 140 min of exercise. After fluid intake in the D0, D40, and D80 trials, there was a time period (approximately 40 min) in which the increases in serum osmolality and sodium concentration and the reduction in blood volume were attenuated. During that same time period, there was an attenuated rise in esophageal temperature (Tes; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory gas exchange and metabolic responses during exercise in McArdle's disease
Authors: Riley M. , Nicholls D. P. , Nugent A. M. , Steele I. C. , Bell N. , Davies P. M. , Stanford C. F. , Patterson V. H.
Published: December 2017

During normal progressive exercise, the gas exchange anaerobic threshold occurs when CO2 production (VCO2) and ventilation (VE) increase so as to depart from a linear relationship to O2 consumption (VO2). This is thought to represent a gas exchange response to metabolic acidosis due to lactate accumulation. Patients with McArdle's disease have previously been reported to exhibit a steepened ventilatory response relative to VCO2, despite an inability to produce lactate. However, the VCO2 response has not been studied. We therefore investigated the VCO2-VO2 and VE-VO2 relationships in seven McArdle's disease patients and seven control subjects during symptom-limited maximal treadmill exercise. Analysis of gas exchange showed that whereas all control subjects had an easily identifiable anaerobic threshold, four of the patients had none and the other three displayed an attenuated threshold. The occurrence of the threshold in one patient was associated with a small rise in lactate and in another patient with an abrupt rise in leg discomfort, suggesting a pain response. Ammonia and the purine metabolite hypoxanthine were elevated during exercise in all patients, suggesting that ammonia may be a product of adenosine monophosphate degradation. Free fatty acid levels were also elevated, and a shift toward utilization of lipid may contribute to abnormal gas exchange responses. It is concluded that lactic acidosis contributes to the gas exchange anaerobic threshold but that other factors, such as discomfort, may be involved in the excess Ve seen during heavy exercise.
Hypoxia-induced differential modulation of adenosinergic and muscarinic receptors in rat heart
Authors: Kacimi R. , Richalet J. P. , Crozatier B.
Published: December 2017

To better understand the decreased chronotropic response to catecholamines in chronic hypoxia, we compared the inhibitory pathways regulating adenylate cyclase in rats exposed for 30 days to hypobaric hypoxia (380 Torr; HX) with those in control rats (CT) by the analysis of adenosinergic A1-receptors (8-cyclopentyl-1,3-[3H]dipropylxanthine) and muscarinic M2-receptors ([3H]quinuclidinyl benzilate). A1-receptor density was decreased by 46% in sarcolemmal preparations without a change in the affinity for agonist [(R)-phenylisopropyladenosine]. M2-receptor density was increased (HX: 280 +/- 16 fmol/mg, CT: 188 +/- 15 fmol/mg; n = 7; P < 0.001) without a change in dissociation constant. Displacement of [3H]quinuclidinyl benzilate by carbachol indicated significant decreases in the dissociation constants of both superhigh- (HX: 73 +/- 19 nM, CT: 182 +/- 42 nM; P < 0.001) and high-affinity binding sites (HX: 4 +/- 1 microM, CT: 12 +/- 3 microM; P < 0.001). Our data show that chronic hypoxia leads to differential modulation of cardiac receptors with a downregulation of adenosine receptors and increases in muscarinic receptor affinity and density, which may contribute to the blunted responsiveness of the heart to catecholamines.
Neurogenic modulation of periodic hemodynamics in rabbit skeletal muscle
Authors: Schmidt J. A. , Borgstrom P. , Intaglietta M.
Published: December 2017

We characterized the effect of various forms of neural blockade and vasopressin infusion on regular slow-wave flux oscillation (RSWFO). RSWFO, measured with laser-Doppler flowmetry (LDF), was induced by local reduction of arterial pressure in the gastrocnemius muscle of 30 New Zealand White rabbits. At normal median femoral arterial mean pressure, LDF only showed irregular variations. With an intact innervation, RSWFO was maximal at a median femoral mean pressure of 30 mmHg (range 25–53), the median frequency was 1.7 cycles/min (range 1.0–3.0), and the maximum amplitude was 50% (range 19–119). Application of lidocaine to the sciatic nerve, or cutting of this nerve, when arterial pressure was reduced, resulted in disappearance of slow waves in all cases. Intravenous application of guanethidine resulted in a significant reduction of the flux oscillation amplitude from 47 to 10% (P < 0.001). In an additional nine animals with sciatic denervation and local blood pressure reduction, RSWFO could be induced by intravenous vasopressin infusion. These results offer a new pathophysiological concept of periodic hemodynamics as a locally controlled and, with intact innervation, a neurally modulated mechanism for blood flow redistribution in cases of reduced blood pressure and flow.
Effects of posture on abdominal muscle shortening in awake dogs
Authors: Leevers A. M. , Road J. D.
Published: December 2017

