bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of water temperature on cooling efficiency during hyperthermia in humans
Authors: Proulx C. I. , Ducharme M. B. , Kenny G. P.
Published: March 2015

We evaluated the cooling rate of hyperthermic subjects, as measured by rectal temperature (Tre), during immersion in a range of water temperatures. On 4 separate days, seven subjects (4 men, 3 women) exercised at 65% maximal oxygen consumption at an ambient temperature of 39°C until Treincreased to 40°C (45.4 ± 4.1 min). After exercise, the subjects were immersed in a circulated water bath controlled at 2, 8, 14, or 20°C until Trereturned to 37.5°C. No difference in cooling rate was observed between the immersions at 8, 14, and 20°C despite the differences in the skin surface-to-water temperature gradient, possibly because of the presence of shivering at 8 and 14°C. Compared with the other conditions, however, the rate of cooling (0.35 ± 0.14°C/min) was significantly greater during the 2°C water immersion, in which shivering was seldom observed. This rate was almost twice as much as the other conditions ( P < 0.05). Our results suggest that 2°C water is the most effective immersion treatment for exercise-induced hyperthermia.
Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation
Authors: LaDisa John F. , Hettrick Douglas A. , Olson Lars E. , Guler Ismail , Gross Eric R. , Kress Tobias T. , Kersten Judy R. , Warltier David C. , Pagel Paul S.
Published: March 2015

Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs ( n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment ( P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.
Influence of age and run training on cardiac Na+/Ca2+ exchange
Authors: Mace Lisa C. , Palmer Bradley M. , Brown David A. , Jew Korinne N. , Lynch Joshua M. , Glunt Jason M. , Parsons Todd A. , Cheung Joseph Y. , Moore Russell L.
Published: March 2015

Effects of age and training on myocardial Na+/Ca2+ exchange were examined in young sedentary (YS; 14-15 mo), aged sedentary (AS; 27-31 mo), and aged trained (AT; 8- to 11-wk treadmill run training) male Fischer Brown Norway rats. Whole heart performance and isolated cardiocyte Na+/Ca2+ exchange characteristics were measured. At the whole heart level, a small but significant slowing of late isovolumic left ventricular (LV) relaxation, which may be indicative of altered Na+/Ca2+ exchange activity, was seen in hearts from AS rats. This subtle impairment in relaxation was not observed in hearts from AT rats. At the single-cardiocyte level, late action potential duration was prolonged, resting membrane potential was more positive, and overshoot potential was greater in cardiocytes from AS rats than from YS rats ( P < 0.05). Training did not influence any of these age-related action potential characteristics. In electrically paced cardiocytes, neither shortening nor intracellular Ca2+ concentration ([Ca2+]i) dynamics was influenced by age or training. Similarly, neither age nor training influenced the rate of [Ca2+]i clearance via forward (Nain+ /Caout2+) Na+/Ca2+ exchange after caffeine-induced Ca2+ release from the sarcoplasmic reticulum or cardiac Na+/Ca2+ exchanger protein (NCX1) expression. However, when whole cell patch-clamp techniques combined with fluorescence microscopy were used to evaluate the ability of Na+/Ca2+ exchange to alter cytosolic [Ca2+] ([Ca2+]c) under conditions where membrane potential ( Vm) and internal and external [Na+] and [Ca2+] could be controlled, we observed age-associated increases in forward Na+/Ca2+ exchange-mediated [Ca2+]c clearance ( P < 0.05) that were not influenced by training. The age-related increase in forward Na+/Ca2+ exchange activity provides a hypothetical explanation for the late action potential prolongation observed in this study.
Gender modulates activation of renin-angiotensin and endothelin systems in hypertension and heart failure
Authors: Radin M. Judith , Holycross Bethany J. , Sharkey Leslie C. , Shiry Laura , McCune Sylvia A.
Published: March 2015

Sexual dimorphism may occur during the development of hypertension and congestive heart failure (CHF). Male and female spontaneous hypertension heart failure (SHHF) rats with established hypertension, but before CHF (age 5–8 mo) and during cardiac decompensation leading to CHF (age 18–20 mo in male rats and 22–24 mo in female rats), were studied. At 5–8 mo, male SHHF rats showed early activation of the renin-angiotensin system (RAS), as indicated by increased plasma renin activity (PRA) and higher serum angiotensin-converting enzyme activity compared with female rats. The increase in PRA in female rats was delayed compared with males rats, but it reached comparable levels just before CHF. Urinary endothelin excretion was significantly greater in 5- to 8-mo-old female rats compared with age-matched male rats. Urinary endothelin excretion increased in both male and female rats as CHF developed. Plasma atrial natriuretic peptide (ANP) was comparable at both time points, and both genders showed similar, marked increases as CHF developed. In conclusion, male rats show early activation of the RAS, whereas female rats show early activation of the endothelin vasopressor system. During cardiac decompensation, generalized activation of the RAS, endothelin, and ANP systems occurs and is similar in male and female SHHF rats.
Central CO2chemoreception in developing bullfrogs: anomalous response to acetazolamide
Authors: Taylor Barbara E. , Harris Michael B. , Coates E. Lee , Gdovin Matthew J. , Leiter J. C.
Published: March 2015

