bluuebunny/crossref_metadata_2025 huggingface dataset:
Human hydrometry: comparison of multifrequency bioelectrical impedance with2H2O and bromine dilution
Authors: Ellis Kenneth J. , Wong William W.
Published: December 2017

The traditional method of assessing total body water (TBW), extracellular water (ECW), and intracellular water (ICW) has been the use of isotopes, on the basis of the dilution principle. Although the development of bioelectrical impedance techniques has eliminated many of the measurement constraints associated with the dilution methods, the degree of interchangeability between the two methods remains uncertain. We used multifrequency bioelectrical impedance spectroscopy (BIS),2H2O dilution, and bromine dilution to assess TBW, ECW, and ICW in 469 healthy subjects (248 males, 221 females) aged 3–29 yr. We found that the TBW, ECW, and ICW estimates for the BIS and dilution methods were significantly correlated ( r 2 = 0.80–0.96, P < 0.0001, SE of the estimate = 2.3–2.7 liters). On the basis of population, the constants used in the BIS analysis could be adjusted so that the mean differences with the dilution methods would become zero. The SD values for the mean differences between the dilution and BIS methods, however, remained significant for both males and females: TBW (±2.1–2.8 liters), ECW (±1.4–1.6 liters), and ICW (2.0–3.1 liters). To improve the accuracy of the BIS measurement for an individual within the age range we have examined, further refinement of the constants used in the BIS analysis is needed.
Does resistive loading decrease diaphragmatic contractility before task failure?
Authors: Laghi Franco , Topeli Arzu , Tobin Martin J.
Published: December 2017

While sustaining a load that leads to task failure, it is unclear whether diaphragmatic fatigue develops progressively or occurs only at task failure. We hypothesized that incremental loading produces a progressive decrease in diaphragmatic contractility ever before task failure. Ten subjects generated 60% of maximal transdiaphragmatic pressure (Pdimax) for 2 min, 4 min, and until task failure. Before loading, 20 min after each period of loading, and ∼20 h after the last period of loading, Pdimax, nonpotentiated and potentiated Pdi twitch pressure (Pditw), and the pattern of respiratory muscle recruitment during a CO2challenge were recorded. Sensation of inspiratory effort at the 4th min of the task-failure protocol was greater than at the same time in the preceding 4-min protocol. Surprisingly, potentiated Pditwand Pdimaxwere reduced after 2 min of loading and decreased further after 4 min of loading and after task failure; nonpotentiated Pditwwas reduced after 4 min of loading and after task failure. The gastric pressure contribution to tidal breathing during a CO2challenge decreased progressively in relation to duration of the preceding loading period, whereas expiratory muscle recruitment progressively increased. A rest period of ∼20 h after task failure was not sufficient to normalize these alterations in respiratory muscle recruitment or fatigue-induced changes in diaphragmatic contractility. In conclusion, while sustaining a mechanical load, the diaphragm progressively fatigued, ever before task failure, and when challenged the rib cage-to-diaphragmatic contribution to tidal breathing and recruitment of the expiratory muscles increased pari passu with duration of the preceding loading.
Image-analysis-based assessment of the effects of the “Ca2+-jump” technique on sarcomere uniformity
Authors: Slawnych M. P. , Morishita L. , Bressler B. H.
Published: December 2017

A new image analysis-based technique was used to quantitatively examine the effects of the “Ca2+-jump” activation protocol on the maintenance of fiber quality in skinned rabbit psoas muscle fiber segments. Specifically, contractions in pCa 4.6 were preceded by short-duration “preactivation” soaks in a solution in which EGTA was replaced with the low-Ca2+ buffering capacity analog hexamethylenediamine- N, N, N′, N′-tetraacetate, which facilitated rapid Ca2+equilibration within the fiber segments. Fiber quality was assessed by examining the Fourier spectra of the muscle fiber images before, during, and after activation. Segment lengths were typically below 500 μm, thus allowing the majority of the sarcomeres to be visualized in the field of view (×200 and ×400 magnification). The preactivation protocol resulted in less deterioration of fiber quality with repetitive activation. In addition, there was also a significant reduction in the time required to reach the 50% level of maximum tension, with no significant change in the maximum tension level.
Effect of nitric oxide synthase inhibition on hypercapnia-induced hypothermia and hyperventilation
Authors: Barros Renata C. H. , Branco Luiz G. S.
Published: December 2017

Hypercapnia elicits hypothermia in a number of vertebrates, but the mechanisms involved are not well understood. In the present study, we assessed the participation of the nitric oxide (NO) pathway in hypercapnia-induced hypothermia and hyperventilation by means of NO synthase inhibition by using N ω-nitro-l-arginine (l-NNA). Measurements of ventilation, body temperature, and oxygen consumption were performed in awake unrestrained rats before and afterl-NNA injection (intraperitoneally) and l-NNA injection followed by hypercapnia (5% CO2). Control animals received saline injections. l-NNA altered the breathing pattern during the control situation but not during hypercapnia. A significant ( P < 0.05) drop in body temperature was measured after bothl-NNA (40 mg/kg) and 5% inspired CO2, with a drop in oxygen consumption in the first situation but not in the second. Hypercapnia had no effect onl-NNA-induced hypothermia. The ventilatory response to hypercapnia was not changed byl-NNA, even thoughl-NNA caused a drop in body temperature. The present data indicate that the two responses elicited by hypercapnia, i.e., hyperventilation and hypothermia, do not share NO as a common mediator. However, thel-arginine-NO pathway participates, although in an unrelated way, in respiratory function and thermoregulation.
Stop-flow studies of solute uptake in rat lungs
Authors: Effros R. M. , Schapira R. , Presberg K. , Ozker K. , Jacobs E. R.
Published: December 2017

