bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ SR function in postinfarction myocytes
Authors: Zhang Xue-Qian , Ng Yuk-Chow , Moore Russell L. , Musch Timothy I. , Cheung Joseph Y.
Published: December 2017

Previous studies have shown lower systolic intracellular Ca2+concentrations ([Ca2+]i) and reduced sarcoplasmic reticulum (SR)-releasable Ca2+contents in myocytes isolated from rat hearts 3 wk after moderate myocardial infarction (MI). Ca2+entry via L-type Ca2+channels was normal, but that via reverse Na+/Ca2+exchange was depressed in 3-wk MI myocytes. To elucidate mechanisms of reduced SR Ca2+contents in MI myocytes, we measured SR Ca2+uptake and SR Ca2+leak in situ, i.e., in intact cardiac myocytes. For sham and MI myocytes, we first demonstrated that caffeine application to release SR Ca2+and inhibit SR Ca2+uptake resulted in a 10-fold prolongation of half-time ( t½) of [Ca2+]itransient decline compared with that measured during a normal twitch. These observations indicate that early decline of the [Ca2+]itransient during a twitch in rat myocytes was primarily mediated by SR Ca2+-ATPase and that the t½of [Ca2+]idecline is a measure of SR Ca2+uptake in situ. At 5.0 mM extracellular Ca2+, systolic [Ca2+]iwas significantly ( P ≤ 0.05) lower (337 ± 11 and 416 ± 18 nM in MI and sham, respectively) and t½of [Ca2+]idecline was significantly longer (0.306 ± 0.014 and 0.258 ± 0.014 s in MI and sham, respectively) in MI myocytes. The 19% prolongation of t½of [Ca2+]idecline was associated with a 23% reduction in SR Ca2+-ATPase expression (detected by immunoblotting) in MI myocytes. SR Ca2+leak was measured by a novel electrophysiological technique that did not require assigning empirical constants for intracellular Ca2+buffering. SR Ca2+leak rate was not different between sham and MI myocytes: the time constants of SR Ca2+loss after thapsigargin were 290 and 268 s, respectively. We conclude that, independent of decreased SR filling by Ca2+influx, the lower SR Ca2+content in MI myocytes was due to reduced SR Ca2+uptake and SR Ca2+-ATPase expression, but not to enhanced SR Ca2+leak.
Skeletal muscle metabolism during short-term, high-intensity exercise in prepubertal and pubertal girls
Authors: Petersen S. R. , Gaul C. A. , Stanton M. M. , Hanstock C. C.
Published: December 2017

To test the hypothesis that glycolytic metabolism in muscle is attenuated in prepubertal children,31P-magnetic resonance spectroscopy was used to determine calf muscle intracellular pH (pHi) in nine prepubertal (Pre) and nine pubertal female swimmers (Pub). Maximal plantar flexion work capacity (100% MWC) was established by using a graded exercise test. Between 5 and 10 days later, calf muscle images (magnetic resonance imaging) and phosphorus spectra were acquired at rest, during 2 min of light exercise (40% MWC), and during 2 min of supramaximal exercise (140% MWC) in a 3.0-T NMR system. End-exercise pHiwas 6.66 ± 0.11 and 6.76 ± 0.17 for Pub and Pre, respectively. No significant differences in the mean values for pHior the Pi-to-phosphocreatine ratio were observed between groups during the protocol; however, an interaction effect was found for the Pi-to-phosphocreatine ratio during the supramaximal exercise challenge. Cross-sectional area of gastrocnemius was 15.12 ± 0.46 and 9.37 ± 0.37 cm2for Pub and Pre, respectively ( P < 0.05). Differences in muscle size must be considered when interpreting the unlocalized magnetic resonance spectroscopy data. These results suggest that glycolytic metabolism in physically active children is not maturity dependent.
Aerosolization of P2Y2-receptor agonists enhances mucociliary clearance in sheep
Authors: Sabater J. R. , Mao Y. M. , Shaffer C. , James M. K. , O'Riordan T. G. , Abraham W. M.
Published: December 2017

The purpose of this study was to determine whether aerosolized INS316 (UTP) stimulates lung mucociliary clearance (MCC) in sheep and, if so, to compare its effects with INS365, a novel P2Y2-receptor agonist. In the first series of studies, we used a previously described roentgenographic technique to measure tracheal mucus velocity (TMV), an index of MCC, before and for 4 h after aerosolization of INS316 (10−1 M and 10−2 M) and INS365 (10−1 M and 10−2 M), or normal saline in a randomized crossover fashion ( n = 6). In a second series of studies, we compared the ability of these agents to enhance total lung clearance. For these tests, the clearance of inhaled technetium-labeled human serum albumin was measured serially over a 2-h period after aerosolization of 10−1 M concentration of each agent ( n = 7). Aerosolization of both P2Y2-receptor agonists induced significant dose-related increases in TMV ( P < 0.05) compared with saline. The greatest increase in TMV was observed between 15 and 30 min after drug treatment. The highest dose (10−1 M) of INS316 produced a greater overall stimulation of TMV than did INS365 (10−1 M). Both compounds, compared with saline, induced a significant increase in MCC ( P < 0.05) within 20 min of treatment. This enhancement in MCC began to plateau at 60 min. Although the response to INS316 started earlier, there was no significant difference between the clearance curves for the two compounds. We conclude that inhaled P2Y2-receptor agonists can increase lung MCC in sheep and that for P2Y2-receptor stimulation TMV accurately reflects changes in whole lung MCC.
Modeling growth and maturation changes in peak oxygen uptake in 11–13 yr olds
Authors: Armstrong Neil , Welsman Joanne R. , Nevill Alan M. , Kirby Brian J.
Published: December 2017

