bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats
Authors: Wood John G. , Mattioli Leone F. , Gonzalez Norberto C.
Published: December 2017

Although the effects of ischemia-reperfusion have received considerable attention, few studies have directly evaluated the microcirculatory response to systemic hypoxia. The overall objective of this study was to assess the effect of environmental hypoxia on adhesive interactions of circulating leukocytes with rat mesenteric venules by using intravital microscopy. Experiments were designed to 1) characterize the adhesive interactions of circulating leukocytes to venules during acute hypoxia produced by a reduction in inspired[Formula: see text], 2) evaluate the role of nitric oxide in these adhesive interactions, 3) determine whether the effect of hypoxia on leukocyte adhesive interactions differs between acclimatized and nonacclimatized rats, and 4) assess whether compensatory changes in nitric oxide formation contribute to this difference. The results showed that acute hypoxia promotes leukocyte-endothelial adherence in mesenteric venules of nonacclimatized rats. The mechanism of this response is consistent with depletion of nitric oxide within the microcirculation. In contrast, no leukocyte-endothelial adherence occurred during hypoxia in rats acclimatized to hypobaric hypoxia. The results are consistent with increased nitric oxide formation due to expression of inducible nitric oxide synthase during the acclimatization period. Further studies are needed to establish the cause of nitric oxide depletion during acute hypoxia as well as to define the compensatory responses that attenuate hypoxia-induced leukocyte-endothelial adherence in the microvasculature of acclimatized rats.
Effects of nasal CPAP therapy on respiratory and spontaneous arousals in infants with OSA
Authors: McNamara Frances , Sullivan Colin E.
Published: December 2017

Obstructive sleep apnea (OSA) in infants has been shown to resolve frequently without a cortical arousal. It is unknown whether infants do not require arousal to terminate apneas or whether this is a consequence of the OSA. We studied the apnea and arousal patterns of eight infants with OSA before and after treatment with nasal continuous positive airway pressure (CPAP). These infants were age matched to eight untreated infants with OSA and eight normal infants. Polysomnographic studies were performed on each infant. We found that the majority of central and obstructive apneas were terminated without arousal in all OSA infants. After several weeks of nasal CPAP treatment, the proportion of apneas terminating with an arousal during rapid-eye-movement sleep increased in treated infants compared with untreated infants. Spontaneous arousals during rapid-eye-movement sleep were reduced in all OSA infants; however, during CPAP treatment, the spontaneous arousals increased to the normal control level. We conclude that OSA in infants possibly depresses the arousal response and treatment of these infants with nasal CPAP partially reverses this depression.
Role of protein kinase G in nitric oxide- and cGMP-induced relaxation of newborn ovine pulmonary veins
Authors: Gao Yuansheng , Dhanakoti Srinivas , Tolsa Jean-Francois , Raj J. Usha
Published: December 2017

In a variety of systemic blood vessels, protein kinase G (PKG) plays a critical role in mediating relaxation induced by agents that elevate cGMP, such as nitric oxide. The role of PKG in nitric oxide- and cGMP-induced relaxation is less certain in the pulmonary circulation. In the present study, we examined the effects of inhibitors of PKG on the responses of isolated fourth-generation pulmonary veins of newborn lambs (10 ± 1 days of age) to nitric oxide and cGMP. In vessels preconstricted with endothelin-1, nitric oxide and 8-bromo-cGMP (a cell-membrane-permeable cGMP analog) induced concentration-dependent relaxation. The relaxation was significantly attenuated by β-phenyl-1, N2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothionate (Rp-8-Br-PET-cGMPS; a PKG inhibitor) and N-[2-(methylamino)ethyl]5-isoquinolinesulfonamide [H-8; an inhibitor of PKG and protein kinase A (PKA)] but was not affected by KT-5720 (a PKA inhibitor). Biochemical study showed that PKG activity in newborn ovine pulmonary veins was inhibited by 8-Br-PET-cGMPS and H-8 but not by KT-5720. PKA activity was not affected by 8-Br-PET-cGMPS but was inhibited by H-8 and KT-5720. These results suggest that PKG is involved in relaxation of pulmonary veins of newborn lambs induced by nitric oxide and cGMP.
Growth hormone restores aged diaphragm myosin composition and performance after chronic undernutrition
Authors: Ameredes Bill T. , Watchko Jon F. , Daood Monica J. , Rosas J. Fernando , Donahoe Michael P. , Rogers Robert M.
Published: December 2017

The effects of growth hormone (GH) on diaphragm muscle myosin heavy chain (MHC) composition and mechanical performance were investigated in Fischer 344 male rats aged to senescence (24.5 mo of age). Chronic undernutrition (UN), refeeding (RF), and RF+GH were compared with ad libitum feeding by using a model of UN that produced a 50% decrease in body weight over a 12-mo period. The effect of aging was assessed by comparing MHC composition of ad libitum-fed rats at 12 and 24.5 mo of age. At senescence, significant decreases in slow type I (−23%) and fast type IIA (−31%) MHC had occurred with aging. Conversely, UN over this aging period increased types I (32–73%) and IIA (22–23%) MHC and decreased fast types IIB (32–54%) and IIX (30–31%) MHC. RF and RF+GH reversed these shifts back toward control values. At senescence, maximal specific force, maximal velocity, and specific power capacity were not different across treatment groups. During repetitive isotonic contraction trials, the diaphragms of UN rats maintained power production over time (54% of initial power at 60 s), whereas the power production of diaphragms of ad libitum-fed rats fell to 0% ( P < 0.05). In comparison with UN rats, the diaphragms of RF and RF+GH rats produced 23 (not significant) and 11% ( P < 0.05) of initial power, respectively, suggesting that RF+GH treatment restored performance characteristics after UN. We conclude that RF+GH can reverse alterations in MHC composition and mechanical performance produced by chronic UN in the aged rat diaphragm.
Metabolic response in type I and type II muscle fibers during a 30-s cycle sprint in men and women
Authors: Esbjörnsson-Liljedahl Mona , Sundberg Carl Johan , Norman Barbara , Jansson Eva
Published: December 2017