Stop-flow studies were used to characterize solute uptake in isolated rat lungs. These lungs were perfused at 8 or 34 ml/min for 10–28 s with solutions containing125I-albumin and two or more of the following diffusible indicators: [3H]mannitol, [14C]urea,3HOH,201Tl+, or86Rb+. After this loading period, flow was stopped for 10–300 s and then resumed to flush out the perfusate that remained in the pulmonary vasculature during the stop interval. Concentrations of201Tl+and86Rb+in the venous outflow decreased after the stop interval, indicating uptake from exchange vessels during the stop interval. The amount of these K+ analogs lost from the circulation during the stop interval was greater when the intervals were longer. However, losses of201Tl+at 90 s approached those at 300 s. Because extraction continued after the vasculature had been flushed, vascular levels had presumably fallen to negligible levels during the stop interval. By 90 s of stop flow the vascular volume that was cleared of201Tl+averaged 0.657 ± 0.034 (SE) ml in the experiments perfused at 8 ml/min and 0.629 ± 0.108 ml in those perfused at 34 ml/min. Increases in perfusate K+decreased the cleared volumes of201Tl+and86Rb+. Uptake of [3H]mannitol, [14C]urea, and3HOH during the stop intervals was observed only when the lungs were loaded at high flow for short intervals. Decreases in201Tl+and86Rb+concentrations in the pulmonary outflow can be used to identify the fraction of the collected samples that were within exchange vessels of the lung during the stop interval and may help determine the distribution of solute and water exchange along the pulmonary vasculature.
Differential responses to endurance training in subsarcolemmal and intermyofibrillar mitochondria
Authors: Bizeau Michael E. , Willis Wayne T. , Hazel Jeffrey R.
Published: December 2017

To examine the effect of endurance training (6 wk of treadmill running) on regional mitochondrial adaptations within skeletal muscle, subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria were isolated from trained and control rat hindlimb muscles. Mitochondrial oxygen consumption (V˙o2) was measured polarographically by using the following substrates: 1 mM pyruvate + 1 mM malate (P+M), 10 mM 2-oxoglutarate, 45 μM palmitoyl-dl-carnitine + 1 mM malate, and 10 mM glutamate. Spectrophotometric assays of cytochrome- c reductase and NAD-specific isocitrate dehydrogenase (IDH) activity were also performed. Maximal (state III) and resting (state IV)V˙o2were lower in SS than in IMF mitochondria in both trained and control groups. In SS mitochondria, training elicited significant 36 and 20% increases in state III V˙o2with P+M and glutamate, respectively. In IMF mitochondria, training resulted in a smaller (20%), yet significant, increase in state IIIV˙o2with P+M as a substrate, whereas state IIIV˙o2increased 33 and 27% with 2-oxoglutarate and palmitoyl-dl-carnitine + malate, respectively. Within groups, cytochrome- c reductase and IDH activities were lower in SS when compared with IMF mitochondria. Training increased succinate-cytochrome- c reductase in both SS (30%) and IMF mitochondria (28%). IDH activity increased 32% in the trained IMF but remained unchanged in SS mitochondria. We conclude that endurance training promotes substantial changes in protein stoichiometry and composition of both SS and IMF mitochondria.
Effect of simulated microgravity on vascular contractility
Authors: Purdy R. E. , Duckles S. P. , Krause D. N. , Rubera K. M. , Sara D.
Published: December 2017

Microgravity was simulated in Sprague-Dawley (SD) and Wistar (W) rats by using a tail harness to elevate the hindquarters, producing hindlimb unweighting (HU). After 20 days of HU treatment, blood vessels from both HU and control rats were cut into 3-mm rings and mounted in tissue baths for the measurement of isometric contraction. HU treatment decreased the contractile response to 68 mM K+ in abdominal aorta from W rats. HU treatment also decreased the contraction to 68 mM K+ in carotid arteries from both rat strains and in femoral arteries from W but not SD rats. HU treatment reduced the maximal response to norepinephrine in all arteries except the femoral from SD rats. HU treatment reduced the maximal response of jugular vein from W rats to 68 mM K+ but had no effect on that response in femoral vein from either rat strain. HU treatment also had no significant effect on the maximal response to norepinephrine in veins. These results demonstrate that HU treatment caused a nearly universal reduction of contractility in arteries, but generally had no effect in veins.
Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure
Authors: Hall Michael J. , Ando Shin-Ichi , Floras John S. , Bradley T. Douglas
Published: December 2017

