bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of myocardial volume overload and heart failure on lactate transport into isolated cardiac myocytes
Authors: Evans Ronald K. , Schwartz Dean D. , Gladden L. Bruce
Published: March 2015

The purpose of this study was to determine lactate transport kinetics in single isolated rat ventricular cardiac myocytes after 1) 8 wk of myocardial volume overload (MVO) and 2) congestive heart failure (CHF). Twenty male Sprague-Dawley rats were assigned to one of four groups: myocardial hypertrophy (MH), MH sham (MHS), CHF, or CHF sham (CHFS). A chronic MVO was induced in the MH and CHF groups by an infrarenal arteriovenous fistula. Postdeath heart and lung weights were significantly greater ( P < 0.05) for the MH and CHF groups compared with controls. Isolated cardiac myocytes were loaded with BCECF to determine intracellular pH (pHi) changes after the addition of lactate to the extracellular superfusate. Alterations in pHi with the addition of varied lactate concentrations were attenuated 72–89% by 5.0 mM α-cyano-4-hydroxycinnamate. Significant differences ( P < 0.05) were found in estimated maximal lactate transport rates between the experimental and sham groups (MH = 19.4 ± 1.1 nmol · μl−1 · min−1vs. MHS = 15.1 ± 1.1 nmol · μl−1 · min−1; CHF = 20.2 ± 2.0 nmol · μl−1 · min−1vs. CHFS = 14.0 ± 0.9 nmol · μl−1 · min−1). Western blot analysis confirmed a 270% increase in monocarboxylate symport protein 1 (MCT1) protein content in CHF compared with CHFS rats. The results of this study suggest that MH and CHF induced by MVO engender a greater maximal lactate transport capacity across the cardiac myocyte sarcolemma along with an increase in MCT1 protein content. These alterations would likely benefit the cell by attenuating intracellular acidification during a period of increased myocardial load.
Effect of the cytoskeletal prestress on the mechanical impedance of cultured airway smooth muscle cells
Authors: Stamenović Dimitrije , Liang Zhuangli , Chen Jianxin , Wang Ning
Published: March 2015

We investigated the effect of the cytoskeletal prestress ( P) on the elastic and frictional properties of cultured human airway smooth muscle cells during oscillatory loading; P is preexisting tensile stress in the actin cytoskeleton generated by the cell contractile apparatus. We oscillated (0.1 Hz, 6 Pa peak to peak) small ferromagnetic beads bound to integrin receptors and computed the storage (elastic) modulus ( G′) and the loss (frictional) modulus ( G") from the applied torque and the corresponding bead rotation. All measurements were done at baseline and after cells were treated with graded doses of either histamine (0.1, 1, 10 μM) or isoproterenol (0.01, 0.1, 1, 10 μM). Values for P for these concentrations were taken from a previous study (Wang et al., Am J Physiol Cell Physiol, in press). It was found that G′ and G", as well as P, increased/decreased with increasing doses of histamine/isoproterenol. Both G′ and G" exhibited linear dependences on P: G′(Pa) = 0.20 P + 82 and G"(Pa) = 0.05 P + 32. The dependence of G′ on P is consistent with our previous findings and with the behavior of stress-supported structures. The dependence of G" on P is a novel finding. It could be attributed to a variety of mechanisms. Some of those mechanisms are discussed in detail. We concluded that, in addition to the central mechanisms by which stress-supported structures develop mechanical stresses, other mechanisms might need to be invoked to fully explain the observed dependence of the cell mechanical properties on the state of cell contractility.
Active glottal closure during central apneas limits oxygen desaturation in premature lambs
Authors: Reix Philippe , Arsenault Julie , Dôme Valérie , Fortier Pierre-Hugues , Lafond Joëlle Rouillard , Moreau-Bussière François , Dorion Dominique , Praud Jean-Paul
Published: March 2015