The objective of this study was to examine the effects of posture on tonic and phasic expiratory activity of the abdominal muscles in awake dogs. Six tracheostomized dogs were chronically instrumented with sonomicrometer transducers and bipolar electromyographic electrodes placed in each of the four abdominal muscles. To determine the effects of posture on tonic and phasic activity of individual abdominal muscles, muscle resting length (Lr) and tidal length changes (%Lr), respectively, were measured in awake dogs in the left lateral decubitus (LLD), sitting, and standing (STAND) positions. The transversus abdominis Lr consistently shortened when the dog was moved from LLD to STAND and lengthened when the dog was moved from LLD to the sitting position, and the external oblique Lr consistently lengthened when the dog went from LLD to STAND. The internal oblique and rectus abdominis had no consistent changes in Lr with a change in position. All four abdominal muscles actively shortened (%Lr) more in the upright positions. In addition, the internal layer (transversus abdominis and internal oblique) actively shortened more than the external layer (rectus abdominis and external oblique). In conclusion, both tonic and phasic respiratory activity of the abdominal muscles, reflected by changes in Lr and %Lr, respectively, were affected by changes in posture.
Effect of growth hormone on gastrocnemius muscle of aged rats after immobilization: biochemistry and morphology
Authors: Carmeli E. , Hochberg Z. , Livne E. , Lichtenstein I. , Kestelboim C. , Silbermann M. , Reznick A. Z.
Published: December 2017

Immobilization of limbs of aged animals is associated with swift muscular damage and atrophy. We investigated the effect of rat growth hormone (rGH) on immobilized hindlimb muscles of 26-mo-old rats. Administration of rGH significantly reduced muscle weight loss and muscle protein oxidation caused by immobilization. Capillary blood volume, measured by photoplethysmography of the hindlimb, showed a 34% reduction in immobilized animals, which was eliminated by rGH. The activity of creatine phosphokinase in immobilized gastrocnemius muscle was significantly reduced by immobilization. This damage was diminished by rGH administration. Similarly, the increase in acid phosphatase activity in immobilized muscle was reduced after rGH treatment. Morphologically, marked muscle atrophy and fiber disorientation were observed in immobilized limbs. Therapy with rGH prevented some of these changes. These results indicate that administration of rGH may provide a useful means to attenuate the degenerative effects of limb immobilization of aged rats, as evident from physiological, biochemical, and morphological parameters.
Determinants of maximal oxygen uptake in rats acclimated to simulated altitude
Authors: Gonzalez N. C. , Clancy R. L. , Wagner P. D.
Published: December 2017

The effect of acclimation to hypoxia on maximal O2 uptake (VO2max), maximal cardiac output (Qmax), and arteriovenous O2 concentration difference (a-vCO2) was studied in male Sprague-Dawley rats acclimated for 3 wk to a barometric pressure of approximately 380 Torr (A rats). Nonacclimated control animals were pair-fed littermates maintained at an ambient barometric pressure of approximately 740 Torr (NA rats). Both A and NA rats exercised maximally on a treadmill with inspired PO2 maintained at either approximately 72 or 145 Torr. Arterial blood O2 concentration was significantly higher in A than in NA rats (16.0 +/- 0.6 vs. 12.4 +/- 0.3 ml/dl in hypoxia and 28.4 +/- 1.5 vs. 20.1 +/- 0.9 ml/dl in normoxia, respectively; both P < 0.05). During hypoxic exercise VO2max was slightly but significantly higher in A than in NA subjects (55.3 +/- 1.3 vs. 48.8 +/- 1.1 ml STPD.min-1 x kg-1; P < 0.05). In hypoxia a-vCO2 was 16.6 +/- 0.6 and 12.4 +/- 0.4 ml/dl and Qmax was 401 +/- 17 and 489 +/- 9 ml.min-1 x kg-1 in A and NA subjects, respectively (both P < 0.05). A rats showed both lower maximal heart rate and lower maximal stroke volume during hypoxic exercise. In normoxia there was no significant difference in VO2max between A and NA rats (71.8 +/- 2.7 vs. 73.9 +/- 3.1 ml.min-1 x kg-1). As with hypoxia, in normoxia a-vCO2 was significantly higher and Qmax was significantly lower in A than in NA animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Alveolar epithelial injury and pleural empyema in acute P. aeruginosa pneumonia in anesthetized rabbits
Authors: Wiener-Kronish J. P. , Sakuma T. , Kudoh I. , Pittet J. F. , Frank D. , Dobbs L. , Vasil M. L. , Matthay M. A.
Published: December 2017