To simulate the immediate hemodynamic effect of negative intrathoracic pressure during obstructive apneas in congestive heart failure (CHF), without inducing confounding factors such as hypoxia and arousals from sleep, eight awake patients performed, at random, 15-s Mueller maneuvers (MM) at target intrathoracic pressures of −20 (MM −20) and −40 cmH2O (MM −40), confirmed by esophageal pressure, and 15-s breath holds, as apneic time controls. Compared with quiet breathing, at baseline, before these interventions, the immediate effects [first 5 cardiac cycles (SD), P values refer to MM −40 compared with breath holds] of apnea, MM −20, and MM −40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 ± 1.9, 7.2 ± 3.5, and 11.3 ± 6.8 mmHg ( P < 0.01); for systolic blood pressure (SBP), 2.9 ± 2.6, −5.5 ± 3.4, and −12.1 ± 6.8 mmHg ( P < 0.01); and for stroke volume (SV) index, 0.4 ± 2.8, −4.1 ± 2.8, and −6.9 ± 2.3 ml/m2( P < 0.001), respectively. Corresponding values over the last five cardiac cycles were for LVPtm 6.4 ± 4.4, 5.4 ± 6.6, and −4.5 ± 9.1 mmHg ( P < 0.01); for SBP 6.9 ± 4.2, −8.2 ± 7.7, and −24.2 ± 6.9 mmHg ( P < 0.01); and for SV index −0.4 ± 2.1, −5.2 ± 2.8, and −9.2 ± 4.8 ml/m2( P < 0.001), respectively. Thus, in CHF patients, the initial hemodynamic response to the generation of negative intrathoracic pressure includes an immediate increase in LV afterload and an abrupt fall in SV. The magnitude of response is proportional to the intensity of the MM stimulus. By the end of a 15-s MM −40, LVPtm falls below baseline values, yet SV and SBP do not recover. Thus, when −40 cmH2O intrathoracic pressure is sustained, additional mechanisms, such as a drop in LV preload due to ventricular interaction, are engaged, further reducing SV. The net effect of MM −40 was a 33% reduction in SV index (from 27 to 18 ml/min2), and a 21% reduction in SBP (from 121 to 96 mmHg). Obstructive apneas can have adverse effects on systemic and, possibly, coronary perfusion in CHF through dynamic mechanisms that are both stimulus and time dependent.
Dynamics of lung collapse and recruitment during prolonged breathing in porcine lung injury
Authors: Neumann Peter , Berglund Jan Erik , Mondéjar Enrique Fernández , Magnusson Anders , Hedenstierna Göran
Published: December 2017

Oleic acid (OA) injection, lung lavage, and endotoxin infusion are three commonly used methods to induce experimental lung injury. The dynamics of lung collapse and recruitment in these models have not been studied, although knowledge of this is desirable to establish ventilatory techniques that keep the lungs open. We measured lung density by computed tomography during breath-holding procedures. Lung injury was induced with OA, lung lavage, or endotoxin in groups of six mechanically ventilated pigs. After a stabilization period, repetitive computed tomography scans of the same slice were obtained during prolonged expirations with and without positive end-expiratory pressure and during prolonged inspirations after 5 and 30 s of expiration. Lung collapse and recruitment occurred mainly within the first 4 s of breath-holding procedures in all three lung injury models, and some collapse and recruitment occurred even within 0.6 s. OA-injured lungs were significantly more unstable than lungs injured by bronchoalveolar lavage or endotoxin infusion. In this experimental setting, expiration times <0.6 s are required to avoid cyclic alveolar collapse during mechanical ventilation without extrinsic positive end-expiratory pressure.
Time course of active and passive liquid and solute movement in the isolated perfused rat lung model
Authors: Saldías F. J. , Comellas A. , Guerrero C. , Ridge K. M. , Rutschman D. H. , Sznajder J. I.
Published: December 2017

The isolated perfused rat lung model (IL) is used to study alveolar epithelial transport properties. Most of the previous studies have been done over a short period of time and have not used the same preparation as a control and intervention group. We evaluated whether the IL preparation could be used for a prolonged period of time (5 h) and studied the rates of active Na+ transport, lung liquid clearance, and passive movement of solutes. Active Na+ transport and lung liquid clearance were stable from 1 to 5 h. The passive movement of small solutes (Na+, mannitol) did not change significantly, and albumin movement increased slightly at the fifth hour. Total RNA isolated from IL after 5 h was intact, and the Na+-K+-ATPase activity in alveolar type II cells isolated at the end of 5-h experiments was equal to Na+-K+-ATPase function from freshly isolated alveolar type II cells. Finally, we measured the stimulatory effect of the β-adrenergic-agonist terbutaline and the inhibitory effect of the Na+-K+-ATPase-antagonist ouabain by using the same animal as a control. Accordingly, the isolated perfused lung model is functionally stable for at least 5 h, and it could be utilized to evaluate the effect of different interventions by using the same preparation.
Ventilatory effects of glial dysfunction in a rat brain stem chemoreceptor region
Authors: Erlichman Joseph S. , Li Aihua , Nattie Eugene E.
Published: December 2017

Glia are thought to be important in brain extracellular fluid ion and pH regulation, but their role in brain stem sites that sense pH and stimulate breathing is unknown. Using a diffusion pipette, we administered the glial toxin, fluorocitrate (FC; 1 mM) into one such brain stem region, the retrotrapezoid nucleus (RTN) for 45–60 min. This dose and time period were chosen so that the effects of FC would be largely reversible. Within minutes, tissue pH decreased, and respiratory output increased. Both recovered almost completely after cessation of FC administration. The response to systemic CO2 stimulation was unaffected by FC treatment compared with that following control diffusion. Anatomic analysis showed, at the center of FC administration, some small (mean diameter = 5.1 μm) cells that stained for DEAD Red, a marker for altered cell membrane permeability, and some fragmented glia (glial fibrillary acidic protein immunohistochemistry). The average RTN tissue volume that contained such DEAD Red-positive cells was 271 nl, ∼23% of the volume of one RTN region. Reversible disruption of glia in the RTN, a region known to contain central chemoreception, results in an acidic local pH and in stimulation of respiratory output.
Phosphotyrosine phosphatase and tyrosine kinase inhibition modulate airway pressure-induced lung injury
Authors: Parker James C. , Ivey Claire L. , Tucker Allan
Published: December 2017