Our laboratory previously reported that active glottal closure was present in 90% of spontaneous central apneas in premature lambs while maintaining a high-apneic lung volume (Renolleau S, Letourneau P, Niyonsenga T, and Praud JP. Am J Respir Crit Care Med 159: 1396–1404, 1999.) The present study aimed at testing whether this mechanism limits postapnea oxygen desaturation. Four premature lambs were instrumented for recording states of alertness, thyroarytenoid muscle and diaphragm electromyographic (EMG) activity, nasal airflow, lung volume changes, and pulse oximetry. One thousand four hundred fifty-two spontaneous central apneas (isolated or during periodic breathing) were analyzed in nonsedated lambs. Apneas, with high lung volume maintained by active glottal closure, were compared with apneas, with a tracheostomy opened at apnea onset. Oxygen desaturation slopes were lower when high-apneic lung volume was actively maintained during both wakefulness and quiet sleep. Furthermore, oxygen desaturation slopes were lower after isolated apneas with continuous thyroarytenoid EMG during wakefulness, compared with apneas with noncontinuous thyroarytenoid EMG (= glottis opened shortly after apnea onset). These results highlight the importance of maintaining high-alveolar oxygen stores during central apneas by active glottal closure to limit desaturation in newborns.
Periodic breathing in the mouse
Authors: Han Fang , Subramanian Shyam , Price Edwin R. , Nadeau Joseph , Strohl Kingman P.
Published: March 2015

The hypothesis was that unstable breathing might be triggered by a brief hypoxia challenge in C57BL/6J (B6) mice, which in contrast to A/J mice are known not to exhibit short-term potentiation; as a consequence, instability of ventilatory behavior could be inherited through genetic mechanisms. Recordings of ventilatory behavior by the plethsmography method were made when unanesthetized B6 or A/J animals were reoxygenated with 100% O2or air after exposure to 8% O2or 3% CO2-10% O2gas mixtures. Second, we examined the ventilatory behavior after termination of poikilocapnic hypoxia stimuli in recombinant inbred strains derived from B6 and A/J animals. Periodic breathing (PB) was defined as clustered breathing with either waxing and waning of ventilation or recurrent end-expiratory pauses (apnea) of ≥2 average breath durations, each pattern being repeated with a cycle number ≥3. With the abrupt return to room air from 8% O2, 100% of the 10 B6 mice exhibited PB. Among them, five showed breathing oscillations with apnea, but none of the 10 A/J mice exhibited cyclic oscillations of breathing. When the animals were reoxygenated after 3% CO2-10% O2challenge, no PB was observed in A/J mice, whereas conditions still induced PB in B6 mice. (During 100% O2reoxygenation, all 10 B6 mice had PB with apnea.) Expression of PB occurred in some but not all recombinant mice and was not associated with the pattern of breathing at rest. We conclude that differences in expression of PB between these strains indicate that genetic influences strongly affect the stability of ventilation in the mouse.
Lengthening contraction-induced inflammation is linked to secondary damage but devoid of neutrophil invasion
Authors: Lapointe Benoît M. , Frenette Jérôme , Côté Claude H.
Published: March 2015

Inflammation triggered by exercise-induced muscle damage (EIMD) has been postulated to influence the extent of tissue destruction. We tested the hypotheses that 1) repressing inflammation decreases secondary damage production and 2) EIMD leads to a sequential appearance of inflammatory cells in which neutrophil accumulation precedes macrophage invasion. Rat ankle dorsiflexor muscles were submitted to in situ lengthening contractions. Measurement of in vitro contractile properties, inflammatory cell concentrations, and histological staining were performed postprotocol. Rats were treated with diclofenac, a nonsteroidal anti-inflammatory drug (NSAID group) to repress inflammation or with the vehicle solution (EIMD group). Muscles from the NSAID group had smaller force deficits on days 2 and 3 postexercise. This effect was associated with significantly smaller increases in the concentration of muscle macrophage ED1+ and ED2+. Surprisingly, neutrophils did not accumulate post-EIMD. These results suggest that inflammation-induced ED1+ macrophage accumulation is responsible for the secondary damage observed 2–3 days post-EIMD. We further conclude that an increase in ED1+ macrophage concentration can occur in absence of previous neutrophil invasion.
Circadian pancreatic enzyme pattern and relationship between secretory and motor activity in fasting humans
Authors: Keller Jutta , Layer Peter
Published: March 2015

