bluuebunny/crossref_metadata_2025 huggingface dataset:
Invited Review: Mechanisms underlying motor unit plasticity in the respiratory system
Authors: Mantilla Carlos B. , Sieck Gary C.
Published: March 2015

Neuromotor control of skeletal muscles, including respiratory muscles, is ultimately dependent on the function of the motor unit (comprising an individual motoneuron and the muscle fibers it innervates). Considerable diversity exists across diaphragm motor units, yet remarkable homogeneity is present (and maintained) within motor units. In recent years, the mechanisms underlying the development and adaptability of respiratory motor units have received great attention, leading to significant advances in our understanding of diaphragm motor unit plasticity. For example, following imposed inactivity of the diaphragm muscle, there are changes at phrenic motoneurons, neuromuscular junctions, and muscle fibers that tend to restore the ability of the diaphragm to sustain ventilation. The role of activity, neurotrophins, and other growth factors in modulating this adaptability is discussed.
Effect of surface tension and surfactant administration on Eustachian tube mechanics
Authors: Ghadiali Samir N. , Banks Julie , Swarts J. Douglas
Published: March 2015

Development of otitis media has been related to abnormal Eustachian tube (ET) mechanics. ET is a collapsible tube that is periodically opened to regulate middle ear pressure and to clear middle ear fluid into the nasopharynx. The ability to perform these physiological functions depends on several mechanical properties, including the ET's opening pressure (Popen), compliance (ETC), and hysteresis (η). In this study, a previously developed modified force-response protocol was used to determine ET mechanical properties after experimental manipulation of the mucosal surface condition. Specifically, these properties were measured in the right ear of six cynomologous monkeys under baseline conditions after “washing out” the normal ET mucous layer and after instillation of a pulmonary surfactant, Infasurf. Removal of the normal mucosa did not significantly alter Popen but did result in a decrease in ETC and η ( P < 0.05). Treatment of the mucosa with Infasurf was effective in reducing Popen and increasing both ETC and η to baseline values ( P < 0.05). These results indicate that the mucosa-air surface tension can affect the overall ETC and η properties of the ET. In addition, this study indicates that surfactant therapy may only be beneficial in patients with rigid or inelastic ETs (large Popen and low ETC and η).
Changes in maximal aerobic capacity with age in endurance-trained women: 7-yr follow-up
Authors: Eskurza Iratxe , Donato Anthony J. , Moreau Kerrie L. , Seals Douglas R. , Tanaka Hirofumi
Published: March 2015

On the basis of cross-sectional data, we previously reported that the absolute, but not the relative (%), rate of decline in maximal oxygen consumption (V˙o 2 max) with age is greater in endurance-trained compared with healthy sedentary women. We tested this hypothesis by using a longitudinal approach. Eight sedentary (63 ± 2 yr at follow-up) and 16 endurance-trained (57 ± 2) women were reevaluated after a mean follow-up period of 7 yr. At baseline,V˙o 2 max was ∼70% higher in endurance-trained women (48.1 ± 1.7 vs. 28.1 ± 0.8 ml · kg−1 · min−1 · yr−1). At follow-up, body mass, fat-free mass, maximal respiratory exchange ratio, and maximal rating of perceived exertion were not different from baseline in either group. The absolute rate of decline inV˙o 2 max was twice as great ( P < 0.01) in the endurance-trained (−0.84 ± 0.15 ml · kg−1 · min−1 · yr−1) vs. sedentary (−0.40 ± 0.12 ml · kg−1 · min−1 · yr−1) group, but the relative rates of decline were not different (−1.8 ± 0.3 vs. −1.5 ± 0.4% per year). Differences in rates of decline in V˙o 2 max were not related to changes in body mass or maximal heart rate. However, among endurance-trained women, the relative rate of decline inV˙o 2 max was positively related to reductions in training volume ( r = 0.63). Consistent with this, the age-related reduction inV˙o 2 max in a subgroup of endurance-trained women who maintained or increased training volume was not different from that of sedentary women. These longitudinal data indicate that the greater decrease in maximal aerobic capacity with advancing age observed in middle-aged and older endurance-trained women in general compared with their sedentary peers is due to declines in habitual exercise in some endurance-trained women. Endurance-trained women who maintain or increase training volume demonstrated age-associated declines in maximal aerobic capacity not different from healthy sedentary women.
Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run
Authors: Nieman D. C. , Davis J. M. , Henson D. A. , Walberg-Rankin J. , Shute M. , Dumke C. L. , Utter A. C. , Vinci D. M. , Carson J. A. , Brown A. , Lee W. J. , McAnulty S. R. , McAnulty L. S.
Published: March 2015

Sixteen experienced marathoners ran on treadmills for 3 h at ∼70% maximal oxygen consumption (V˙o 2 max) on two occasions while receiving 1 l/h carbohydrate (CHO) or placebo (Pla) beverages. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise. Plasma was analyzed for IL-6, IL-10, IL-1 receptor agonist (IL-1ra), IL-8, cortisol, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of 13 cytokines by using real-time quantitative RT-PCR. Plasma glucose and insulin were higher, and cortisol, IL-6, IL-10, and IL-1ra, but not IL-8, were significantly lower postexercise in CHO vs. Pla. Change in muscle glycogen content did not differ between CHO and Pla ( P = 0.246). Muscle cytokine mRNA content was detected preexercise for seven cytokines in this order (highest to lowest): IL-15, TNF-α, IL-8, IL-1β, IL-12p35, IL-6, and IFN-γ. After subjects ran for 3 h, gene expression above prerun levels was measured for five of these cytokines: IL-1β, IL-6, and IL-8 (large increases), and IL-10 and TNF-α (small increases). The increase in mRNA (fold difference from preexercise) was attenuated in CHO (15.9-fold) compared with Pla (35.2-fold) for IL-6 ( P = 0.071) and IL-8 (CHO, 7.8-fold; Pla, 23.3-fold; P = 0.063). CHO compared with Pla beverage ingestion attenuates the increase in plasma IL-6, IL-10, and IL-1ra and gene expression for IL-6 and IL-8 in athletes running 3 h at 70%V˙o 2 max despite no differences in muscle glycogen content.
Sex differences in human skeletal muscle fatigue are eliminated under ischemic conditions
Authors: Russ David W. , Kent-Braun Jane A.
Published: March 2015