We determined whether drugs which modulate the state of protein tyrosine phosphorylation could alter the threshold for high airway pressure-induced microvascular injury in isolated perfused rat lungs. Lungs were ventilated for successive 30-min periods with peak inflation pressures (PIP) of 7, 20, 30, and 35 cmH2O followed by measurement of the capillary filtration coefficient ( Kfc), a sensitive index of hydraulic conductance. In untreated control lungs, Kfcincreased by 1.3- and 3.3-fold relative to baseline (7 cmH2O PIP) after ventilation with 30 and 35 cmH2O PIP. However, in lungs treated with 100 μM phenylarsine oxide (a phosphotyrosine phosphatase inhibitor), Kfcincreased by 4.7- and 16.4-fold relative to baseline at these PIP values. In lungs treated with 50 μM genistein (a tyrosine kinase inhibitor), Kfcincreased significantly only at 35 cmH2O PIP, and the three groups were significantly different from each other. Thus phosphotyrosine phosphatase inhibition increased the susceptibility of rat lungs to high-PIP injury, and tyrosine kinase inhibition attenuated the injury relative to the high-PIP control lungs.
Distribution of TmDOTP5−in rat tissues: TmDOTP5−vs. CoEDTA−as markers of extracellular tissue space
Authors: Makos J. D. , Malloy C. R. , Sherry A. D.
Published: December 2017

The distribution of TmDOTP5−in rat tissue was compared with CoEDTA−, an anionic complex previously used as a marker of extracellular space. Heart, liver, muscle, blood, and urine were collected from rats after infusion of either complex and were quantitatively analyzed by atomic absorption spectroscopy. Although total TmDOTP5−in blood and tissue was consistently lower (0.88 ± 0.04; n = 6) than CoEDTA−after an identical infusion protocol (presumably because of some association of the phosphonate complex with bone), a comparison of blood and tissue contents indicated that the two anionic complexes distributed into identical extracellular spaces. Relative extracellular space in the in vivo liver, as determined by TmDOTP5−and CoEDTA−, was 0.18 ± 0.02 and 0.15 ± 0.01, respectively. The corresponding relative extracellular space values for the in vivo heart reported by the two agents were identical (0.11 ± 0.02). Experiments were also performed to evaluate the washout kinetics of TmDOTP5−from anesthesized rats. In rats given a total dose of 0.16 mmol TmDOTP5−, 81% appeared in urine by 180 min, <2% was found in all remaining soft tissue, leaving ∼18% undetected. The rate of Tm appearance in urine was fit to a standard pharmacokinetic model that included four tissue compartments: plasma, one fast equilbrating space, one slow equilibrating space, and one very slow equilibrating space (presumably bone). The best fit result suggests that the highly charged TmDOTP5−complex is cleared from plasma more rapidly than is the typical lower charged Gd-based contrast agents and that release from bone is slow compared with renal clearance.
Influence of localized auxiliary heating on hand comfort during cold exposure
Authors: Brajkovic Dragan , Ducharme Michel B. , Frim John
Published: December 2017

There is a need for a hand-heating system that will keep the hands warm during cold exposure without hampering finger dexterity. The purpose of this study was to examine the effects of torso heating on the vasodilative responses and comfort levels of cooled extremities during a 3-h exposure to −15°C air. Subjects were insulated, but their upper extremities were left exposed to the cold ambient air. The effect of heating the torso [torso-heating test (THT)] on hand comfort was compared with a control condition in which no torso heating was applied, but Arctic mitts were worn [control test (CT)]. The results indicate that mean finger temperature, mean finger blood flow, mean toe temperature, mean body skin temperature, body thermal comfort, mean finger thermal comfort, and rate of body heat storage were all significantly ( P< 0.05) higher on average ( n = 6) during THT. Mean body heat flow was significantly ( P < 0.05) lower during THT. There were no significant differences ( P ≥ 0.05) in rectal temperature between CT and THT. Mean unheated body skin temperature and mean unheated body heat flow (both of which did not include the torso area in the calculation of mean body skin temperature and mean body heat flow) were also calculated. There were no significant differences ( P ≥ 0.05) in mean unheated body skin temperature and mean unheated body heat flow between CT and THT. It is concluded that the application of heat to the torso can maintain finger and toe comfort for an extended period of time during cold exposure.
Effects of hyperthermia on contraction and dilatation of rabbit femoral arteries
Authors: Padilla Jaime , García-Villalón Angel Luis , Fernández Nuria , Monge Luis , Gómez Bernardino , Diéguez Godofredo
Published: December 2017

To analyze the effect of hyperthermia on the vascular response, the isometric response of isolated rabbit femoral artery segments was recorded at 37°C and hyperthermia (41 and 44°C). Contraction to potassium (5 × 10−3-5 × 10−2 M) was significantly greater at 41 and 44 than at 37°C and increased by inhibition of nitric oxide (NO) synthesis with N ω-nitro-l-arginine (l-NNA; 10−4 M) or endothelium removal at 37°C but not at 41 or 44°C. Norepinephrine (10−9-10−4M) produced a concentration-dependent contraction greater at 41 or 44 than at 37°C and not modified by endothelium removal orl-NNA at either temperature. Phenylephrine (10−9-10−4M) produced a contraction increased by warming to 44°C but not to 41°C. The specific α2-adrenoceptor agonist BHT-920 produced a weak contraction, reduced by the α1-adrenoceptor antagonist prazosin (10−6 M) and increased at 44°C but not at 41°C. The concentration-dependent contraction to endothelin-1 (ET-1; 10−11-10−7M) was increased by warming to 41 and 44°C and by endothelium removal or l-NNA at 37°C but not at 41 or 44°C. Response to ET-1 was reduced by endothelin ETA-receptor antagonist BQ-123 (10−5 M) and ETB-receptor antagonist BQ-788 (10−5 M). In arteries precontracted with ET-1 (10−8-3 × 10−8 M), relaxation to sodium nitroprusside (10−8-10−4M) was increased at 41 and 44°C vs. at 37°C, but that of ACh (10−8-10−4M) or adenosine (10−8-10−4M) was not different at all temperatures studied. Relaxation to ACh, but not adenosine, was reduced similarly byl-NNA at all temperatures studied. These results suggest hyperthermia in muscular arteries may inhibit production of, and increase dilatation to, NO, resulting in unchanged relaxation to ACh and increased constriction to KCl and ET-1, and may increase constriction to stimulation of α1-adrenoceptors by NO-independent mechanisms.
Limitations to exercise- and maximal insulin-stimulated muscle glucose uptake
Authors: Halseth Amy E. , Bracy Deanna P. , Wasserman David H.
Published: December 2017