Central CO2chemoreception and the role of carbonic anhydrase were assessed in brain stems from Rana catesbeiana tadpoles and frogs. Buccal and lung rhythms were recorded from cranial nerve VII and spinal nerve II during normocapnia and hypercapnia before and after treatment with 25 μM acetazolamide. The lung response to acetazolamide mimicked the hypercapnic response in early-stage and midstage metamorphic tadpoles and frogs. In late-stage tadpoles, acetazolamide actually inhibited hypercapnic responses. Acetazolamide and hypercapnia decreased the buccal frequency but had no effect on the buccal duty cycle. Carbonic anhydrase activity was present in the brain stem in every developmental stage. Thus more frequent lung ventilation and concomitantly less frequent buccal ventilation comprised the hypercapnic response, but the response to acetazolamide was not consistent during metamorphosis. Therefore, acetazolamide is not a useful tool for central CO2chemoreceptor studies in this species. The reversal of the effect of acetazolamide in late-stage metamorphosis may reflect reorganization of central chemosensory processes during the final transition from aquatic to aerial respiration.
Assessment of O2uptake dynamics in isolated single skeletal myocytes
Authors: Kindig Casey A. , Kelley Kevin M. , Howlett Richard A. , Stary Creed M. , Hogan Michael C.
Published: March 2015

The purpose of this research was to develop a technique for rapid measurement of O2uptake (V˙o2) kinetics in single isolated skeletal muscle cells. Previous attempts to measure single cellV˙o2have utilized polarographic-style electrodes, thereby mandating large fluid volumes and relatively poor sensitivity. Thus our laboratory has developed an ∼100-μl, well-stirred chamber for the measurement ofV˙o2in isolated Xenopus laevismyocytes using a phosphorescence quenching technique [Ringer solution with 0.05 mM Pd- meso-tetra(4-carboxyphenyl)porphine] to monitor the fall in extracellular Po2(which is proportional to cellular V˙o2within the sealed chamber). V˙o2in single living myocytes dissected from Xenopus lumbrical muscles was measured from rest across a bout of repetitive tetanic contractions (0.33 Hz) and in response to a ramp protocol utilizing an increasing contraction frequency. In response to the square-wave contraction bout, the increase in V˙o2to steady state (SS) was 16.7 ± 1.3 ml · 100 g−1· min−1(range 13.0–21.9 ml · 100 g−1· min−1; n = 6). The rise in V˙o2at contractions onset ( n = 6) was fit with a time delay (2.1 ± 1.2 s, range 0.0–7.7 s) plus monoexponential rise to SS (time constant = 9.4 ± 1.5 s, range 5.2–14.9 s). Furthermore, in two additional myocytes,V˙o2increased progressively as contraction frequency increased (ramp protocol). This technique for measuring V˙o2in isolated, single skeletal myocytes represents a novel and powerful investigative tool for gaining mechanistic insight into mitochondrial function andV˙o2dynamics without potential complications of the circulation and other myocytes.
Analysis of left ventricular hemodynamics in physiological hyperspace
Authors: Eucker Stephanie A. , Lisauskas Jennifer , Courtois Michael R. , Kovács Sándor J.
Published: March 2015

10.1152/japplphysiol.00560. 2001.—Our laboratory has previously shown that it is possible to elucidate novel physiological relationships by analyzing the left ventricular pressure (P) contour in the phase [time derivative of P (dP/d t) vs. P] plane (Eucker SA, Lisauskas JB, Singh J, and Kovács SJ, J Appl Physiol 90: 2238–2244, 2001). To further characterize cardiac physiology, we introduce a method that combines P-volume (V) and phase plane-derived information in physiological hyperspace. From four-dimensional (P, V, dP/d t, time derivative of V) hyperspace, we consider three-dimensional embedding diagrams having dP/d t, P, and V as coordinate axes. Our method facilitates analysis of physiological function independent of inotropic state and permits assessment of P-V-based relationships in the phase plane and vice versa. To test feasibility, the method was applied to murine hemodynamic data. As predicted from first principles, the area of the P-V loop (ventricular external work) correlated closely ( r = 0.97) with phase plane limit cycle area (external power). The P-V plane-derived linear ( r = 0.99) end-systolic P-V relationship (maximum elastance) appeared linear in the phase plane ( r = 0.85). We conclude that analysis of data in physiological hyperspace is generalizable: it facilitates quantitative characterization of ventricular systolic and diastolic function and can guide discovery of novel physiological relationships.
Effect of somatic growth, strain, and sex on double-chamber plethysmographic respiratory function values in healthy mice
Authors: Flandre Thierry D. , Leroy Pascal L. , Desmecht Daniel J.-M.
Published: March 2015

Double-chamber plethysmography has been recognized since 1979 as a reference technique to measure pulmonary function values in guinea pigs, but it has not gained attention for use in mice. Theoretically, however, this technique combines the advantages of single-chamber plethysmography with a quantitative assessment of flow and/or volume and a calculated resistance, the interpretation of which in terms of bronchoconstriction is not disputed. Here we show that, when appropriately preconditioned, mice are able to gradually grow accustomed to the apparatus and display extremely stable nasal and thoracoabdominal flow tracings. Overall, strain, sex, and somatic growth had a significant effect on pulmonary function values. The changes in specific airway resistance (sRaw) and enhanced pause (Penh) values were never in the same direction, indicating that they measure different things. The respiratory frequency was far higher in C57BL/6 compared with BALB/c mice. Peak flows, minute volume, specific tidal and minute volumes, and sRaw were also higher, but Penh was smaller. Males breathed at a higher frequency than females, leading to a higher minute volume. Nevertheless, the specific volumes were considerably higher among females. Penh was lower in males, whereas sRaw was identical in both sexes. Changes associated with somatic growth were rapid and important between 5 and 9 wk, then slowed down between 9 and 12–13 wk and became almost imperceptible after.
Pleural surface fluorescence measurement of Na+and Cl− transport across the air space-capillary barrier
Authors: Jiang Jinjun , Song Yuanlin , Bai Chunxue , Koller Beverly H. , Matthay Michael A. , Verkman A. S.
Published: March 2015