We developed an experimental model of acute Pseudomonas aeruginosa pneumonia in anesthetized ventilated rabbits to determine whether bacterial-induced injury to the alveolar epithelium would occur and the effect of the injury on the pleural space. Dose-response studies established that 10(9) colony-forming units of P. aeruginosa (wild-type strain, PAO-1) were required to injure the epithelial barrier and to cause pleural empyema with exudative pleural effusions that contained both the instilled alveolar protein tracer and P. aeruginosa. We explored the mechanisms of P. aeruginosa-induced lung and pleural injury by using three isogenic bacterial strains to compare several extracellular virulence products. PAO-S21, which carries an insertion mutation in a regulatory gene that prevents the production of exoenzyme S, resulted in no lung or pleural injury. PAO-R1, which carries a deletion in a regulatory gene that controls the production of elastase and alkaline protease, caused the same degree of lung and pleural injury as PAO-1 did. Instillation of PLC-SRN, which has both structural genes encoding phospholipase C activity deleted, resulted in a moderate reduction in alveolar epithelial injury. Although other products may be involved, exoenzyme S and phospholipase C are important in mediating injury to the alveolar epithelial barrier in acute P. aeruginosa pneumonia in rabbits.
Partitioning of work of breathing in mechanically ventilated COPD patients
Authors: Coussa M. L. , Guerin C. , Eissa N. T. , Corbeil C. , Chasse M. , Braidy J. , Matar N. , Milic-Emili J.
Published: December 2017

In 10 sedated paralyzed mechanically ventilated chronic obstructive pulmonary disease (COPD) patients, we measured the inspiratory mechanical work done per breath on the respiratory system (WI,rs). We measured the tracheal and esophageal pressures to assess the lung (L) and chest wall (W) components of WI and used the technique of rapid airway occlusion during constant-flow inflation to partition WI into static work [Wst, including work due to intrinsic positive end-expiratory pressure (WPEEPi)], dynamic work due to airway resistance, and the additional resistance offered by the respiratory tissues. Although the patients were hyperinflated, the slope of the static volume-pressure relationships of the lung did not decrease with inflation volume up to 0.8 liter. WI,W was similar in COPD patients and normal subjects. All components of WI,L were higher in COPD patients. The increase in Wst,rs was due entirely to WPEEPi. Our data suggest that, during spontaneous breathing, COPD patients would probably develop inspiratory muscle fatigue, unless continuous positive airway pressure were applied to reduce WPEEPi.
Persistent peripheral vasodilation and sympathetic activity in hypotension after maximal exercise
Authors: Piepoli M. , Coats A. J. , Adamopoulos S. , Bernardi L. , Feng Y. H. , Conway J. , Sleight P.
Published: December 2017

Hemodynamics (by aortic Doppler), autonomic factors (power spectrum analysis of heart rate and blood pressure variabilities and baroreceptor sensitivity), and plasma renin activity during the hypotension after maximal exercise were studied in 10 normal subjects on two separate days: a nonexercise (control) day (30 min of upright rest followed by 60 min of supine rest) and an exercise day (maximal upright bicycle exercise followed by 60 min supine) in random order. After exercise, diastolic pressure was reduced for the entire hour, cardiac output increased (+33.8%, P < 0.05), stroke volume was unchanged, and systemic vascular resistance fell (-28.6%, P < 0.01). Indexes of vagal activity were reduced for 60 min, whereas the sympathetic indexes were elevated. Baroreflex sensitivity was also reduced for the first 10 min after exercise. Renin activity increased threefold after exercise. The postexercise hypotension results from a persisting peripheral vasodilation despite an increase in renin activity: the persistent sympathetic activity and reduced vagal tone are probably reflex responses to this vasodilatation.
Bradykinin contributes to the exercise pressor reflex: mechanism of action
Authors: Pan H. L. , Stebbins C. L. , Longhurst J. C.
Published: December 2017