It is unknown whether nonparallel pancreatic enzyme output occurs under basal conditions in humans. We aimed to determine whether the circadian or wake-sleep cycle influences the relationship among pancreatic enzymes or between pancreatic secretory and jejunal motor activity. Using orojejunal multilumen intubation, we measured enzyme outputs and proximal jejunal motility index during consecutive daytime and nighttime periods in each of seven fasting, healthy volunteers. Enzyme outputs were correlated tightly during daytime phases of wakefulness and nighttime phases of sleep ( r > 0.72, P < 0.001). During nocturnal phases of wakefulness, output of proteases ( r = 0.84, P < 0.001), but not of amylase and trypsin ( r = 0.12), remained associated. Nocturnally, particularly during sleep, pancreatic secretory activity was directly correlated with jejunal motility index ( r > 0.50, P < 0.001). In conclusion, parallel secretion of pancreatic enzymes dominates throughout the circadian cycle. Nonparallel secretion during nocturnal phases of wakefulness may be due to merely circadian effects or to the coupling of the wake-sleep and the circadian cycle. The association between fluctuations of secretory and motor activity appears to be particularly tight during the night.
Determinants of maximal O2 uptake in rats selectively bred for endurance running capacity
Authors: Henderson Kyle K. , Wagner Harrieth , Favret Fabrice , Britton Steven L. , Koch Lauren G. , Wagner Peter D. , Gonzalez Norberto C.
Published: March 2015

O2 transport during maximal exercise was studied in rats bred for extremes of exercise endurance, to determine whether maximal O2 uptake (V˙o 2 max) was different in high- (HCR) and low-capacity runners (LCR) and, if so, which were the phenotypes responsible for the difference. V˙o 2 maxwas determined in five HCR and six LCR female rats by use of a progressive treadmill exercise protocol at inspired Po 2 of ∼145 (normoxia) and ∼70 Torr (hypoxia). Normoxic V˙o 2 max (in ml · min−1 · kg−1) was 64.4 ± 0.4 and 57.6 ± 1.5 ( P < 0.05), whereas V˙o 2 max in hypoxia was 42.7 ± 0.8 and 35.3 ± 1.5 ( P < 0.05) in HCR and LCR, respectively. Lack of significant differences between HCR and LCR in alveolar ventilation, alveolar-to-arterial Po 2difference, or lung O2 diffusing capacity indicated that neither ventilation nor efficacy of gas exchange contributed to the difference in V˙o 2 max between groups. Maximal rate of blood O2 convection (cardiac output times arterial blood O2 content) was also similar in both groups. The major difference observed was in capillary-to-tissue O2transfer: both the O2 extraction ratio (0.81 ± 0.002 in HCR, 0.74 ± 0.009 in LCR, P < 0.001) and the tissue diffusion capacity (1.18 ± 0.09 in HCR and 0.92 ± 0.05 ml · min−1 · kg−1 · Torr−1in LCR, P < 0.01) were significantly higher in HCR. The data indicate that selective breeding for exercise endurance resulted in higher V˙o 2 max mostly associated with a higher transfer of O2 at the tissue level.
Chronic O2 exposure enhances vascular and airway smooth muscle contraction in the newborn but not adult rat
Authors: Belik J. , Jankov R. P. , Pan J. , Tanswell A. K.
Published: March 2015

Neonatal rats exposed to 60% O2 for 14 days develop lung changes compatible with human bronchopulmonary dysplasia and pulmonary hypertension. Our aim was to evaluate and compare the newborn and adult rat pulmonary vascular and airway smooth muscle force generation and relaxation potential after exposure to 60% O2 for 14 days. Vascular and airway intrapulmonary rings 100 μm in diameter were mounted on a myograph and bathed in Krebs-Henseleit solution bubbled with air- 6% CO2 at 37°C. Significant age-dependent changes in intrapulmonary arteries and their neighboring airway muscle properties were observed. Whereas hyperoxia enhanced force in neonatal vascular and airway muscle, the opposite was seen in adult samples. No changes in endothelium-dependent vascular relaxation were observed at either age, but the dose response to an endothelium-independent NO donor was altered. In the newborn experimental animals, the relaxation was reduced, whereas, in their adult counterparts, it was enhanced. After O2 exposure, the bronchial muscle relaxation response to epithelium-dependent and -independent stimulation was not altered in either age group, whereas the epithelium-dependent response was decreased only in the adult. The antioxidant Trolox, or an endothelin-A and -B receptor antagonist, reversed the vascular and airway muscle's hyperoxia-induced changes. We conclude that chronic O2 exposure in the newborn rat results in enhanced lung vascular and airway muscle contraction potential via a mechanism involving reactive oxygen species and the endothelin pathway. The present findings also suggest that the newborn is more susceptible to airway hyperresponsiveness after chronic O2 exposure.
Citrate synthase expression and enzyme activity after endurance training in cardiac and skeletal muscles
Authors: Siu Parco M. , Donley David A. , Bryner Randall W. , Alway Stephen E.
Published: March 2015

