bluuebunny/crossref_metadata_2025 huggingface dataset:
Decrease in maximal voluntary contraction by tonic vibration applied to a single synergist muscle in humans
Authors: Kouzaki Motoki , Shinohara Minoru , Fukunaga Tetsuo
Published: December 2017

The purpose of the study was to examine the effect of prolonged tonic vibration applied to a single synergist muscle on maximal voluntary contraction (MVC) and maximal rate of force development (dF/d t max). The knee extension MVC force and surface electromyogram (EMG) from the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) during MVC were recorded before and after vibration of RF muscle at 30 Hz for 30 min. MVC, dF/d t max, and the integrated EMG (iEMG) of RF decreased significantly after prolonged tonic vibration in spite of no changes in iEMG of VL and VM. The present results indicate that MVC and dF/d t max may be influenced by the attenuated Ia afferent functions of a single synergist muscle.
Hyperbaric oxygen improves contractile function of regenerating rat skeletal muscle after myotoxic injury
Authors: Gregorevic Paul , Lynch Gordon S. , Williams David A.
Published: December 2017

There is growing interest in hyperbaric oxygen (HBO) as an adjunctive treatment for muscle injuries. This experiment tested the hypothesis that periodic inhalation of HBO hastens the functional recovery and myofiber regeneration of skeletal muscle after myotoxic injury. Injection of the rat extensor digitorum longus (EDL) muscle with bupivacaine hydrochloride causes muscle degeneration. After injection, rats breathed air with or without periodic HBO [100% O2 at either 2 or 3 atmospheres absolute (ATA)]. In vitro maximum isometric tetanic force of injured EDL muscles and regenerating myofiber size were unchanged between 2 ATA HBO-treated and untreated rats at 14 days postinjury but were ∼11 and ∼19% greater, respectively, in HBO-treated rats at 25 days postinjury. Maximum isometric tetanic force of injured muscles was ∼27% greater, and regenerating myofibers were ∼41% larger, in 3 ATA HBO-treated rats compared with untreated rats at 14 days postinjury. These findings demonstrate that periodic HBO inhalation increases maximum force-producing capacity and enhances myofiber growth in regenerating skeletal muscle after myotoxic injury with greater effect at 3 than at 2 ATA.
A novel cell culture model for studying ischemia-reperfusion injury in lung transplantation
Authors: Cardella Jonathan A. , Keshavjee Shaf , Mourgeon Eric , Cassivi Stephen D. , Fischer Stefan , Isowa Noritaka , Slutsky Arthur , Liu Mingyao
Published: December 2017

Many cell culture models have been developed to study ischemia-reperfusion injury; however, none is specific to the conditions of lung preservation and transplantation. The objective of this study was to design a cell culture model that mimics clinical lung transplantation, in which preservation is aerobic and hypothermic. A549 cells, a human pulmonary epithelial cell line, were preserved in 100% O2at 4°C for varying periods in low-potassium dextran glucose solution, simulating ischemia, followed by the introduction of warm (37°C) DMEM plus 10% fetal bovine serum to simulate reperfusion. Cultures were assayed for cell attachment and viability. Sequential extension of ischemic times to 24 h showed a time-dependent loss of cells. There was a further decrease in cell number after simulated reperfusion. Cell detachment was due mainly to cell death, as determined by cell viability. The effects of chemical components such as dextran 40 and calcium in the preservation solution and various preservation gas mixtures were examined by use of this model system. With its design and validation, this model could be used to study mechanisms related to ischemia-reperfusion injury at the cellular and molecular level.
Influence of microgravity on crystal formation in biomineralization
Authors: Becker Wilhelm , Marxen Julia , Epple Matthias , Reelsen Oliver
Published: December 2017

Biomineralized tissues are widespread in animals. They are essential elements in skeletons and in statocysts. The function of both can only be understood with respect to gravitational force, which has always been present. Therefore, it is not astonishing to identify microgravity as a factor influencing biomineralization, normally resulting in the reduction of biomineralized materials. All known biominerals are composite materials, in which the organic matrix and the inorganic materials, organized in crystals, interact. If, during remodeling and turnover processes under microgravity, a defective organization of these crystals occurs, a reduction in biomineralized materials could be the result. To understand the influence of microgravity on the formation of biocrystals, we studied the shell-building process of the snail Biomphalaria glabrataas a model system. We show that, under microgravity (space shuttle flights STS-89 and STS-90), shell material is built in a regular way in both adult snails and snail embryos during the beginning of shell development. Microgravity does not influence crystal formation. Because gravity has constantly influenced evolution, the organization of biominerals with densities near 3 must have gained independence from gravitational forces, possibly early in evolution.
Effect ofl-arginine on endothelial injury and hemostasis in rabbit endotoxin shock
Authors: Wiel Eric , Pu Qian , Corseaux Delphine , Robin Emmanuel , Bordet Régis , Lund Niels , Jude Brigitte , Vallet Benoît
Published: December 2017

