bluuebunny/crossref_metadata_2025 huggingface dataset:
Reductions in cardiac output in hypoxic young pigs: systemic and regional perfusion and oxygen metabolism
Authors: Stonestreet Barbara S. , Ocampo Sylvia Santos , Oh William
Published: December 2017

We tested the hypotheses that, in hypoxic young pigs, reductions in cardiac output restrict systemic oxygen transport to a greater extent than does hypoxia alone and that compensatory responses to this restriction are more effective in higher than in lower priority vasculatures. To study this, 10- to 14-day-old instrumented awake hypoxic (arterial oxygen tension = 39 Torr) pigs were exposed to reduced venous return by inflation of a right atrial balloon-tipped catheter. Blood flow was measured with radionuclide-labeled microspheres, and oxygen metabolism was determined with arterial and venous oxygen contents from appropriate vessels. Hypoxia resulted in a reduction in oxygen tension; increases in cardiac output and perfusion to brain (72% over baseline), heart, adrenal glands, and liver without reductions to other organs except for the spleen; reductions in systemic and intestinal oxygen delivery; and increases in systemic and intestinal oxygen extraction without changes in systemic, cerebral, or intestinal oxygen uptake. During hypoxia, decreasing venous return was associated with increases in arterial lactic acid concentration and central venous pressure; attenuation of the hypoxia-related increase in cardiac output; sustained increases in brain (72% over baseline) and heart perfusion; reductions in lung (bronchial artery), pancreatic, renal, splenic, and intestinal (−50% below baseline) perfusion; decreases in systemic and gastrointestinal oxygen delivery; sustained increases in systemic and intestinal oxygen extraction; and decreases in intestinal oxygen uptake, without changes in cerebral oxygen metabolism. We conclude that when venous return to the heart is reduced in hypoxic young pigs, the hypoxia-related increase in cardiac output was attenuated and the relative reduction in cardiac output was associated with preserved cerebral oxygen uptake and compromised intestinal oxygen uptake. Regional responses to hypoxia combined with relative reductions in cardiac output differ from that of hypoxia alone, with the greatest effects on lower priority organs such as the gastrointestinal tract.
Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise
Authors: Hansen Polly A. , Nolte Lorraine A. , Chen May M. , Holloszy John O.
Published: December 2017

The purpose of this study was to determine whether the increase in insulin sensitivity of skeletal muscle glucose transport induced by a single bout of exercise is mediated by enhanced translocation of the GLUT-4 glucose transporter to the cell surface. The rate of 3- O-[3H]methyl-d-glucose transport stimulated by a submaximally effective concentration of insulin (30 μU/ml) was approximately twofold greater in the muscles studied 3.5 h after exercise than in those of the sedentary controls (0.89 ± 0.10 vs. 0.43 ± 0.05 μmol ⋅ ml−1⋅ 10 min−1; means ± SE for n = 6/group). GLUT-4 translocation was assessed by using the ATB-[2-3H]BMPA exofacial photolabeling technique. Prior exercise resulted in greater cell surface GLUT-4 labeling in response to submaximal insulin treatment (5.36 ± 0.45 dpm × 103/g in exercised vs. 3.00 ± 0.38 dpm × 103/g in sedentary group; n = 10/group) that closely mirrored the increase in glucose transport activity. The signal generated by the insulin receptor, as reflected in the extent of insulin receptor substrate-1 tyrosine phosphorylation, was unchanged after the exercise. We conclude that the increase in muscle insulin sensitivity of glucose transport after exercise is due to translocation of more GLUT-4 to the cell surface and that this effect is not due to potentiation of insulin-stimulated tyrosine phosphorylation.
Force heterogeneity in a two-dimensional network model of lung tissue elasticity
Authors: Maksym Geoffrey N. , Fredberg Jeffrey J. , Bates Jason H. T.
Published: December 2017

We have developed a model of forces developed in lung tissue in which the stress-bearing units are heterogeneous. Each element of the fiber network is composed of an idealized elastin and collagen element in parallel. Elastin is represented by linear springs and collagen by stiff strings that extend without resistance until taut. The model can quantitatively account for the nonlinear shape of the length-tension curve of lung tissue strips when the knee lengths of the collagen fibers are distributed according to an inverse power law. The novel feature of this model is that as macroscopic strain increases the load is carried by progressively fewer elements with progressively higher forces, and preferential pathways of force transmission emerge within the matrix. The topology of these self-organizing pathways of force transmission takes the rough appearance of cracks, but, unlike real cracks, they represent the locus of force concentration rather than force release.
Energy metabolism and interstitial fluid displacement in human gastrocnemius during short ischemic cycles
Authors: Binzoni T. , Quaresima V. , Barattelli G. , Hiltbrand E. , Gürke L. , Terrier F. , Cerretelli P. , Ferrari M.
Published: December 2017

Energy metabolism and interstitial fluid displacement were studied in the human gastrocnemius during three subsequent 5-min ischemia-reperfusion periods [ischemic preconditioning (IP)]. The muscle energy balance was assessed by combining near-infrared spectroscopy (NIRS) and31P-nuclear magnetic resonance spectroscopy (31P-NMRS). The interstitial fluid displacement was determined by combining NIRS and23Na-NMRS. No changes in total energy consumption or in the fractional contribution of the underlying energy sources (aerobic glycolysis, anaerobic glycolysis, and Lohmann reaction) were observed in the muscle during the tested IP protocol. Oxygen consumption in the muscle region of interest, as estimated by NIRS, was ∼8 μmol ⋅ 100 g−1 ⋅ min−1and did not change during IP. Phosphocreatine and ATP concentrations did not change over the whole experimental period. A slight but significant ( P < 0.05) increase in intracellular pH was observed. Compared with the control, a 10% greater interstitial fluid content per muscle unit volume was observed at the end of the IP protocol. It is concluded that, at variance with cardiac muscle, repeated 5-min ischemia-reperfusion cycles do not induce metabolic changes in human gastrocnemius but alter the interstitial fluid readjustment. The techniques developed in the present study may be useful in identifying protocols suitable for skeletal muscle preconditioning and to explain the functional basis of this procedure.
Effects of ovariectomy and hindlimb unloading on skeletal muscle
Authors: Fisher Jonathan S. , Hasser Eileen M. , Brown Marybeth
Published: December 2017