The acute metabolic response to sprint exercise was studied in 20 male and 19 female students. We hypothesized that the reduction of muscle glycogen content during sprint exercise would be smaller in women than in men and that a possible gender difference in glycogen reduction would be higher in type II than in type I fibers. The exercise-induced increase in blood lactate concentration was 22% smaller in women than in men. A considerable reduction of ATP (50%), phosphocreatine (83%), and glycogen (35%) was found in type II muscle fibers, and it did not differ between the genders. A smaller reduction of ATP (17%) and phosphocreatine (78%) was found in type I fibers, and it did not differ between the genders. However, the exercise-induced reduction in glycogen content in type I fibers was 50% smaller in women than in men. The hypothesis was indeed partly confirmed: the exercise-induced glycogen reduction was attenuated in women compared with men, but the gender difference was in type I rather than in type II fibers. Fiber-type-specific and gender-related differences in the metabolic response to sprint exercise might have implications for the design of training programs for men and women.
The adenosine A1-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements
Authors: Watson C. S. , White S. E. , Homan J. H. , Fraher L. , Brien J. F. , Bocking A. D.
Published: December 2017

Administration of either ethanol or adenosine inhibits fetal breathing movements (FBM), eye movements, and low-voltage electrocortical activity (LV ECoG). The concentration of adenosine in ovine fetal cerebral extracellular fluid increases during ethanol-induced inhibition of FBM. The purpose of this study was to determine the effect of a selective adenosine A1-receptor antagonist, 8-cyclopentyltheophylline (8-CPT) on the incidence of FBM during ethanol exposure. After a 2-h control period, seven pregnant ewes received a 1-h intravenous infusion of ethanol (1 g/kg maternal body wt), followed 1 h later by a 2-h fetal intravenous infusion of either 8-CPT (3.78 ± 0.08 μg ⋅ kg−1⋅ min−1) or vehicle. Ethanol reduced the incidence of FBM from 44.0 ± 10.4 to 2.7 ± 1.3% ( P < 0.05) and 51.2 ± 7.6 to 11.9 ± 5.0% ( P < 0.05) in fetuses destined to receive 8-CPT or vehicle, respectively. In the vehicle group, FBM remained suppressed for 7 h. In contrast, during the first hour of 8-CPT infusion, FBM returned to baseline (31 ± 11%) and was not different from control throughout the rest of the experiment. Ethanol also decreased the incidence of both low-voltage electrocortical activity and eye movements, but there were no differences in the incidences of these behavioral parameters between the 8-CPT and vehicle groups throughout the experiment. These data are consistent with the hypothesis that adenosine, acting via A1receptors, may play a role in the mechanism of ethanol-induced inhibition of FBM.
Muscle pump and central command during recovery from exercise in humans
Authors: Carter Robert , Watenpaugh Donald E. , Wasmund Wendy L. , Wasmund Stephen L. , Smith Michael L.
Published: December 2017

We sought to determine the relative contributions of cessation of skeletal muscle pumping and withdrawal of central command to the rapid decrease in arterial pressure during recovery from exercise. Twelve healthy volunteers underwent three exercise sessions, each consisting of a warm-up, 3 min of cycling at 60% of maximal heart rate, and 5 min of one of the following recovery modes: seated (inactive), loadless pedaling (active), and passive cycling. Mean arterial pressure (MAP), cardiac output, thoracic impedance, and heart rate were measured. When measured 15 s after exercise, MAP decreased less ( P < 0.05) during the active (−3 ± 1 mmHg) and passive (−6 ± 1 mmHg) recovery modes than during inactive (−18 ± 2 mmHg) recovery. These differences in MAP persisted for the first 4 min of recovery from exercise. Significant maintenance of central blood volume (thoracic impedance), stroke volume, and cardiac output paralleled the maintenance of MAP during active and passive conditions during 5 min of recovery. These data indicate that engaging the skeletal muscle pump by loadless or passive pedaling helps maintain MAP during recovery from submaximal exercise. The lack of differences between loadless and passive pedaling suggests that cessation of central command is not as important.
A model of extravascular bubble evolution: effect of changes in breathing gas composition
Authors: Himm J. F. , Homer L. D.
Published: December 2017

Observations of bubble evolution in rats after decompression from air dives (O. Hyldegaard and J. Madsen. Undersea Biomed. Res. 16: 185–193, 1989; O. Hyldegaard and J. Madsen. Undersea Hyperbaric Med. 21: 413–424, 1994; O. Hyldegaard, M. Moller, and J. Madsen. Undersea Biomed. Res. 18: 361–371, 1991) suggest that bubbles may resolve more safely when the breathing gas is a heliox mixture than when it is pure O2. This is due to a transient period of bubble growth seen during switches to O2breathing. In an attempt to understand these experimental results, we have developed a multigas-multipressure mathematical model of bubble evolution, which consists of a bubble in a well-stirred liquid. The liquid exchanges gas with the bubble via diffusion, and the exchange between liquid and blood is described by a single-exponential time constant for each inert gas. The model indicates that bubbles resolve most rapidly in spinal tissue, in adipose tissue, and in aqueous tissues when the breathing gas is switched to O2after surfacing. In addition, the model suggests that switching to heliox breathing may prolong the existence of the bubble relative to breathing air for bubbles in spinal and adipose tissues. Some possible explanations for the discrepancy between model and experiment are discussed.
Measurement of limb venous compliance in humans: technical considerations and physiological findings
Authors: Halliwill John R. , Minson Christopher T. , Joyner Michael J.
Published: December 2017