The present study was designed to examine the acute and chronic effects of endurance treadmill training on citrate synthase (CS) gene expression and enzymatic activity in rat skeletal and cardiac muscles. Adult rats were endurance trained for 8 wk on a treadmill. They were killed 1 h (T1, n = 8) or 48 h (T48, n= 8) after their last bout of exercise training. Eight rats were sedentary controls (C) during the training period. CS mRNA levels and enzymatic activities of the soleus and ventricle muscles were determined. Training resulted in higher CS mRNA levels in both the soleus muscles (21% increase in T1; 18% increase in T48, P < 0.05) and ventricle muscles (23% increase in T1; 17% increase in T48, P < 0.05) when compared with the C group. The CS enzyme activities were 42 ( P < 0.01) and 25% ( P < 0.01) greater in the soleus muscles of T1and T48groups, respectively, when compared with that of the C group. Soleus CS enzyme activity was significantly greater in the T1vs. T48groups ( P < 0.05). However, no appreciable alterations in CS enzyme activities were observed in the ventricle muscles in both training groups. These findings suggest differential responses of skeletal and cardiac muscles in CS enzymatic activity but similar responses in CS gene expression at 1 and 48 h after the last session of endurance training. Moreover, our data support the existence of an acute effect of exercise on the training-induced elevation in CS activity in rat soleus but not ventricle muscles.
High concentrations of 17β-estradiol attenuate the exercise pressor reflex in male cats
Authors: Schmitt Petra M. , Kaufman Marc P.
Published: March 2015

Previously, intravenous injection of 17β-estradiol in decerebrate male cats was found to attenuate central command but not the exercise pressor reflex. This latter finding was surprising because the dorsal horn, the spinal site receiving synaptic input from thin-fiber muscle afferents, is known to contain estrogen receptors. We were prompted, therefore, to reexamine this issue. Instead of injecting 17β-estradiol intravenously, we applied it topically to the L7 and S1 spinal cord of male decerebrate cats. We found that topical application (150–200 μl) of 17β-estradiol in concentrations of 0.01, 0.1, and 1 μg/ml had no effect on the exercise pressor reflex, whereas a concentration of 10 μg/ml attenuated the reflex. We conclude that, in male cats, estrogen can only attenuate the exercise pressor reflex in concentrations that exceed the physiological level.
Alterations in corticospinal excitability with imposed vs. voluntary fatigue in human hand muscles
Authors: Pitcher Julia B. , Miles Timothy S.
Published: March 2015

We aimed to determine whether postexercise depression of motor-evoked potentials (MEPs) could be demonstrated without voluntary muscle activation in humans. Voluntary fatigue was induced with a 2-min maximal voluntary contraction (MVC) of the first dorsal interosseous (FDI) muscle. On another occasion, “electrical fatigue” was induced with trains of shocks delivered for 2 min over the FDI motor point. Five of the twelve subjects also underwent “sequential fatigue” consisting of a 2-min MVC of FDI followed by 20 min of rest and then 2 min of motor point stimulation. Voluntary fatigue induced MEP depression that persisted for at least 20 min. Electrical fatigue induced a transient MEP facilitation that subsided 20 min after the stimulation and became depressed within 30 min. Thus MEP depression can be induced by both voluntary and electrical fatigue. With electrical fatigue, the initial depression is “masked” by transient MEP facilitation, reflecting cortical plasticity induced by the prolonged electrical stimulation. MEP depression probably reflects tonic afferent input from the exercising muscle that alters cortical excitability without altering spinal excitability.
Nonuniform shortening in the biceps brachii during elbow flexion
Authors: Pappas George P. , Asakawa Deanna S. , Delp Scott L. , Zajac Felix E. , Drace John E.
Published: March 2015