Female rats (7–8 mo old, n = 40) were randomly placed into the intact control (Int) and ovariectomized control (Ovx) groups. Two weeks after ovariectomy, animals were further divided into intact 2-wk hindlimb unloaded (Int-HU) and ovariectomized hindlimb unloaded (Ovx-HU). We hypothesized that there would be greater hindlimb unloading-related atrophy in Ovx than in Int rats. In situ contractile tests were performed on soleus (Sol), plantaris (Plan), peroneus longus (Per), and extensor digitorum longus (EDL) muscles. Body weight and Sol mass were ∼22% larger in Ovx than in Int group and ∼18% smaller in both HU groups than in Int rats (Ovx × HU interaction, P < 0.05), and there was a similar trend in Plan muscle ( P< 0.07). There were main effects ( P< 0.05) for both ovariectomy (growth) and hindlimb unloading (atrophy) on gastrocnemius mass. Mass of the Per and EDL muscles was unaffected by either ovariectomy or hindlimb unloading. Time to peak twitch tension for EDL and one-half relaxation times for Sol, Plan, Per, and EDL muscles were faster ( P< 0.05) in Ovx than in Int animals. The results suggest that 1) ovariectomy led to similar increases of ∼20% in body weight and plantar flexor mass; 2) hindlimb unloading may have prevented ovariectomy-related muscle growth; 3) greater atrophy may have occurred in Sol and Plan of Ovx animals compared with controls; and 4) removal of ovarian hormonal influence decreased skeletal muscle contraction times.
Moderate exercise increases postexercise thresholds for vasoconstriction and shivering
Authors: Kenny G. P. , Chen A. A. , Nurbakhsh B. A. , Denis P. M. , Proulx C. E. , Giesbrecht G. G.
Published: December 2017

The purpose of this study was to evaluate the effect of exercise on the subsequent postexercise thresholds for vasoconstriction and shivering. On two separate days, with six subjects (3 women), a whole body water-perfused suit slowly decreased mean skin temperature (∼7.0°C/h) until thresholds for vasoconstriction and shivering were clearly established. Subjects were then rewarmed by increasing water temperature until both esophageal and mean skin temperatures returned to near-baseline values. Subjects either performed 15 min of cycle ergometry (65% maximal O2 consumption) followed by 30 min of recovery (Exercise) or remained seated with no exercise for 45 min (Control). Subjects were then cooled again. We mathematically compensated for changes in skin temperatures by using the established linear cutaneous contribution of skin to the control of vasoconstriction and shivering (20%). The calculated core temperature threshold (at a designated skin temperature of 30.0°C) for vasoconstriction increased significantly from 36.64 ± 0.20 to 36.89 ± 0.22°C postexercise ( P < 0.01). Similarly, the shivering threshold increased from 35.73 ± 0.13 to 36.13 ± 0.12°C postexercise ( P < 0.01). In contrast, sequential measurements, without exercise, demonstrate a time-dependent decrease in both the vasoconstriction (0.10°C) and shivering (0.12°C) thresholds. These data indicate that exercise has a prolonged effect by increasing the postexercise thresholds for both cold thermoregulatory responses.
Effect of caffeine on metabolism, exercise endurance, and catecholamine responses after withdrawal
Authors: Van Soeren M. H. , Graham T. E.
Published: December 2017

In this study the effects of acute caffeine ingestion on exercise performance, hormonal (epinephrine, norepinephrine, insulin), and metabolic (free fatty acids, glycerol, glucose, lactate, expired gases) parameters during short-term withdrawal from dietary caffeine were investigated. Recreational athletes who were habitual caffeine users ( n = 6) (maximum oxygen uptake 54.5 ± 3.3 ml ⋅ kg−1⋅ min−1and daily caffeine intake 761.3 ± 11.8 mg/day) were tested under conditions of no withdrawal and 2-day and 4-day withdrawal from dietary caffeine. There were seven trials in total with a minimum of 10 days between trials. On the day of the exercise trial, subjects ingested either dextrose placebo or 6 mg/kg caffeine in capsule form 1 h before cycle ergometry to exhaustion at 80–85% of maximum oxygen uptake. Test substances were assigned in a random, double-blind manner. A final placebo control trial completed the experiment. There was no significant difference in any measured parameters among days of withdrawal after ingestion of placebo. At exhaustion in the 2- and 4-day withdrawal trials, there were significant increases in plasma norepinephrine in response to caffeine ingestion. Caffeine-induced increases in serum free fatty acids occurred after 4 days and only at rest. Subjects responded to caffeine with increases in plasma epinephrine ( P < 0.05) at exhaustion and prolonged exercise time in all caffeine trials compared with placebo, regardless of withdrawal from caffeine. It is concluded that increased endurance is unrelated to hormonal or metabolic changes and that it is not related to prior caffeine habituation in recreational athletes.
Ozone enhances excitabilities of pulmonary C fibers to chemical and mechanical stimuli in anesthetized rats
Authors: Ho Ching-Yin , Lee Lu-Yuan
Published: December 2017