The influence of gender, growth, and maturation on peak O2 consumption (V˙o 2 peak) in 11–13 yr olds were examined by using multilevel regression modeling. Subjects were 119 boys and 115 girls, aged 11.2 ± 0.4 (SD) yr at the onset of the study. Sexual maturation was classified according to Tanner's indexes of pubic hair.V˙o 2 peak was determined annually for 3 yr. The initial model identified body mass and stature as significant explanatory variables, with an additional positive effect for age and incremental effects for stage of maturation. A significant gender difference was apparent with lower values for girls, and an age-by-gender interaction indicated a progressive divergence in boys' and girls'V˙o 2 peak. Subsequent incorporation of the sum of two skinfold thicknesses into the model negated stature effects, reduced the gender term, and explained much of the observed maturity effects. The body mass exponent almost doubled, but the age-by-gender interaction term was consistent with the initial model.
Skeletal muscle energy metabolism during prolonged, fatiguing exercise
Authors: Febbraio Mark A. , Dancey Jane
Published: December 2017

A depletion of phosphocreatine (PCr), fall in the total adenine nucleotide pool (TAN = ATP + ADP + AMP), and increase in TAN degradation products inosine 5′-monophosphate (IMP) and hypoxanthine are observed at fatigue during prolonged exercise at 70% maximal O2uptake in untrained subjects [J. Baldwin, R. J. Snow, M. F. Carey, and M. A. Febbraio. Am. J. Physiol. 277 ( Regulatory Integrative Comp. Physiol.46): R295–R300, 1999]. The present study aimed to examine whether these metabolic changes are also prevalent when exercise is performed below the blood lactate threshold (LT). Six healthy, untrained humans exercised on a cycle ergometer to voluntary exhaustion at an intensity equivalent to 93 ± 3% of LT (∼65% peak O2uptake). Muscle biopsy samples were obtained at rest, at 10 min of exercise, ∼40 min before fatigue (F−40 =143 ± 13 min), and at fatigue (F = 186 ± 31 min). Glycogen concentration progressively declined ( P < 0.01) to very low levels at fatigue (28 ± 6 mmol glucosyl U/kg dry wt). Despite this, PCr content was not different when F−40 was compared with F and was only reduced by 40% when F was compared with rest (52.8 ± 3.7 vs. 87.8 ± 2.0 mmol/kg dry wt; P < 0.01). In addition, TAN concentration was not reduced, IMP did not increase significantly throughout exercise, and hypoxanthine was not detected in any muscle samples. A significant correlation ( r = 0.95; P < 0.05) was observed between exercise time and glycogen use, indicating that glycogen availability is a limiting factor during prolonged exercise below LT. However, because TAN was not reduced, PCr was not depleted, and no correlation was observed between glycogen content and IMP when glycogen stores were compromised, fatigue may be related to processes other than those involved in muscle high-energy phosphagen metabolism.
Afferent input from rat slow skeletal muscle inhibits bioassayable growth hormone release
Authors: Gosselink K. L. , Grindeland R. E. , Roy R. R. , Zhong H. , Bigbee A. J. , Edgerton V. R.
Published: December 2017

The release of a bioassayable form of growth hormone (BGH), distinct from growth hormone as measured by immunoassay (IGH), from the rat pituitary into the blood is differentially regulated by afferent input from fast and slow skeletal muscles. Specifically, activation of low-threshold fast muscle afferents for 15 min increased plasma BGH by 217 and 295% and decreased pituitary BGH by 68 and 45% in male and female rats, respectively. In contrast, activation of slow muscle afferents inhibited BGH release, decreasing plasma BGH by ∼60% and increasing pituitary BGH by 30–50% in male rats. Female rats from which food had been withheld for ∼12 h had elevated basal plasma BGH levels, which then were decreased by 81% after slow muscle nerve stimulation. Plasma IGH concentrations were unchanged after any nerve stimulation condition. These results demonstrate that regulation of BGH release can be differentially mediated through low-threshold afferent inputs from fast or slow skeletal muscle. Furthermore, the results indicate that BGH responses are independent of gender or feeding status.
Effect of delivery temperature on endocrine stimulation of thermoregulation in lambs born by cesarean section
Authors: Symonds M. E. , Bird J. A. , Sullivan C. , Wilson V. , Clarke L. , Stephenson T.
Published: December 2017

We examined the hypothesis that exogenous stimulation with physiological doses of 3,5,3′-triiodothyronine (T3) and/or norepinephrine at birth can improve thermoregulation in near-term lambs delivered by cesarean section. This was achieved by investigating the effect of delivery temperature [i.e., warm (30°C) vs. cool (15°C) ambient temperatures] on hormonal stimulation on uncoupling protein-1 (UCP1) abundance in brown adipose tissue. In vivo measurements of temperature control (i.e., colonic temperature, oxygen consumption, and incidence of shivering) were made over the first 2.5 h after birth. Each lamb was injected with saline with or without T3, norepinephrine, or T3plus norepinephrine. Irrespective of delivery temperature, abundance of UCP1 increased and incidence of shivering decreased by all hormonal treatments, but this only reduced the rate of decline in colonic temperature of cool-delivered lambs. Oxygen consumption was higher in cool-delivered lambs that were able to fully restore body temperature, an adaptation not observed in controls or any warm-delivered groups. Exogenous administration of endocrine stimulatory factors can enhance the abundance of UCP1 in cesarean-section-delivered lambs with the magnitude of thermoregulatory response being greater at cool than warm delivery temperatures.
Dexamethasone and thyroid hormone pretreatment upregulate alveolar epithelial fluid clearance in adult rats
Authors: Folkesson Hans G. , Norlin Andreas , Wang Yibing , Abedinpour Parisa , Matthay Michael A.
Published: December 2017