We conducted a series of studies to develop and test a rapid, noninvasive method to measure limb venous compliance in humans. First, we measured forearm volume (mercury-in-Silastic strain gauges) and antecubital intravenous pressure during inflation of a venous collecting cuff around the upper arm. Intravenous pressure fit the regression line, −0.3 ± 0.7 + 0.95 ± 0.02 ⋅ cuff pressure ( r = 0.99 ± 0.00), indicating cuff pressure is a good index of intravenous pressure. In subsequent studies, we measured forearm and calf venous compliance by inflating the venous collecting cuff to 60 mmHg for 4 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg, using cuff pressure as an estimate of venous pressure. This method produced pressure-volume curves fitting the quadratic regression (Δlimb volume) = β0 + β1 ⋅ (cuff pressure) + β2 ⋅ (cuff pressure)2, where Δ is change. Curves generated with this method were reproducible from day to day (coefficient of variation: 4.9%). In 11 subjects we measured venous compliance via this method under two conditions: with and without (in random order) superimposed sympathetic activation (ischemic handgrip exercise to fatigue followed by postexercise ischemia). Calf and forearm compliance did not differ between control and sympathetic activation ( P > 0.05); however, the data suggest that unstressed volume was reduced by the maneuver. These studies demonstrate that venous pressure-volume curves can be generated both rapidly and noninvasively with this technique. Furthermore, the results suggest that although whole-limb venous compliance is under negligible sympathetic control in humans, unstressed volume can be affected by the sympathetic nervous system.
Low glycogen and branched-chain amino acid ingestion do not impair anaplerosis during exercise in humans
Authors: Gibala Martin J. , Lozej Marco , Tarnopolsky Mark A. , McLean Cyndy , Graham Terry E.
Published: December 2017

We examined the hypothesis that increasing the rate of branched-chain amino acid (BCAA) oxidation, during conditions of low glycogen availability, reduces the level of muscle tricarboxylic acid cycle intermediates (TCAI) by placing a carbon “drain” on the cycle at the level of 2-oxoglutarate. Six men cycled at ∼70% of maximal oxygen uptake for 15 min under two conditions: 1) low preexercise muscle glycogen (placebo) and 2) low glycogen combined with BCAA ingestion. We have previously shown that BCAA ingestion increased the activity of branched-chain oxoacid dehydrogenase, the rate-limiting enzyme for BCAA oxidation in muscle, compared with low glycogen alone [M. L. Jackman, M. J. Gibala, E. Hultman, and T. E. Graham. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E233–E238, 1997]. Muscle glycogen concentration was 185 ± 22 and 206 ± 22 mmol/kg dry wt at rest for the placebo and BCAA-supplemented trials, respectively, and decreased to 109 ± 18 and 96 ± 10 mmol/kg dry wt after exercise. The net increase in the total concentration of six measured TCAI (∼95% of TCAI pool) during exercise was not different between trials (3.97 ± 0.34 vs. 3.88 ± 0.34 mmol/kg dry wt for the placebo and BCAA trials, respectively). Muscle 2-oxoglutarate concentration decreased from ∼0.05 at rest to ∼0.03 mmol/kg dry wt after exercise in both trials. The magnitude of TCAI pool expansion in both trials was similar to that seen previously in subjects who performed an identical exercise bout after a normal mixed diet [M. J. Gibala, M. A. Tarnopolsky, and T. E. Graham. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E239–E244, 1997]. These data suggest that increasing the rate of BCAA oxidation has no measurable effect on muscle TCAI during exercise with low glycogen in humans. Moreover, it appears that low resting glycogen per se does not impair the increase in TCAI during moderate exercise.
Influence of female reproductive hormones on local thermal control of skin blood flow
Authors: Charkoudian Nisha , Stephens Dan P. , Pirkle Kenna C. , Kosiba Wojciech A. , Johnson John M.
Published: December 2017

Progesterone and estrogen modify thermoregulatory control such that, when both steroids are elevated, body temperature increases and the reflex thermoregulatory control of cutaneous vasodilation is shifted to higher internal temperatures. We hypothesized that the influence of these hormones would also include effects on local thermal control of skin blood flow. Experiments were conducted in women in high-hormone (HH) and low-hormone (LH) phases of oral contraceptive use. Skin blood flow was measured by laser-Doppler flowmetry, and local temperature (Tloc) was controlled over 12 cm2 around the sites of blood flow measurement. Tloc was held at 32°C for 10–15 min and was then decreased at one site from 32 to 20°C in a ramp over 20 min. Next, Tloc was increased from 32 to 42°C in a ramp over 15 min at a separate site. Finally, Tloc at both sites was held at 42°C for 30 min to elicit maximum vasodilation; data for cutaneous vascular conductance (CVC) are expressed relative to that maximum. Whole body skin temperature (Tsk) was held at 34°C throughout each study to minimize reflex effects from differences in Tsk between experiments. Baseline CVC did not differ between phases [8.18 ± 1.38 (LH) vs. 8.41 ± 1.31% of maximum (HH); P > 0.05]. The vasodilator response to local warming was augmented in HH ( P < 0.05, ANOVA). For example, at Tloc of 40–42°C, CVC averaged 76.41 ± 3.08% of maximum in HH and 67.71 ± 4.43% of maximum in LH ( P < 0.01 LH vs. HH). The vasoconstrictor response to local cooling was unaffected by phase ( P > 0.05). These findings indicate that modifications in cutaneous vascular control by female steroid hormones include enhancement of the vasodilator response to local warming and are consistent with reports of the influence of estrogen to enhance nitric oxide-dependent vasodilator responses.
Myonuclear domain and myosin phenotype in human soleus after bed rest with or without loading
Authors: Ohira Y. , Yoshinaga T. , Ohara M. , Nonaka I. , Yoshioka T. , Yamashita-Goto K. , Shenkman B. S. , Kozlovskaya I. B. , Roy R. R. , Edgerton V. R.
Published: December 2017