Acute exposure to ozone (O3) enhances pulmonary chemoreflex response to capsaicin, and an increased sensitivity of bronchopulmonary C-fiber afferent endings may be involved. The present study was aimed at determining the effect of O3 on the responses of pulmonary C fibers to chemical and mechanical stimuli. A total of 31 C fibers were studied in anesthetized, open-chest, and vagotomized rats. During control, right atrial injection of a low dose of capsaicin abruptly evoked a short and mild burst of discharge [0.77 ± 0.28 impulses (imp)/s, 2-s average]. After acute exposure to O3 (3 parts/million for 30 min), there was no significant change in arterial blood pressure, tracheal pressure, or baseline activity of C fibers. However, the stimulatory effect of the same dose of capsaicin on these fibers was markedly enhanced (6.05 ± 0.88 impulses/s; P < 0.01) and prolonged immediately after O3 exposure, and returned toward control in 54 ± 6 min. Similarly, the pulmonary C-fiber response to injection of a low dose of lactic acid was also elevated after O3 exposure. Furthermore, O3 exposure significantly potentiated the C-fiber response to constant-pressure (tracheal pressure = 30 cmH2O) lung inflation (control: 0.19 ± 0.07 imp/s; after O3: 1.12 ± 0.26 imp/s; P < 0.01). In summary, these results show that the excitabilities of pulmonary C-fiber afferents to lung inflation and injections of chemical stimulants are markedly potentiated after acute exposure to O3, suggesting a possible involvement of these afferents in the O3-induced changes in breathing pattern and chest discomfort in humans.
Effects of hindlimb contraction on pressor and muscle interstitial metabolite responses in the cat
Authors: MacLean Dave A. , LaNoue Kathryn F. , Gray Kristen S. , Sinoway Lawrence I.
Published: December 2017

We used the microdialysis technique to measure the interstitial concentration of several putative metabolic stimulants of the exercise pressor reflex during 3- and 5-Hz twitch contractions in the decerebrate cat. The peak increases in heart rate and mean arterial pressure during contraction were 20 ± 5 beats/min and 21 ± 8 mmHg and 27 ± 9 beats/min and 37 ± 12 mmHg for the 3- and 5-Hz stimulation protocols, respectively. All variables returned to baseline after 10 min of recovery. Interstitial lactate rose ( P < 0.05) by 0.41 ± 0.15 and 0.56 ± 0.16 mM for the 3- and 5-Hz stimulation protocols, respectively, and were not statistically different from one another. Interstitial lactate levels remained above ( P < 0.05) baseline during recovery in the 5-Hz group. Dialysate phosphate concentrations (corrected for shifts in probe recovery) rose with stimulation ( P < 0.05) by 0.19 ± 0.08 and 0.11 ± 0.03 mM for the 3- and 5-Hz protocols. There were no differences between groups. The resting dialysate K+ concentrations for the 3- and 5-Hz conditions were 4.0 ± 0.1 and 3.9 ± 0.1 meq/l, respectively. During stimulation the dialysate K+ concentrations rose steadily for both conditions, and the increase from rest to stimulation ( P < 0.05) was 0.57 ± 0.19 and 0.81 ± 0.06 meq/l for the 3- and 5-Hz conditions, respectively, with no differences between groups. Resting dialysate pH was 6.915 ± 0.055 and 6.981 ± 0.032 and rose to 7.013 ( P < 0.05) and 7.053 ( P < 0.05) for the 3- and 5-Hz conditions, respectively, and then became acidotic (6.905, P < 0.05) during recovery (5 Hz only). This study represents the first time simultaneous measurements of multiple skeletal muscle interstitial metabolites and pressor responses to twitch contractions have been made in the cat. These data suggest that interstitial K+ and phosphate, but not lactate and H+, may contribute to the stimulation of thin fiber muscle afferents during contraction.
Renal hemodynamic responses to dynamic exercise in rabbits
Authors: Mueller Patrick J. , O’Hagan Kathleen P. , Skogg Kara A. , Buckwalter John B. , Clifford Philip S.
Published: December 2017

Cardiovascular hemodynamics, including renal blood flow, were measured in rabbits with one intact and one denervated kidney during various intensities of treadmill exercise. Within the first 10 s of exercise, there was rapid vasoconstriction in the innervated kidney associated with decreases in renal blood flow (range −10 to −17%). The vasoconstriction in the innervated kidney was evident at all workloads and was intensity dependent. There was no significant vasoconstriction or change in renal blood flow (range 0.5 to −3.1%) in the denervated kidney at the onset of exercise. However, a slowly developing vasoconstriction occurred in the denervated kidney as exercise progressed to 2 min at all workloads. Examination of responses to exercise performed under α-adrenergic blockade with phentolamine (5 mg/kg iv) revealed that the vasoconstriction in the innervated kidney at the onset of exercise and the delayed vasoconstriction in the denervated kidney were due primarily to activation of α-adrenergic receptors. In addition, a residual vasoconstriction was also present in the innervated kidney after α-adrenergic blockade, suggesting that, during exercise, activation of other renal vasoconstrictor mechanisms occurs which is dependent on the presence of renal nerves.
Postexercise recovery of skeletal muscle malonyl-CoA, acetyl-CoA carboxylase, and AMP-activated protein kinase
Authors: Rasmussen B. B. , Hancock C. R. , Winder W. W.
Published: December 2017