The in vivo effect of 48-h glucocorticoid and thyroid hormone 3,3′,5-triiodine-l-thyronine (T3) pretreatment on alveolar epithelial fluid transport was studied in adult rats. An isosmolar 5% albumin solution was instilled, and alveolar fluid clearance was studied for 1 h. Compared with controls, dexamethasone pretreatment increased alveolar fluid clearance by 80%. T3pretreatment stimulated alveolar fluid clearance by 65%, and dexamethasone and T3had additive effects (132%). Propranolol did not inhibit alveolar fluid clearance in either group, indicating that stimulation was not secondary to endogenous β-adrenergic stimulation. With the use of bromodeoxyuridine in vivo labeling, there was no evidence of cell proliferation. Alveolar fluid clearance was partially inhibited by amiloride in all groups. Fractional amiloride inhibition was greater in dexamethasone- and dexamethasone-plus-T3-pretreated rats than in control animals, but less in T3-pretreated rats. In summary, pretreatment with dexamethasone, T3, or both in combination upregulate in vivo alveolar fluid clearance similarly to short-term β-adrenergic stimulation. The effects are mediated partly by increased amiloride-sensitive Na+transport, because the stimulated alveolar fluid clearance was more amiloride sensitive than in control rats. These observations may have clinical relevance because glucocorticoid therapy is commonly used with acute lung injury.
Chronic exercise training improves ACh-induced vasorelaxation in pulmonary arteries of pigs
Authors: Johnson Lynelle R. , Parker Janet L. , Laughlin M. Harold
Published: December 2017

We hypothesized that exercise training would lead to enhanced endothelium-dependent vasodilation in porcine pulmonary arteries. Pulmonary artery rings (2- to 3-mm OD) were obtained from female Yucatan miniature swine with surgically induced coronary artery occlusion (ameroid occluder). Exercise training was performed for 16 wk, and vasomotor responses were studied by using standard isometric techniques. Contractile responses to 80 mM KCl, isosmotic KCl (10–100 mM), and norepinephrine (10−8 to 10−4 M) did not differ between sedentary (Sed) and exercise-trained (Ex) pigs. Relaxation was assessed to endothelium-dependent and endothelium-independent vasodilators after norepinephrine contraction. Pulmonary arteries of Ex pigs exhibited greater maximal relaxation to ACh (61.9 ± 3.5%) than did those of Sed pigs (52.3 ± 3.9%; P < 0.05). Endothelium-independent relaxation to sodium nitroprusside did not differ. Inhibition of nitric oxide synthase significantly decreased acetylcholine-induced relaxation, with greater inhibition in arteries from Ex pigs (P< 0.05). Inhibition of cyclooxygenase enhanced relaxation to acetylcholine in arteries from Sed pigs. We conclude that exercise training enhances endothelium-dependent (ACh-mediated) vasorelaxation in pulmonary arteries by mechanisms of increased reliance on nitric oxide and reduced production of a prostanoid constrictor.
Measuring leg muscle and fat mass in humans: comparison of CT and dual-energy X-ray absorptiometry
Authors: Levine James A. , Abboud Lana , Barry Mitchel , Reed Judd E. , Sheedy Patrick F. , Jensen Michael D.
Published: December 2017

Dual-energy X-ray absorptiometry (DEXA) is reported to be inferior to computed tomography (CT) to measure changes in appendicular soft tissue composition. We compared CT- and DEXA-measured thigh muscle and fat mass to evaluate the random and systematic discrepancies between these two methods. Thigh skeletal muscle area (single-slice CT) was suboptimally ( r2= 0.74, P < 0.0001) related to DEXA-measured thigh fat-free mass (FFM). In contrast, thigh muscle and adipose tissue volumes (multislice CT) were highly related to DEXA-measured thigh FFM and fat (both r2= 0.96, P < 0.0001). DEXA-measured leg fat was significantly less than multislice-CT-measured leg adipose tissue volume, whereas multislice-CT-measured leg muscle mass was less ( P < 0.0001) than DEXA-measured leg FFM. The systematic discrepancies between the two approaches were consistent with the 10–15% nonfat components of adipose tissue. In conclusion, CT and DEXA measures of appendicular soft tissue are highly related. Systematic differences between DEXA and CT likely relate to the underlying principles of the techniques.
Hypoxemia-induced modification of troponin I and T in canine diaphragm
Authors: Simpson Jeremy A. , van Eyk Jennifer E. , Iscoe Steve
Published: December 2017

Impaired muscle function (fatigue) may result, in part, from modification of contractile proteins due to inadequate O2delivery. We hypothesized that severe hypoxemia would modify skeletal troponin I (TnI) and T (TnT), two regulatory contractile proteins, in respiratory muscles. Severe isocapnic hypoxemia (arterial partial pressure of O2of ∼25 Torr) in six pentobarbital sodium-anesthetized spontaneously breathing dogs increased respiratory frequency and electromyographic activity of the diaphragm and internal and external obliques, with death occurring after 131–285 min. Western blot analysis revealed proteolyis of TnI and TnT, 17.5- and 28-kDa fragments, respectively, and higher molecular mass covalent complexes, one of which (42 kDa) contained TnI (or some fragment of it) and probably TnT in the costal and crural diaphragms but not the intercostal or abdominal muscles. These modifications of myofibrillar proteins may provide a molecular basis for contractile dysfunction, including respiratory failure, under conditions of limited O2delivery.
Mechanical properties of the tracheal mucosal membrane in the rabbit. I. Steady-state stiffness as a function of age
Authors: Wang Lu , Tepper Robert , Bert Joel L. , Pinder Kenneth L. , Paré Peter D. , Okazawa Mitsushi
Published: December 2017