This study tested the common assumption that skeletal muscle shortens uniformly in the direction of its fascicles during low-load contraction. Cine phase contrast magnetic resonance imaging was used to characterize shortening of the biceps brachii muscle in 12 subjects during repeated elbow flexion against 5 and 15% maximum voluntary contraction (MVC) loads. Mean shortening was relatively constant along the anterior boundary of the muscle and averaged 21% for both loading conditions. In contrast, mean shortening was nonuniform along the centerline of the muscle during active elbow flexion. Centerline shortening in the distal region of the biceps brachii (7.3% for 5% MVC and 3.7% for 15% MVC) was significantly less ( P < 0.001) than shortening in the muscle midportion (26.3% for 5% MVC and 28.2% for 15% MVC). Nonuniform shortening along the centerline was likely due to the presence of an internal aponeurosis that spanned the distal third of the longitudinal axis of the biceps brachii. However, muscle shortening was also nonuniform proximal to the centerline aponeurosis. Because muscle fascicles follow the anterior contour and centerline of the biceps brachii, our results suggest that shortening is uniform along anterior muscle fascicles and nonuniform along centerline fascicles.
Phosphorylation of the regulatory light chains of myosin affects Ca2+sensitivity of skeletal muscle contraction
Authors: Szczesna Danuta , Zhao Jiaju , Jones Michelle , Zhi Gang , Stull James , Potter James D.
Published: March 2015

The role of phosphorylation of the myosin regulatory light chains (RLC) is well established in smooth muscle contraction, but in striated (skeletal and cardiac) muscle its role is still controversial. We have studied the effects of RLC phosphorylation in reconstituted myosin and in skinned skeletal muscle fibers where Ca2+sensitivity and the kinetics of steady-state force development were measured. Skeletal muscle myosin reconstituted with phosphorylated RLC produced a much higher Ca2+sensitivity of thin filament-regulated ATPase activity than nonphosphorylated RLC (change in −log of the Ca2+concentration producing half-maximal activation = ∼0.25). The same was true for the Ca2+sensitivity of force in skinned skeletal muscle fibers, which increased on reconstitution of the fibers with the phosphorylated RLC. In addition, we have shown that the level of endogenous RLC phosphorylation is a crucial determinant of the Ca2+sensitivity of force development. Studies of the effects of RLC phosphorylation on the kinetics of force activation with the caged Ca2+, DM-nitrophen, showed a slight increase in the rates of force development with low statistical significance. However, an increase from 69 to 84% of the initial steady-state force was observed when nonphosphorylated RLC-reconstituted fibers were subsequently phosphorylated with exogenous myosin light chain kinase. In conclusion, our results suggest that, although Ca2+binding to the troponin-tropomyosin complex is the primary regulator of skeletal muscle contraction, RLC play an important modulatory role in this process.
Hyperbaric oxygen and chemical oxidants stimulate CO2/H+-sensitive neurons in rat brain stem slices
Authors: Mulkey Daniel K. , Henderson Richard A. , Putnam Robert W. , Dean Jay B.
Published: March 2015

Hyperoxia, a model of oxidative stress, can disrupt brain stem function, presumably by an increase in O2 free radicals. Breathing hyperbaric oxygen (HBO2) initially causes hyperoxic hyperventilation, whereas extended exposure to HBO2 disrupts cardiorespiratory control. Presently, it is unknown how hyperoxia affects brain stem neurons. We have tested the hypothesis that hyperoxia increases excitability of neurons of the solitary complex neurons, which is an important region for cardiorespiratory control and central CO2/H+ chemoreception. Intracellular recordings were made in rat medullary slices during exposure to 2-3 atm of HBO2, HBO2 plus antioxidant (Trolox C), and chemical oxidants ( N-chlorosuccinimide, chloramine-T). HBO2 increased input resistance and stimulated firing rate in 38% of neurons; both effects of HBO2 were blocked by antioxidant and mimicked by chemical oxidants. Hypercapnia stimulated 32 of 60 (53%) neurons. Remarkably, these CO2/H+-chemosensitive neurons were preferentially sensitive to HBO2; 90% of neurons sensitive to HBO2 and/or chemical oxidants were also CO2/H+ chemosensitive. Conversely, only 19% of HBO2-insensitive neurons were CO2/H+ chemosensitive. We conclude that hyperoxia decreases membrane conductance and stimulates firing of putative central CO2/H+-chemoreceptor neurons by an O2 free radical mechanism. These findings may explain why hyperoxia, paradoxically, stimulates ventilation.
Glycogen availability does not affect the TCA cycle or TAN pools during prolonged, fatiguing exercise
Authors: Baldwin Jacinta , Snow Rodney J. , Gibala Martin J. , Garnham Andrew , Howarth Krista , Febbraio Mark A.
Published: March 2015