We developed a pleural surface fluorescence method to measure Na+ and Cl−transport in perfused mouse lungs. The air space was filled with aqueous fluid containing membrane-impermeant fluorescent indicators of Cl− (lucigenin) or Na+ (Sodium Green). After instillation of a Cl−-free solution into the air space, an increase in perfusate Cl− concentration from 0 to 30 mM produced a decrease in surface lucigenin fluorescence (6.5%/min) corresponding to Cl− influx of 1.0 mM/min. Cl− influx was increased to 2.1 ± 0.3 mM/min by forskolin, and the increase was inhibited by glibenclamide. cAMP-stimulated Cl− influx was decreased by 57% in CFTR null mice. After instillation of a Na+-free solution into the air space, an increase in perfusate Na+ concentration from 0 to 30 mM gave increased Sodium Green fluorescence (Na+ influx of 1.2 mM/min), which increased approximately fivefold after cAMP agonists. Cl− and Na+transport were not affected in lungs from mice lacking aquaporins AQP1 or AQP5. Our results establish a pleural surface fluorescence method to measure unidirectional Cl− and Na+ flux in intact lung and provide evidence for cAMP-stimulated transcellular Cl− and Na+ transport.
Role of components of the phagocytic NADPH oxidase in oxygen sensing
Authors: Sanders K. A. , Sundar K. M. , He L. , Dinger B. , Fidone S. , Hoidal J. R.
Published: March 2015

It has been hypothesized that O2sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O2sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study unanesthetized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91phox-null mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47phox-null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 ± 18.0 vs. 20.0 ± 13.0% ( n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47phox-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47phox-null mutant than in wild-type mice: 109.61 ± 13.29 vs. 72.54 ± 7.65 impulses/s ( n = 8 and 7, respectively, P = 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was ∼58% larger in p47phox-null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91phox- and p47phox-null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91phoxcomponent of the phagocytic NADPH oxidase does not alter the O2-sensing mechanism of the carotid body. However, absence of the p47phoxcomponent significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O2sensing in EPO-producing cells of the kidney appears to be independent of the gp91phoxand p47phoxcomponents of the phagocytic NADPH oxidase.
Site of phrenic nerve stimulation-induced upper airway collapse: influence of expiratory time
Authors: Sériès F. , Éthier G.
Published: March 2015

Electrical phrenic nerve stimulation (EPNS) applied at end expiration during exclusive nasal breathing can be used to characterize upper airway (UA) dynamics during wakefulness by dissociating phasic activation of UA and respiratory muscles. The UA level responsible for the EPNS-induced increase in UA resistance is unknown. The influence of the twitch expiratory timing (200 ms and 2 s) on UA resistance was studied in nine normal awake subjects by looking at instantaneous flow, esophageal and pharyngeal pressures, and genioglossal electromyogram (EMG) activity during EPNS at baseline and at −10 cmH2O. The majority of twitches had a flow-limited pattern. Twitches realized at 200 ms and 2 s did not differ in their maximum inspiratory flows, but esophageal pressure measured at maximum inspiratory flow was significantly less negative with late twitches (−6.6 ± 2.7 and −5.0 ± 3.0 cmH2O respectively, P = 0.04). Pharyngeal resistance was higher when twitches were realized at 2 s than at 200 ms (6.4 ± 2.4 and 2.7 ± 1.1 cmH2O · l−1 · s, respectively). EMG activity significant rose at peak esophageal pressure with a greater increase for late twitches. We conclude that twitch-induced UA collapse predominantly occurs at the pharyngeal level and that UA stability assessed by EPNS depends on the expiratory time at which twitches are performed.
ATP synthesis and proton handling in muscle during short periods of exercise and subsequent recovery
Authors: Bendahan David , Kemp Graham J. , Roussel Magali , Fur Yann Le , Cozzone Patrick J.
Published: March 2015

We used31P-magnetic resonance spectroscopy to study proton buffering in finger flexor muscles of eight healthy men (25–45 yr), during brief (18-s) voluntary finger flexion exercise (0.67-Hz contraction at 10% maximum voluntary contraction; 50/50 duty cycle) and 180-s recovery. Phosphocreatine (PCr) concentration fell 19 ± 2% during exercise and then recovered with half time = 0.24 ± 0.01 min. Cell pH rose by 0.058 ± 0.003 units during exercise as a result of H+consumption by PCr splitting, which (assuming no lactate production or H+efflux) implies a plausible non-Pibuffer capacity of 20 ± 3 mmol · l intracellular water−1· pH unit−1. There was thus no evidence of significant glycogenolysis to lactate during exercise. Analysis of PCr kinetics as a classic linear response suggests that oxidative ATP synthesis reached 48 ± 2% of ATP demand by the end of exercise; the rest was met by PCr splitting. Postexercise pH recovery was faster than predicted, suggesting “excess proton” production, with a peak value of 0.6 ± 0.2 mmol/l intracellular water at 0.45 min of recovery, which might be due to, e.g., proton influx driven by cellular alkalinization, or a small glycolytic contribution to PCr resynthesis in recovery.
O2 uptake kinetics during exercise at peak O2 uptake
Authors: Scheuermann Barry W. , Barstow Thomas J.
Published: March 2015