Airway responsiveness is exaggerated in infancy and declines with maturation. These age-related differences (R.S. Tepper, T. Du, A. Styhler, M. Ludwig, and J.G. Martin. Am. J. Respir. Crit. Care Med. 151: 836–840, 1995; R.S. Tepper, S.J. Gunst, C.M. Doerschuk, Y. Shen, and W. Bray. J. Appl. Physiol.78: 505–512, 1995; R.S. Tepper, J. Stevens, and H. Eigen. Am. J. Respir. Crit. Care Med. 149: 678–681, 1994) could be due to changes in the smooth muscle, the lung, and/or the airway wall. Folding of the mucosal membrane can provide an elastic load (R.K. Lambert, J. Appl. Physiol. 71: 666–673, 1991), which impedes smooth muscle shortening. We hypothesized that increased stiffness of the mucosal membrane occurs during aging, causing an increased mechanical load on airway smooth muscle and a decrease in airway responsiveness. Forty female New Zealand White rabbits between 0.75 and 35 mo of age were studied. Rectangular mucosal membrane strips oriented both longitudinally and circumferentially to the long axis of the trachea were dissected, and the stress-strain relationships of each strip were tested. The results showed that the membrane was stiffer in the longitudinal than in the circumferential direction of the airway. However, there was no significant change with age in either orientation. We conclude that the mechanical properties of the airway mucosal membrane did not change during maturation and were not likely to influence age-related changes in airway responsiveness.
Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro
Authors: Ojuka Edward O. , Nolte Lorraine A. , Holloszy John O.
Published: December 2017

Exercise acutely stimulates muscle glucose transport and also brings about an adaptive increase in the capacity of muscle for glucose uptake by inducing increases in GLUT-4 and hexokinase.1Recent studies have provided evidence that activation of AMP protein kinase (AMPK) is involved in the stimulation of glucose transport by exercise. The purpose of this study was to determine whether activation of AMPK is also involved in mediating the adaptive increases in GLUT-4 and hexokinase. To this end, we examined the effect of incubating rat epitrochlearis muscles in culture medium for 18 h in the presence or absence of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), which enters cells and is converted to the AMP analog ZMP, thus activating AMPK. Exposure of muscles to 0.5 mM AICAR in vitro for 18 h resulted in an ∼50% increase in GLUT-4 protein and an ∼80% increase in hexokinase. This finding provides strong evidence in support of the hypothesis that the activation of AMPK that occurs in muscle during exercise is involved in mediating the adaptive increases in GLUT-4 and hexokinase.
Oxidant-increased endothelial permeability: prevention with phosphodiesterase inhibition vs. cAMP production
Authors: Waypa Gregory B. , Morton Christine A. , Vincent Peter A. , Mahoney John R. , Johnston William K. , Minnear Fred L.
Published: December 2017

The present objective was to determine whether hydrogen peroxide (H2O2) increases transvascular albumin clearance and lung weight in an isolated rat lung and whether posttreatment with cAMP-enhancing agents can prevent these increases. Transvascular albumin clearance was assessed by125I-labeled albumin clearance (125I-albumin flux/perfusate concentration of125I-albumin) at a given fluid filtration. Nonlinear regression analysis of transvascular albumin clearance vs. fluid filtration yielded values for the permeability-surface area product ( PS) and the reflection coefficient (ς). H2O2decreased ς from a control value of 0.93 to 0.38, did not change PS, and increased lung weight. Posttreatment with isoproterenol, a β2-adrenergic-receptor agonist, reduced the H2O2-induced decrease in ς to 0.65 and augmented the increase in lung weight. Posttreatment with CP-80633, a phosphodiesterase 4 inhibitor, further reduced the H2O2-induced decrease in ς to 0.79 and blocked the rise in lung weight. In the presence of isoproterenol or CP-80633, H2O2increased PS. Therefore, H2O2increased the convective and diffusive clearances of albumin across an intact pulmonary vasculature. Furthermore, inhibition of cAMP metabolism more effectively attenuated the H2O2-induced increases in convective albumin clearance and lung weight as compared with stimulation of cAMP production.
A comparison of bioimpedance methods for detection of body cell mass change in HIV infection
Authors: Earthman Carrie P. , Matthie James R. , Reid Phyllis M. , Harper Ingeborg T. , Ravussin Eric , Howell Wanda H.
Published: December 2017

The maintenance of body cell mass (BCM) is critical for survival in human immunodeficiency virus (HIV) infection. Accuracy of bioimpedance for measuring change (Δ) in intracellular water (ICW), which defines BCM, is uncertain. To evaluate bioimpedance-estimated ΔBCM, the ICW of 21 weight-losing HIV patients was measured before and after anabolic steroid therapy by dilution (total body water by deuterium − extracellular water by bromide) and bioimpedance. Multiple-frequency modeling- and dilution-determined ΔICW did not differ. The ΔICW was predicted poorly by 50-kHz parallel reactance, 50-kHz impedance, and 200 − 5-kHz impedance. The ΔICW predicted by 500 − 5-kHz impedance was closer to, but statistically different from, dilution-determined ΔICW. However, the effect of random error on the measurement of systematic error in the 500 − 5-kHz method was 12–13% of the average measured ΔICW; this was nearly twice the percent difference between obtained and threshold statistics. Although the 500 − 5-kHz method cannot be fully rejected, these results support the conclusion that only the multiple-frequency modeling approach accurately monitors ΔBCM in HIV infection.
Rat small mesenteric artery function after hindlimb suspension
Authors: Looft-Wilson R. C. , Gisolfi C. V.
Published: December 2017