To investigate whether impaired endothelial function was related to alteration of nitric oxide (NO) formation during endotoxic shock, we studied the effects of supplementation of l-arginine (l-Arg),d-arginine (d-Arg), and NG-nitro-l-arginine methyl ester (l-NAME), on endothelial function and structure in a rabbit model. Endotoxic shock was induced by a single lipopolysaccharide bolus (0.5 mg/kg iv, Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor were determined by functional assays. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess damaged endothelial cell surface of the abdominal aorta. These parameters were studied 5 days after the onset of endotoxic shock and were compared under three conditions: in absence of treatment, with l-Arg or d-Arg supplementation, or with l-NAME. Bothl-Arg and d-Arg significantly improved endothelium-dependent relaxation and endothelial morphological injury.l-NAME did not alter endothelial histological injury induced by lipopolysaccharide. These data indicate that arginine supplementation nonspecifically prevents endothelial dysfunction and histological injury in rabbit endotoxic shock. Moreover,l-Arg has no effect on coagulation activation and expression of monocyte tissue factor induced by endotoxic shock.
Impaired interval exercise responses in elite female cyclists at moderate simulated altitude
Authors: Brosnan Maria J. , Martin David T. , Hahn Allan G. , Gore Christopher J. , Hawley John A.
Published: December 2017

The effect of hypoxia on the response to interval exercise was determined in eight elite female cyclists during two interval sessions: a sustained 3 × 10-min endurance set (5-min recovery) and a repeat sprint session comprising three sets of 6 × 15-s sprints (work-to-relief ratios were 1:3, 1:2, and 1:1 for the 1st, 2nd, and 3rd sets, respectively, with 3 min between each set). During exercise, cyclists selected their maximum power output and breathed either atmospheric air (normoxia, 20.93% O2) or a hypoxic gas mix (hypoxia, 17.42% O2). Power output was lower in hypoxia vs. normoxia throughout the endurance set (244 ± 18 vs. 226 ± 17, 234 ± 18 vs. 221 ± 25, and 235 ± 18 vs. 221 ± 25 W for 1st, 2nd, and 3rd sets, respectively; P < 0.05) but was lower only in the latter stages of the second and third sets of the sprints (452 ± 56 vs. 429 ± 49 and 403 ± 54 vs. 373 ± 43 W, respectively; P < 0.05). Hypoxia lowered blood O2 saturation during the endurance set (92.9 ± 2.9 vs. 95.4 ± 1.5%; P < 0.05) but not during repeat sprints. We conclude that, when elite cyclists select their maximum exercise intensity, both sustained (10 min) and short-term (15 s) power are impaired during hypoxia, which simulated moderate (∼2,100 m) altitude.
Controlled 5-mo aerobic training improves heart rate but not heart rate variability or baroreflex sensitivity
Authors: Loimaala Antti , Huikuri Heikki , Oja Pekka , Pasanen Matti , Vuori Ilkka
Published: December 2017

Endurance-trained athletes have increased heart rate variability (HRV), but it is not known whether exercise training improves the HRV and baroreflex sensitivity (BRS) in sedentary persons. We compared the effects of low- and high-intensity endurance training on resting heart rate, HRV, and BRS. The maximal oxygen uptake and endurance time increased significantly in the high-intensity group compared with the control group. Heart rate did not change significantly in the low-intensity group but decreased significantly in the high-intensity group (−6 beats/min, 95% confidence interval; −10 to −1 beats/min, exercise vs. control). No significant changes occurred in either the time or frequency domain measures of HRV or BRS in either of the exercise groups. Exercise training was not able to modify the cardiac vagal outflow in sedentary, middle-aged persons.
Regional blood flow during exercise in humans measured by near-infrared spectroscopy and indocyanine green
Authors: Boushel Robert , Langberg Henning , Olesen Jens , Nowak Markus , Simonsen Lene , Bülow Jens , Kjær Michael
Published: December 2017

Using near-infrared spectroscopy (NIRS) and the tracer indocyanine green (ICG), we quantified blood flow in calf muscle and around the Achilles tendon during plantar flexion (1–9 W). For comparison, blood flow in calf muscle was determined by dye dilution in combination with magnetic resonance imaging measures of muscle volume, and, for the peritendon region, blood flow was measured by 133Xe washout. From rest to a peak load of 9 W, NIRS-ICG blood flow in calf muscle increased from 2.4 ± 0.2 to 74 ± 5 ml · 100 ml tissue−1 · min−1, similar to that measured by reverse dye (77 ± 6 ml · 100 ml tissue−1 · min−1). Achilles peritendon blood flow measured by NIRS-ICG rose with exercise from 2.2 ± 0.5 to 15.1 ± 0.2 ml · 100 ml−1 · min−1, which was similar to that determined by 133Xe washout (2.0 ± 0.6 to 14.6 ± 0.3 ml · 100 ml tissue−1 · min−1). This is the first study using NIRS and ICG to quantify regional tissue blood flow during exercise in humans. Due to its high spatial and temporal resolution, the technique may be useful for determining regional blood flow distribution and regulation during exercise in humans.
Quantitative analysis of feedforward sympathetic coronary vasodilation in exercising dogs
Authors: Gorman Mark W. , Tune Johnathan D. , Richmond Keith Neu , Feigl Eric O.
Published: December 2017