Previous studies have demonstrated that oxygen consumption and fat oxidation remain elevated in the postexercise period. The purpose of this study was to determine whether malonyl-CoA, an inhibitor of fatty acid oxidation, remains depressed in muscle after exercise. Rats were sprinted for 5 min (40 m/min, 5% grade) or run for 30 min (21 m/min, 15% grade). Red quadriceps malonyl-CoA returned to resting values by 90 min postexercise in the sprinting rats and remained significantly lower at least 90 min postexercise in the 30-min exercise group. AMP-activated protein kinase activity remained significantly elevated ( P < 0.05) for 10 min after exercise in both groups. The most rapid rate of glycogen repletion was in the first 30 min postexercise. The respiratory exchange ratio decreased from a nonexercise value of 0.87 ± 0.01 to an average 0.82 ± 0.01 during the 90-min period after 30 min of exercise. Thus muscle malonyl-CoA remains depressed and fat oxidation is elevated for relatively prolonged periods after a single bout of exercise. This may allow fat oxidation to contribute more to muscle energy requirements, thus leaving more glucose for replenishment of muscle glycogen.
Modulation of whole body protein metabolism, during and after exercise, by variation of dietary protein
Authors: Bowtell J. L. , Leese G. P. , Smith K. , Watt P. W. , Nevill A. , Rooyackers O. , Wagenmakers A. J. M. , Rennie M. J.
Published: December 2017

The aim of this study was to investigate dietary protein-induced changes in whole body leucine turnover and oxidation and in skeletal muscle branched chain 2-oxo acid dehydrogenase (BCOADH) activity, at rest and during exercise. Postabsorptive subjects received a primed constant infusion ofl-[1-13C,15N]leucine for 6 h, after previous consumption of a high- (HP; 1.8 g ⋅ kg−1⋅ day−1, n = 8) or a low-protein diet (LP; 0.7 g ⋅ kg−1⋅ day−1, n = 8) for 7 days. The subjects were studied at rest for 2 h, during 2-h exercise at 60% maximum oxygen consumption, then again for 2 h at rest. Exercise induced a doubling of both leucine oxidation from 20 μmol ⋅ kg−1⋅ h−1and BCOADH percent activation from 7% in all subjects. Leucine oxidation was greater before (+46%) and during (+40%, P < 0.05) the first hour of exercise in subjects consuming the HP rather than the LP diet, but there was no additional change in muscle BCOADH activity. The results suggest that leucine oxidation was increased by previous ingestion of an HP diet, attributable to an increase in leucine availability rather than to a stimulation of the skeletal muscle BCOADH activity.
Increased compliance in diaphragm muscle of the cardiomyopathic Syrian hamster
Authors: Coirault Catherine , Samuel Jane-Lyse , Chemla Denis , Pourny Jean-Claude , Lambert Francine , Marotte Françoise , Lecarpentier Yves
Published: December 2017

We investigated the hypothesis that diaphragm compliance was abnormal in cardiomyopathic Syrian hamsters (CSH), an experimental model of myopathy. The passive elastic properties of isolated diaphragm muscles were analyzed at both the muscle and sarcomere levels. We used the following passive exponential relationship between stress (ς) and strain (ε): ς = (Eo/β) ( eβε− 1), where Eois the initial elastic modulus and β is the stiffness constant. Immunocytochemistry procedures were used to analyze the distribution of two key elastic components of muscle, extracellular collagen and intracellular titin elastic components, as well as the extracellular matrix glycoprotein laminin. Muscle and sarcomere values of β were nearly twofold lower in CSH (8.7 ± 1.9 and 8.3 ± 1.4, respectively) than in control animals (19.7 ± 1.7 and 16.8 ± 2.1, respectively) ( P < 0.01 for each). Compared with controls, Eowas higher in CSH. Sarcomere slack length was significantly longer in CSH than in control animals (2.1 ± 0.1 vs. 1.9 ± 0.1 μm, P < 0.05). The surface area of collagen I was significantly larger in CSH (17.4 ± 1.8%) than in control animals (12.4 ± 0.7%, P< 0.05). There was no change in the distribution of titin or laminin labelings between the groups. These results demonstrate increased diaphragm compliance in cardiomyopathic hamsters. The increase in CSH diaphragm compliance was observed despite an increase in the surface area of collagen and was not associated with an abnormal distribution of titin or laminin.
Quantitation of intracellular [Na+] in vivo by using TmDOTP5− as an NMR shift reagent and extracellular marker
Authors: Winter Patrick M. , Seshan Viswanathan , Makos Janice D. , Sherry A. Dean , Malloy Craig R. , Bansal Navin
Published: December 2017

A method is presented to measure the absolute concentration of intracellular Na+([Na+]i) in vivo by using interleaved 23Na- and 31P-nuclear magnetic resonance (NMR) spectroscopy and TmDOTP5− as shift reagent and chemical marker of tissue extracellular space (ECS). The technique was used to determine [Na+]iand relative ECS in livers of control rats (21 ± 3 and 0.11 ± 0.02 mM, respectively) and in rats exposed to carbon tetrachloride (103 ± 29 and 0.23 ± 0.03 mM, respectively). The NMR measurements were confirmed independently on excised tissue samples by using atomic absorption spectroscopy. The results confirm that TmDOTP5− can be used as a combined cation shift reagent and ECS marker, thereby allowing quantitation of [Na+]iin vivo by NMR.
V˙o 2 max is associated with ACE genotype in postmenopausal women
Authors: Hagberg James M. , Ferrell Robert E. , McCole Steve D. , Wilund Kenneth R. , Moore Geoffrey E.
Published: December 2017