After 2 or 4 mo of bed rest (6° head-down tilt) and 1 mo of ambulation, there was a tendency toward a higher percentage of fibers expressing fast myosin heavy chain (MHC) isoforms and a de novo appearance of fibers coexpressing type I+IIa+IIx and IIa+IIx MHC in human soleus fibers. After 2 and 4 mo of bed rest, the mean size of type I fibers decreased by 12 ( P > 0.05) and 39%, respectively. Because myonuclear number/mm of fiber length was unchanged, myonuclear domain was smaller after bed rest than before. The mean size and myonuclear domain of type I fibers were largest after 1 mo of recovery. The effects of wearing an antigravity device (Penguin suit), which had a modest but continuous resistance at the knee and ankle (Penguin-1) or knee resistance without loading on the ankle (Penguin-2), for 10 consecutive h/day were determined during 2 mo of bed rest. Mean fiber sizes in Penguin-1, but not Penguin-2, group were maintained at or above pre-bed-rest levels, whereas neither group showed phenotype changes. Myonuclear domain in type I fibers was larger in Penguin-1 and smaller in Penguin-2 group post- compared with pre-bed rest, indicating that a single daily 10-h bout of modest muscle loading can prevent bed-rest-induced soleus fiber atrophy but has minimal effect on myosin phenotype. The specific adaptive cellular strategies involved may be a function of the duration and magnitude of the adaptive stimulus as well as the immediate activity history of the fiber before the newly changed functional demands.
Strength training improves the steadiness of slow lengthening contractions performed by old adults
Authors: Laidlaw Douglass H. , Kornatz Kurt W. , Keen Douglas A. , Suzuki Shuji , Enoka Roger M.
Published: December 2017

When old adults participate in a strength-training program with heavy loads, they experience an increase in muscle strength and an improvement in the steadiness of submaximal isometric contractions. The purpose of this study was to determine the effect of light- and heavy-load strength training on the ability of old adults to perform steady submaximal isometric and anisometric contractions. Thirty-two old adults (60–91 yr) participated in a 4-wk training program of a hand muscle. Both the light- and heavy-load groups increased one-repetition maximum and maximal voluntary contraction (MVC) strength and experienced similar improvements in the steadiness of the isometric and shortening and lengthening contractions. The increase in MVC strength was greater for the heavy-load group and could not be explained by changes in muscle activation. Before training, the lengthening contractions were less steady than the shortening contractions with the lightest loads (10% MVC). After training, there was no difference in steadiness between the shortening and lengthening contractions, except with the lightest load. These improvements were associated with a reduced level of muscle activation, especially during the lengthening contractions.
Sensory nerve-mediated immediate nasal responses to inspired acrolein
Authors: Morris John B. , Stanek John , Gianutsos Gerald
Published: December 2017

To investigate the role of sensory C-fiber stimulation and tachykinin release in the immediate nasal responses to the sensory irritant acrolein, the upper respiratory tract of the urethan-anesthetized male Fischer 344 rat was isolated via insertion of an endotracheal tube, and acrolein-laden air [2, 5, 10, or 20 parts/million (ppm)] was drawn continuously through that site at a flow rate of 100 ml/min for 50 min. Uptake of the inert vapor acetone was measured throughout the exposure to assess nasal vascular function. Plasma protein extravasation into nasal tissue and nasal lavage fluid was also assessed via injection of Evans blue dye. At 20 ppm, acrolein induced 1) a twofold increase in acetone uptake, indicative of vasodilation, followed by a progressive decline toward basal levels and 2) increased plasma protein extravasation, as indicated by dye leakage into nasal tissue and nasal lavage. These responses were inhibited by capsaicin pretreatment and the neurokinin type 1 antagonist N-acetyltrifluoromethyl tryptophan benzyl ester and were potentiated by the peptidase inhibitors phosphoramidon and captopril, suggesting that these responses were mediated by tachykinin. At lower exposure concentrations, acrolein was without effect on dye leakage but produced vasodilation, as indicated by increased acetone uptake. The responses at the lower concentrations were inhibited by capsaicin pretreatment, implicating nasal sensory C-fiber involvement, but were not influenced by N-acetyltrifluoromethyl tryptophan benzyl ester, phosphoramidon, or captopril, suggesting the involvement of a mediator other than the tachykinins substance P and neurokinin A.
Measurement of cerebral blood volume using near-infrared spectroscopy and indocyanine green elimination
Authors: Hopton P. , Walsh T. S. , Lee A.
Published: December 2017