To determine whether simulated microgravity in rats is associated with vascular dysfunction, we measured responses of isolated, pressurized mesenteric resistance artery segments (157- to 388-μm ID) to vasoconstrictors, pressure, and shear stress after 28-day hindlimb suspension (HS). Results indicated no differences between HS and control (C) groups in 1) sensitivity or maximal responses to vasoconstrictors (norepinephrine, phenylephrine, serotonin, KCl); 2) ID, external diameter, or ratio of wall thickness to ID; 3) distensibility; or 4) vasodilatory responses to shear stress. Myogenic tone was attenuated ( P < 0.05) in HS arteries vs. C, as evidenced by 1) decreased magnitude of tone in larger vessels (second-order branch off superior mesenteric artery, 261- to 388-μm ID) at pressures ≥40 mmHg in the presence of phenylephrine (10−7 M) and 2) decreased magnitude of tone in smaller vessels (third-order branch off superior mesenteric artery, 157- to 277-μm ID), which exhibited spontaneous tone, at pressures ≥70 mmHg. This attenuation of myogenic tone after HS could contribute to orthostatic intolerance because myogenic tone contributes to the overall tone of resistance arteries.
Cardiovascular response to hypoxia after endurance training at altitude and sea level and after detraining
Authors: Katayama Keisho , Sato Yasutake , Morotome Yoshifumi , Shima Norihiro , Ishida Koji , Mori Shigeo , Miyamura Miharu
Published: December 2017

The purpose of this study was to elucidate 1) the effects of endurance exercise training during hypoxia or normoxia and of detraining on ventilatory and cardiovascular responses to progressive isocapnic hypoxia and 2) whether the change in the cardiovascular response to hypoxia is correlated to changes in the hypoxic ventilatory response (HVR) after training and detraining. Seven men (altitude group) performed endurance training using a cycle ergometer in a hypobaric chamber of simulated 4,500 m, whereas the other seven men (sea-level group) trained at sea level (K. Katayama, Y. Sato, Y. Morotome, N. Shima, K. Ishida, S. Mori, and M. Miyamura. J. Appl. Physiol. 86: 1805–1811, 1999). The HVR, systolic and diastolic blood pressure responses (ΔSBP/[Formula: see text], ΔDBP/[Formula: see text]), and heart rate response (ΔHR/[Formula: see text];[Formula: see text] is arterial oxygen saturation) to progressive isocapnic hypoxia were measured before and after training and during detraining. ΔSBP/[Formula: see text] increased significantly in the altitude group and decreased significantly in the sea-level group after training. The changed ΔSBP/[Formula: see text] in both groups was restored during 2 wk of detraining, as were the changes in HVR, whereas there were no changes in the ΔDBP/[Formula: see text] and ΔHR/[Formula: see text] throughout the experimental period. The changes in ΔSBP/[Formula: see text] after training and detraining were significantly correlated with those in HVR. These results suggest that ΔSBP/[Formula: see text] to progressive isocapnic hypoxia is variable after endurance training during hypoxia and normoxia and after detraining, as is HVR, but ΔDBP/[Formula: see text] and ΔHR/[Formula: see text] are not. It also suggests that there is an interaction between the changes in ΔSBP/[Formula: see text] and HVR after endurance training or detraining.
A new model of chronic cardiac ischemia in rabbits
Authors: Operschall Christine , Falivene Loretta , Clozel Jean-Paul , Roux Sébastien
Published: December 2017

Chronic cardiac ischemia has mainly been studied in large species such as pigs or dogs. Little research has been performed using small species such as rabbits. In the present study, 1–3 wk after implantation of a novel device (ameroid) on the circumflex coronary artery of New Zealand White rabbits, vessel patency was evaluated by coronary angiography, corrosion cast, and radiolabeled microspheres. Coronary angiograms showed, after 21 days, either total occlusion or severe stenosis in seven of eight arteries, which was confirmed by corrosion casts. The ameroid group had less blood flow in the epicardial (−62%) and endocardial (−54%) layers of the ischemic area compared with sham-operated rabbits ( P < 0.05). Blood flow increased in the ischemic area compared with day 0during acute occlusion, suggesting that progressive coronary occlusion initiated the growth of de novo collateral vessels. Thus we have developed a new model of chronic cardiac ischemia in rabbits with documented progressive coronary stenosis and occlusion that is suitable to test various therapeutic angiogenesis strategies.
Aging, physical conditioning, and exercise-induced changes in hemostatic factors and reaction products
Authors: van den Burg P. J. M. , Hospers J. E. H. , Mosterd W. L. , Bouma B. N. , Huisveld I. A.
Published: December 2017

The influence of age on training-induced changes in resting and stimulated hemostatic potential was studied in three age categories (Cat I–III; 20–30 yr, 35–45 yr, and 50–60 yr, respectively) of sedentary men before and after 12 wk of training. Coagulation, fibrinolytic activity, and activation markers (reflecting fibrin formation and degradation) were determined. Physical conditioning resulted in a more pronounced increase in von Willebrand factor (vWF) and factor VIII clotting activity (FVIII:c) in Cat I and II and a more pronounced shortening of the activated partial thromboplastin time in all categories at maximal exertion and during recovery. Enhanced increases in tissue-type plasminogen activator (t-PA) antigen and activity and single-chain (sc) urokinase-type plasminogen activator (u-PA) at maximal exercise and 5 min of recovery were observed in all age groups after training. The effects on FVIII:c, vWF, and scu-PA were most pronounced in the youngest age group (Cat I). Increases in the marker of thrombin generation were highest in Cat III; no effect was seen on thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer in any of the age groups. We concluded that training enhances both coagulation and fibrinolytic potential during strenuous exercise. The effect on FVIII/vWF and t-PA/u-PA is most pronounced in younger individuals, whereas thrombin formation is most pronounced in older individuals.
Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans
Authors: Takarada Yudai , Takazawa Haruo , Sato Yoshiaki , Takebayashi Shigeo , Tanaka Yasuhiro , Ishii Naokata
Published: December 2017