The hypothesis of this investigation was that insulin and muscle contraction, by increasing the rate of skeletal muscle glucose transport, would bias control so that glucose delivery to the sarcolemma (and t tubule) and phosphorylation of glucose intracellularly would exert more influence over glucose uptake. Because of the substantial increases in blood flow (and hence glucose delivery) that accompany exercise, we predicted that glucose phosphorylation would become more rate determining during exercise. The transsarcolemmal glucose gradient (TSGG; the glucose concentration difference across the membrane) is inversely related to the degree to which glucose transport determines the rate of glucose uptake. The TSGG was determined by using isotopic methods in conscious rats during euglycemic hyperinsulinemia [Ins; 20 mU/(kg ⋅ min); n = 7], during treadmill exercise (Ex, n = 6), and in sedentary, saline-infused rats (Bas, n = 13). Rats received primed, constant intravenous infusions of trace 3- O-[3H] methyl-d-glucose and [U-14C]mannitol. Then 2-deoxy-[3H]glucose was infused for the calculation of a glucose metabolic index (Rg). At the end of experiments, rats were anesthetized, and soleus muscles were excised. Total soleus glucose concentration and the steady-state ratio of intracellular to extracellular 3- O-[3H] methyl-d-glucose (which distributes on the basis of the TSGG) were used to calculate ranges of possible glucose concentrations ([G]) at the inner and outer sarcolemmal surfaces ([G]imand [G]om, respectively). Soleus Rgwas increased in Ins and further increased in Ex. In Ins, total soleus glucose, [G]om, and the TSGG were decreased compared with Bas, while [G]imremained near 0. In Ex, total soleus glucose and [G]imwere increased compared with Bas, and there was not a decrease in [G]omas was observed in Ins. In addition, accumulation of intracellular free 2-deoxy-[3H]glucose occurred in soleus in both Ex and Ins. Taken together, these data indicate that, in Ex, glucose phosphorylation becomes an important limitation to soleus glucose uptake. In Ins, both glucose delivery and glucose phosphorylation influence the rate of soleus glucose uptake more than under basal conditions.
Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs
Authors: Pearse David B. , Wagner Elizabeth M. , Permutt Solbert
Published: December 2017

Ventilation during ischemia attenuates ischemia-reperfusion lung injury, but the mechanism is unknown. Increasing tissue cyclic nucleotide levels has been shown to attenuate lung ischemia-reperfusion injury. We hypothesized that ventilation prevented increased pulmonary vascular permeability during ischemia by increasing lung cyclic nucleotide concentrations. To test this hypothesis, we measured vascular permeability and cGMP and cAMP concentrations in ischemic (75 min) sheep lungs that were ventilated (12 ml/kg tidal volume) or statically inflated with the same positive end-expiratory pressure (5 Torr). The reflection coefficient for albumin (ςalb) was 0.54 ± 0.07 and 0.74 ± 0.02 (SE) in nonventilated and ventilated lungs, respectively ( n = 5, P < 0.05). Filtration coefficients and capillary blood gas tensions were not different. The effect of ventilation was not mediated by cyclic compression of alveolar capillaries, because negative-pressure ventilation ( n = 4) also was protective (ςalb= 0.78 ± 0.09). The final cGMP concentration was less in nonventilated than in ventilated lungs (0.02 ± 0.02 and 0.49 ± 0.18 nmol/g blood-free dry wt, respectively, n = 5, P < 0.05). cAMP concentrations were not different between groups or over time. Sodium nitroprusside increased cGMP (1.97 ± 0.35 nmol/g blood-free dry wt) and ςalb(0.81 ± 0.09) in nonventilated lungs ( n = 5, P < 0.05). Isoproterenol increased cAMP in nonventilated lungs ( n = 4, P < 0.05) but had no effect on ςalb. The nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester had no effect on lung cGMP ( n = 9) or ςalb( n = 16) in ventilated lungs but did increase pulmonary vascular resistance threefold ( P < 0.05) in perfused sheep lungs ( n = 3). These results suggest that ventilation during ischemia prevented an increase in pulmonary vascular protein permeability, possibly through maintenance of lung cGMP by a nitric oxide-independent mechanism.
Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans
Authors: Ikarugi Hideo , Taka Tomomi , Nakajima Shoko , Noguchi Takanori , Watanabe Sadahiro , Sasaki Yasuto , Haga Shukoh , Ueda Takashi , Seki Junji , Yamamoto Junichiro
Published: December 2017