Compared with moderate- and heavy-intensity exercise, the adjustment of O2 uptake (V̇o2) to exercise intensities that elicit peak V̇o2 has received relatively little attention. This study examined the V̇o2 response of 21 young, healthy subjects (25 ± 6 yr; mean ± SD) during cycle ergometer exercise to step transitions in work rate (WR) corresponding to 90, 100, and 110% of the peak WR achieved during a preliminary ramp protocol (15-30 W/min). Gas exchange was measured breath by breath and interpolated to 1-s values. V̇o2 kinetics were determined by use of a two- or three-component exponential model to isolate the time constant (τ2) as representative of V̇o2 kinetics and the amplitude (Amp) of the primary fast component independent of the appearance of any V̇o2 slow component. No difference in V̇o2 kinetics was observed between WRs (τ90 = 24.7 ± 9.0; τ100 = 22.8 ± 6.7; τ110 = 21.5 ± 9.2 s, where subscripts denote percent of peak WR; P > 0.05); nor in a subgroup of eight subjects was τ2 different from the value for moderate-intensity ( 0.05). As expected, the Amp increased with increasing WRs (Amp90 = 2,089 ± 548; Amp100 = 2,165 ± 517; Amp110 = 2,225 ± 559 ml/min; Amp90 vs. Amp110, P < 0.05). However, the gain (G) of the V̇o2 response (ΔV̇o2/ΔWR) decreased with increasing WRs (G90 = 8.5 ± 0.6; G100 = 7.9 ± 0.6; G110 = 7.3 ± 0.6 ml·min-1·W-1; P < 0.05). The Amp of the primary component approximated 85, 88, and 89% of peak V̇o2 during 90, 100, and 110% WR transitions, respectively. The results of the present study demonstrate that, compared with moderate- and heavy-intensity exercise, the gain of the V̇o2 response (as ΔV̇o2/ΔWR) is reduced for exercise transitions in the severe-intensity domain, but the approach to this gain is well described by a common time constant that is invariant across work intensities. The lower ΔV̇o2/ΔWR may be due to an insufficient adjustment of the cardiovascular and/or pulmonary systems that determine O2 delivery to the exercising muscles or due to recruitment of motor units with lower oxidative capacity, after the onset of exercise in the severe-intensity domain.
Frequency dependence of respiratory system mechanics during induced constriction in a murine model of asthma
Authors: Evans Kenda L. J. , Bond Richard A. , Corry David B. , Shardonofsky Felix R.
Published: March 2015

Airway dysfunction in asthma is characterized by hyperresponsiveness, heterogeneously narrowed airways, and closure of airways. To test the hypothesis that airway constriction in ovalbumin (OVA)-sensitized OVA-intranasally challenged (OVA/OVA) mice produces mechanical responses that are similar to those reported in asthmatic subjects, respiratory system resistance (Rrs) and elastance (Edyn,rs) spectra were obtained in OVA/OVA and control mice during intravenous methacholine (MCh) infusions. In control mice, MCh at 1,700 μg · kg−1 · min−1produced 1) a 495 and 928% increase of Rrs at 0.5 Hz and 19.75 Hz, respectively, 2) a 33% rise in Edyn,rs at 0.5 Hz, and 3) a mild frequency (f)-dependent increase of Edyn,rs. The same MCh dose in OVA/OVA mice produced 1) elevations of Rrs at 0.5 Hz and 19.75 Hz of 1,792 and 774%, respectively, 2) a 390% rise in Edyn,rs at 0.5 Hz, and 3) marked f-dependent increases of Edyn,rs. During constriction, the f dependence of mechanics in control mice was consistent with homogeneous airway narrowing; however, in OVA/OVA mice, f dependence was characteristic of heterogeneously narrowed airways, closure of airways, and airway shunting. These mechanisms amplify the pulmonary mechanical responses to constrictor stimuli at physiological breathing rates and have important roles in the pathophysiology of human asthma.
Effects of body position on the ventilatory response following an impulse exercise in humans
Authors: Haouzi Philippe , Chenuel Bruno , Chalon Bernard
Published: March 2015

The aim of this study was to identify some of the mechanisms that could be involved in blunted ventilatory response (V˙e) to exercise in the supine (S) position. The contribution of the recruitment of different muscle groups, the activity of the cardiac mechanoreceptors, the level of arterial baroreceptor stimulation, and the hemodynamic effects of gravity on the exercising muscles was analyzed during upright (U) and S exercise. Delayed rise in V˙e and pulmonary gas exchange following an impulselike change in work rate (supramaximal leg cycling at 240 W for 12 s) was measured in seven healthy subjects and six heart transplant patients both in U and S positions. This approach allows study of the relationship between the rise inV˙e and O2 uptake (V˙o 2) without the confounding effects of contractions of different muscle groups. These responses were compared with those triggered by an impulselike change in work rate produced by the arms, which were positioned at the same level as the heart in S and U positions to separate effects of gravity on postexercising muscles from those on the rest of the body. Despite superimposableV˙o 2 and CO2 output responses, the delayed V˙e response after leg exercise was significantly lower in the S posture than in the U position for each control subject and cardiac-transplant patient (−2.58 ± 0.44 l and −3.52 ± 1.11 l/min, respectively). In contrast, when impulse exercise was performed with the arms, reduction of ventilatory response in the S posture reached, at best, one-third of the deficit after leg exercise and was always associated with a reduction inV˙o 2 of a similar magnitude. We concluded that reduction in V˙e response to exercise in the S position is independent of the types (groups) of muscles recruited and is not critically dependent on afferent signals originating from the heart but seems to rely on some of the effects of gravity on postexercising muscles.
Repeated contractions alter the geometry of human skeletal muscle
Authors: Maganaris Constantinos N. , Baltzopoulos Vasilios , Sargeant Anthony J.
Published: March 2015