Recent experiments demonstrate that feedforward sympathetic β-adrenoceptor coronary vasodilation occurs during exercise. The present study quantitatively examined the contributions of epinephrine and norepinephrine to exercise coronary hyperemia and tested the hypothesis that circulating epinephrine causes feedforward β-receptor-mediated coronary dilation. Dogs ( n = 10) were chronically instrumented with a circumflex coronary artery flow transducer and catheters in the aorta and coronary sinus. During strenuous treadmill exercise, myocardial oxygen consumption increased by ∼3.9-fold, coronary blood flow increased by ∼3.6-fold, and arterial plasma epinephrine concentration increased by ∼2.4-fold over resting levels. At arterial concentrations matching those during strenuous exercise, epinephrine infused at rest ( n = 6) produced modest increases (18%) in flow and myocardial oxygen consumption but no evidence of direct β-adrenoceptor-mediated coronary vasodilation. Arterial norepinephrine concentration increased by ∼5.4-fold during exercise, and coronary venous norepinephrine was always higher than arterial, indicating norepinephrine release from cardiac sympathetic nerves. With the use of a mathematical model of cardiac capillary norepinephrine transport, these norepinephrine concentrations predict an average interstitial norepinephrine concentration of ∼12 nM during strenuous exercise. Published dose-response data indicate that this norepinephrine concentration increases isolated coronary arteriolar conductance by ∼67%, which can account for ∼25% of the increase in flow observed during exercise. It is concluded that a significant portion of coronary exercise hyperemia (∼25%) can be accounted for by direct feedforward β-adrenoceptor coronary vascular effects of norepinephrine, with little effect from circulating epinephrine.
State influences on ventral medullary surface and physiological responses to sodium cyanide challenges
Authors: Macey Paul M. , Richard Christopher A. , Rector David M. , Harper Rebecca K. , Harper Ronald M.
Published: December 2017

Intravenous sodium cyanide (NaCN) administration lowers ventral medullary surface (VMS) activity in anesthetized cats. Sleep states modify spontaneous and blood pressure-evoked VMS activity and may alter VMS responses to chemoreceptor input. We studied VMS activation during peripheral chemoreceptor stimulation by intravenous NaCN using optical procedures in six cats instrumented for recording sleep physiology during sham saline and control site trials. Images of scattered 660-nm light were collected at 50 frames/s with an optical device after 80–100 μg total bolus intravenous NaCN delivery during waking and sleep states. Cyanide elicited an initial ventilatory decline, followed by large inspiratory efforts and an increase in respiratory rate, except in rapid eye movement sleep, in which an initial breathing increase occurred. NaCN evoked a pronounced decrease in VMS activity in all states; control sites and sham injections showed little effect. The activity decline was faster in rapid eye movement sleep, and the activity nadir occurred later in waking. Sleep states alter the time course but not the extent of decline in VMS activity.
Expression of hypoxia-inducible factor-1α in the brain of rats during chronic hypoxia
Authors: Chávez Juan C. , Agani Faton , Pichiule Paola , LaManna Joseph C.
Published: December 2017

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates adaptive responses to the lack of oxygen in mammalian cells. HIF-1 consists of two proteins, HIF-1α and HIF-1β. HIF-1α accumulates under hypoxic conditions, whereas HIF-1β is constitutively expressed. HIF-1α and HIF-1β expression were measured during adaptation to hypobaric hypoxia (0.5 atm) in rat cerebral cortex. Western blot analyses indicated that HIF-1α rapidly accumulated during the onset of hypoxia and did not fall for 14 days but fell to normal by 21 days despite the continuous low arterial oxygen tension. Immunostaining showed that neurons, astrocytes, ependymal cells, and possibly endothelial cells were the cell types expressing HIF-1α. Genes with hypoxia-responsive elements were activated under these conditions, as evidenced by elevated vascular endothelial growth factor and glucose transporter-1 mRNA levels. When 21-day-adapted rats were exposed to a more severe hypoxic challenge (8% oxygen), HIF-1α accumulated again. On the basis of these results, we speculate that the vascular remodeling and metabolic changes triggered during prolonged hypoxia are capable of restoring normal tissue oxygen levels.
Airway function after cyclooxygenase inhibition during hyperpnea-induced bronchoconstriction in guinea pigs
Authors: Suman O. E. , Morrow J. D. , O'Malley K. A. , Beck K. C.
Published: December 2017

Airway function deteriorates significantly on cessation of exercise or isocapnic hyperventilation challenges but is largely preserved during the challenge in humans and guinea pigs. PGE2, an endogenous bronchodilator, might be responsible for the preservation of lung function during hyperventilation (HV). We hypothesized that PGE2might have a protective effect during HV, partially explaining the minimal changes in respiratory system resistance (Rrs) usually seen during HV in humans and guinea pigs. Therefore, changes in Rrs were measured during and after HV in anesthetized, mechanically ventilated guinea pigs treated with flurbiprofen (FBN) or placebo. With HV, there was an initial bronchodilation that was unaffected by FBN. Rrs then increased with time during HV, an effect that was blocked by FBN. After HV, Rrs increased further in all groups, but the increase in Rrs was less in the FBN-treated groups. FBN treatment reduced the PGE2concentration slightly in lung lavage fluid compared with placebo. We found no enhancement or refractoriness of the Rrs response to repeat bouts of HV and no effect of FBN treatment on the response of Rrs to repeat HV. These results suggest that a constrictor PG is released during and possibly after HV and that the post-HV increase in Rrs is the sum of effects of the PG released during HV and a second constrictor mechanism operating after HV. We found no evidence for bronchodilator PG during or after HV in the guinea pig.
Counteraction of aortic baroreflex to carotid sinus baroreflex in a neck suction model
Authors: Kawada Toru , Inagaki Masashi , Takaki Hiroshi , Sato Takayuki , Shishido Toshiaki , Tatewaki Teiji , Yanagiya Yusuke , Sugimachi Masaru , Sunagawa Kenji
Published: December 2017