Methods for measuring cerebral blood volume (CBV) have traditionally used radioisotopes. More recently, near-infrared spectroscopy (NIRS) has been used to measure CBV by using a technique involving O2 desaturation of cerebral tissue, where the observed change in the concentration of oxygenated hemoglobin is a marker of the volume of blood contained within the brain. A new integration method employing NIRS is described by using indocyanine green (ICG) as the intravascular marker. After bolus injection, concentration-time integrals of cerebral tissue ICG concentration ([ICG]tissue) measured by NIRS are compared with corresponding integrals of the cerebral blood ICG concentrations ([ICG]blood) estimated by high-performance liquid chromatography of peripheral blood samples with allowance for cerebral-to-large-vessel hematocrit ratio. It is shown that[Formula: see text] Measurements in 10 adult volunteers gave a mean value of 1.1 ± 0.39 (SD) ml/100 g illuminated tissue. This result, although lower than previous NIRS estimations, is consistent with the long extracerebral path of light in the adult head. Scaling of results is required to take into account this component of the optical pathlength.
Analysis of intrapulmonary O2concentration by MR imaging of inhaled hyperpolarized helium-3
Authors: Eberle B. , Weiler N. , Markstaller K. , Kauczor H.-U. , Deninger A. , Ebert M. , Grossmann T. , Heil W. , Lauer L. O. , Roberts T. P. L. , Schreiber W. G. , Surkau R. , Dick W. F. , Otten E. W. , Thelen M.
Published: December 2017

Inhalation of hyperpolarized 3He allows magnetic resonance imaging (MRI) of ventilated airspaces.3He hyperpolarization decays more rapidly when interacting with paramagnetic O2. We describe a method for in vivo determination of intrapulmonary O2 concentrations ([O2]) based on MRI analysis of the fate of measured amounts of inhaled hyperpolarized3He in imaged regions of the lung. Anesthetized pigs underwent controlled normoventilation in a 1.5-T MRI unit. The inspired O2 fraction was varied to achieve different end-tidal [O2] fractions ([Formula: see text]). With the use of a specifically designed applicator,3He (100 ml, 35–45% polarized) was administered at a predefined time within single tidal volumes. During subsequent inspiratory apnea, serial two-dimensional images of airways and lungs were acquired. At least once in each animal studied, the radio-frequency excitation used for imaging was doubled at constant[Formula: see text]. Signal intensity measurements in regions of interest of the animals' lungs (volume range, 54–294 cm3), taken at two different radio-frequency excitations, permitted calculation of [O2] in these regions of interest. The [O2] fractions in the regions of interest correlated closely with[Formula: see text]( R = 0.879; P < 0.0001). O2-sensitive3He-MRI may allow noninvasive study of regional distribution of ventilation and alveolar[Formula: see text] in the lung.
Blood pressure and plasma catecholamines in acute and prolonged hypoxia: effects of local hypothermia
Authors: Kanstrup Inge-Lis , Poulsen Troels Dirch , Hansen Jesper Melchior , Andersen Lars Juel , Bestle Morten Heiberg , Christensen Niels Juel , Olsen Niels Vidiendal
Published: December 2017

This study measured the pressor and plasma catecholamine response to local hypothermia during adaptation to hypobaric hypoxia. Eight healthy men were studied at rest and after 10 and 45 min of local cooling of one hand and forearm as well as after 30 min of rewarming at sea level and again 24 h and 5 days after rapid, passive transport to high altitude (4,559 m). Acute mountain sickness scores ranged from 5 to 16 (maximal attainable score: 20) on the first day but were reduced to 0–8 by the fifth day. Systolic blood pressure, heart rate, and plasma epinephrine increased on day 1 at altitude compared with sea level but declined again on day 5, whereas diastolic and mean blood pressures continued to rise in parallel with plasma norepinephrine. With local cooling, an increased vasoactive response was seen on the fifth day at altitude. Very high pressures were obtained, and the pressure elevation was prolonged. Heart rate increased twice as much on day 5 compared with the other two occasions. Thoracic fluid index increased with cooling on day 5, suggesting an increase in pulmonary vascular resistance. In conclusion, prolonged hypoxia seems to elicit an augmented pressor response to local cooling in the systemic and most likely also the pulmonary circulation.
Exercise-induced stimulation of K+transport in human erythrocytes
Authors: Lindinger Michael I. , Horn Peggy L. , Grudzien Simon P.
Published: December 2017

The hypothesis was tested that exercise-induced changes in plasma composition stimulate unidirectional K+transport ( JinK) in human red blood cells (RBCs). Ten men performed two 30-s high-intensity leg-cycling tests separated by 4 min of rest. Antecubital venous blood was sampled before exercise and at the end of the second exercise bout. RBCs were separated from true exercise plasma,42K was added to plasma, and RBC K+transport was studied in vitro at 37°C. In the second part of the study, blood from nine healthy men studied in vitro at 37°C was used to test the hypothesis that exercise-simulated (ES) plasma stimulates net K+transport and JinK (measured using86Rb) in human RBCs. The JinK of resting RBCs added to true exercise plasma was 1,574 ± 200 (SE) μmol ⋅ h−1⋅ l−1vs. 1,236 ± 256 μmol ⋅ h−1⋅ l−1in true resting plasma at 2 min (controls). In true exercise and ES plasma, JinK was increased through activation of the ouabain-sensitive Na+-K+pump and the bumetanide-sensitive Na+-K+-2Cl−cotransporter. Increases in plasma osmolality and K+, H+, and epinephrine concentrations independently and in combination stimulated K+transport into human RBCs. In a third series of experiments, in which ES plasma K+concentration was continuously measured during the first 5 min of incubation of RBCs, a 1.6 ± 0.3 mmol/l decrease in plasma K+concentration occurred during the first 2 min. It is concluded that RBCs transport K+at elevated rates in response to exercise-induced changes in plasma composition.
Respiratory function in lambs after in utero treatment of lung hypoplasia by tracheal obstruction
Authors: Davey M. G. , Hooper S. B. , Tester M. L. , Johns D. P. , Harding R.
Published: December 2017