Several studies have suggested that women may be more resistant to muscle fatigue than men (Fulco CS, Rock PB, Muza SA, Lammi E, Cymerman A, Butterfield G, Moore, LG, Braun B, and Lewis SF. Acta Physiol Scand 167: 233–239, 1999) possibly because of differences in muscle oxidative metabolism. We evaluated muscle fatigue produced by intermittent, maximal volitional isometric contractions of the dorsiflexor muscles of healthy young (21–34 yr) men ( n = 8) and women ( n = 8) under two conditions: free-flow (FF) circulation and ischemia. Measures of voluntary and stimulated (10- and 50-Hz) force, central activation ratio (CAR), and compound muscle action potential (CMAP) were collected in each session. The ischemic protocol induced greater fatigue than the FF protocol, in both sexes, and was associated with greater reductions in CAR, CMAP, stimulated force, and the ratio of 10- to 50-Hz force compared with the FF condition. Women fatigued less than men in FF but not during ischemia, and this difference was roughly paralleled by a difference in CAR. No sex effects on the CMAP, tetanic force, and measures of excitation-contraction coupling function were found in the FF condition, suggesting that the primary mechanism behind the difference in fatigue was a relatively greater impairment of central activation in men. The observation that ischemia eliminated the sex differences in fatigue is consistent with a number of studies (Kent-Braun JA, Ng AV, Doyle JW, and Towse TF. J Appl Physiol93: 1813–1823, 2002) relating fatigue to muscle metabolism and might be the result of sex-based differences in metabolic pathway utilization during muscle contraction.
Evidence for central command activation of the human insular cortex during exercise
Authors: Williamson J. W. , McColl R. , Mathews D.
Published: March 2015

The purpose of this investigation was to determine whether central command activated regions of the insular cortex, independent of muscle metaboreflex activation and blood pressure elevations. Subjects ( n = 8) were studied during 1) rest with cuff occlusion, 2) static handgrip exercise (SHG) sufficient to increase mean blood pressure (MBP) by 15 mmHg, and 3) post-SHG exercise cuff occlusion (PECO) to sustain the 15-mmHg blood pressure increase. Data were collected for heart rate, MBP, ratings of perceived exertion and discomfort, and regional cerebral blood flow (rCBF) by using single-photon-emission computed tomography. When time periods were compared when MBP was matched during SHG and PECO, heart rate (7 ± 3 beats/min; P < 0.05) and ratings of perceived exertion (15 ± 2 units; P < 0.05) were higher for SHG. During SHG, there were significant increases in rCBF for hand sensorimotor (9 ± 3%), right inferior posterior insula (7 ± 3%), left inferior anterior insula (8 ± 2%), and anterior cingluate regions (6 ± 2%), not found during PECO. There was significant activation of the inferior (ventral) thalamus and right inferior anterior insular for both SHG and PECO. Although prior studies have shown that regions of the insular cortex can be activated independent of mechanoreflex input, it was not presently assessed. These findings provide evidence that there are rCBF changes within regions of the insular and anterior cingulate cortexes related to central command per se during handgrip exercise, independent of metaboreflex activation and blood pressure elevation.
Altered ion transporter expression in bronchial epithelium in mountaineers with high-altitude pulmonary edema
Authors: Mairbäurl Heimo , Schwöbel Florian , Höschele Sabine , Maggiorini Marco , Gibbs Simon , Swenson Erik R. , Bärtsch Peter
Published: March 2015

Hypoxia inhibits activity and expression of transport proteins of cultured lung alveolar epithelial cells. Here we tested whether hypoxia at high altitude affected the expression of ion transport proteins in tissues obtained from controls and mountaineers with high-altitude pulmonary edema (HAPE) at the Capanna Margherita (4,559 m). Expression was determined by RT-PCR and Western blots from brush biopsies of bronchial epithelium and from leukocytes obtained before and during the stay at high altitude. At low altitude, amounts of mRNAs were not different between control and HAPE-susceptible subjects. At high altitude, the amount of mRNA of Na-K-ATPase, CFTR, and β-actin of brush biopsies did not change in controls but decreased significantly (-60%) in HAPE-susceptible subjects. There was no change in Na channel mRNAs at high altitude in controls and HAPE. No statistically significant correlation was found between the expression of Na transporters and Po2 and O2 saturation. In leukocytes, 28S-rRNA and Na-K-ATPase decreased at altitude in control and HAPE-susceptible subjects, but no significant change in Na-K-ATPase protein was found. Hypoxia-inducible factor-1α mRNA and GAPDH mRNA tended to increase in leukocytes obtained from HAPE-susceptible subjects at high altitude but did not change in controls. These results show that hypoxia induces differences in mRNA expression of ion transport-related proteins between HAPE-susceptible and control subjects but that these changes may not necessarily predict differences in protein concentration or activity. It is therefore unclear whether these differences are related to the pathophysiology of HAPE.
Improved coronary vascular function evoked by high-intensity treadmill training is maintained in arteries exposed to ischemia and reperfusion
Authors: Symons J. David , Hayashi Yoko , Ensunsa Jodi L.
Published: March 2015