Although neck suction has been widely used in the evaluation of carotid sinus baroreflex function in humans, counteraction of the aortic baroreflex tends to complicate any interpretation of observed arterial pressure (AP) response. To determine whether a simple linear model can account for the AP response during neck suction, we developed an animal model of the neck suction procedure in which changes in carotid distension pressure during neck suction were directly imposed on the isolated carotid sinus. In six anesthetized rabbits, a 50-mmHg pressure perturbation on the carotid sinus decreased AP by −27.4 ± 4.8 mmHg when the aortic baroreflex was disabled. Enabling the aortic baroreflex significantly attenuated the AP response (−21.5 ± 3.8 mmHg, P< 0.01). The observed closed-loop gain during simulated neck suction was well predicted by the open-loop gains of the carotid sinus and aortic baroreflexes using the linear model (−0.43 ± 0.13 predicted vs. −0.41 ± 0.10 measured). We conclude that the linear model can be used as the first approximation to interpret AP response during neck suction.
Kinetics of intramuscular triglyceride fatty acids in exercising humans
Authors: Guo Zengkui , Burguera Bartolome , Jensen Michael D.
Published: December 2017

A pulse ([14C]palmitate)-chase ([3H]palmitate) approach was used to study intramuscular triglyceride (imTG) fatty acid and plasma free fatty acid (FFA) kinetics during exercise at ∼45% peak O2consumption in 12 adults. Vastus lateralis muscle was biopsied before and after 90 min of bicycle exercise;3H2O production, breath14CO2excretion and lipid oxidation (indirect calorimetry) rates were measured during exercise. Results: during exercise, 8.2 ± 1.2 and 8.4 ± 0.7 μmol · kg−1· min−1of imTG fatty acids and plasma FFA, respectively, were oxidized according to isotopic measurements. The sum of these two values was not different ( P = 0.6) from lipid oxidation by indirect calorimetry (15.4 ± 1.6 μmol · kg−1· min−1); the isotopic and indirect calorimetry values were correlated ( r = 0.79, P < 0.005). During exercise, imTG turnover rate was 0.32 ± 0.07%/min (6.0 ± 2.0 μmol of imTG · kg wet muscle−1· min−1) and plasma FFA were incorporated into imTG at a rate of 0.7 ± 0.1 μmol · kg wet muscle−1· min−1. The imTG pool size did not change during exercise. This pulse-chase, dual tracer appears to be a reasonable approach to measure oxidation and synthesis kinetics of imTG.
Response of arterial smooth muscle to length perturbation
Authors: Seow Chun Y.
Published: December 2017

The ability of arterial smooth muscle to generate tension is influenced by muscle length. An unsettled question is whether the length-tension relationship is a simple reflection of the contractile filament overlap, as it is in skeletal muscle. There are several factors that could potentially affect tension generation in arterial smooth muscle; these include stretch-induced myogenic response and length-oscillation-induced disruption of the contractile filament organization. In this study, in which rabbit carotid arterial preparations were used, we found that different length-tension curves could be obtained at different times after a length change. In addition, length oscillation at a frequency of normal pulse rate and with small to moderate oscillation amplitude was found to potentiate tension generation but reduced tension at large amplitudes. The observed response could be attributed to adaptation of the muscle to length change over time and to myogenic potentiation associated with stretching of the muscle.
Selected Contribution: Axial stretch increases spontaneous pacemaker activity in rabbit isolated sinoatrial node cells
Authors: Cooper Patricia J. , Lei Ming , Cheng Long-Xian , Kohl Peter
Published: December 2017

Isolated, spontaneously beating rabbit sinoatrial node cells were subjected to longitudinal stretch, using carbon fibers attached to both ends of the cell. Their electrical behavior was studied simultaneously in current-clamp or voltage-clamp mode using the perforated patch configuration. Moderate stretch (∼7%) caused an increase in spontaneous beating rate (by ∼5%) and a reduction in maximum diastolic and systolic potentials (by ∼2.5%), as seen in multicellular preparations. Mathematical modeling of the stretch intervention showed the experimental results to be compatible with stretch activation of cation nonselective ion channels, similar to those found in other cardiac cell populations. Voltage-clamp experiments validated the presence of a stretch-induced current component with a reversal potential near −11 mV. These data confirm, for the first time, that the positive chronotropic response of the heart to stretch is, at least in part, encoded on the level of individual sinoatrial node pacemaker cells; all reported data are in agreement with a major contribution of stretch-activated cation nonselective channels to this response.
Hypertonic saline aerosol increases airway reactivity in the canine lung periphery
Authors: Suzuki Ryoichi , Freed Arthur N.
Published: December 2017

Hyperventilation with dry air increases airway surface fluid (ASF) osmolality and causes acute mucosal injury, leukocyte infiltration, and delayed airway obstruction and hyperreactivity in canine peripheral airways. The purpose of this study was to determine whether ASF hypertonicity per se can account for these hyperventilation-associated effects. We first measured ASF osmolality before and after normal (NSC) and hypertonic (HSC) saline aerosol challenges to document the magnitude of hypertonicity produced by these stimuli. We then measured canine peripheral airway resistance and reactivity to hypocapnia and aerosolized histamine before and after NSC and HSC. Cells and eicosanoid mediators recovered in bronchoalveolar lavage fluid at 5 and 24 h after NSC and HSC were examined. We found that HSC but not NSC caused acute ASF hyperosmolality, increased mediator release, and delayed airway hyperreactivity in the absence of mucosal injury and leukocyte infiltration. These observations suggest that ASF hyperosmolality contributes to the development of the late-phase response to hyperventilation and further suggest that hyperventilation-induced mucosal injury independently initiates leukocyte infiltration and late-phase airway obstruction.
Biaxial constitutive relations for the passive canine diaphragm
Authors: Boriek Aladin M. , Kelly Neil G. , Rodarte Joseph R. , Wilson Theodore A.
Published: December 2017