Tracheal obstruction (TO) stimulates growth of hypoplastic lungs in the fetus, but there is little knowledge of subsequent postnatal respiratory function. We have determined the effectiveness of TO in fetal sheep with existing lung hypoplasia in restoring postnatal respiratory function. Lung hypoplasia was induced by lung liquid drainage from 112 days of gestation to term (∼148 days). We used an untreated group (ULH), a treated group (TLH) in which the trachea was obstructed for 10 days, and a control group. ULH lambs died within 4 h of birth. TLH lambs were hypoxic for the first week and were hypercapic at 2 days. Pulmonary diffusing capacity, gas volumes, and respiratory compliances were not different between control and TLH lambs. Minute ventilation was not different between the two groups; however, tidal volumes were lower and respiratory frequencies were higher in TLH lambs than in controls for 2 wk after birth. We conclude that 10 days of TO in the presence of initial lung hypoplasia prevents death at birth and returns most aspects of pulmonary function to normal by 1–2 wk after birth.
Effect of zonal conditions and posture on pulmonary blood flow distribution to subpleural and interior lung
Authors: Lamm W. J. E. , Albert R. K.
Published: December 2017

Observations made on vessels seen directly beneath the pleura may not accurately reflect what occurs in vessels located deeper in the interior of the lung. We quantified flow to subpleural and deeper, interior regions under zone 1 or 2 conditions in excised ( n = 5) and in vivo ( n = 6) rabbit lungs, in the head-up or inverted position. After infusion of radiolabeled microspheres, lungs were dried at alveolar pressure of 25 cmH2O and sliced in 1-cm sections along the gravitational plane and in three planes in the dorsal-ventral axis. Regions located <1 mm from the pleural surface were dissected away from the remaining tissue. In both zonal conditions, 1) weight-normalized flow to the interior exceeded that found in subpleural regions; and 2) flow followed the gravitational gradient, with the correlation varying with the scale of measurement. We conclude that flow through subpleural vessels is less than that which occurs deeper in the interior, but the regional distributions of flow and the effects of zonal conditions are similar in the two regions.
Respiratory muscle blood flows during physiological and chemical hyperpnea in the rat
Authors: Poole David C. , Sexton William L. , Behnke Bradley J. , Ferguson Christine S. , Hageman K. Sue , Musch Timothy I.
Published: December 2017

Whether the diaphragm retains a vasodilator reserve at maximal exercise is controversial. To address this issue, we measured respiratory and hindlimb muscle blood flows and vascular conductances using radiolabeled microspheres in rats running at their maximal attainable treadmill speed (96 ± 5 m/min; range 71–116 m/min) and at rest while breathing either room air or 10% O2-8% CO2 (balance N2). All hindlimb and respiratory muscle blood flows measured increased during exercise ( P < 0.001), whereas increases in blood flow while breathing 10% O2-8% CO2 were restricted to the diaphragm only. During exercise, muscle blood flow increased up to 18-fold above rest values, with the greatest mass specific flows (in ml ⋅ min−1 ⋅ 100 g−1) found in the vastus intermedius (680 ± 44), red vastus lateralis (536 ± 18), red gastrocnemius (565 ± 47), and red tibialis anterior (602 ± 44). During exercise, blood flow was higher ( P < 0.05) in the costal diaphragm (395 ± 31 ml ⋅ min−1 ⋅ 100 g−1) than in the crural diaphragm (286 ± 17 ml ⋅ min−1 ⋅ 100 g−1). During hypoxia+hypercapnia, blood flows in both the costal and crural diaphragms (550 ± 70 and 423 ± 53 ml ⋅ min−1 ⋅ 100 g−1, respectively) were elevated ( P < 0.05) above those found during maximal exercise. These data demonstrate that there is a substantial functional vasodilator reserve in the rat diaphragm at maximal exercise and that hypoxia + hypercapnia-induced hyperpnea is necessary to elevate diaphragm blood flow to a level commensurate with its high oxidative capacity.
Pulmonary vasoregulation by endothelin in conscious dogs after left lung transplantation
Authors: Doi Shouzaburoh , Smedira Nicholas , Murray Paul A.
Published: December 2017

We tested the hypothesis that regulation of the pulmonary circulation by endogenous endothelin (ET) during normoxia and hypoxia was altered in conscious dogs 1 mo after left lung autotransplantation (LLA). Sham-operated control and post-LLA dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LP-Q˙) relationship. LP-Q˙plots were generated on separate days during normoxia and hypoxia (arterial [Formula: see text] ∼50 Torr) in the intact condition, after selective ETA-receptor inhibition (BQ-485), and after combined ETA+B-receptor inhibition (bosentan). Although LLA resulted in a chronic increase in pulmonary vascular resistance, the ET-receptor antagonists had no effect on the LP-Q˙ relationship during normoxia in either group. The magnitude of hypoxic pulmonary vasoconstriction (HPV) was flow dependent in both groups, and the HPV response was potentiated post-LLA compared with control. ETA-receptor inhibition attenuated the HPV response to the same extent in both groups. ETA+B-receptor inhibition attenuated the HPV response to a greater extent than did ETA-receptor inhibition alone, and this effect was greater post-LLA compared with control. Plasma ET-1 concentration only increased during hypoxia in the LLA group. These results indicate that ET does not regulate the baseline LP-Q˙ relationship in either group. Both ETA- and ETB-receptor activation mediate a component of HPV in conscious dogs, and the vasoconstrictor influence of ETB-receptor activation is enhanced post-LLA.
Nandrolone decanoate does not enhance training effects but increases IGF-I mRNA in rat diaphragm
Authors: Gayan-Ramirez Ghislaine , Rollier Hélène , Vanderhoydonc Frank , Verhoeven Guido , Gosselink Rik , Decramer Marc
Published: December 2017