The aim of this study was to investigate the effect of repeated contractions on the geometry of human skeletal muscle. Six men performed two sets ( sets Aand B) of 10 repeated isometric plantarflexion contractions at 80% of the moment generated during plantarflexion maximal voluntary contraction (MVC), with a rest interval of 15 min between sets. By use of ultrasound, the geometry of the medial gastrocnemius (MG) muscle was measured in the contractions of set A and the displacement of the MG tendon origin in the myotendinous junction was measured in the contractions of set B. In the transition from the 1st to the 10th contractions, the fascicular length at 80% of MVC decreased from 34 ± 4 (means ± SD) to 30 ± 3 mm ( P < 0.001), the pennation angle increased from 35 ± 3 to 42 ± 3° ( P < 0.001), the myotendinous junction displacement increased from 5 ± 3 to 10 ± 3 mm ( P < 0.001), and the average fascicular curvature remained constant ( P > 0.05) at ∼4.3 m−1. No changes ( P > 0.05) were found in fascicular length, pennation angle, and myotendinous junction displacement after the fifth contraction. Electrogoniometry showed that the ankle rotated by ∼6.5° during contraction, but no differences ( P > 0.05) were obtained between contractions. The present results show that repeated contractions induce tendon creep, which substantially affects the geometry of the in-series contracting muscles, thus altering their potential for force and joint moment generation.
Effect of pregnancy on joint contracture in the rat knee
Authors: Ohtera K. , Zobitz M. E. , Luo Z. P. , Morrey B. F. , O'Driscoll S. W. , Ramin K. D. , An K.-N.
Published: March 2015

As there is evidence that ligamentous laxity is affected by the female hormones, we hypothesized that hormonal changes occurring during pregnancy could have a therapeutic role in preventing the development of a joint contracture. Knee joint contractures were created in pregnant and nonpregnant rats. After 2 wk of immobilization, the degree of contracture was measured with structural properties of the medial collateral and anterior cruciate ligaments and the pubic symphysis. Although not statistically significant, there was a general trend toward reduced contracture in pregnant compared with nonpregnant rats. Cutting the posterior capsule significantly decreased contracture for both the pregnant and nonpregnant groups, confirming the contribution of capsular structures to contracture. Ultimate loads of the medial collateral and anterior cruciate ligaments significantly decreased after immobilization compared with control, but there was no significant effect due to pregnancy. Stiffness and ultimate load of the pubic symphysis were not significantly different between pregnant and nonpregnant groups. The trend toward reduced contracture with pregnancy points toward a possible therapeutic role for female hormones in the prevention of postoperative and/or posttraumatic joint contracture.
O 2 − -mediated impairment of coronary arterial relaxation is prevented by overnight treatment with 1 nM β-estradiol
Authors: Bell David R. , Gochenaur Kristen E. , Hecht Jennifer
Published: March 2015

We tested the hypothesis that the ability of coronary arteries to withstand functional damage from superoxide (O[Formula: see text]) is altered by exposure of the arteries to a physiological concentration of β-estradiol. Female porcine coronary arterial rings were incubated in an O2-CO2incubator, under normoxic conditions, at 37°C for 22–24 h. Arteries were then placed in baths containing a physiological salt solution at 37°C with 95% O2-5% CO2for isometric force recordings. In rings from 14 female pigs, vasorelaxation to A-23187 and diethylamine-NONOate (DEA-NONOate) was determined with and without prior 15-min exposure to 400 μM pyrogallol. Sensitivity (−logM ED50) and maximum relaxation to A-23187, but not DEA-NONOate, were significantly impaired by exposure to pyrogallol (pyrogallol treated: 7.39 ± 0.09, 82 ± 5%; control: 7.76 ± 0.11, 99 ± 1%, means ± SE; P < 0.01 and P < 0.05, respectively). This effect was attenuated by concurrent exposure to equimolar ascorbate. Arterial rings from 12 separate female pigs were incubated for 22–24 h with or without 1 nM β-estradiol before pyrogallol exposure. β-Estradiol significantly enhanced arterial sensitivity to A-23187 and prevented pyrogallol impairment without affecting DEA-NONOate responses. Therefore, superoxide-mediated endothelial damage and impaired endothelium-dependent relaxation of coronary arteries are prevented by overnight exposure of the arteries to a physiological concentration of β-estradiol.
Changes in actomyosin ATP consumption rate in rat diaphragm muscle fibers during postnatal development
Authors: Sieck Gary C. , Prakash Y. S. , Han Young-Soo , Fang Yun-Hua , Geiger Paige C. , Zhan Wen-Zhi
Published: March 2015