We hypothesized that myocardial contractile function and coronary arterial function are greater after ischemia and reperfusion in high-intensity treadmill-trained vs. sedentary rats. Rats performed 10 × 4-min bouts of treadmill running consisting of 2 min at 13 m/min + 2 min at 45-60 m/min (Etr) or were sedentary (Sed) for 12 wk. Animals then were instrumented to measure left ventricular (LV) contractility in response to three 15-min coronary occlusion (O) and 5-min reperfusion (R) cycles (Isc) or a sham operation (Sham). After the Isc and Sham protocols, hearts were excised and coronary arterial (∼105 μm ID) function was evaluated by using isometric techniques. LV developed pressure, the first derivative of LV pressure at a developed pressure of 40 mmHg, and systolic blood pressure were not different between Etr ( n = 14) and Sed ( n = 7) rats before or after the Sham protocol. Furthermore, hemodynamic variables were similar in Etr ( n = 14) and Sed ( n = 13) animals before the Isc protocol and were depressed to the same degree by the three O-R cycles. Therefore, Etr did not alter myocardial contractile function in rats that were (i.e., Isc) or were not (i.e., Sham) exposed to ischemia and reperfusion. Acetylcholine-evoked relaxation (10-8 to 3 × 10-5 M) was greater ( P < 0.05) in coronary arteries from Sham-Etr vs. Sham-Sed animals (5 of 8 doses tested) and Isc-Etr vs. Isc-Sed rats (3 of 8 doses tested). Maximal relaxation produced by sodium nitroprusside (10-4 M) was similar among groups. Vasocontractile responses produced by KCl (10-100 mM) and endothelin-1 (10-11-10-4 M) were greater ( P < 0.05) in the presence vs. the absence of nitric oxide synthase inhibition (10-6 M NG-monomethyl-l-arginine) in vessels from Sham-Etr but not Sham-Sed rats and from Isc-Etr but not Isc-Sed rats. These findings suggest that Etr-evoked improvements in coronary function are maintained in small arteries even when exposed to ischemia and reperfusion.
Creatine supplementation influences substrate utilization at rest
Authors: Huso M. Erik , Hampl Jeffrey S , Johnston Carol S. , Swan Pamela D.
Published: March 2015

The influence of creatine supplementation on substrate utilization during rest was investigated using a double-blind crossover design. Ten active men participated in 12 wk of weight training and were given creatine and placebo (20 g/day for 4 days, then 2 g/day for 17 days) in two trials separated by a 4-wk washout. Body composition, substrate utilization, and strength were assessed after weeks 2, 5, 9, and 12. Maximal isometric contraction [1 repetition maximum (RM)] leg press increased significantly ( P < 0.05) after both treatments, but 1-RM bench press was increased (33 ± 8 kg, P < 0.05) only after creatine. Total body mass increased (1.6 ± 0.5 kg, P < 0.05) after creatine but not after placebo. Significant ( P < 0.05) increases in fat-free mass were found after creatine and placebo supplementation (1.9 ± 0.8 and 2.2 ± 0.7 kg, respectively). Fat mass did not change significantly with creatine but decreased after the placebo trial (−2.4 ± 0.8 kg, P < 0.05). Carbohydrate oxidation was increased by creatine (8.9 ± 4.0%, P < 0.05), whereas there was a trend for increased respiratory exchange ratio after creatine supplementation (0.03 ± 0.01, P = 0.07). Changes in substrate oxidation may influence the inhibition of fat mass loss associated with creatine after weight training.
Impaired muscle Ca2+and K+regulation contribute to poor exercise performance post-lung transplantation
Authors: McKenna Michael J. , Fraser Steve F. , Li Jia L. , Wang Xiao N. , Carey Michael F. , Side Eleonora A. , Morton Judith , Snell Gregory I. , Kjeldsen Keld , Williams Trevor J.
Published: March 2015

Lung transplant recipients (LTx) exhibit marked peripheral limitations to exercise. We investigated whether skeletal muscle Ca2+and K+regulation might be abnormal in eight LTx and eight healthy controls. Peak oxygen consumption and arterialized venous plasma [K+] (where brackets denote concentration) were measured during incremental exercise. Vastus lateralis muscle was biopsied at rest and analyzed for sarcoplasmic reticulum Ca2+release, Ca2+uptake, and Ca2+-ATPase activity rates; fiber composition; Na+-K+-ATPase (K+-stimulated 3- O-methylfluorescein phosphatase) activity and content ([3H]ouabain binding sites); as well as for [H+] and H+-buffering capacity. Peak oxygen consumption was 47% less in LTx ( P < 0.05). LTx had lower Ca2+release (34%), Ca2+uptake (31%), and Ca2+-ATPase activity (25%) than controls ( P < 0.05), despite their higher type II fiber proportion (LTx, 75.0 ± 5.8%; controls, 43.5 ± 2.1%). Muscle [H+] was elevated in LTx ( P < 0.01), but buffering capacity was similar to controls. Muscle 3- O-methylfluorescein phosphatase activity was 31% higher in LTx ( P < 0.05), but [3H]ouabain binding content did not differ significantly. However, during exercise, the rise in plasma [K+]-to-work ratio was 2.6-fold greater in LTx ( P < 0.05), indicating impaired K+regulation. Thus grossly subnormal muscle calcium regulation, with impaired potassium regulation, may contribute to poor muscular performance in LTx.
Effects ofall-transretinoic acid on angiotensin II-induced myocyte hypertrophy
Authors: Wang Hao-Jie , Zhu Yi-Chun , Yao Tai
Published: March 2015