Samples of the muscular sheet excised from the midcostal region of dog diaphragms were subjected to biaxial loading. That is, stresses in the direction of the muscle fibers and in the direction perpendicular to the fibers in the plane of the sheet were measured at different combinations of strains in the two directions. Stress-strain relations were obtained by fitting equations to these data. In the direction of the muscle fibers, for strains up to 0.7, stress is a modestly nonlinear function of strain and ranges up to ∼60 g/cm. In the direction perpendicular to the fibers, the sheet is stiffer and more strongly nonlinear. At a strain in the perpendicular direction of ∼0.35, stress increases abruptly. The stress-strain relation in the muscle direction is consistent with observations of passive muscle shortening in vivo. However, the stiffness in the perpendicular direction is not high enough to explain the observation that strains in the perpendicular direction in vivo are nearly zero. We conclude that, in the passive diaphragm in vivo, stress in the direction perpendicular to the muscle fibers is small.
Early morphological remodeling of neuromuscular junction in a murine model of diabetes
Authors: Fahim M. A. , Hasan M. Y. , Alshuaib W. B.
Published: December 2017

Although skeletal muscle weakness is documented in diabetes, the time course for its development is not established. The present study examined the dorsiflexor muscle from animals that had been diabetic for 2 wk. Adult male c57BL mice were injected once with streptozotocin (STZ) to induce diabetes (60 mg/kg ip). Two weeks later, resting membrane potential and miniature end-plate potentials were recorded, and electron microscopy was utilized for ultrastructural evaluations. After STZ-induced diabetes, both resting membrane potential and miniature end-plate potentials were reduced. Nerve terminals showed less synaptic vesicles and had degenerated mitochondria. Furthermore, in the intramuscular nerves, disorganization of microtubules and neurofilaments was evidenced. Myelin-like figures were present in intramuscular nerves, neuromuscular junctions, and muscle fibers. At the muscle level, mitochondria were swollen, with disorganization of their cristae, disruption of T tubules, and myofibers with more deposition of glycogen granules. The present results revealed early STZ-induced nerve and muscle alterations. Observed ultrastructural modifications resemble those of motoneuron disorders and aging processes. These changes are possibly related to alterations in Ca2+mobilization across muscle membrane. Other mechanisms such as free radical-mediated actions may also be implicated in STZ-induced effects on skeletal muscle.
Pharmacological characterization of vasomotor activity of human musculocutaneous perforator artery and vein
Authors: Zhang Jianrong , Lipa Joan E. , Black Claire E. , Huang Ning , Neligan Peter C. , Ling Francis T. K. , Levine Ronald H. , Semple John L. , Pang Cho Y.
Published: December 2017

Vasospasm is one of the main causes of skin ischemic necrosis in cutaneous and musculocutaneous flap surgery, but the pathogenic mechanism is unclear. We planned to test the hypothesis derived from clinical impression that veins are more susceptible to vasospasm than arteries in flap surgery and, once established, that venous vasospasm is difficult to resolve and more detrimental than arterial vasospasm. To this end, we investigated the differences in sensitivity to vasoconstrictors and vasodilators between the human musculocutaneous perforator (MCP) artery and vein by measuring the isometric tension of arterial and venous rings suspended in organ chambers. Vascular contraction was expressed as a percentage of the tension induced by 50 mM KCl. Relaxation was expressed as a percentage of contraction induced by a submaximal concentration (3 × 10−9M) of endothelin-1 (ET-1). We observed that the vasoconstrictor potency of norepinephrine was significantly higher in the MCP vein than in the MCP artery. The vasoconstrictor potency of ET-1 and the thromboxane A2mimetic U-46619 were similar in the MCP vein and artery, but the maximal contraction induced by ET-1 and U-46619 was significantly higher in the MCP vein than in the MCP artery. On the other hand, the MCP vein was less sensitive than the MCP artery to the relaxation effect of nitroglycerin, nifedipine, and lidocaine. These differences between the human MCP artery and vein in response to vasoactive agents lend support to the clinical impression in flap surgery that veins appear to be more susceptible to vasospasm than arteries and venous vasospasm seems to be more difficult to resolve than arterial vasospasm in cutaneous and musculocutaneous flap surgery.
Heat storage in horses during submaximal exercise before and after humid heat acclimation
Authors: Geor Raymond J. , McCutcheon Laura Jill , Ecker Gayle L. , Lindinger Michael I.
Published: December 2017

The effect of humid heat acclimation on thermoregulatory responses to humid and dry exercise-heat stress was studied in six exercise-trained Thoroughbred horses. Horses were heat acclimated by performing moderate-intensity exercise for 21 days in heat and humidity (HH) [34.2–35.7°C; 84–86% relative humidity (RH); wet bulb globe temperature (WBGT) index ∼32°C]. Horses completed exercise tests at 50% of peak O2uptake until a pulmonary arterial temperature (Tpa) of 41.5°C was attained in cool dry (CD) (20–21.5°C; 45–50% RH; WBGT ∼16°C), hot dry (HD 0) [32–34°C room temperature (RT); 45–55% RH; WBGT ∼25°C], and HH conditions (HH 0), and during the second hour of HH on days 3, 7, 14, and 21, and in HD on the 18th day (HD 18) of heat acclimation. The ratios of required evaporative capacity to maximal evaporative capacity of the environment (Ereq/Emax) for CD, HD, and HH were ∼1.2, 1.6, and 2.5, respectively. Preexercise Tpaand rectal temperature were ∼0.5°C lower ( P < 0.05) on days 7, 14, and 21 compared with day 0. With exercise in HH, there was no effect of heat acclimation on the rate of rise in Tpa(and therefore exercise duration) nor the rate of heat storage. In contrast, exercise duration was longer, rate of rise in Tpawas significantly slower, and rate of heat storage was decreased on HD 18 compared with HD 0. It was concluded that, during uncompensable heat stress in horses, heat acclimation provided modest heat strain advantages when Ereq/Emaxwas ∼1.6, but at higher Ereq/Emaxno advantages were observed.
Adaptations in β-adrenergic cardiovascular responses to training in older women
Authors: Spina Robert J. , Rashid Saima , Dávila-Román Victor G. , Ehsani Ali A.
Published: December 2017