The effects of exercise and catecholamines on platelet reactivity or coagulation and fibrinolysis appear to be inconsistent. This may be partly due to the methods employed in previous studies. In the present study, we investigated the effects of acute aerobic exercise and catecholamines on the thrombotic status by a novel in vitro method, shear-induced hemostatic plug formation (hemostatometry), using nonanticoagulated (native) blood. Aerobic exercise (60% maximal O2consumption) was performed by healthy male volunteers for 20 min, and the effect on platelet reactivity and coagulation was assessed by performing hemostatometry before and immediately after exercise. Exercise significantly increased shear-induced platelet reactivity, coagulation, and catecholamine levels. The effect of catecholamines on platelet reactivity and coagulation was assessed in vitro by adding catecholamines to blood collected in the resting state. The main findings of the present study are that elevation of circulating norepinephrine at levels that are attained during exercise causes platelet hyperreactivity and a platelet-mediated enhanced coagulation. This may be a mechanism of an association of aerobic exercise with thrombotic risk.
Alveolar epithelial fluid clearance persists in the presence of moderate left atrial hypertension in sheep
Authors: Campbell Andre R. , Folkesson Hans G. , Berthiaume Yves , Gutkowska Jolanta , Suzuki Sotashi , Matthay Michael A. ,   (With the Technical Assistance of Oscar Osorio)
Published: December 2017

The effect of moderate left atrial (LA) hypertension on alveolar liquid clearance (ALC) was investigated in anesthetized, ventilated sheep, surgically prepared to measure lung lymph flow as well as hemodynamics. To simulate alveolar edema, 3–4 ml/kg of isosmolar 5% albumin in Ringer lactate were instilled into each lower lobe, and ALC was measured. After 4 h of LA hypertension (24 cmH2O), ALC was similar to that in control sheep (31 ± 3% with LA hypertension vs. 34 ± 10% with normal LA pressure). Because plasma epinephrine levels were moderately elevated in the presence of LA hypertension, ALC was then studied in the presence of LA hypertension following bilateral adrenalectomy. Without endogenous release of epinephrine, ALC was significantly reduced compared with normal LA pressure (20 ± 7% compared with 34 ± 10%, P < 0.05). Thus endogenous catecholamines caused a submaximal stimulation of ALC in the presence of LA hypertension. Exogenous administration of aerosolized β2-agonist therapy with salmeterol increased ALC in the presence of normal LA pressure but had no stimulatory effect in the presence of moderate LA hypertension. Therefore, we tested the hypothesis that endogenous release of atrial natriuretic factor (ANF) may downregulate alveolar epithelial Na+ and fluid transport in the presence of LA hypertension. There was a modest twofold increase in plasma ANF levels after LA hypertension. Additional in vitro studies demonstrated that, in the presence of β2-agonist stimulation, ANF decreased Na+ pump activity (Na+-K+-ATPase) in isolated rat alveolar epithelial type II cells. ANF may downregulate vectorial Na+ and fluid transport stimulated by endogenous or exogenous β-adrenergic agonist stimulation in the presence of LA hypertension. In summary, ALC continues even in the presence of moderate LA hypertension. Aerosolized β2-adrenergic agonist therapy significantly increased ALC, but only when LA pressure was normal.
Modeling diffusion limitation of gas exchange in lungs containing perfluorocarbon
Authors: Mates vanLöbensels Elisabeth , Anderson Joseph C. , Hildebrandt Jacob , Hlastala Michael P.
Published: December 2017

We reported changes in alveolar-arterial Po 2 gradient, ventilation-perfusion heterogeneity, and arterial-alveolar Pco 2 gradient during partial liquid ventilation (PLV) in healthy piglets (E. A. Mates, P. Tarczy-Hornoch, J. Hildebrandt, J. C. Jackson, and M. P. Hlastala. In: Oxygen Transport to Tissue XVII, edited by C. Ince. New York: Plenum, 1996, vol. 388, p. 585–597). Here we develop two mathematical models to predict transient and steady-state (SS) gas exchange conditions during PLV and to estimate the contribution of diffusion limitation to SS arterial-alveolar differences. In the simplest model, perfluorocarbon is represented as a uniform flat stirred layer and, in a more complex model, as an unstirred spherical layer in a ventilated terminal alveolar sac. Time-dependent solutions of both models show that SS is established for various inert and respiratory gases within 5–150 s. In fluid-filled unventilated terminal units, all times to SS increased sometimes by hours, e.g., SF6 exceeded 4 h. SS solutions for the ventilated spherical model predicted minor end-capillary disequilibrium of inert gases and significant disequilibrium of respiratory gases, which could explain a large portion of the arterial-alveolar Pco 2 gradient measured during PLV (14). We conclude that, during PLV, diffusion gradients for gases are generally small, except for CO2.
Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men
Authors: Campbell Wayne W. , Joseph Lyndon J. O. , Davey Stephanie L. , Cyr-Campbell Deanna , Anderson Richard A. , Evans William J.
Published: December 2017

The effects of chromium picolinate (CrPic) supplementation and resistance training (RT) on skeletal muscle size, strength, and power and whole body composition were examined in 18 men (age range 56–69 yr). The men were randomly assigned (double-blind) to groups ( n = 9) that consumed either 17.8 μmol Cr/day (924 μg Cr/day) as CrPic or a low-Cr placebo for 12 wk while participating twice weekly in a high-intensity RT program. CrPic increased urinary Cr excretion ∼50-fold ( P < 0.001). RT-induced increases in muscle strength ( P < 0.001) were not enhanced by CrPic. Arm-pull muscle power increased with RT at 20% ( P = 0.016) but not at 40, 60, or 80% of the one repetition maximum, independent of CrPic. Knee-extension muscle power increased with RT at 20, 40, and 60% ( P < 0.001) but not at 80% of one repetition maximum, and the placebo group gained more muscle power than did the CrPic group (RT by supplemental interaction, P < 0.05). Fat-free mass ( P < 0.001), whole body muscle mass ( P < 0.001), and vastus lateralis type II fiber area ( P < 0.05) increased with RT in these body-weight-stable men, independent of CrPic. In conclusion, high-dose CrPic supplementation did not enhance muscle size, strength, or power development or lean body mass accretion in older men during a RT program, which had significant, independent effects on these measurements.
Analytic calculation of physiological acid-base parameters in plasma
Authors: Wooten E. Wrenn
Published: December 2017