Acute and long-term effects of resistance exercise combined with vascular occlusion on muscular function were investigated. Changes in integrated electromyogram with respect to time (iEMG), vascular resistive index, and plasma lactate concentration were measured in five men either during or after elbow flexion exercises with the proximal end of the arm occluded at 0–100 mmHg. The mean iEMG, postexercise hyperemia, and plasma lactate concentration were all elevated with the increase in occlusion pressure at a low-intensity exercise, whereas they were unchanged with the increase in occlusion pressure at high-intensity exercise. To investigate the long-term effects of low-intensity exercise with occlusion, older women ( n = 24) were subjected to a 16-wk exercise training for elbow flexor muscles, in which low-intensity [∼50–30% one repetition maximum (1 RM)] exercise with occlusion at ∼110 mmHg (LIO), low-intensity exercise without occlusion (LI), and high- to medium-intensity (∼80–50% 1 RM) exercise without occlusion (HI) were performed. Percent increases in both cross-sectional area and isokinetic strength of elbow flexor muscles after LIO were larger than those after LI ( P < 0.05) and similar to those after HI. The results suggest that resistance exercise at an intensity even lower than 50% 1 RM is effective in inducing muscular hypertrophy and concomitant increase in strength when combined with vascular occlusion.
Near-maximal fractional oxygen extraction by active skeletal muscle in patients with chronic heart failure
Authors: Katz Stuart D. , Maskin Carol , Jondeau Guillaume , Cocke Thomas , Berkowitz Robert , LeJemtel Thierry
Published: December 2017

Systemic oxygen uptake and deep femoral vein oxygen content were determined at peak exercise in 53 patients with chronic heart failure with impaired systolic function (mean left ventricular ejection fraction 0.18; n = 41) or preserved systolic function (mean left ventricular ejection fraction 0.70; n = 12) and in 6 age-matched sedentary normal subjects. At peak exercise, deep femoral vein oxygen content in heart failure patients with impaired systolic function and preserved systolic function were similar, both significantly lower than that of normal subjects (2.5 ± 0.1, 2.9 ± 0.2, and 5.0 ± 0.1 ml/100 ml, respectively; P< 0.05). Deep femoral venous oxygen content was lower in patients with the greater impairment of aerobic capacity, regardless of the underlying systolic function ( r = 0.72, P < 0.01). Fractional oxygen extraction in the skeletal muscle at peak exercise is enhanced in patients with chronic heart failure when compared with normal subjects, in proportion to the degree of aerobic impairment.
Imaging obstructed ventilation with NMR using inert fluorinated gases
Authors: Kuethe Dean O. , Caprihan Arvind , Gach H. Michael , Lowe Irving J. , Fukushima Eiichi
Published: December 2017

We partially obstructed the left bronchi of rats and imaged an inert insoluble gas, SF6, in the lungs with NMR using a technique that clearly differentiates obstructed and normal ventilation. When the inhaled fraction of O2is high, SF6 concentrates dramatically in regions of the lung with low ventilation-to-perfusion ratios (V˙a/Q˙); therefore, these regions are brighter in an image than whereV˙a/Q˙ values are normal or high. A second image, made when the inhaled fraction of O2 is low, serves as a reference because the SF6 fraction is nearly uniform, regardless ofV˙a/Q˙. The quotient of the first and second images displays the low-V˙a/Q˙ regions and is corrected for other causes of brightness variation. The technique may provide sufficient quantification ofV˙a/Q˙ to be a useful research tool. The noise in the quotient image is described by the probability density function for the quotient of two normal random variables. When the signal-to-noise ratio of the denominator image is >10, the signal-to-noise ratio of the quotient image is similar to that of the parent images and decreases with pixel value.
Effects of short-term oral salbutamol administration on exercise endurance and metabolism
Authors: Collomp K. , Candau R. , Lasne F. , Labsy Z. , Préfaut C. , De Ceaurriz J.
Published: December 2017

The present study examined whether oral short-term administration of salbutamol (Sal) modifies performance and selected hormonal and metabolic variables during submaximal exercise. Eight recreational male athletes completed two cycling trials at 80–85% peak O2 consumption until exhaustion after either gelatin placebo (Pla) or oral Sal (12 mg/day for 3 wk) treatment, according to a double-blind and randomized protocol. Blood samples were collected at rest, after 5, 10, and 15 min, and at exhaustion to determine growth hormone (GH), cortisol, testosterone, triiodothyronine (T3), C peptide, free fatty acid (FFA), blood glucose, lactate, and blood urea values. Time of cycling was significantly increased after chronic Sal intake (Sal: 30.5 ± 3.1 vs. Pla: 23.7 ± 1.6 min, P < 0.05). No change in any variable was found before cycling except a decrease in blood urea concentration and an increase in T3 after Sal that remained significant throughout the exercise test ( P < 0.05). Compared with rest, exercise resulted in a significant increase in GH, cortisol, testosterone, T3, FFAs, and lactate and a decrease in C peptide after both treatments with higher exercise FFA levels and exhaustion GH concentrations after Sal ( P < 0.05). Sal but not Pla significantly decreased exercise blood glucose levels. From these data, short-term Sal intake did appear to improve performance during intense submaximal exercise with concomitant increase in substrate availability and utilization, but the exact mechanisms involved need further investigation.
Natural history of severe decompression sickness after rapid ascent from air saturation in a porcine model
Authors: Dromsky David M. , Toner Charles B. , Survanshi Shalini , Fahlman Andreas , Parker Erich , Weathersby Paul
Published: December 2017