To determine whether endurance exercise training can alter the β-adrenergic-stimulated inotropic response in older women, we studied 10 postmenopausal healthy women (65.4 ± 0.9 yr old) who exercised for 11 mo. Left ventricular (LV) function was evaluated with two-dimensional echocardiography during infusion of isoproterenol after atropine. Maximal O2 consumption increased 23% in response to training (from 1.35 ± 0.06 to 1.66 ± 0.07 l/min; P = 0.004). Training had no effect on baseline LV function, end-diastolic diameter, LV wall thickness, or LV mass. The increase in LV systolic function in response to isoproterenol was unaffected by training. Furthermore, neither the systolic shortening-to-end-systolic wall stress relationship nor the end-systolic wall stress-to-end-systolic diameter relationship during isoproterenol infusion changed with training. We conclude that older postmenopausal women can increase their maximal O2consumption with exercise training without eccentric LV hypertrophy or enhancement of β-adrenergic-mediated LV contractile function. These observations provide an explanation for the finding that maximal cardiac output and stroke volume are not increased in older women in response to training.
Gender differences in muscle inflammation after eccentric exercise
Authors: Stupka N. , Lowther S. , Chorneyko K. , Bourgeois J. M. , Hogben C. , Tarnopolsky M. A.
Published: December 2017

Unaccustomed exercise is followed by delayed-onset muscle soreness and morphological changes in skeletal muscle. Animal studies have demonstrated that women have an attenuated response to muscle damage. We studied the effect of eccentric exercise in untrained male ( n = 8) and female ( n = 8) subjects using a unilateral exercise design [exercise (Ex) and control (Con) legs]. Plasma granulocyte counts [before (Pre) and 48 h after exercise (+48h)] and creatine kinase activity [Pre, 24 h after exercise (+24h), +48h, and 6 days after exercise (+6d)] were determined before (Pre) and after (+24h, +48h, +6d) exercise, with biopsies taken from the vastus lateralis of each leg at +48h for determination of muscle damage and/or inflammation. Plasma granulocyte counts increased for men and decreased for women at +48h ( P < 0.05), and creatine kinase activity increased for both genders at +48h and +6d ( P < 0.01). There were significantly greater areas of both focal ( P < 0.001) and extensive ( P < 0.01) damage in the Ex vs. Con leg for both genders, which was assessed by using toluidine blue staining. The number of leukocyte common antigen-positive cells/mm2tissue increased with exercise ( P< 0.05), and men tended to show more in their Ex vs. Con leg compared with women ( P = 0.052). Men had a greater total (Ex and Con legs) number of bcl-2-positive cells/mm2tissue vs. women ( P < 0.05). Atrophic fibers with homogeneous bcl-2-positive staining were seen only in men ( n = 3). We conclude that muscle damage is similar between genders, yet the inflammatory response is attenuated in women vs. men. Finally, exercise may stimulate the expression of proteins involved in apoptosis in skeletal muscle.
Diperoxovanadate alters endothelial cell focal contacts and barrier function: role of tyrosine phosphorylation
Authors: Garcia Joe G. N. , Schaphorst Kane L. , Verin Alexander D. , Vepa Suryanarayana , Patterson Carolyn E. , Natarajan Viswanathan
Published: December 2017

Diperoxovanadate (DPV), a potent tyrosine kinase activator and protein tyrosine phosphatase inhibitor, was utilized to explore bovine pulmonary artery endothelial cell barrier regulation. DPV produced dose-dependent decreases in transendothelial electrical resistance (TER) and increases in permeability to albumin, which were preceded by brief increases in TER (peak TER effect at 10–15 min). The significant and sustained DPV-mediated TER reductions were primarily the result of decreased intercellular resistance, rather than decreased resistance between the cell and the extracellular matrix, and were reduced by pretreatment with the tyrosine kinase inhibitor genistein but not by inhibition of p42/p44 mitogen-activating protein kinases. Immunofluorescent analysis after DPV challenge revealed dramatic F-actin polymerization and stress-fiber assembly and increased colocalization of tyrosine phosphoproteins with F-actin in a circumferential pattern at the cell periphery, changes that were abolished by genistein. The phosphorylation of focal adhesion and adherens junction proteins on tyrosine residues was confirmed in immunoprecipitates of focal adhesion kinase and cadherin-associated proteins in which dramatic dose-dependent tyrosine phosphorylation was observed after DPV stimulation. We speculate that DPV enhances endothelial cell monolayer integrity via focal adhesion plaque phosphorylation and produces subsequent monolayer destabilization of adherens junctions initiated by adherens junction protein tyrosine phosphorylation catalyzed by p60srcor Src-related tyrosine kinases.
Dual-energy X-ray absorptiometry: analysis of pediatric fat estimate errors due to tissue hydration effects
Authors: Testolin Corrado G. , Gore Robert , Rivkin Tommy , Horlick Mary , Arbo John , Wang Zimian , Chiumello Giuseppe , Heymsfield Steven B.
Published: December 2017