This study determined the receptors responsible for mediating bradykinin's effect on skeletal muscle afferents that cause the pressor reflex in anesthetized cats. In eight cats, 1 microgram of bradykinin was injected intra-arterially into the gracilis muscle before and after intravenous injection of a kinin B2-receptor antagonist (NPC 17731, 20 micrograms/kg). Initial injection of bradykinin reflexly increased mean arterial pressure by 23 +/- 7 mmHg, maximal change in pressure over time by 439 +/- 272 mmHg/s, and heart rate by 11 +/- 4 beats/min. The hemodynamic response to bradykinin was abolished by kinin B2-receptor blockade. Similar injection of the kinin B1-receptor agonist des-Arg9-bradykinin caused no cardiovascular responses (n = 6). In eight different animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses to 30 s of electrically stimulated hindlimb contraction were attenuated by 50 +/- 6, 55 +/- 7, and 41 +/- 8%, respectively, after kinin B2-receptor blockade. In eight other animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses were reduced by 58 +/- 8, 66 +/- 6, and 40 +/- 12%, respectively, after inhibition of prostaglandin synthesis with indomethacin (2.5–3 mg/kg iv) and were then abolished by subsequent B2-receptor blockade. These data suggest that bradykinin contributes to the exercise pressor reflex through its action on kinin B2 receptors located on the nerve endings of the muscle afferents.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung responses to ultrasound-guided fetal treatments with corticosteroids in preterm lambs
Authors: Jobe A. H. , Polk D. , Ikegami M. , Newnham J. , Sly P. , Kohen R. , Kelly R.
Published: December 2017

Maternal corticosteroid treatments augment lung function in the human preterm infant. However, not all fetuses respond, the response requires > or = 48 h of exposure, and multiple maternal doses expose the mother to potential risks. To evaluate the potential of direct fetal therapy, we used ultrasound to direct fetal intramuscular or intravascular injections of corticosteroids or saline in sheep and subsequently delivered the preterm lambs at 128 days gestational age to assess postnatal lung function. Relative to saline-injected controls, 0.5 or 2 mg/kg betamethasone given as a single intramuscular dose 48 h before delivery increased compliance and the efficiency of ventilation (as measured by an indicator that included ventilatory pressures and CO2 values) nearly twofold (P < 0.05). Lung volumes, measured from deflation pressure-volume curves, also increased (P < 0.05). However, the 2 mg/kg dose caused severe pulmonary interstitial emphysema in 5 of 13 lambs, suggesting adverse effects. An intravascular fetal dose of 12.5 mg/kg hydrocortisone or an intramuscular dose of 0.1 mg/kg betamethasone had no effect on postnatal lung function. In separate studies, the 2 mg/kg dose improved all indicators of lung function almost twofold after only 24 h of fetal exposure and delivery at 128 days gestational age (P < 0.01). There was a dose-dependent suppression of the postnatal cortisol surge in treated animals, although fetal treatment did not alter cord cortisol levels. Single-dose fetal hormone treatments can cause large and rapid improvements in postnatal lung function in preterm lambs.
Reflex control of the tracheal vasculature of sheep
Authors: Webber S. E. , Widdicombe J. G.
Published: December 2017

Arteries to the cervical trachea were perfused at constant flow in anesthetized sheep. Perfusion pressures (PP), blood pressure (BP), and changes in tracheal smooth muscle tone (Ptr) were measured. Stimulation of pulmonary C-fiber receptors decreased PP (-6.5%) and BP (-16.8%) and increased Ptr (+61.5%), changes prevented by vagotomy and therefore reflex. Stimulation of cardiac receptors and slowly adapting pulmonary stretch receptors decreased PP (-7.9%) and BP (-21.0) and increased Ptr (+19.0%), changes reversed by vagotomy and therefore reflex. Stimulation and inhibition of slowly adapting pulmonary stretch receptors had no vagal-dependent effect on PP and BP, but inflation decreased (-20.3%) and deflation increased Ptr (+35.2%), effects abolished by vagotomy and therefore reflex. Systemic hypoxia increased PP and BP before and after vagotomy (+12.2 and +40.3%), effects greatly reduced by cutting the carotid body nerves; it increased Ptr (+29.8%), an effect abolished by vagotomy and cutting the carotid body nerves. Systemic hypercapnia increased PP (+16.9%), BP (+20.5%), and Ptr (+36.2%), the first two responses being unaffected by vagotomy and the last almost abolished. Stimulation of carotid body chemoreceptors by KCN increased PP (+22.5%), BP (+104.7%), and Ptr (+8.5%), all responses prevented by cutting the carotid body nerves. Responses to intravenous injections of KCN were similar.
CO2 homeostasis during periodic breathing: predictions from a computer model
Authors: Rapoport D. M. , Norman R. G. , Goldring R. M.
Published: December 2017