We used cultured neonatal rat cardiac myocytes to test the hypothesis that all-trans retinoic acid ( atRA) may act to modulate ANG II actions in inducing myocyte hypertrophy. Our observations were as follows. 1) atRA (10−7to ∼10−5M ) inhibited ANG II-induced hyperplasia of fibroblasts in a dose-dependent manner. 2) Treatment of atRA attenuated the ANG II-induced increase in total cell protein content. 3) Treated with ANG II (10−7M) for 5 days, the cultured neonatal rat cardiac myocytes demonstrated an apparent accumulation of sarcomeric fiber proteins and Golgi's complex, as well as reorganization of the sarcomeric unit within individual myocytes. atRA (10−6M) treatment reduced the accumulation of contractile proteins and Golgi's complex without affecting the ANG II-induced reorganization of the sarcomeric unit. 4) atRA attenuated the ANG II-induced increase in intracellular Ca2+. Our results show that atRA inhibits some effects of ANG II on neonatal rat cardiac myocytes and suggest that atRA may be a therapeutic candidate for the prevention and therapy of cardiac hypertrophy and remodeling.
ACE gene and physical activity, blood pressure, and hypertension: a population study in Finland
Authors: Fuentes Ricardo M. , Perola Markus , Nissinen Aulikki , Tuomilehto Jaakko
Published: March 2015

The study evaluated the association of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene (ACE I/D) with self-reported moderate-intensity leisure time physical activity (MILTPA), arterial blood pressure (BP) and history of hypertension (HT). A representative population-based sample of 721 middle-aged adults (358 women) from two areas of Finland was genotyped for the ACE I/D. After exclusion criteria were applied, 455 subjects (288 women) were selected for the analysis. The distribution of the ACE I/D genotypes did not differ significantly among frequent vs. nonfrequent MILTPA groups (χ2 = 2.556; df = 2; P value = 0.279). The main predictors of BP were male gender, age, body mass index, and arterial pulse. Additionally, tobacco smoking and alcohol consumption also had a significant main effect on diastolic BP. HT was significantly more frequent in subjects with obesity, family history of cardiovascular disease, or lower educational level. As for BP, neither ACE I/D nor MILTPA was associated with HT. The study confirmed recent reports from population-based studies of no association between ACE I/D and physical fitness. The study also confirmed a lack of association between ACE I/D and BP or HT.
Time course of lung ischemia-reperfusion-induced ICAM-1 expression and its role in ischemia-reperfusion lung injury
Authors: Lu Yen-Ta , Chen Pai-Gene , Liu Shu Fang
Published: March 2015

Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is an important mechanism underlying ischemia-reperfusion (I/R) induced neutrophil activation and tissue injury in other organs. However, I/R of the lungs has not been shown to upregulate ICAM-1 expression. We determined the time course profile of lung I/R-induced ICAM-1 expression and assessed the role of ICAM-1 in mediating neutrophil sequestration, transmigration, and I/R injury in the isolated blood-perfused rat lungs. I/R had a biphasic effect on ICAM-1 expression, an early downregulation and a late-phase upregulation. Superoxide dismutase and neutrophil depletion prevented the early ICAM-1 downregulation. The late-phase ICAM-1 upregulation coincided with the I/R-induced increase in pulmonary microvascular leakage index. ICAM-1 monoclonal antibody (MAb) reversed the I/R-induced increase in pulmonary microvascular leakage index, with control antibody being ineffective. Neither I/R nor ICAM-1 MAb affected lung MPO activity and circulating neutrophil count. Lung I/R significantly increased bronchoalveolar lavage fluid neutrophil count and the GSSG-to-(GSSG+GSH) ratio. ICAM-1 MAb blocked the I/R-induced increase in GSSG-to-(GSSG+GSH) ratio but had no effect on bronchoalveolar lavage fluid neutrophil count. Our results demonstrated that lung I/R up- and downregulates ICAM-1 expression depending on the duration of reperfusion. ICAM-1 upregulation is an important mechanism of I/R-induced pulmonary endothelial injury.
Effects of prior heavy exercise onV˙o 2 kinetics during heavy exercise are related to changes in muscle activity
Authors: Burnley Mark , Doust Jonathan H. , Ball Derek , Jones Andrew M.
Published: March 2015

We hypothesized that the elevated primary O2 uptake (V˙o 2) amplitude during the second of two bouts of heavy cycle exercise would be accompanied by an increase in the integrated electromyogram (iEMG) measured from three leg muscles (gluteus maximus, vastus lateralis, and vastus medialis). Eight healthy men performed two 6-min bouts of heavy leg cycling (at 70% of the difference between the lactate threshold and peakV˙o 2) separated by 12 min of recovery. The iEMG was measured throughout each exercise bout. The amplitude of the primary V˙o 2 response was increased after prior heavy leg exercise (from mean ± SE 2.11 ± 0.12 to 2.44 ± 0.10 l/min, P < 0.05) with no change in the time constant of the primary response (from 21.7 ± 2.3 to 25.2 ± 3.3 s), and the amplitude of theV˙o 2 slow component was reduced (from 0.79 ± 0.08 to 0.40 ± 0.08 l/min, P < 0.05). The elevated primary V˙o 2 amplitude after leg cycling was accompanied by a 19% increase in the averaged iEMG of the three muscles in the first 2 min of exercise (491 ± 108 vs. 604 ± 151% increase above baseline values, P < 0.05), whereas mean power frequency was unchanged (80.1 ± 0.9 vs. 80.6 ± 1.0 Hz). The results of the present study indicate that the increased primaryV˙o 2 amplitude observed during the second of two bouts of heavy exercise is related to a greater recruitment of motor units at the onset of exercise.
Skeletal muscle capillary hemodynamics from rest to contractions: implications for oxygen transfer
Authors: Kindig Casey A. , Richardson Troy E. , Poole David C.
Published: March 2015