We developed a swine model to describe the untreated natural history of severe decompression sickness (DCS) after direct ascent from saturation conditions. In a recompression chamber, neutered male Yorkshire swine were pressurized to a predetermined depth from 50–150 feet of seawater [fsw; 2.52–5.55 atmospheres absolute (ATA)]. After 22 h, they returned to the surface (1 ATA) at 30 fsw/min (0.91 ATA/min) without decompression stops and were observed. Depth was the primary predictor of DCS incidence ( R = 0.52, P < 0.0001) and death ( R = 0.54, P < 0.0001). Severe DCS, defined as neurological or cardiopulmonary impairment, occurred in 78 of 128 animals, and 42 of 51 animals with cardiopulmonary DCS died within 1 h after surfacing. Within 24 h, 29 of 30 survivors with neurological DCS completely resolved their deficits without intervention. Pretrial Monte Carlo analysis decreased subject requirement without sacrificing power. This model provides a useful platform for investigating the pathophysiology of severe DCS and testing therapeutic interventions. The results raise important questions about present models of human responses to similar decompressive insults.
β-Adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats
Authors: Frank James A. , Wang Yibing , Osorio Oscar , Matthay Michael A.
Published: December 2017

To determine whether β-adrenergic agonist therapy increases alveolar liquid clearance during the resolution phase of hydrostatic pulmonary edema, we studied alveolar and lung liquid clearance in two animal models of hydrostatic pulmonary edema. Hydrostatic pulmonary edema was induced in sheep by acutely elevating left atrial pressure to 25 cmH2O and instilling 6 ml/kg body wt isotonic 5% albumin (prepared from bovine albumin) in normal saline into the distal air spaces of each lung. After 1 h, sheep were treated with a nebulized β-agonist (salmeterol) or nebulized saline (controls), and left atrial pressure was then returned to normal. β-Agonist therapy resulted in a 60% increase in alveolar liquid clearance over 3 h ( P< 0.001). Because the rate of alveolar fluid clearance in rats is closer to human rates, we studied β-agonist therapy in rats, with hydrostatic pulmonary edema induced by volume overload (40% body wt infusion of Ringer lactate). β-Agonist therapy resulted in a significant decrease in excess lung water ( P < 0.01) and significant improvement in arterial blood gases by 2 h ( P < 0.03). These preclinical experimental studies support the need for controlled clinical trials to determine whether β-adrenergic agonist therapy would be of value in accelerating the resolution of hydrostatic pulmonary edema in patients.
Differential effects of furosemide on porcine bronchial arterial and airway smooth muscle
Authors: Corboz Michel R. , Ballard Stephen T. , Gao Hong , Benoit Joseph N. , Inglis Sarah K. , Taylor Aubrey E.
Published: December 2017

Furosemide attenuates airway obstruction in asthmatic subjects when administered as an aerosol pretreatment. This protective effect of furosemide could be related to relaxation of bronchial smooth muscle or to increased bronchial blood flow. To determine whether furosemide dilates bronchial smooth muscle, isometric contractile responses in distal bronchi from young pigs were studied. In bronchial smooth muscle rings that were precontracted with 10−5 M acetylcholine, significant relaxation occurred with 10−8 to 3 × 10−6 M isoproterenol but not with 10−8 to 10−3 M furosemide. In contrast, bronchial arteries that were precontracted with either 10−4 M norepinephrine or 10−8 M vasopressin significantly relaxed in response to 10−4 to 3 × 10−3 M and 10−3 to 3 × 10−3 M furosemide, respectively. We conclude that furosemide, under the described experimental conditions, relaxes airway vascular smooth muscle but not bronchial smooth muscle. These results are consistent with previous suggestions that inhaled furosemide increases blood flow to airway tissues (Gilbert IA, Lenner KA, Nelson JA, Wolin AD, and Fouke JM. J Appl Physiol 76: 409–415, 1994).
Insulin and exercise differentially regulate PI3-kinase and glycogen synthase in human skeletal muscle
Authors: O'Gorman Donal J. , Del Aguila Luis F. , Williamson David L. , Krishnan Raj K. , Kirwan John P.
Published: December 2017

The purpose of this study was to determine the separate and combined effects of exercise and insulin on the activation of phosphatidylinositol 3-kinase (PI3-kinase) and glycogen synthase in human skeletal muscle in vivo. Seven healthy men performed three trials in random order. The trials included 1) ingestion of 2 g/kg body wt carbohydrate in a 10% solution (CHO); 2) 75 min of semirecumbent cycling exercise at 75% of peak O2 consumption; followed by 5 × 1-min maximal sprints (Ex); and 3) Ex, immediately followed by ingestion of the carbohydrate solution (ExCHO). Plasma glucose and insulin were increased ( P < 0.05) at 15 and 30 (Post-15 and Post-30) min after the trial during CHO and ExCHO, although insulin was lower for ExCHO. Hyperinsulinemia during recovery in CHO and ExCHO led to an increase ( P < 0.001) in PI3-kinase activity at Post-30 compared with basal, although the increase was lower ( P < 0.004) for ExCHO. Furthermore, PI3-kinase activity was suppressed ( P < 0.02) immediately after exercise (Post-0) during Ex and ExCHO. Area under the insulin response curve for all trials was positively associated with PI3-kinase activity ( r = 0.66, P < 0.001). Glycogen synthase activity did not increase during CHO but was increased ( P < 0.05) at Post-0 and Post-30 during Ex and ExCHO. Ingestion of the drink increased ( P < 0.05) carbohydrate oxidation during CHO and ExCHO, although the increase after ExCHO was lower ( P < 0.05) than CHO. Carbohydrate oxidation was directly correlated with PI3-kinase activity for all trials ( r = 0.63, P < 0.001). In conclusion, under resting conditions, ingestion of a carbohydrate solution led to activation of the PI3-kinase pathway and oxidation of the carbohydrate. However, when carbohydrate was ingested after intense exercise, the PI3-kinase response was attenuated and glycogen synthase activity was augmented, thus facilitating nonoxidative metabolism or storage of the carbohydrate. Activation of glycogen synthase was independent of PI3-kinase.
Bioassayable growth hormone release in rats in response to a single bout of treadmill exercise
Authors: Bigbee A. J. , Gosselink K. L. , Roy R. R. , Grindeland R. E. , Edgerton V. R.
Published: December 2017