Analytic expressions for plasma total titratable base, base excess (ΔCB), strong-ion difference, change in strong-ion difference (ΔSID), change in Van Slyke standard bicarbonate (ΔVSSB), anion gap, and change in anion gap are derived as a function of pH, total buffer ion concentration, and conditional molar equilibrium constants. The behavior of these various parameters under respiratory and metabolic acid-base disturbances for constant and variable buffer ion concentrations is considered. For constant noncarbonate buffer concentrations, ΔSID = ΔCB= ΔVSSB, whereas these equalities no longer hold under changes in noncarbonate buffer concentration. The equivalence is restored if the reference state is changed to include the new buffer concentrations.
Influence of complete spinal cord injury on skeletal muscle within 6 mo of injury
Authors: Castro Michael J. , Apple David F. , Staron Robert S. , Campos Gerson E. R. , Dudley Gary A.
Published: December 2017

This study examined the influence of spinal cord injury (SCI) on affected skeletal muscle. The right vastus lateralis muscle was biopsied in 12 patients as soon as they were clinically stable (average 6 wk after SCI), and 11 and 24 wk after injury. Samples were also taken from nine able-bodied controls at two time points 18 wk apart. Surface electrical stimulation (ES) was applied to the left quadriceps femoris muscle to assess fatigue at these same time intervals. Biopsies were analyzed for fiber type percent and cross-sectional area (CSA), fiber type-specific succinic dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (GPDH) activities, and myosin heavy chain percent. Controls showed no change in any variable over time. Patients showed 27–56% atrophy ( P = 0.000) of type I, IIa, and IIax+IIx fibers from 6 to 24 wk after injury, resulting in fiber CSA approximately one-third that of controls. Their fiber type specific SDH and GPDH activities increased ( P ≤ 0.001) from 32 to 90% over the 18 wk, thereby approaching or surpassing control values. The relative CSA of type I fibers and percentage of myosin heavy chain type I did not change. There was apparent conversion among type II fiber subtypes; type IIa decreased and type IIax+IIx increased ( P ≤ 0.012). Force loss during ES did not change over time for either group but was greater ( P = 0.000) for SCI patients than for controls overall (27 vs. 9%). The results indicate that vastus lateralis muscle shows marked fiber atrophy, no change in the proportion of type I fibers, and a relative independence of metabolic enzyme levels from activation during the first 24 wk after clinically complete SCI. Over this time, quadriceps femoris muscle showed moderately greater force loss during ES in patients than in controls. It is suggested that the predominant response of mixed human skeletal muscle within 6 mo of SCI is loss of contractile protein. Therapeutic interventions could take advantage of this to increase muscle mass.
Elastic moduli of excised constricted rat lungs
Authors: Salerno Francesco G. , Ludwig Mara S.
Published: December 2017

When airways constrict, the surrounding parenchyma undergoes stretch and distortion. Because of the mechanical interdependence between airways and parenchyma, the material properties of the parenchyma are important factors that modulate the degree of bronchoconstriction. The purpose of this study was to investigate the effect of changes in transpulmonary pressure (Ptp) and induced constriction on parenchymal bulk ( k) and shear (μ) moduli. In excised rat lungs, pressure was measured at the airway opening, and pressure-volume curves were obtained by imposing step decreases in volume with a calibrated syringe from total lung inflation. Calculation was made of k during small-volume oscillations (1 Hz). Absolute lung volume at 0 cmH2O Ptp was obtained by saline displacement. To calculate μ, a lung-indentation test was performed. The lung surface was deformed with a cylindrical punch (diameter = 0.45 cm) in 0.25-mm increments, and the force required to effect this displacement was measured by a weight balance. Measurements of k and μ were obtained at 4 and 10 cmH2O Ptp, and again at 4 cmH2O Ptp, after delivery of methacholine aerosol (100 mg/ml) into the trachea. Values of k and μ in rat lungs were similar to those reported in other species. In addition, k and μ were dependent on Ptp. After induced constriction, k and μ increased significantly. That k and μ can increase after induced constriction has important implications vis a vis the factors modulating airway narrowing.
Convertase activity in alveolar surfactant and lamellar bodies in fetal, newborn, and adult rabbits
Authors: Oulton Margaret , Edwards Elizabeth , Handa Kiren
Published: December 2017

Conversion of heavy-aggregate alveolar surfactant (H) to a light-aggregate, nonsurface active form (L) is believed to involve the activity of an enzyme, namely, convertase. This conversion can be reproduced in vitro by the surface-area cycling technique. The purpose of the present study was to use this technique to investigate the developmental aspects of convertase activity in fetal, newborn, and adult rabbits. H was isolated from alveolar lavage from term [31-day gestation (31d)] fetal rabbit pups, 1-, 4-, and 7-day-old newborns, and adults, and the percent conversion to L was determined. To assess lamellar bodies (LB) as a potential source of activity in this species, these structures were isolated from lung tissue of 27-day-gestation (27d) and 31d fetuses, 1-, 4-, and 7-day-old newborns, and adults and were cycled the same as for H. LB contained considerable activity at each developmental stage i.e., ∼82% of a 27d LB preparation converted to L after 3 h of cycling. In the adult, this value was 78%. Very little conversion of H was obtained from fetal lung (i.e., <20% of the 31d fetal preparation converted to L), but, by postnatal day 4, this value was greatly increased (i.e., >80% conversion) and stayed elevated to adulthood. The activity for each H and LB fraction was temperature and concentration dependent and diminished with storage at 4°C. These data suggest the LB as the source of convertase activity in the rabbit and demonstrate dramatic developmental changes in this activity after release of the LB contents to the alveoli.
Bed rest increases the amount of mismatched fibers in human skeletal muscle
Authors: Andersen J. L. , Gruschy-Knudsen T. , Sandri C. , Larsson L. , Schiaffino S.
Published: December 2017