Muscle contractions evoke an immediate rise in blood flow. Distribution of this hyperemia within the capillary bed may be deterministic for muscle O2diffusing capacity and remains unresolved. We developed the exteriorized rat ( n = 4) spinotrapezius muscle for evaluation of capillary hemodynamics before (rest), during, and immediately after (post) a bout of twitch contractions to resolve (second-by-second) alterations in red blood cell velocity ( V RBC) and flux ( f RBC). Contractions increased (all P < 0.05) capillary V RBC (rest: 270 ± 62 μm/s; post: 428 ± 47 μm/s), f RBC (rest: 22.4 ± 5.5 cells/s; post: 44.3 ± 5.5 cells/s), and hematocrit but not the percentage of capillaries supporting continuous RBC flow (rest: 84.0 ± 0.7%; post: 89.5±1.4%; P > 0.05). V RBC peaked within the first one or two contractions, whereas f RBC increased to an initial short plateau (first 12–20 s) followed by a secondary rise to steady state. Hemodynamic temporal profiles were such that capillary hematocrit tended to decrease rather than increase over the first ∼15 s of contractions. We conclude that contraction-induced alterations in capillary RBC flux and distribution augment both convective and diffusive mechanisms for blood-myocyte O2 transfer. However, across the first 10–15 s of contractions, the immediate and precipitous rise in V RBC compared with the biphasic and prolonged increase of f RBC may act to lower O2 diffusing capacity by not only reducing capillary transit time but by delaying the increase in the instantaneous RBC-to-capillary surface contact thought crucial for blood-myocyte O2 flux.
Detection of porcine oleic acid-induced acute lung injury using pulmonary acoustics
Authors: Räsänen Jukka , Gavriely Noam
Published: March 2015

To evaluate the utility of monitoring the sound-filtering characteristics of the respiratory system in the assessment of acute lung injury (ALI), we injected a multifrequency broadband sound signal into the airway of five anesthetized, intubated pigs, while recording transmitted sound over the trachea and on the chest wall. Oleic acid injections effected a severe lung injury predominantly in the dependent lung regions, increasing venous admixture from 6 ± 1 to 54 ± 8% ( P < 0.05) and reducing dynamic respiratory system compliance from 19 ± 0 to 12 ± 2 ml/cmH2O ( P < 0.05). A two- to fivefold increase in sound transfer function amplitude was seen in the dependent ( P < 0.05) and lateral ( P < 0.05) lung regions; no change occurred in the nondependent areas. High within-subject correlations were found between the changes in dependent lung sound transmission and venous admixture ( r = 0.82 ± 0.07; range 0.74–0.90) and dynamic compliance ( r = −0.87 ± 0.05; −0.80 to −0.93). Our results indicate that the acoustic changes associated with oleic acid-induced lung injury allow monitoring of its severity and distribution.
Effect of aerobic and resistance exercise on central hemodynamic responses in severe chronic heart failure
Authors: Cheetham Craig , Green Daniel , Collis Julie , Dembo Lawrence , O'Driscoll Gerard
Published: March 2015

Exercise is now considered an important component of management in chronic heart failure (CHF), but little is known about central hemodynamic changes that occur during different exercise modalities in these patients. Seventeen patients (ejection fraction 25 ± 2%) undertook brachial artery and right heart catheterization and oxygen consumption assessment at rest, during submaximal and peak cycling (Cyc), and during submaximal upper and lower limb resistance exercise. Cardiac output (CO) increased relative to baseline during peak Cyc ( P < 0.05) but did not change during submaximal Cyc or upper or lower limb exercise. Heart rate (HR) was lowest during upper limb exercise and progressively increased during lower limb exercise, submaximal Cyc, and peak Cyc, with significant differences between each of these ( P< 0.01). Conversely, stroke volume (SV) decreased during submaximal Cyc and lower limb exercise and was lower during peak and submaximal Cyc and lower limb exercise than during upper limb exercise ( P < 0.05). CHF patients are dependent on increases in HR to increase CO during exercise when SV may decline. Resistance exercise, performed at appropriate intensity, induces a similar hemodynamic burden to aerobic exercise in patients with CHF.
Energy balance, metabolism, hydration, and performance during strenuous hill walking: the effect of age
Authors: Ainslie P. N. , Campbell I. T. , Frayn K. N. , Humphreys S. M. , MacLaren D. P. M. , Reilly T. , Westerterp K. R.
Published: March 2015

We aimed to examine the effect of age on energy balance, metabolism, hydration, and performance during 10 days of strenuous hill walking. Seventeen male subjects were divided into two groups according to their age. The nine subjects in group 1 constituted the younger group (age 24 ± 3 yr), whereas eight older subjects were in group 2 (age 56 ± 3 yr). Both groups completed 10 consecutive days of high-intensity hill walking. Mean (range) daily walking distances and ascent were 21 km (10–35 km) and 1,160 m (800–2,540 m), respectively. Energy intake was calculated from weighed food intake, and energy expenditure was measured by the doubly labeled water method. Blood and urine were sampled on alternative days to determine any changes in metabolism and hydration during the 10 days. Subjects also completed a battery of tests that included muscular strength (handgrip), jump performance, cognitive processing time, and flexibility. The younger group remained hydrated, whereas the older group became progressively dehydrated, indicated by a near twofold increase in urine osmolality concentration on day 11. This increased urine osmolality in the older group was highly correlated with impairment in vertical-jump performance ( r = −0.86; P < 0.05) and decreased cognitive processing time ( r = 0.79; P < 0.05). Despite energy expenditure of ∼21 MJ/day, body mass was well maintained in both groups. Both groups displayed a marked increase in fat mobilization, reflected in significantly lowered prewalk insulin concentrations and elevated postwalk glycerol and nonesterified fatty acid concentrations. Despite the dehydration and impaired performance in the older group, blood glucose concentrations were well maintained in both groups, probably mediated via the increased mobilization of fat.
Differential changes of lung diffusing capacity and tissue volume in hypergravity
Authors: Rohdin Malin , Linnarsson Dag
Published: March 2015