To examine whether concomitant anabolic steroid treatment combined with training might enhance previously observed training effects (A. Bisschop, G. Gayan-Ramirez, H. Rollier, R. Gosselink, R. Dom, V. de Bock, and M. Decramer. Am. J. Respir. Crit. Care Med. 155: 1583–1589, 1997) and whether insulin-like growth factor I (IGF-I) was involved in these changes, male and female rats were submitted to inspiratory muscle training (IMT) for 8 wk (30 min/day, 5 times/wk) and were compared with untrained controls. During the last 5 wk of training, trained rats were divided to receive weekly either low-dose (LD; 1.5 mg/kg) or high-dose (HD; 7.5 mg/kg) nandrolone decanoate or saline for the IMT and control rats. In both sexes, diaphragm muscle mass and contractile properties were unchanged with treatment. In males, HD resulted in decreased diaphragm type I cross-sectional area (−15%; P < 0.05, HD vs. IMT), whereas no changes were observed in females. Finally, an increase in IGF-I mRNA levels was present in HD male (+73%; P < 0.05, HD vs. IMT) and female treated rats [LD (+58%) and HD (+96%) vs. IMT; P < 0.001]. We conclude that administration of nandrolone decanoate did not enhance the previously observed training effects in rat diaphragm, although it increased the IGF-I mRNA expression levels.
Contribution of supraglottal mechanoreceptor afferents to respiratory-related evoked potentials in humans
Authors: Daubenspeck J. Andrew , Manning Harold L. , Akay Metin
Published: December 2017

We used the global field power (GFP) to estimate the magnitude and timing of activation of the somatosensory cortex by respiratory mechanoreceptor afferents in normal humans in response to brief, negative oral pressure pulses applied at the onset of inspiration. We compared responses before (test) and after insertion of a laryngeal mask airway (LMA) that prevented supraglottal airway receptors from sensing the applied stimulus. Evoked potential responses without supraglottic stimulation were smaller, with delayed or missing features, than those with all receptors stimulated. Supraglottic receptors contribute about one-half of the GFP summed over the 100 ms poststimulus, and subglottal receptors, including those in the larynx, provide a GFP response ∼38% above baseline. The most obvious difference between test and LMA responses occurred at 55 ms on average, when the LMA GFP lacked activation features seen in the test condition. We conclude that mechanoreceptors above the larynx are responsible for a major portion of the midlatency afferent information arriving at the somatosensory cortex in response to applied pressure pulses.
The Na+-K+-ATPase α2 gene and trainability of cardiorespiratory endurance: the HERITAGE Family Study
Authors: Rankinen Tuomo , Pérusse Louis , Borecki Ingrid , Chagnon Yvon C. , Gagnon Jacques , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Rao D. C. , Bouchard Claude
Published: December 2017

The Na+-K+-ATPase plays an important role in the maintenance of electrolyte balance in the working muscle and thus may contribute to endurance performance. This study aimed to investigate the associations between genetic variants at the Na+-K+-ATPase α2 locus and the response (Δ) of maximal oxygen consumption (V˙o2 max) and maximal power output (W˙max) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. V˙o2 maxandW˙maxwere measured during two maximal cycle ergometer exercise tests before and again after the training program, and restriction fragment length polymorphisms at the Na+-K+-ATPase α2 (exons 1 and 21–22 with Bgl II) gene were typed. Sibling-pair linkage analysis revealed marginal evidence for linkage between the α2 haplotype and ΔV˙o2 max( P= 0.054) and stronger linkages between the α2 exon 21–22 marker ( P = 0.005) and α2 haplotype ( P = 0.003) and ΔW˙max. In the whole cohort, ΔV˙o2 maxin the 3.3-kb homozygotes of the exon 1 marker ( n = 5) was 41% lower than in the 8.0/3.3-kb heterozygotes ( n = 87) and 48% lower than in the 8.0-kb homozygotes ( n = 380; P = 0.018, adjusted for age, gender, baselineV˙o2 max, and body weight). Among offspring, 10.5/10.5-kb homozygotes ( n = 14) of the exon 21–22 marker showed a 571 ± 56 (SE) ml O2/min increase inV˙o2 max, whereas the increases in the 10.5/4.3-kb ( n = 93) and 4.3/4.3-kb ( n= 187) genotypes were 442 ± 22 and 410 ± 15 ml O2/min, respectively ( P = 0.017). These data suggest that genetic variation at the Na+-K+-ATPase α2 locus influences the trainability ofV˙o2 maxin sedentary Caucasian subjects.
Heat stress attenuates skeletal muscle atrophy in hindlimb-unweighted rats
Authors: Naito Hisashi , Powers Scott K. , Demirel Haydar A. , Sugiura Takao , Dodd Stephen L. , Aoki Junichiro
Published: December 2017