The Bohr/Riley model of CO2 homeostasis describes the relationship between CO2 production, ventilation, and arterial PCO2 and assumes that ventilation and CO2 delivery to the lung are both anatomically and temporally well matched. In contrast to normal breathing, periodic patterns of ventilation show temporal mismatch of ventilation to CO2 delivery. We developed a computer model of lung CO2 clearance that uses CO2 transfer equations to generate iterative solutions for PCO2 in multiple body compartments as a function of time. During continuous ventilatory patterns our model predicts steady-state arterial PCO2 identical to that of the Bohr model. During periodic ventilation, we predict mean PCO2 will be elevated unless mean ventilation is increased above that required by the Bohr model. Waxing and waning tidal volumes, low functional residual capacity, and low capillary blood volume potentiate the hypercapnia. However, if cardiac output oscillates in phase with breathing, hypercapnia is minimized. This analysis suggests a new mechanism for the development of sustained hypercapnia, separate from absolute hypoventilation or the presence of lung disease.
Oxidation rates of orally ingested carbohydrates during prolonged exercise in men
Authors: Wagenmakers A. J. , Brouns F. , Saris W. H. , Halliday D.
Published: December 2017

Six male volunteers exercised on a cycle ergometer at 65% of maximal work load for 120 min on six occasions while ingesting water (W) only, four doses of maltodextrin (M) [0.92, 1.85, 2.77, and 3.70 g/kg body wt (4, 8, 12, and 16% M, respectively)], and sucrose (S) [1.85 g/kg body wt (8% S)]. Drinks were given during warm-up (8 ml/kg body wt) and each 15 min during exercise (2 ml/kg body wt). M and S were of high 13C natural abundance. Total carbohydrate (CHO) and fat oxidations were calculated from the nonprotein respiratory exchange ratio. M and S increased total CHO oxidation compared with W; no difference was observed between CHO solutions. Total CHO oxidation decreased continuously with time and more rapidly after W than after M or S. Fat oxidation increased continuously in all treatments. Oxidation rates of ingested CHO were 52 +/- 19, 76 +/- 12, 86 +/- 10, and 91 +/- 9 g/2 h for 4, 8, 12, and 16% M, respectively. The oxidation rate of S was 81 +/- 10 g/2 h (not different from 8% M), which indicated that the glucose polymer had no advantage over S. Oxidation rates of M and S increased to a plateau after 90–120 min of exercise. For all solutions except 4% M, the plateau oxidation rate was close to 1.0 g/min. Differences between 8, 12, and 16% M and 8% S were minimal such that ingestion of 8% M or S may well have had an optimal ergogenic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Discrimination of transiently applied mechanical loads: breathing vs. pulling
Authors: Axen K. , Noble D. , Zimmer S. , Capponi L. , Haas F.
Published: December 2017