In normal gravity, lung diffusing capacity (Dl CO) and lung tissue volume (LTV; including pulmonary capillary blood volume) change in concert, for example, during shifts between upright and supine. Accordingly, Dl CO and LTV might be expected to decrease together in sitting subjects in hypergravity due to peripheral pooling of blood and reduced central blood volume. Nine sitting subjects in a human centrifuge were exposed to one, two, and three times increased gravity in the head-to-feet direction (Gz+) and rebreathed a gas containing trace amounts of acetylene and carbon monoxide. Dl CO was 25.2 ± 2.6, 20.0 ± 2.1, and 16.7 ± 1.7 ml · min−1 · mbar−1(means ± SE) at 1, 2, and 3 Gz+, respectively (ANOVA P < 0.001). Corresponding values for LTV increased from 541 ± 34 to 677 ± 43, and 756 ± 71 ml ( P < 0.001) at 2 and 3 Gz+. Results are compatible with sequestration of blood in the dependent part of the pulmonary circulation just as in the systemic counterpart. Dl CO, which under normoxic conditions is mainly determined by its membrane component, decreased despite an increased pulmonary capillary blood volume, most likely as a consequence of a less homogenous distribution of alveolar volume with respect to pulmonary capillary blood volume.
Who Discovered the Frank-Starling Mechanism?
Authors: Zimmer Heinz-Gerd
Published: March 2015

In 1866 at Carl Ludwig’s Physiological Institute at Leipzig, Elias Cyon described the influence of diastolic filling of the isolated perfused frog heart on ejection volume. A study performed at the institute of the effect of filling pressure on contraction amplitude was published in 1869 by Joseph Coats, based on a recording made by Henry P. Bowditch.
Agrin in the Developing CNS: New Roles for a Synapse Organizer
Authors: Kröger Stephan , Schröder Jörn E.
Published: March 2015

The heparan sulfate proteoglycan agrin is responsible for the formation, maintenance, and regeneration of the neuromuscular junction. In the central nervous system, agrin is widely expressed and concentrated at interneuronal synapses, but its function during synaptogenesis remains controversial. Instead, evidence for additional functions of agrin during axonal growth, establishment of the blood-brain barrier, and Alzheimer’s disease is accumulating.
Spatial Heterogeneity in the Heart: Recent Insights and Open Questions
Authors: Decking Ulrich K. M.
Published: March 2015

Within the left ventricular myocardium and despite its rather homogeneous structure, local myocardial perfusion varies substantially. Areas of low and high local flow differ with regard to substrate uptake, energy turnover, and demand. This spatial heterogeneity is related to distinct differences in local protein expression, forming the basis of a novel homeostatic mechanism.
Fusion Pore in Live Cells
Authors: Jena Bhanu P.
Published: March 2015

Earlier electrophysiological measurements on live secretory cells suggested the presence of fusion pores at the plasma membrane, where secretory vesicles fuse to release vesicular contents. Recent studies using atomic force microscopy demonstrate for the first time the presence of the fusion pore and reveal its morphology and dynamics at near-nanometer resolution and in real time.
Angioadaptation: Keeping the Vascular System in Shape
Authors: Zakrzewicz Andreas , Secomb Timothy W. , Pries Axel R.
Published: March 2015

The development and maintenance of the vascular system requires not only the formation of new vessels (vasculogenesis, angiogenesis) but also the continuous adjustment of vessel and network structures in response to functional needs. This “angioadaptation” depends on the interplay of vascular responses to growth factors, to the metabolic status of the tissue, and to hemodynamic forces exerted by the flowing blood.
It Takes “Heart” to Win: What Makes the Heart Powerful?
Authors: McDonald Kerry S. , Herron Todd J.
Published: March 2015

The pumping action of the heart varies considerably on a beat-to-beat basis and is ultimately determined by the extent of ventricular myocyte shortening during systole. The use of isolated myocardial preparations has provided new insights about the subcellular factors that modulate power output of the ventricles.
The Physiological and Evolutionary Significance of Cardiovascular Shunting Patterns in Reptiles
Authors: Hicks James W.
Published: March 2015

The morphology of the reptilian heart results in the mixing of oxygenated and deoxygenated blood (cardiac shunts). In birds and mammals cardiac shunts are detrimental, but in reptiles this condition is often considered a derived trait, conveying important physiological functions and favored by natural selection. Alternative views are advanced suggesting that, in reptiles, cardiac shunts represent either an ancestral condition or an embryonic trait.
Functional Imaging of Physiological Processes by Positron Emission Tomography
Authors: Westera Gerrit , Schubiger P. August
Published: March 2015

Tracer technology makes it possible to observe physiological and biochemical processes in the living organism in a dynamic mode. Positron emission tomography adds the use of chemically unchanged biomolecules and of quantification. This opens up fascinating possibilities for both fundamental research and routine diagnostic applications.
Immune Adherence Revisited: Novel Players in an Old Game
Authors: Hess Christoph , Schifferli Jürg A.
Published: March 2015