Relationships have frequently been found between angiotensin-converting enzyme (ACE) genotype and various pathological and physiological cardiovascular outcomes and functions. Thus we sought to determine whether ACE genotype affected maximal O2 consumption (V˙o 2 max) and maximal exercise hemodynamics in postmenopausal women with different habitual physical activity levels. Age, body composition, and habitual physical activity levels did not differ among ACE genotype groups. However, ACE insertion/insertion (II) genotype carriers had a 6.3 ml ⋅ kg−1 ⋅ min−1higher V˙o 2 max( P < 0.05) than the ACE deletion/deletion (DD) genotype group after accounting for the effect of physical activity levels. The ACE II genotype group also had a 3.3 ml ⋅ kg−1 ⋅ min−1higher V˙o 2 max( P < 0.05) than the ACE insertion/deletion (ID) genotype group. The ACE ID group tended to have a higher V˙o 2 max than the DD genotype group, but the difference was not significant. ACE genotype accounted for 12% of the variation inV˙o 2 max among women after accounting for the effect of habitual physical activity levels. The entire difference inV˙o 2 max among ACE genotype groups was the result of differences in maximal arteriovenous O2 difference (a-vDo 2). ACE genotype accounted for 17% of the variation in maximal a-vDo 2 in these women. Maximal cardiac output index did not differ whatsoever among ACE genotype groups. Thus it appears that ACE genotype accounts for a significant portion of the interindividual differences inV˙o 2 max among these women. However, this difference is the result of genotype-dependent differences in maximal a-vDo 2 and not of maximal stroke volume and maximal cardiac output.
Cocaine administration induces human splenic constriction and altered hematologic parameters
Authors: Kaufman Marc J. , Siegel Arthur J. , Mendelson Jack H. , Rose Stephanie L. , Kukes Thellea J. , Sholar Michelle B. , Lukas Scott E. , Renshaw Perry F.
Published: December 2017

Cocaine is a potent vasoconstrictor that has been shown to alter hemoglobin, hematocrit, and red blood cell counts in both animals and humans. The present study evaluated whether cocaine administration induces splenic constriction in men and whether spleen-volume changes temporally correlate with altered hematologic parameters. Spleen volume was assessed at baseline and after cocaine administration (0.4 mg/kg) by using magnetic resonance imaging. A group of five healthy men, aged 31 ± 2 (SE) yr and reporting occasional cocaine use (13 ± 5 lifetime exposures), participated. Cocaine reduced spleen volume by 20 ± 4% ( P < 0.03) 10 min after drug administration. Spleen volume returned to normal (101 ± 3% baseline) within 35 min after cocaine administration, indicating that the reduction is a transient phenomenon. In subjects administered cocaine from whom blood samples were obtained ( n = 3), cocaine increased hemoglobin levels, hematocrit, and red blood cell count to 104.5 ± 0.9, 105.6 ± 1.2, and 106.5 ± 1.0% of baseline levels, respectively ( P < 0.03), but it did not alter white blood cell and platelet counts. Placebo administration ( n = 5) did not alter hematologic parameters. These results suggest that cocaine induces splenic constriction in humans, and this may contribute to temporally concordant hematologic parameter changes. These events may help to preserve or increase tissue oxygenation in periods of high oxygen demand and/or increased vascular resistance.
Measurement of pulmonary resistance and dynamic compliance with airway obstruction
Authors: Officer Todd M. , Pellegrino Riccardo , Brusasco Vito , Rodarte Joseph R.
Published: December 2017

We compared four algorithms by using least squares regression for determination of pulmonary resistance and dynamic elastance in subjects with emphysema, normal subjects, and subjects with asthma before and after bronchoconstriction. The four methods evaluated include 1) a single resistance and elastance, 2) separate resistances and elastances for each half breath, 3) separate inspiratory and expiratory resistances with a single elastance, and 4) separate inspiratory and expiratory resistances, an expiratory volume interaction term, and a single elastance. All methods gave comparable results in normal and asthmatic subjects. We found expiratory resistance was larger than inspiratory resistance in normal and asthmatic subjects during control conditions, but inspiratory resistance was higher than expiratory resistance in subjects who experienced severe bronchoconstriction in response to methacholine. In subjects who are flow limited, method 2 gives a higher inspiratory resistance than would be computed by assuming that the elastic pressure-volume curve passes through the zero-flow points. Methods 1 and 3 overestimate dynamic elastance and inspiratory resistance. Method 4appears to identify flow limitation and dynamic hyperinflation and gives a good measure of inspiratory resistance and dynamic elastance.
Letters to the Editor
Authors: Sonander Hans-G.
Published: December 2017

The following is the abstract of the article discussed in the subsequent letter:

Venegas, José G., R. Scott Harris, and Brett A. Simon. A comprehensive equation for the pulmonary pressure-volume curve. J. Appl. Physiol. 84(1): 389–395, 1998.—Quantification of pulmonary pressure-volume (P-V) curves is often limited to calculation of specific compliance at a given pressure or the recoil pressure (P) at a given volume (V). These parameters can be substantially different depending on the arbitrary pressure or volume used in the comparison and may lead to erroneous conclusions. We evaluated a sigmoidal equation of the form, V = a + b[1 +  e −(P− c)/ d ]−1, for its ability to characterize lung and respiratory system P-V curves obtained under a variety of conditions including normal and hypocapnic pneumoconstricted dog lungs ( n = 9), oleic acid-induced acute respiratory distress syndrome ( n = 2), and mechanically ventilated patients with acute respiratory distress syndrome ( n = 10). In this equation, a corresponds to the V of a lower asymptote, b to the V difference between upper and lower asymptotes, c to the P at the true inflection point of the curve, and d to a width parameter proportional to the P range within which most of the V change occurs. The equation fitted equally well inflation and deflation limbs of P-V curves with a mean goodness-of-fit coefficient ( R 2) of 0.997 ± 0.02 (SD). When the data from all analyzed P-V curves were normalized by the best-fit parameters and plotted as (V −  a)/ b vs. (P −  c)/ d, they collapsed into a single and tight relationship ( R 2 = 0.997). These results demonstrate that this sigmoidal equation can fit with excellent precision inflation and deflation P-V curves of normal lungs and of lungs with alveolar derecruitment and/or a region of gas trapping while yielding robust and physiologically useful parameters.
Inhaled nitric oxide prevents left ventricular impairment during endotoxemia
Authors: Ishihara Satoshi , Ward John A. , Tasaki Osamu , Pruitt Basil A. , Goodwin Cleon W. , Mozingo David W. , Cioffi William G.
Published: December 2017