Early postnatal development of rat diaphragm muscle (Diam) is marked by dramatic transitions in myosin heavy chain (MHC) isoform expression. We hypothesized that the transition from the neonatal isoform of MHC (MHCNeo) to adult fast MHC isoform expression in Diamfibers is accompanied by an increase in both the maximum velocity of the actomyosin ATPase reaction ( VmaxATPase) and the ATP consumption rate during maximum isometric activation (ATPiso). Rat Diamfibers were evaluated at postnatal days 0, 14, and 28 and in adults ( day 84). Across all ages, VmaxATPase of fibers was significantly higher than ATPiso. The reserve capacity for ATP consumption [1 − (ratio of ATPisoto VmaxATPase)] was remarkably constant (∼55–60%) across age groups, although at day 28 and in adults the reserve capacity for ATP consumption was slightly higher for fibers expressing MHCSlowcompared with fast MHC isoforms. At day 28 and in adults, both VmaxATPase and ATPisowere lower in fibers expressing MHCSlowfollowed in rank order by fibers expressing MHC2A, MHC2X, and MHC2B. For fibers expressing MHCNeo, VmaxATPase, and ATPisowere comparable to values for adult fibers expressing MHCSlowbut significantly lower than values for fibers expressing fast MHC isoforms. We conclude that postnatal transitions from MHCNeoto adult fast MHC isoform expression in Diamfibers are associated with corresponding but disproportionate changes in VmaxATPase and ATPiso.
ATP consumption rate per cross bridge depends on myosin heavy chain isoform
Authors: Han Young-Soo , Geiger Paige C. , Cody Mark J. , Macken Rebecca L. , Sieck Gary C.
Published: March 2015

In the present study, we tested the hypothesis that intrinsic differences in ATP consumption rate per cross bridge exist across rat diaphragm muscle (Diam) fibers expressing different myosin heavy chain (MHC) isoforms. During maximum Ca2+activation (pCa 4.0) of single, Triton X-permeabilized Diamfibers, isometric ATP consumption rate was determined by using an NADH-linked fluorometric technique. The MHC concentration in single Diamfibers was determined by densitometric analysis of SDS-PAGE gels and comparison to a standard curve of known MHC concentrations. Isometric ATP consumption rate varied across Diamfibers expressing different MHC isoforms, being highest in fibers expressing MHC2X(1.14 ± 0.08 nmol · mm−3· s−1) and/or MHC2B(1.33 ± 0.08 nmol · mm−3· s−1), followed by fibers expressing MHC2A(0.77 ± 0.11 nmol · mm−3· s−1) and MHCSlow(0.46 ± 0.03 nmol · mm−3· s−1). These differences in ATP consumption rate also persisted when it was normalized for MHC concentration in single Diamfibers. Normalized ATP consumption rate for MHC concentration varied across Diamfibers expressing different MHC isoforms, being highest in fibers expressing MHC2X(2.02 ± 0.19 s−1) and/or MHC2B(2.64 ± 0.15 s−1), followed by fibers expressing MHC2A(1.57 ± 0.16 s−1) and MHCSlow(0.77 ± 0.05 s−1). On the basis of these results, we conclude that there are intrinsic differences in ATP consumption rate per cross bridge in Diamfibers expressing MHC isoforms.
Duration of coffee- and exercise-induced changes in the fatty acid profile of human serum
Authors: Mougios Vassilis , Ring Susanne , Petridou Anatoli , Nikolaidis Michalis G.
Published: March 2015

Prolonged moderate exercise increases the concentration of nonesterified fatty acids (NEFA) and the ratio of unsaturated to saturated (U/S) NEFA in human plasma. The present study examined the duration of these effects and compared them with the effects of coffee ingestion. On separate days and in random order, seven men and six women 1) cycled for 1 h, 2) ingested coffee containing 5 mg caffeine/kg body mass, 3) ingested coffee followed by exercise 1 h later, and 4) did nothing. Blood samples were drawn at 0, 1, 2, 4, 8, 12, and 24 h. Serum was analyzed for lactate, glucose, glycerol, individual NEFA, triacylglycerols, total cholesterol, and HDL cholesterol. Exercise elevated the U/S NEFA and the percentage of oleate, while decreasing the percentages of palmitate and stearate, at the end of exercise but not subsequently. Consumption of coffee triggered a lower lipolytic response with no alterations in U/S or percentages of individual NEFA. These findings may prove useful in discovering mechanisms mediating the effects of exercise training on the fatty acid profile of human tissues.
Effect of exercise on mRNA expression of select adrenal medullary catecholamine biosynthetic enzymes
Authors: Erdem S. Remzi , Demirel Haydar A. , Broxson Christopher S. , Nankova Bistra B. , Sabban Esther L. , Tümer Nihal
Published: March 2015

The effect of submaximal endurance training (SET) on sympathoadrenal activity is not clear. We tested the hypothesis that SET (90 min/day, 5 days/wk, for 12 wk) elevates mRNA expression of catecholamine (CA) biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DβH) in the adrenal medullae of adult, female Sprague-Dawley rats. SET increased TH protein level by 35%, TH activity by 62%, TH mRNA expression by 40%, and DβH mRNA expression by 67%. In addition, we examined the effect of SET on Fos-related antigens (FRAs), FRA-2 immunoreactivity, and activator protein (AP)-1 binding activity. SET increased AP-1 binding activity by 78%; however, it did not affect late FRAs and FRA-2 immunoreactivity. Because the regulation of neuropeptide Y (NPY) often parallels that of CAs, we also examined the effect of SET on NPY mRNA expression. Indeed, SET elevated NPY mRNA expression as well. We conclude that 1) SET elicits a pretranslational stimulatory effect on adrenomedullary CA biosynthetic enzymes, 2) another immediate early mRNA product, rather than FRA-2, may contribute to the increase in AP-1 binding activity in response to SET, and 3) SET increases NPY mRNA expression.
Mast cells mediate the microvascular inflammatory response to systemic hypoxia
Authors: Steiner Dawn R. S. , Gonzalez Norberto C. , Wood John G.
Published: March 2015