Dual-energy X-ray absorptiometry (DXA) percent (%) fat estimates may be inaccurate in young children, who typically have high tissue hydration levels. This study was designed to provide a comprehensive analysis of pediatric tissue hydration effects on DXA %fat estimates. Phase 1 was experimental and included three in vitro studies to establish the physical basis of DXA %fat-estimation models. Phase 2 extended phase 1models and consisted of theoretical calculations to estimate the %fat errors emanating from previously reported pediatric hydration effects. Phase 1 experiments supported the two-compartment DXA soft tissue model and established that pixel ratio of low to high energy (R values) are a predictable function of tissue elemental content. In phase 2, modeling of reference body composition values from birth to age 120 mo revealed that %fat errors will arise if a “constant” adult lean soft tissue R value is applied to the pediatric population; the maximum %fat error, ∼0.8%, would be present at birth. High tissue hydration, as observed in infants and young children, leads to errors in DXA %fat estimates. The magnitude of these errors based on theoretical calculations is small and may not be of clinical or research significance.
Effect of fat adaptation and carbohydrate restoration on metabolism and performance during prolonged cycling
Authors: Burke Louise M. , Angus Damien J. , Cox Gregory R. , Cummings Nicola K. , Febbraio Mark A. , Gawthorn Kathryn , Hawley John A. , Minehan Michelle , Martin David T. , Hargreaves Mark
Published: December 2017

For 5 days, eight well-trained cyclists consumed a random order of a high-carbohydrate (CHO) diet (9.6 g · kg−1 · day−1 CHO, 0.7 g · kg−1 · day−1 fat; HCHO) or an isoenergetic high-fat diet (2.4 g · kg−1 · day−1 CHO, 4 g · kg−1 · day−1 fat; Fat-adapt) while undertaking supervised training. On day 6,subjects ingested high CHO and rested before performance testing on day 7 [2 h cycling at 70% maximal O2consumption (SS) + 7 kJ/kg time trial (TT)]. With Fat-adapt, 5 days of high-fat diet reduced respiratory exchange ratio (RER) during cycling at 70% maximal O2 consumption; this was partially restored by 1 day of high CHO [0.90 ± 0.01 vs. 0.82 ± 0.01 ( P < 0.05) vs. 0.87 ± 0.01 ( P < 0.05), for day 1, day 6, and day 7, respectively]. Corresponding RER values on HCHO trial were [0.91 ± 0.01 vs. 0.88 ± 0.01 ( P < 0.05) vs. 0.93 ± 0.01 ( P < 0.05)]. During SS, estimated fat oxidation increased [94 ± 6 vs. 61 ± 5 g ( P < 0.05)], whereas CHO oxidation decreased [271 ± 16 vs. 342 ± 14 g ( P < 0.05)] for Fat-adapt compared with HCHO. Tracer-derived estimates of plasma glucose uptake revealed no differences between treatments, suggesting muscle glycogen sparing accounted for reduced CHO oxidation. Direct assessment of muscle glycogen utilization showed a similar order of sparing (260 ± 26 vs. 360 ± 43 mmol/kg dry wt; P = 0.06). TT performance was 30.73 ± 1.12 vs. 34.17 ± 2.48 min for Fat-adapt and HCHO ( P = 0.21). These data show significant metabolic adaptations with a brief period of high-fat intake, which persist even after restoration of CHO availability. However, there was no evidence of a clear benefit of fat adaptation to cycling performance.
Noninvasive motion ventilation (NIMV): a novel approach to ventilatory support
Authors: Adams Jose A. , Mangino Martin J. , Bassuk Jorge , Inman D. Michael , Sackner Marvin A.
Published: December 2017

A motion platform was developed that oscillates an animal in a foot-to-head direction ( z-plane). The platform varies the frequency and intensity of acceleration, imparting periodic sinusoidal inertial forces (pGz) to the body. The aim of the study was to characterize ventilation produced by the noninvasive motion ventilator (NIMV) in animals with healthy and diseased lungs. Incremental increases in pGz(acceleration) with the frequency held constant ( f = 4 Hz) produced almost linear increases in minute ventilation (V˙e). Frequencies of 2–4 Hz produced the greatest V˙eand tidal volume (Vt) for any given acceleration between ±0.2 and ±0.8 G. Increasing the force due to acceleration produced proportional increases in both transpulmonary and transdiaphragmatic pressures. Increasing transpulmonary pressure by increasing pGzproduced linear increases in Vt, similar to spontaneous breathing. NIMV reversed deliberately induced hypoventilation and normalized the changes in arterial blood gases induced by meconium aspiration. In conclusion, a novel motion platform is described that imparts periodic sinusoidal acceleration forces at moderate frequencies (4 Hz) to the whole body in the z-plane. These forces, when properly adjusted, are capable of highly effective ventilation of normal and diseased lungs. Such noninvasive ventilation is accomplished at airway pressures equivalent to atmospheric or continuous positive airway pressure, with acceleration forces less than ±1 Gz.
Hemodynamic effects of periodic Gz acceleration in meconium aspiration in pigs
Authors: Adams Jose A. , Mangino Martin J. , Bassuk Jorge , Sackner Marvin A.
Published: December 2017