We evaluated the effect of long-term inhalation of nitric oxide (NO) on cardiac contractility after endotoxemia by using the end-systolic elastance of the left ventricle (LV) as a load-independent contractility index. Chronic instrumentation in 12 pigs included implantation of two pairs of endocardial dimension transducers to measure LV volume and a micromanometer to measure LV pressure. One week later, the animals were divided into a control group ( n = 6) or a NO group ( n = 6). All animals received intravenous Escherichia coliendotoxin (10 μg ⋅ kg−1 ⋅ h−1) and equivalent lactated Ringer solution. NO inhalation (20 parts/million) was begun 30 min after the initiation of endotoxemia and was continued for 24 h. In both groups, tachycardia, pulmonary hypertension, and systemic hyperdynamic changes were noted. The end-systolic elastance in the control group was significantly decreased beyond 7 h. NO inhalation maintained the end-systolic elastance at baseline levels and prevented its impairment. These findings indicate that NO exerts a protective effect on LV contractility in this model of endotoxemia.
Capillary growth in relation to blood flow and performance in overloaded rat skeletal muscle
Authors: Egginton S. , Hudlická O. , Brown M. D. , Walter H. , Weiss J. B. , Bate A.
Published: December 2017

Rat extensor digitorum longus muscles were overloaded by stretch after removal of the synergist tibialis anterior muscle to determine the relationship between capillary growth, muscle blood flow, and presence of growth factors. After 2 wk, sarcomere length increased from 2.4 to 2.9 μm. Capillary-to-fiber ratio, estimated from alkaline phosphatase-stained frozen sections, was increased by 33% ( P < 0.0001) and 60% ( P < 0.01), compared with control muscles (1.44 ± 0.06) after 2 and 8 wk, respectively. At 2 wk, the increased capillary-to-fiber ratio was not associated with any changes in mRNA for basic fibroblast growth factor (FGF-2) or its protein distribution. FGF-2 immunoreactivity was present in nerves and large blood vessels but was negative in capillaries, whereas the activity of low-molecular endothelial-cell-stimulating angiogenic factor (ESAF) was 50% higher in stretched muscles. Muscle blood flows measured by radiolabeled microspheres during contractions were not significantly different after 2 or 8 wk (132 ± 37 and 177 ± 22 ml ⋅ min−1⋅ 100 g−1, respectively) from weight-matched controls (156 ± 12 and 150 ± 10 ml ⋅ min−1⋅ 100 g−1, respectively). Resistance to fatigue during 5-min isometric contractions (final/peak tension × 100) was similar in 2-wk overloaded and contralateral muscles (85 vs. 80%) and enhanced after 8 wk to 92%, compared with 77% in contralateral muscles and 67% in controls. We conclude that increased blood flow cannot be responsible for initiating expansion of the capillary bed, nor does it explain the reduced fatigue within overloaded muscles. However, stretch can present a mechanical stimulus to capillary growth, acting either directly on the capillary abluminal surface or by upregulating ESAF, but not FGF-2, in the extracellular matrix.
Influence of volume dependency and timing of airway occlusions on the Hering-Breuer reflex in infants
Authors: Rabbette Patricia S. , Stocks Janet
Published: December 2017

Both end-inspiratory (EIO) and end-expiratory (EEO) airway occlusions are used to calculate the strength of the Hering-Breuer inflation reflex (HBIR) in infants. However, the influence of the timing of such occlusions is unknown, as is the extent to which changes in volume within and above the tidal range affect this reflex. The purpose of this study was to compare both techniques and to evaluate the volume dependency of the HBIR in healthy, sleeping infants up to 1 yr of age. The strength of the HBIR was expressed as the ratio of expiratory or inspiratory time during EIO or EEO, respectively, to that recorded during spontaneous breathing, i.e., as the “inhibitory ratio” (IR). Paired measurements of the EIO and EEO in 26 naturally sleeping newborn and 15 lightly sedated infants at ∼1 yr showed no statistically significant differences in the IR according to technique: mean (95% CI) of the difference (EIO − EEO) being −0.02 (−0.17, 0.13) during the first week of life and 0.04 (−0.14, 0.22) at 1 yr. During tidal breathing, a volume threshold of ∼4 ml/kg was required to evoke the HBIR. Marked volume and age dependency were observed. In newborn infants, occlusions at ∼10 ml/kg during sighs always resulted in an IR > 4, whereas a similar response was only evoked at 25 ml/kg in older infants. Age-related changes in the volume threshold may reflect maturational changes in the control of breathing and respiratory mechanics throughout the first year of life.
Nonchemical influence of inspiratory pressure support on inspiratory activity in humans
Authors: Fauroux Brigitte , Isabey Daniel , Desmarais Gilbert , Brochard Laurent , Harf Alain , Lofaso Frédéric
Published: December 2017