The effects of a 37-day period of bed rest on myosin heavy chain (MHC) expression on both mRNA and protein level in human skeletal muscle fibers were studied. Muscle biopsies from vastus lateralis muscle were obtained from seven healthy young male subjects before and after the bed-rest period. Combined in situ hybridization, immunocytochemistry, and ATPase histochemistry analysis of serial sections of the muscle biopsies demonstrated that fibers showing a mismatch between MHC isoforms at the mRNA and protein level increased significantly after the bed-rest period, suggesting an increase in the amount of muscle fibers in a transitional state. Accordingly, fibers showing a match in expression of MHC-1 and of MHC-2A at the mRNA and protein level decreased, whereas fibers showing a match between MHC-2X mRNA and protein increased after bed rest. Overall, there was an increase in fibers in a transitional state from phenotypic type 1 → 2A and 2A → 2X. Furthermore, a number of fibers with unusual MHC mRNA and isoprotein combinations were observed after bed rest (e.g., type 1 fibers with only mRNA for 2X and type 1 fibers negative for mRNA for MHC-β/slow, 2A, and 2X). In contrast, no changes were revealed after an examination at the protein level alone. These data suggest that the reduced load-bearing activity imposed on the skeletal muscles through bed rest will alter MHC gene expression, resulting in combinations of mRNA and MHC isoforms normally not (or only rarely) observed in muscles subjected to load-bearing activity. On the other hand, the present data also show that 37 days of bed rest are not a sufficient stimulus to induce a similar change at the protein level, as was observed at the gene level.
Respiratory gas-exchange ratios during graded exercise in fed and fasted trained and untrained men
Authors: Bergman Bryan C. , Brooks George A.
Published: December 2017

We evaluated the hypotheses that endurance training increases relative lipid oxidation over a wide range of relative exercise intensities in fed and fasted states and that carbohydrate nutrition causes carbohydrate-derived fuels to predominate as energy sources during exercise. Pulmonary respiratory gas-exchange ratios [(RER) = CO2production/O2consumption (V˙o2)] were determined during four relative, graded exercise intensities in both fed and fasted states. Seven untrained (UT) men and seven category 2 and 3 US Cycling Federation cyclists (T) exercised in the morning in random order, with target power outputs of 20 and 40% peakV˙o2(V˙o2 peak) for 2 h, 60% V˙o2 peakfor 1.5 h, and 80%V˙o2 peakfor a minimum of 30 min after either a 12-h overnight fast or 3 h after a standardized breakfast. Actual metabolic responses were 22 ± 0.33, 40 ± 0.31, 59 ± 0.32, and 75 ± 0.39%V˙o2 peak. T subjects showed significantly ( P < 0.05) decreased RER compared with UT subjects at absolute workloads when fed and fasted. Fasting significantly decreased RER values compared with the fed state at 22, 40, and 59%V˙o2 peakin T and at 40 and 59%V˙o2 peakin UT subjects. Training decreased ( P < 0.05) mean RER values compared with UT subjects at 22%V˙o2 peakwhen they fasted, and at 40%V˙o2 peakwhen fed or fasted, but not at higher relative exercise intensities in either nutritional state. Our results support the hypothesis that endurance training enhances lipid oxidation in men after a 12-h overnight fast at low relative exercise intensities (22 and 40%V˙o2 peak). However, a training effect on RER was not apparent at high relative exercise intensities (59 and 75%V˙o2 peak). Because most athletes train and compete at exercise intensities >40% maximalV˙o2, they will not oxidize a greater proportion of lipids compared with untrained subjects, regardless of nutritional state.
Cardiovascular and hemorheological effects of three modified human hemoglobin solutions in hemodiluted rabbits
Authors: Caron Alexis , Menu Patrick , Faivre-Fiorina Beatrice , Labrude Pierre , Alayash Abdu I. , Vigneron Claude
Published: December 2017

The cardiovascular effects of human albumin (Alb) and three human hemoglobin (Hb) solutions, dextran-benzene-tetracarboxylate Hb, αα-crosslinked Hb, and o-raffinose-polymerized Hb were compared in anesthetized rabbits undergoing acute isovolemic hemodilution with Hct reduction from 41.4 ± 2.7 to 28.8 ± 1.6%. The impact of the vasoconstricting properties of Hb was examined by measuring heart rate (HR), mean arterial pressure (MAP), abdominal aortic, and femoral arterial blood flow, vascular resistance (VR), and aortic distension during the first 3 h after hemodilution. The impact of the hemorheological parameters was assessed by measurements of hemodiluted blood viscosity. In contrast to Alb, the Hb solutions elicited an immediate increase in MAP (20–38%). The effects of Alb and Hb solutions on HR, as well as on aortic and femoral arterial blood flow, were similar. VR decreased with Alb (20–28%) and increased with all three Hb solutions (30–90%), but the MAP and VR rising trends were different with each Hb solution. Aortic distension decreased in Hb groups compared with the Alb group for the first 60 min. The viscosity of hemodiluted blood was similar for all groups at high shear rates but was dependent on the viscosity of the solutions at low shear rates. We conclude that the vasoconstriction elicited by the Hb solutions overrides the vasodilation associated with viscosity changes due to hemodilution and would be the major factor responsible to the cardiovascular changes.