This study tested the hypothesis that elevation of heat stress proteins by whole body hyperthermia is associated with a decrease in skeletal muscle atrophy induced by reduced contractile activity (i.e., hindlimb unweighting). Female adult rats (6 mo old) were assigned to one of four experimental groups ( n = 10/group): 1) sedentary control (Con), 2) heat stress (Heat), 3) hindlimb unweighting (HLU), or 4) heat stress before hindlimb unweighting (Heat+HLU). Animals in the Heat and Heat+HLU groups were exposed to 60 min of hyperthermia (colonic temperature ∼41.6°C). Six hours after heat stress, both the HLU and Heat+HLU groups were subjected to hindlimb unweighting for 8 days. After hindlimb unweighting, the animals were anesthetized, and the soleus muscles were removed, weighed, and analyzed for protein content and the relative levels of heat shock protein 72 (HSP72). Compared with control and HLU animals, the relative content of HSP72 in the soleus muscle was significantly elevated ( P < 0.05) in both the Heat and Heat+HLU animals. Although hindlimb unweighting resulted in muscle atrophy in both the HLU and Heat+HLU animals, the loss of muscle weight and protein content was significantly less ( P < 0.05) in the Heat+HLU animals. These data demonstrate that heat stress before hindlimb unweighting can reduce the rate of disuse muscle atrophy. We postulate that HSP70 and/or other stress proteins play a role in the control of muscle atrophy induced by reduced contractile activity.
Human calf microvascular compliance measured by near-infrared spectroscopy
Authors: Binzoni T. , Quaresima V. , Ferrari M. , Hiltbrand E. , Cerretelli P.
Published: December 2017

The purpose of this study is to develop a new method for the measurement in humans of the compliance of the microvascular superficial venous system of the lower limb by near-infrared spectroscopy (NIRS). This method is complementary to strain-gauge plethysmography, which does not allow compliance between deep and superficial venous or between venous and arterial compartments to be distinguished. In practice, hydrostatic pressure (P) changes were induced in a calf region of interest by head-up tilt of the subject from α = −10 to 75°. For P ≤ 24 mmHg, the measured compliance [0.086 ± 0.005 (SD) ml ⋅ l− 1 ⋅ mmHg− 1] based on NIRS data of total, deoxygenated, and oxygenated hemoglobin, reflects essentially that of the superficial venous system. For P ≥ 24 mmHg, no distinction can be made between arterial and venous volumes changes. However, by following the changes in oxy- and deoxyhemoglobin in the P range −16 to 100 mmHg, it appears to be possible to assess the characteristics of the vasomotor response of the arteriolar system.
Modulation of arterial baroreflex control of heart rate by skin cooling and heating in humans
Authors: Yamazaki Fumio , Sone Ryoko
Published: December 2017

The purpose of this study was to examine the effects of skin cooling and heating on the heart rate (HR) control by the arterial baroreflex in humans. The subjects were 15 healthy men who underwent whole body thermal stress (esophageal temperatures, ∼36.8 and ∼37.0°C; mean skin temperatures, ∼26.4 and ∼37.7°C, in skin cooling and heating, respectively) produced by a cool or hot water-perfused suit during supine rest. The overall arterial baroreflex sensitivity in the HR control was calculated from spontaneous changes in beat-to-beat arterial pressure and HR during normothermic control and thermal stress periods. The carotid baroreflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure, calculated as mean arterial pressure minus neck pressure. The overall arterial baroreflex sensitivity at existing arterial pressure increased during cooling (−1.32 ± 0.25 vs. −2.13 ± 0.20 beats ⋅ min− 1 ⋅ mmHg− 1 in the control and cooling periods, respectively, P < 0.05), whereas it did not change significantly during heating (−1.39 ± 0.23 vs. −1.40 ± 0.15 beats ⋅ min− 1 ⋅ mmHg− 1in the control and heating periods, respectively). Neither the cool nor heat loadings altered the carotid baroreflex sensitivity in the HR control. These results suggest that the sensitivity of HR control by the extracarotid (presumably aortic) baroreflex was augumented by whole body skin cooling, whereas the sensitivities of HR control by arterial baroreflex remain unchanged during mild whole body heating in humans.
Contractile and fatigue properties of the rat diaphragm musculature during the perinatal period
Authors: Martin-Caraballo Miguel , Campagnaro Paul A. , Gao Yuan , Greer John J.
Published: December 2017

The following two hypotheses regarding diaphragm contractile properties in the perinatal rat were tested. First, there is a major transformation of contractile and fatigue properties during the period between the inception of inspiratory drive transmission in utero and birth. Second, the diaphragm muscle properties develop to functionally match changes occurring in phrenic motoneuron electrophysiological properties. Muscle force recordings and intracellular recordings of end-plate potentials were measured by using phrenic nerve-diaphragm muscle in vitro preparations isolated from rats on embryonic day 18 and postnatal days 0–1. The following age-dependent changes occurred: 1) twitch contraction and half relaxation times decreased approximately two- and threefold, respectively; 2) the tetanic force levels increased approximately fivefold; 3) the ratio of peak twitch force to maximum tetanic force decreased 2.3-fold; 4) the range of forces generated by the diaphragm in response to graded nerve stimulation increased approximately twofold; 5) the force-frequency curve was shifted to the right; and 6) the propensity for neuromuscular transmission failure decreased. In conclusion, the diaphragm contractile and phrenic motoneuron repetitive firing properties develop in concert so that the full range of potential diaphragm force recruitment can be utilized and problems associated with diaphragm fatigue are minimized.