To determine whether nonchemical inhibition of respiratory activity occurs during inspiratory pressure support (IPS) ventilation (IPSV), respiratory motor output (in 9 subjects), obtained by calculating transdiaphragmatic pressure-time products, and central respiratory output (in 5 subjects), obtained by integrating the electromyographic activity of the diaphragm (EMGdi) during mechanical inspiratory time, EMGdi per minute, and electrical inspiratory time, as determined from onset to peak EMGdi, were compared during spontaneous ventilation (control) and IPSV with (IPS+CO2) and without (IPS) correction of hypocapnia. Both IPS and IPS+CO2induced significant decreases in transdiaphragmatic pressure-time products (46 ± 31 and 53 ± 23%, respectively), EMGdi during mechanical inspiratory time (49 ± 12 and 57 ± 14%, respectively), EMGdi per minute (65 ± 22 and 69 ± 15%, respectively), and electrical inspiratory time (73 ± 8 and 65 ± 6%, respectively). Because correction of hypocapnia failed to eliminate the marked inhibition of both respiratory and central motor output seen with IPS, we conclude that nonchemical inhibition of respiratory activity occurs during IPSV.
Carbohydrate intake during prolonged cycling minimizes effect of glycemic index of preexercise meal
Authors: Burke Louise M. , Claassen Amanda , Hawley John A. , Noakes Timothy D.
Published: December 2017

We studied the effects of the glycemic index (GI) of preexercise meals on metabolism and performance when carbohydrate (CHO) was ingested throughout exercise. Six well-trained cyclists performed three counterbalanced trials of 2-h cycling at ∼70% of maximal oxygen uptake, followed by a performance ride of 300 kJ. Meals consumed 2 h before exercise consisted of 2 g CHO/kg body mass of either high-GI potato (HGI trial) or low-GI pasta (LGI trial), or of a low-energy jelly (Con trial). Immediately before and throughout exercise, subjects ingested a 10 g/100 ml [U-14C]glucose solution for a total of 24 ml/kg body mass. Despite differences in preexercise glucose, insulin, and free fatty acids concentrations among trials, both total CHO oxidation for HGI, LGI, and Con trials, respectively, during steady-state exercise [403 ± 16, 376 ± 29, and 373 ± 24 (SE) g/2 h] and oxidation of the ingested CHO (65 ± 6, 57 ± 6, and 63 ± 5 g/2 h) were similar. There was no difference in time to complete the subsequent performance ride (946 ± 23, 954 ± 35, and 970 ± 26 s for HGI, LGI, and Con trials, respectively). When CHO is ingested during exercise in amounts presently recommended by sports nutrition guidelines, preexercise CHO intake has little effect on metabolism or on subsequent performance during prolonged cycling (∼2.5 h).
Contribution of vasomotion to vascular resistance: a comparison of arteries from virgin and pregnant rats
Authors: Gratton Robert J. , Gandley Robin E. , McCarthy John F. , Michaluk Walter K. , Slinker Bryan K. , McLaughlin Margaret K.
Published: December 2017

Intrinsic oscillatory activity, or vasomotion, within the microcirculation has many potential functions, including modulation of vascular resistance. Alterations in oscillatory activity during pregnancy may contribute to the marked reduction in vascular resistance. The purpose of this study was 1) to mathematically model the oscillatory changes in vessel diameter and determine the effect on vascular resistance and 2) to characterize the vasomotion in resistance arteries of pregnant and nonpregnant (virgin) rats. Mesenteric arteries were isolated from Sprague-Dawley rats and studied in a pressurized arteriograph. Mathematical modeling demonstrated that the resistance in a vessel with vasomotion was greater than that in a static vessel with the same mean radius. During constriction with the α1-adrenergic agonist phenylephrine, the amplitude of oscillation was less in the arteries from pregnant rats. We conclude that vasomotor activity may provide a mechanism to regulate vascular resistance and blood flow independent of static changes in arterial diameter. During pregnancy the decrease in vasomotor activity in resistance arteries may contribute to the reduction in peripheral vascular resistance.
Pulmonary gas-exchange analysis by using simultaneous deposition of aerosolized and injected microspheres
Authors: Altemeier William A. , Robertson H. Thomas , Glenny Robb W.
Published: December 2017

Numerical methods for determining end-capillary gas contents for ventilation-to-perfusion ratios were first developed in the late 1960s. In the 1970s these methods were applied to validate distributions of ventilation-to-perfusion ratios measured by the multiple inert-gas-elimination technique. We combined numerical gas analysis and fluorescent-microsphere measurements of ventilation and perfusion to predict gas exchange at a resolution of ∼2.0-cm3 lung volume in pigs. Oxygen, carbon dioxide, and inert gas exchange were calculated in 551–845 compartments/animal before and after pulmonary embolization with 780-μm beads. Whole lung gas exchange was estimated from the perfusion- and ventilation-weighted end-capillary gas contents. Before lung injury, no significant difference existed between microsphere-estimated arterial [Formula: see text]and [Formula: see text] and measured values. After lung injury, the microsphere method predicted a decrease in arterial[Formula: see text] but consistently underestimated its magnitude. Correlation between predicted and measured inert gas retentions was 0.99. Overestimation of low-solubility inert gas retentions suggests underestimation of areas with low ventilation-to-perfusion ratios by microspheres after lung injury. Regional deposition of aerosolized and injected microspheres is a valid method for investigating regional gas exchange with high spatial resolution.
Bronchial vasodilator pathways in the vagus nerve of dogs
Authors: Pisarri T. E. , Zimmerman M. P. , Adrian T. E. , Coleridge J. C. G. , Coleridge H. M.
Published: December 2017