Plasma growth hormone (GH) measured by immunoassay [immunoassayable GH (IGH)] and by tibial bioassay [bioassayable GH (BGH)] increases in humans in response to exercise. In rats, however, IGH does not change in response to exercise. The objective of this study was to determine the BGH response to an acute exercise bout in rats. The rats ran on a treadmill at a rate of 27 m/min for 15 min, after which plasma and pituitary hormones, including IGH and BGH, and plasma metabolites were measured. Plasma and pituitary IGH were unchanged from control groups after the acute exercise bout, whereas plasma BGH was increased by 300% and pituitary BGH was decreased by 50%. Plasma thyroxine and corticosterone levels were significantly increased after a single exercise bout, but plasma testosterone, 3,5,3′-triiodothyronine, glucose, lactate, and triglyceride concentrations were unchanged. Given previous results from in situ nerve stimulation studies (Gosselink KL, Grindeland RE, Roy RR, Zhong H, Bigbee AJ, Grossman EJ, and Edgerton VR. J Appl Physiol 84: 1425–1430, 1998), these in vivo results are consistent with the rapid BGH response during exercise being induced by the activation of muscle afferents.
Ventricular activation during sympathetic imbalance and its computational reconstruction
Authors: Nash Martyn P. , Thornton Judith M. , Sears Claire E. , Varghese Anthony , O'Neill Mark , Paterson David J.
Published: December 2017

We characterized the epicardial activation sequence during a norepinephrine (NE)-induced ventricular arrhythmia in anesthetized pigs and studied factors that modulated it. Subepicardial NE infusion caused the QRS complex to invert within a single beat ( n = 35 animals, 101 observations), and the earliest epicardial activation consistently shifted to the randomly located infusion site ( n = 14). This preceded right atrial activation, whereas the total ventricular epicardial activation time increased from 20 ± 4 to 50 ± 9 ms ( P < 0.01). These events were accompanied by a ventricular tachycardia and a drop in left ventricular pressure, which were fully reversed after the infusion was stopped. Epicardial pacing at the infusion site mimicked all electrical and hemodynamic changes induced by NE. The arrhythmia was prevented by propranolol and abolished by cardiac sympathetic or vagal nerve stimulation. Focal automaticity was computationally reconstructed using a two-dimensional sheet of 256 × 256 resistively coupled ventricular cells, where calcium handling was abnormally high in the central region. We conclude that adrenergic stimulation to a small region of the ventricle elicits triggered automaticity and that computational reconstruction implicates calcium overload. Interventions that reduce spatial inhomogeneities of intracellular calcium may prevent this type of arrhythmia.
Effect of carbohydrate ingestion on glucose kinetics during exercise in the heat
Authors: Angus Damien J. , Febbraio Mark A. , Lasini David , Hargreaves Mark
Published: December 2017

Six endurance-trained men [peak oxygen uptake (V˙o 2) = 4.58 ± 0.50 (SE) l/min] completed 60 min of exercise at a workload requiring 68 ± 2% peak V˙o 2 in an environmental chamber maintained at 35°C (<50% relative humidity) on two occasions, separated by at least 1 wk. Subjects ingested either a 6% glucose solution containing 1 μCi [3-3H]glucose/g glucose (CHO trial) or a sweet placebo (Con trial) during the trials. Rates of hepatic glucose production [HGP = glucose rate of appearance (Ra) in Con trial] and glucose disappearance (Rd), were measured using a primed, continuous infusion of [6,6-2H]glucose, corrected for gut-derived glucose (gut Ra) in the CHO trial. No differences in heart rate, V˙o 2, respiratory exchange ratio, or rectal temperature were observed between trials. Plasma glucose concentrations were similar at rest but increased ( P < 0.05) to a greater extent in the CHO trial compared with the Con trial. This was due to the absorption of ingested glucose in the CHO trial, because gut Ra after 30 and 50 min (16 ± 5 μmol · kg−1 · min−1) was higher ( P < 0.05) compared with rest, whereas HGP during exercise was not different between trials. Glucose Rd was higher ( P < 0.05) in the CHO trial after 30 and 50 min (48.0 ± 6.3 vs 34.6 ± 3.8 μmol · kg−1 · min−1, CHO vs. Con, respectively). These results indicate that ingestion of carbohydrate, at a rate of ∼1.0 g/min, increases glucose Rd but does not blunt the rise in HGP during exercise in the heat.
Single-breath washouts in a rotating stretcher
Authors: Rodríguez-Nieto M. J. , Peces-Barba G. , Mangado N. González , Verbanck S. , Paiva M.
Published: December 2017

Vital capacity single-breath washouts using 90% O2-5% He-5% SF6 as a test gas mixture were performed with subjects sitting on a stool (upright) or recumbent on a stretcher (prone, supine, lateral left, lateral right, with or without rotation at end of inhalation). On the basis of the combinations of supine and prone maneuvers, gravity-dependent contributions to N2 phase III slope and N2 phase IV height in the supine posture were estimated at 18% and 68%, respectively. Whereas both He and SF6 slope decreased from supine to prone, the SF6-He slope difference actually increased ( P = 0.015). N2 phase III slopes, phase IV heights, and cardiogenic oscillations were smallest in the prone posture, and we observed similarities between the modifications of He and SF6 slopes from upright to prone and from upright to short-term microgravity. These results suggest that phase III slope is partially due to emptying patterns of small units with different ventilation-to-volume ratios, corresponding to acini or groups of acini. Of all body postures under study, the prone position most reduces the inhomogeneities of ventilation during a vital capacity maneuver at both inter- and intraregional levels.