Two groups of 24 subjects each attempted to discriminate between large elastic and resistive loads during 50 randomized presentations of each load. Breathers inspired from the loads through a J valve, whereas pullers reciprocally stroked the plunger of a 2-liter syringe connected to the J valve. A range of load durations was obtained in each subject by prematurely unloading approximately one-half of the trials at graded times from their onset. Breathers produced random discrimination scores [50.8 +/- 2.5% (SE) correct] when loaded inspirations were shorter than unloaded inspirations [trials in which both loads induced equal airway pressure (and probably respiratory muscle tension) waveforms] and nonrandom discrimination scores (65.7 +/- 2.8% correct) when loaded inspirations were longer than unloaded inspirations (trials in which both loads induced different waveforms). In contrast, pullers produced nonrandom discrimination scores (62.2 +/- 2.9% correct) when loaded airflow durations were shorter than unloaded inspirations [trials in which both loads induced equal line pressure (and therefore limb muscle tension) waveforms]. Supplemental audio feedback related to instantaneous airflow (an expression of movement) improved load perception in breathers (to 64.2 +/- 3.0% correct; P < 0.01), indicating that airflow feedback introduced load-specific information that was lacking during breathing but redundant during pulling. In support of this hypothesis, airflow feedback by itself enabled a third group of listeners to identify load type with equal accuracy as pullers but with greater accuracy than breathers. These findings suggest that 1) uniformed subjects rely heavily on feedback from airway pressure and/or muscle tension receptors to perceive added loads to breathing and 2) limb mechanoreceptors provide a more sensitive appreciation of movement than do respiratory mechanoreceptors.
Effects of inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of ARDS
Authors: Rovira I. , Chen T. Y. , Winkler M. , Kawai N. , Bloch K. D. , Zapol W. M.
Published: December 2017

Inhaling low concentrations of nitric oxide (NO) gas causes selective pulmonary vasodilation of ventilated lung regions. NO activates soluble guanylate cyclase, increasing guanosine 3′,5′-cyclic monophosphate (cGMP). Inhibition of NO synthesis enhances hypoxic pulmonary vasoconstriction. Therefore we examined independent and combined effects of NO inhalation and infusion of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthesis inhibitor, on pulmonary vascular pressure-flow relationships, gas exchange, and plasma cGMP levels in anesthetized and mechanically ventilated sheep with acute lung injury induced by bilateral lavage. After lavage, inhaling 60 ppm by volume of NO decreased pulmonary arterial pressure (PAP) and resistance without any systemic hemodynamic effects, increased arterial PO2, and decreased venous admixture (Qva/QT; all P < 0.05) without altering cardiac output (QT), mixed venous PO2, or O2 uptake, major determinants of intrapulmonary shunt. During NO inhalation, PAP-left atrial pressure gradient (PAP-LAP) and Qva/QT were reduced (both P < 0.05) independently of QT, which was varied mechanically. L-NAME infusion produced systemic and pulmonary vasoconstriction and increased PAP-LAP gradient across the entire range of QT, whereas Qva/QT, was not changed. NO inhalation after L-NAME infusion produced pulmonary vasodilation and decreased Qva/QT to the same degree as NO inhalation alone. Five to 10 min after inhalation of 60 ppm NO, before and after L-NAME infusion, arterial plasma cGMP levels were increased by 80% (both P < 0.05). With NO breathing after L-NAME, we measured a consistent transpulmonary cGMP arteriovenous gradient [31 +/- 8 and 33 +/- 7 (SE) pmol/ml at 5 and 10 min, respectively; both P < 0.05]. NO inhalation before or after L-NAME administration in this acute lung injury model reduced Qva/QT, most likely by increasing cGMP concentration in ventilated lung regions and causing selective pulmonary vasodilation.
Effect of pulmonary edema on transfer of gas from acinus to airways
Authors: Barnas G. M. , Randalls P. B. , Forrest F. C. , Hoff B. H. , Donahue P. L. , Kong C. S. , MacKenzie C. F.
Published: December 2017

We directly measured the effect of progressive pulmonary edema on gas transfer from the acinus by injecting 133Xe dissolved in saline through a pulmonary artery catheter into an acinar region with occluded blood flow and measuring 133Xe washout by gamma scintillation scanning. We measured washout in six anesthetized paralyzed dogs during mechanical ventilation with O2 before and after injection of 0.6 mg/kg of oleic acid into the right atrium, which induces severe pulmonary edema within 2 h. Changes in the elastance and resistance of the lung were also calculated from measurements of airway flow, airway pressure, and esophageal pressure. Before injection of oleic acid, the monoexponential rate constant for 133Xe washout was 3.6 +/- 1.4 (SE) min-1; from this we estimated that the rate of gas transfer of 133Xe from the acini was 1.0 l/min. The rate constant decreased gradually after the injection and was correlated with increases in elastance and resistance (r = -0.66) and decreases in alveolar PO2 (r = 0.71). At 2 h after injection, the rate constant (1.2 +/- 0.8 min-1) was lower than control (P < 0.01), and the rate of gas transfer of 133Xe from the acini was < 0.32 l/min. We conclude that resistance in the acini is increased during pulmonary edema and that it is correlated, in the oleic acid model, with changes in overall lung mechanical properties.