Systemic hypoxia produces an inflammatory response characterized by increases in reactive O2 species (ROS), venular leukocyte-endothelial adherence and emigration, and vascular permeability. Inflammation is typically initiated by mediators released from activated perivascular cells that generate the chemotactic gradient responsible for extravascular leukocyte accumulation. These experiments were directed to study the possible participation of mast cells in hypoxia-induced microvascular inflammation. Mast cell degranulation, ROS levels, leukocyte adherence and emigration, and vascular permeability were studied in the mesenteric microcirculation by using intravital microscopy of anesthetized rats. The main findings were 1) activation of mast cells with compound 48/80 in normoxia produced microvascular effects similar, but not identical, to those of hypoxia; 2) systemic hypoxia resulted in rapid mast cell degranulation; 3) blockade of mast cell degranulation with cromolyn prevented or attenuated the hypoxia-induced increases in ROS, leukocyte adherence/emigration, and vascular permeability; and 4) mast cell degranulation during hypoxia was prevented by administration of the antioxidant lipoic acid and of nitric oxide. These results show that mast cells play a key role in hypoxia-induced inflammation and suggest that alterations in the ROS-nitric oxide balance may be involved in mast cell activation during hypoxia.
Postnatal changes in cytochrome oxidase expressions in brain stem nuclei of rats: implications for sensitive periods
Authors: Liu Qiuli , Wong-Riley Margaret T. T.
Published: March 2015

Previously, we reported that cytochrome oxidase (CO) activity in the rat pre-Bötzinger complex (PBC) exhibited a plateau on postnatal days (P) 3–4 and a prominent decrease on P12 (Liu and Wong-Riley, J Appl Physiol 92: 923–934, 2002). These changes were correlated with a concomitant reduction in the expression of glutamate and N-methyl-d-aspartate receptor subunit 1 and an increase in GABA, GABAB, glycine receptor, and glutamate receptor 2. To determine whether changes were limited to the PBC, the present study aimed at examining the expression of CO in a number of brain stem nuclei, with or without known respiratory functions from P0 to P21 in rats: the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, nucleus raphe obscurus, dorsal motor nucleus of the vagus nerve, medial accessory olivary nucleus, spinal nucleus of the trigeminal nerve, and medial vestibular nucleus (MVe). Results indicated that, in all of the brain stem nuclei examined, CO activity exhibited a general increase with age from P0 to P21, with MVe having the slowest rise. Notably, in all of the nuclei examined except for MVe, there was a plateau or decrease at P3–P4 and a prominent rise-fall-rise pattern at P11–P13, similar to that observed in the PBC. In addition, there was a fall-rise-fall pattern at P15–P17 in these nuclei, instead of a plateau pattern in the PBC. Our data suggest that the two postnatal periods with reduced CO activity, P3–P4 and especially P12, may represent common sensitive periods for most of the brain stem nuclei with known or suspected respiratory control functions.
5′-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle
Authors: Nielsen Jakob N. , Mustard Kirsty J. W. , Graham Drew A. , Yu Haiyan , MacDonald Christopher S. , Pilegaard Henriette , Goodyear Laurie J. , Hardie D. Grahame , Richter Erik A. , Wojtaszewski Jørgen F. P.
Published: March 2015

5′-AMP-activated protein kinase (AMPK) has been proposed to be a pivotal factor in cellular responses to both acute exercise and exercise training. To investigate whether protein levels and gene expression of catalytic (α1, α2) and regulatory (β1, β2, γ1, γ2, γ3) AMPK subunits and exercise-induced AMPK activity are influenced by exercise training status, muscle biopsies were obtained from seven endurance exercise-trained and seven sedentary young healthy men. The α1- and α2-AMPK mRNA contents in trained subjects were both 117 ± 2% of that in sedentary subjects (not significant), whereas mRNA for γ3was 61 ± 1% of that in sedentary subjects (not significant). The level of α1-AMPK protein in trained subjects was 185 ± 34% of that in sedentary subjects ( P < 0.05), whereas the levels of the remaining subunits (α2, β1, β2, γ1, γ2, γ3) were similar in trained and sedentary subjects. At the end of 20 min of cycle exercise at 80% of peak O2uptake, the increase in phosphorylation of α-AMPK (Thr172) was blunted in the trained group (138 ± 38% above rest) compared with the sedentary group (353 ± 63% above rest) ( P < 0.05). Acetyl CoA-carboxylase β-phosphorylation (Ser221), which is a marker for in vivo AMPK activity, was increased by exercise in both groups but to a lower level in trained subjects (32 ± 5 arbitrary units) than in sedentary controls (45 ± 1 arbitrary units) ( P < 0.01). In conclusion, trained human skeletal muscle has increased α1-AMPK protein levels and blunted AMPK activation during exercise.
Hypochlorous acid modifies calcium release channel function from skeletal muscle sarcoplasmic reticulum
Authors: Favero Terence G. , Webb Jason , Papiez Maria , Fisher Erin , Trippichio Robert J. , Broide Michael , Abramson Jonathan J.
Published: March 2015