Erythrocytes bind immune complexes (ICs) composed of antibodies binding their respective antigen (e.g., bacteria, parasites, viruses, or autoantigen) plus complement proteins via complement receptors [immune adherence (IA)]. In vivo studies have shown that erythrocytes act as an inert shuttle, targeting ICs to fixed macrophages in liver and spleen. Here we outline established and emerging implications of IA in health and disease.
Pathophysiological Basis of Smoke Inhalation Injury
Authors: Murakami Kazunori , Traber Daniel L.
Published: March 2015

Smoke inhalation injury results in serious respiratory failure. When smoke inhalation injury is combined with burn injury or pneumonia, the physiological responses are different and more severe than those of smoke inhalation injury alone. Treatment strategies should be planned based on these pathophysiological aspects.
Epithelial Cell Polarity From the Outside Looking In
Authors: Nelson W. James
Published: March 2015

Epithelial cell polarity may be regulated by protein sorting in the Golgi and delivery to different membrane domains, a view from the inside looking out. But from the outside looking in, cell adhesion may be required first to establish sites for delivery, retention, and separation of membrane proteins, and delivery of presorted proteins from the Golgi subsequently reinforces and maintains different membrane domains.
Understanding Trabecular Meshwork Physiology: A Key to the Control of Intraocular Pressure?
Authors: Llobet Artur , Gasull Xavier , Gual Arcadi
Published: March 2015

The trabecular meshwork is a tissue located in the anterior chamber angle of the eye, and it is a crucial determinant of intraocular pressure values because of its resistance to the evacuation of aqueous humor from the eye. Here we bring together classical and recent discoveries on the function of the trabecular meshwork, keys to understanding eye pathophysiology.
Leukocyte Adhesion: An Exquisite Balance of Hydrodynamic and Molecular Forces
Authors: Tees David F. J. , Goetz Douglas J.
Published: March 2015

Leukocyte adhesion to the vascular endothelium involves a disruptive force exerted on the leukocyte by the flow of the blood and an adhesive force that forms at the leukocyte-endothelial interface. The relative strengths of these two competing forces govern leukocyte adhesion.
The Engine of ABC Proteins
Authors: Altenberg Guillermo A.
Published: March 2015

Proteins that belong to the ATP-binding cassette superfamily span from bacteria to humans and comprise one of the largest protein families. These proteins are characterized by the presence of two nucleotide-binding domains, and recent studies suggest that association and dissociation of these domains is a common basic molecular mechanism of operation that couples ATP binding/hydrolysis to substrate transport across membranes.
Allosteric Proteins: Lessons to be Learned From the Hemoglobin Intermediates
Authors: Perrella Michele , Russo Rosaria
Published: March 2015

Allosteric proteins, such as hemoglobin, are assemblies of functional units, which undergo quaternary structural transitions in response to concentration changes of a specific ligand. Functional properties of hemoglobin ligation intermediates indicate that the tertiary structural changes induced by the ligand do not promote an equilibrium of quaternary structures.
The Renal Pelvis: Machinery That Concentrates Urine in the Papilla
Authors: Dwyer Terry M. , Schmidt-Nielsen Bodil
Published: March 2015

Two decades ago, Bodil Schmidt-Nielsen and Bruce Graves documented the rhythmic contractions of the renal pelvis in a remarkable video, visually demonstrating how peristaltic waves empty the papilla and how the subsequent elastic recoil draws water from the collecting duct and into the tethered-open ascending vasa recta. Thus a periodic hydrostatic gradient generates an axial osmotic gradient. This review recapitulates the video and offers a link to figures and scenes digitized from the original tape.
Time-dependent changes in ARE-driven gene expression by use of a noise-filtering process for microarray data
Authors: Li Jiang , Johnson Jeffrey A.
Published: March 2015

The current study was designed to identify the time-dependent gene expression profiles of antioxidant responsive element (ARE)-driven genes induced by tert-butylhydroquinone (tBHQ). A set of simple noise-filtering methods was introduced to evaluate and minimize the variance of microarray datasets. Gene expression induced by tBHQ (10 μM) in IMR-32 human neuroblastoma cells was analyzed by means of large-scale oligonucleotide microarray. Rank analysis was used to determine the acceptable number of independent samples necessary to eliminate false positives from the dataset. A dramatic reduction in the number of genes passing the rank analysis was achieved by using a 3 × 3 matrix comparison. Reproducibility was evaluated based on the coefficient of variation for average difference change. Completion of these analyses revealed that 101 of the 9,670 genes examined showed dynamic changes with treatment ranging from 4 h to 48 h. Since certain ARE-driven genes have been already identified, gene clustering would presumably group them together based on similar regulation. Self-organizing map grouped the genes induced by tBHQ into 12 (4×3) distinct clusters. Those previously identified ARE-driven genes were shown to group into different clusters. Since all potential ARE-driven genes did not cluster together, we speculate that multiple transcription factors and/or multiple signal transduction pathways contribute to transcriptional activation of the ARE. In conclusion, many novel potential ARE-driven genes were identified in this study. They function in detoxification and antioxidant defense, neuronal proliferation and differentiation, and signal transduction. The noise-filtering process applied to these microarray data, therefore, has proven to be very useful in identification of the time-dependent changes in ARE-drive gene expression.
The hypertrophic heart rat: a new normotensive model of genetic cardiac and cardiomyocyte hypertrophy
Authors: Harrap Stephen B. , Danes Vennetia R. , Ellis Justine A. , Griffiths Cory D. , Jones Elizabeth F. , Delbridge Leanne M. D.
Published: March 2015