The hemodynamic effects of periodic acceleration (pGz), induced in the spinal axis with noninvasive motion ventilation (NIMV), were studied in a piglet model of pulmonary hypertension associated with meconium aspiration. Animals ( n = 12) were anesthetized, paralyzed, intubated, and supported by conventional mechanical ventilation (CMV). Thirty minutes after tracheal instillation of meconium solution (6 ml/kg), either CMV ( n = 6) was continued or NIMV ( n = 6) was initiated. Changes in systemic and pulmonary hemodynamics and arterial blood gases were tracked for 2 h after aspiration. Thermodilution, cardiac output, and heart rate were not significantly different after meconium aspiration in the pGz group relative to the CMV controls. Aortic pressure and systemic vascular resistance were significantly lower (∼30%) after meconium aspiration in NIMV animals relative to CMV animals. Pulmonary arterial pressure and pulmonary vascular resistance were also significantly lower, by 100%, after aspiration of meconium in the NIMV animals compared with the CMV controls. Meconium aspiration significantly decreased total respiratory compliance by ∼50% and increased total respiratory resistance by ∼100% in both CMV and NIMV animals, but such alterations did not differ between the two groups. Both CMV and NIMV satisfactorily supported ventilation in these paralyzed animals. In conclusion, NIMV through pGz in the spinal axis decreased systemic and pulmonary vascular resistance in piglets after meconium aspiration.
Invited Review: Pulmonary capillary stress failure
Authors: West John B.
Published: December 2017

The pulmonary blood-gas barrier is an extraordinary bioengineering structure because of its vast area but extreme thinness. Despite this, almost no attention has been given to its mechanical properties. The remarkable area and thinness come about because gas exchange occurs by passive diffusion. However, the barrier also needs to be immensely strong to withstand the very high stresses in the capillary wall when capillary pressure rises during exercise. The strength of the thin region of the barrier comes from type IV collagen in the basement membranes. When the stresses in the capillary walls rise to high levels, ultrastructural changes occur in the barrier, a condition known as stress failure. Physiological conditions that alter the properties of the barrier include severe exercise in elite human athletes. Animals that have been selectively bred for high aerobic activity, such as Thoroughbred racehorses, consistently break their pulmonary capillaries during galloping. Pathophysiological conditions causing stress failure include high-altitude pulmonary edema and overinflation of the lung, which frequently occurs with mechanical ventilation. Remodeling of the capillary wall occurs in response to increased wall stress in diseases such as mitral stenosis. The barrier is able to maintain its extreme thickness with sufficient strength as a result of continual regulation of its wall structure. How it does this is a central problem in lung biology.
Invited Review: Plasma membrane stress failure in alveolar epithelial cells
Authors: Vlahakis Nicholas E. , Hubmayr Rolf D.
Published: December 2017

In this review, we examine the hypothesis that plasma membrane stress failure is a central event in the pathophysiology of injury from alveolar overdistension. This hypothesis leads us to consider alveolar micromechanics and specifically the mechanical interactions between lung matrix and alveolar epithelial cell cytoskeleton and plasma membrane. We then explore events that are central to the regulation of plasma membrane tension and detail the lipid-trafficking responses of in vitro deformed and/or injured cells. We conclude with a reference to upregulation of stress-responsive genes after membrane injury and resealing.
Selected Contribution: A three-dimensional model for assessment of in vitro toxicity inBalaena mysticetusrenal tissue
Authors: Goodwin T. J. , Coate-Li L. , Linnehan R. M. , Hammond T. G.
Published: December 2017

This study established two- and three-dimensional renal proximal tubular cell cultures of the endangered species bowhead whale ( Balaena mysticetus), developed SV40-transfected cultures, and cloned the 61-amino acid open reading frame for the metallothionein protein, the primary binding site for heavy metal contamination in mammals. Microgravity research, modulations in mechanical culture conditions (modeled microgravity), and shear stress have spawned innovative approaches to understanding the dynamics of cellular interactions, gene expression, and differentiation in several cellular systems. These investigations have led to the creation of ex vivo tissue models capable of serving as physiological research analogs for three-dimensional cellular interactions. These models are enabling studies in immune function, tissue modeling for basic research, and neoplasia. Three-dimensional cellular models emulate aspects of in vivo cellular architecture and physiology and may facilitate environmental toxicological studies aimed at elucidating biological functions and responses at the cellular level. Marine mammals occupy a significant ecological niche (72% of the Earth's surface is water) in terms of the potential for information on bioaccumulation and transport of terrestrial and marine environmental toxins in high-order vertebrates. Few ex vivo models of marine mammal physiology exist in vitro to accomplish the aforementioned studies. Techniques developed in this investigation, based on previous tissue modeling successes, may serve to facilitate similar research in other marine mammals.
Cardiovascular responses to nonrespiratory and respiratory arousals in a porcine model
Authors: Launois Sandrine H. , Averill Nathan , Abraham Joseph H. , Kirby Debra A. , Weiss J. Woodrow
Published: December 2017

Spontaneous and provoked nonrespiratory arousals can be accompanied by a patterned hemodynamic response. To investigate whether a patterned response is also elicited by respiratory arousals, we compared nonrespiratory arousals (NRA) to respiratory arousals (RA) induced by airway occlusion during non-rapid eye movement sleep. We monitored mean arterial blood pressure (MAP), heart rate, iliac and renal blood flow, and sleep stage in 7 pigs during natural sleep. Iliac and renal vascular resistance were calculated. Airway occlusions were obtained by manually inflating a chronically implanted tracheal balloon during sleep. The balloon was quickly deflated as soon as electroencephalogram arousal occurred. As previously reported, NRA generally elicited iliac vasodilation, renal vasoconstriction, little change in MAP, and tachycardia. In contrast, RA generally elicited iliac and renal vasoconstriction, an increase in MAP and tachycardia. The frequent occurrence of iliac vasoconstriction and arterial pressure elevation following RA but not NRA suggests that sleep state change alone does not account for the hemodynamic response to airway occlusion during sleep.