We have previously demonstrated that H2O2at millimolar concentrations induces Ca2+release from actively loaded sarcoplasmic reticulum (SR) vesicles and induces biphasic [3H]ryanodine binding behavior. Considering that hypochlorous acid (HOCl) is a related free radical and has been demonstrated to be a more effective oxidant of proteins, we evaluated the effects of HOCl on sarcoplasmic reticulum Ca2+-channel release mechanism. In a concentration-dependent manner, HOCl activates the SR Ca2+release channel and induces rapid release of Ca from actively loaded vesicles. HOCl-induced Ca2+release is inhibited in the presence of millimolar concentrations of DMSO. High-affinity [3H]ryanodine binding is also enhanced at concentrations from 10 to 100 μM. At HOCl concentrations of >100 μM, equilibrium binding is inhibited. HOCl stimulation of binding is inhibited by the addition of dithiothreitol. The direct interaction between HOCl and the Ca2+release mechanism was further demonstrated in single-channel reconstitution experiments. HOCl, at 20 μM, activated the Ca2+release channel after fusion of a SR vesicle to a bilayer lipid membrane. At 40 μM, Ca2+-channel activity was inhibited. Pretreatment of SR vesicles with HOCl inhibited the fluorescence development of a fluorogenic probe specific to thiol groups critical to channel function. These results suggest that HOCl at micromolar concentrations can modify SR Ca2+handling.
Effect of stretching training on the viscoelastic properties of human tendon structures in vivo
Authors: Kubo Keitaro , Kanehisa Hiroaki , Fukunaga Tetsuo
Published: March 2015

The purpose of this study was to examine whether stretching training altered the viscoelastic properties of human tendon structures in vivo. Eight men performed the stretching training for 3 wk. Before and after the stretching training, the elongation of the tendon and aponeurosis of medial gastrocnemius muscle was directly measured by ultrasonography while the subjects performed ramp isometric plantar flexion up to the voluntary maximum, followed by a ramp relaxation. The relationship between the estimated muscle force (Fm) and tendon elongation ( L) during the ascending phase was fitted to a linear regression, the slope of which was defined as stiffness of tendon structures. The percentage of the area within the Fm- L loop to the area beneath the curve during ascending phase was calculated as an index representing hysteresis. To assess the flexibility, the passive torque of the plantar flexor muscles was measured during the passive stretch from 0° (anatomic position) to 25° of dorsiflexion with a constant velocity of 5°/s. The slope of the linear portion of the passive torque-angle curve during stretching was defined as flexibility index. Flexibility index decreased significantly after stretching training (−13.4 ± 4.6%). On the other hand, the stretching training produced no significant change in stiffness but significantly decreased hysteresis from 19.9 ± 11.7 to 12.5 ± 9.5%. The present results suggested that stretching training affected the viscosity of tendon structures but not the elasticity.
Validation of measurements of ventilation-to-perfusion ratio inequality in the lung from expired gas
Authors: Prisk G. Kim , Guy Harold J. B. , West John B. , Reed James W.
Published: March 2015

The analysis of the gas in a single expirate has long been used to estimate the degree of ventilation-perfusion (V˙a/Q˙) inequality in the lung. To further validate this estimate, we examined three measures ofV˙a/Q˙ inhomogeneity calculated from a single full exhalation in nine anesthetized mongrel dogs under control conditions and after exposure to aerosolized methacholine. These measurements were then compared with arterial blood gases and with measurements of V˙a/Q˙ inhomogeneity obtained using the multiple inert gas elimination technique. The slope of the instantaneous respiratory exchange ratio (R slope) vs. expired volume was poorly correlated with independent measures, probably because of the curvilinear nature of the relationship due to continuing gas exchange. When R was converted to the intrabreathV˙a/Q˙ (iV˙/Q˙), the best index was the slope of iV˙/Q˙ vs. volume over phase III (iV˙/Q˙slope). This was strongly correlated with independent measures, especially those relating to inhomogeneity of perfusion. The correlations for iV˙/Q˙ slope and R slope considerably improved when only the first half of phase III was considered. We conclude that a useful noninvasive measurement ofV˙a/Q˙ inhomogeneity can be derived from the intrabreath respiratory exchange ratio.
Theoretical analysis of effects of blood substitute affinity and cooperativity on organ oxygen transport
Authors: Kavdia Mahendra , Pittman Roland N. , Popel Aleksander S.
Published: March 2015

Hemoglobin-based O2carriers (HBOCs), which are developed as an alternative to blood transfusion, provide O2 delivery. At present, there is no model to predict the O2 transport for a red blood cell-HBOC mixture on a whole organ basis. On the basis of the first principles of mass balance, a model of O2 transport for an organ was derived to calculate venous Po 2(PvO2 ) for a given inlet arterial Po 2 (PaO2 ), blood flow, and oxygen consumption. The model was validated by using several in vivo animal studies on HBOC administration for a wide range of HBOC oxygen-binding parameters and predicted PvO2 for various PaO2 in the same species. The model was also used to predict the effect of HBOC affinity and cooperativity on PvO2 for humans. The results indicate that PvO2 can be increased at a constant blood flow-to-oxygen consumption ratio by reducing the affinity of HBOC for normoxia and mild hypoxia; however, a high-affinity HBOC would be more efficient in maintaining higher PvO2 for severe hypoxia (PaO2 < 40 Torr).