We describe a new line of rats with inherited cardiomyocyte and ventricular hypertrophy. From a second-generation cross of spontaneously hypertensive and Fischer 344 rats, we selected for low blood pressure and either high or low echocardiographic left ventricular (LV) mass over four generations to establish the hypertrophic heart rat (HHR) and normal heart rat (NHR) lines, respectively. After 13 generations of inbreeding, HHR had significantly greater ( P < 0.0001) LV mass-to-body weight ratio (2.68 g/kg, SE 0.14) than NHR matched for age (1.94 g/kg, SE 0.02) or body weight (2.13 g/kg, SE 0.03). The isolated cardiomyocytes of HHR were significantly ( P < 0.0001) longer and wider (161 μm, SE 0.83; 35.6 μm, SE 2.9) than NHR (132 μm, SE 1.2; 29.5 μm, SE 0.35). Telemetric 24-h recordings of mean arterial pressure revealed no significant differences between HHR and NHR. The HHR offers a new model of primary cardiomyocyte hypertrophy with normal blood pressure in which to examine genotypic causes and pathogenetic mechanisms of hypertrophy and its complications.
Gene expression profile of mouse myocardium with transgenic overexpression of A1adenosine receptors
Authors: Lankford Amy R. , Byford Anne M. , Ashton Kevin J. , French Brent A. , Lee Jae K. , Headrick John P. , Matherne G. Paul
Published: March 2015

Transgenic mice with cardiac-specific overexpression of adenosine A1receptors (A1AR) have demonstrated metabolic and functional tolerance to myocardial ischemia. We utilized cDNA microarrays to test the hypothesis that the cardioprotective mechanism(s) of A1overexpression involves altered gene expression. Total RNA extracted from the left ventricles from A1transgenic ( n = 4) and wild-type ( n = 6) mice was hybridized to Affymetrix mgU74A chips. Comparison of RNA expression levels in transgenic to wild-type myocardium revealed ∼636 known genes with expression significantly altered by greater than 25%. We observed increased expressions of genes including NADH dehydrogenase, the GLUT4 glucose transporter, Na-K-ATPase, sarcolemmal KATPchannels, and Bcl-xl in A1AR-overexpressing hearts. We also observed decreased expression of pro-apoptotic genes including a 50% reduction in message level of caspase-8. Protein expression of GLUT4 and caspase-8 was also altered comparable to the differences in gene expression. These data illustrate genes with chronically altered patterns of expression in A1transgenic mouse myocardium that may be related to adenosine receptor overexpression-mediated cardioprotection.
Mapping blood pressure loci in (A/J × B6)F2 mice
Authors: Woo David D. L. , Kurtz Ira
Published: March 2015

Although the genetics of rare, monogenic, forms of human hypertension are fairly well defined, the genetics of the common polygenic form of human essential hypertension is only emerging. With the ability to control environmental variables, animal models have provided valuable tools with which to study blood pressure (BP) homeostasis. We have now studied BP genetics in a model consisting of 1,521 F2 mice from a series of (A/J × B6) intercrosses kept under standardized conditions. Using whole genome quantitative trait loci (QTL) mapping, we have identified four novel significant BP loci. These included Abbp1 on mouse chromosome MMU1 [maximum LOD score (MLS) at ∼35 cM = 6.8], Abbp2 on MMU4 (MLS at ∼25 cM = 9.8), Abbp3 on MMU7 (MLS at ∼25 cM = 5.4), and Abbp4 on MMU11 (MLS at ∼58 cM = 6.3). Compared with A/J homozygotes, homozygosity for the B6 alleles of Abbp1, Abbp2, or Abbp4 is independently associated with a 7–12 mmHg increase in BP. In contrast Abbp3 interacts epistatically with a locus on MMU17 (near D17Mit180) to modulate BPs in female (A/J × B6)F2 mice. Interestingly, Abbp4 on MMU11 is homologous to a major confirmed BP locus, BP1, on rat chromosome 10 and to a major confirmed BP locus, HYT1, on human chromosome 17. Defining the molecular differences between the A/J and the B6 alleles at these novel loci with major influences on the BP phenotype will contribute to our understanding of the complex genetics of BP control.
Developmental anatomy of the heart: a tale of mice and man
Authors: Wessels Andy , Sedmera David
Published: March 2015

Because of the increasing availability of tools for genetic manipulation, the mouse has become the most popular animal model for studying normal and abnormal cardiac development. However, despite the enormous advances in mouse genetics, which have led to the production of numerous mutants with cardiac abnormalities resembling those seen in human congenital heart disease, relatively little comparative work has been published to demonstrate the similarities and differences in the developmental cardiac anatomy in both species. In this review we discuss some aspects of the comparative anatomy, with emphasis on the atrial anatomy, the valvuloseptal complex, and ventricular myocardial development. From the data presented it can be concluded that, apart from the obvious differences in size, the mouse and human heart are anatomically remarkably similar throughout development. The partitioning of the cardiac chambers (septation) follows the same sequence of events, while also the maturation of the cardiac valves and myocardium is quite similar in both species. The major anatomical differences are seen in the venous pole of the heart. We conclude that, taking note of the few anatomical “variations,” the use of the mouse as a model system for the human heart is warranted. Thus the analysis of mouse mutants with impaired septation will provide valuable information on cellular mechanisms involved in valvuloseptal morphogenesis (a process often disrupted in congenital heart disease), while the study of embryonic lethal mouse mutants that present with lack of compaction of ventricular trabeculae will ultimately provide clues on the etiology of this abnormality in humans.