Bronchial vasodilation in dogs is mediated largely by vagal pathways. To examine the relative contribution of cholinergic and noncholinergic parasympathetic pathways and of sensory axon reflexes to vagal bronchial vasodilation, we electrically stimulated the peripheral vagus nerve in 10 chloralose-anesthetized dogs and measured bronchial artery flow. Moderate-intensity electrical stimulation (which did not activate C-fiber axons) caused a rapid voltage- and frequency-dependent vasodilation. After atropine, vasodilation was slower in onset and reduced at all voltages and frequencies: bronchial vascular conductance increased by 9.0 ± 1.5 (SE) ml ⋅ min−1 ⋅ 100 mmHg−1 during stimulation before atropine and 5.5 ± 1.4 ml ⋅ min−1 ⋅ 100 mmHg−1 after ( P < 0.02). High-intensity stimulation (sufficient to recruit C fibers) was not studied before atropine because of the resulting cardiac arrest. After atropine, high-intensity stimulation increased conductance by 12.0 ± 2.5 ml ⋅ min−1 ⋅ 100 mmHg−1. Subsequent blockade of ganglionic transmission, with arterial blood pressure maintained by a pressure reservoir, abolished the response to moderate-intensity stimulation and reduced the increase to high-intensity stimulation by 82 ± 5% ( P < 0.01). In 13 other dogs, we measured vasoactive intestinal peptide-like immunoreactivity in venous blood draining from the bronchial veins. High-intensity vagal stimulation increased vasoactive intestinal peptide concentration from 5.7 ± 1.8 to 18.4 ± 4.1 fmol/ml ( P = 0.001). The results suggest that in dogs cholinergic and noncholinergic parasympathetic pathways play the major role in vagal bronchial vasodilation.
Effects of lung volume on lung and chest wall mechanics in rats
Authors: Hirai T. , McKeown K. A. , Gomes R. F. M. , Bates J. H. T.
Published: December 2017

To investigate the effect of lung volume on chest wall and lung mechanics in the rats, we measured the impedance (Z) under closed- and open-chest conditions at various positive end-expiratory pressures (0–0.9 kPa) by using a computer-controlled small-animal ventilator (T. F. Schuessler and J. H. T. Bates. IEEE Trans. Biomed. Eng. 42: 860–866, 1995) that we have developed for determining accurately the respiratory Z in small animals. The Z of total respiratory system and lungs was measured with small-volume oscillations between 0.25 and 9.125 Hz. The measured Z was fitted to a model that featured a constant-phase tissue compartment (with dissipation and elastance characterized by constants G and H, respectively) and a constant airway resistance (Z. Hantos, B. Daroczy, B. Suki, S. Nagy, and J. J. Fredberg. J. Appl. Physiol. 72: 168–178, 1992). We matched the lung volume between the closed- and open-chest conditions by using the quasi-static pressure-volume relationship of the lungs to calculate Z as a function of lung volume. Resistance decreased with lung volume and was not significantly different between total respiratory system and lungs. However, G and H of the respiratory system were significantly higher than those of the lungs. We conclude that chest wall in rats has a significant influence on tissue mechanics of the total respiratory system.
Effects of dopamine and domperidone on ventilatory sensitivity to hypoxia after 8 h of isocapnic hypoxia
Authors: Pedersen Michala E. F. , Dorrington Keith L. , Robbins Peter A.
Published: December 2017

Acclimatization to altitude involves an increase in the acute hypoxic ventilatory response (AHVR). Because low-dose dopamine decreases AHVR and domperidone increases AHVR, the increase in AHVR at altitude may be generated by a decrease in peripheral dopaminergic activity. The AHVR of nine subjects was determined with and without a prior period of 8 h of isocapnic hypoxia under each of three pharmacological conditions: 1) control, with no drug administered; 2) dopamine (3 μg ⋅ min−1 ⋅ kg−1); and 3) domperidone (Motilin, 40 mg). AHVR increased after hypoxia ( P ≤ 0.001). Dopamine decreased ( P ≤ 0.01), and domperidone increased ( P ≤ 0.005) AHVR. The effect of both drugs on AHVR appeared larger after hypoxia, an observation supported by a significant interaction between prior hypoxia and drug in the analysis of variance ( P ≤ 0.05). Although the increased effect of domperidone after hypoxia of 0.40 l ⋅ min−1 ⋅ %saturation−1[95% confidence interval (CI) −0.11 to 0.92 l ⋅ min−1 ⋅ %−1] did not reach significance, the lower limit for this confidence interval suggests that little of the increase in AHVR after sustained hypoxia was brought about by a decrease in peripheral dopaminergic inhibition.
PGAM-M expression is regulated pretranslationally in hindlimb muscles and under altered loading conditions
Authors: Kell Rachel , Pierce Heather , Swoap Steven J.
Published: December 2017

Enzymatic activity from the muscle-specific isoform of phosphoglycerate mutase (PGAM-M) is higher within glycolytic skeletal muscles than in oxidative muscles. The hypothesis that PGAM-M is regulated pretranslationally among muscles of the hindlimb was tested using enzymatic assays, Western blots, and Northern blots. We further investigated the regulatory level(s) at which PGAM-M gene expression is controlled during hindlimb unweighting. PGAM-M mRNA and immunoreactive protein levels were fourfold lower in the rat soleus muscle than in the tibialis anterior (TA), plantaris, and extensor digitorum longus muscles. Four weeks of unweighting induced a 2.5-fold increase in PGAM enzymatic activity within the soleus muscle, a 1.8-fold increase in PGAM-M immunoreactivity, and a 3.5-fold increase in PGAM-M mRNA. To examine potential transcriptional regulatory mechanisms, the proximal 400 bp of the rat PGAM-M promoter were linked to a firefly luciferase and injected into normal and unweighted TA and soleus muscles. Firefly luciferase activity was elevated two- to threefold in the TA and the unweighted soleus over the normal soleus muscle. These data suggest that PGAM-M expression is pretranslationally regulated among muscle types and within unweighted slow-twitch muscle. Furthermore, the proximal 400 bp of the PGAM-M promoter contains cis-acting sequences to allow muscle-type-specific expression of a reporter gene and responsiveness to soleus muscle unweighting.