The hypothesis that fatigue during prolonged exercise arises from insufficient intramuscular glycogen, which limits tricarboxylic acid cycle (TCA) activity due to reduced TCA cycle intermediates (TCAI), was tested in this experiment. Seven endurance-trained men cycled at ∼70% of peak O2uptake (V˙o 2 peak) until exhaustion with low (LG) or high (HG) preexercise intramuscular glycogen content. Muscle glycogen content was lower ( P < 0.05) at fatigue than at rest in both trials. However, the increase in the sum of four measured TCAI (>70% of the total TCAI pool) from rest to 15 min of exercise was not different between trials, and TCAI content was similar after 103 ± 15 min of exercise (2.62 ± 0.31 and 2.59 ± 0.28 mmol/kg dry wt for LG and HG, respectively), which was the point of volitional fatigue during LG. Subjects cycled for an additional 52 ± 9 min during HG, and although glycogen was markedly reduced ( P < 0.05) during this period, no further change in the TCAI pool was observed, thus demonstrating a clear dissociation between exercise duration and the size of the TCAI pool. Neither the total adenine nucleotide pool (TAN = ATP + ADP + AMP) nor IMP was altered compared with rest in either trial, whereas creatine phosphate levels were not different when values measured at fatigue were compared with those measured after 15 min of exercise. These data demonstrate that altered glycogen availability neither compromises TCAI pool expansion nor affects the TAN pool or creatine phosphate or IMP content during prolonged exercise to fatigue. Therefore, our data do not support the concept that a decrease in muscle TCAI during prolonged exercise in humans compromises aerobic energy provision or is the cause of fatigue.
Stretch-activated ion channels and c-fosexpression remain active after repeated eccentric bouts
Authors: McBride Todd A.
Published: March 2015

This study was undertaken to measure the response of stretch-activated ion channels (SAC) and transcript levels of the oncogene c- fos to separate bouts of eccentric contractions (EC). It was hypothesized that SAC in rat skeletal muscle would contribute to resting membrane potential depolarization after separate repeated bouts of EC. Blockage of SAC during an EC training regime also tested the necessity of SAC for a training response. It was also hypothesized that transcript levels of c- fos would be maximally elevated after the first exposure to EC and diminish with repeated exposures. The results indicate less depolarization after multiple bouts of EC, which could be reversed by blocking the SAC. Transcript levels of c- fos were elevated to a similar degree after either a single or multiple exposures to EC. EC training resulted in significant increases in contractile force and muscle wet and dry weights in nontreated animals. Training in the presence of the SAC-blocker streptomycin produced similar changes in contractile force without changes in muscle weight. SAC and c- fos are activated after several exposures to EC and therefore remain as possible signals in EC training responses.
Nonlinearity of respiratory mechanics during bronchoconstriction in mice with airway inflammation
Authors: Wagers Scott , Lundblad Lennart , Moriya Henrique T. , Bates Jason H. T. , Irvin Charles G.
Published: March 2015

Respiratory system resistance (R) and elastance (E) are commonly estimated by fitting the linear equation of motion P = EV + RV˙ + P0 ( Eq. 1 ) to measurements of respiratory pressure (P), lung volume (V), and flow (V˙). However, the respiratory system is unlikely to behave linearly under many circumstances. We determined the importance of respiratory system nonlinearities in two groups of mechanically ventilated Balb/c mice [controls and mice with allergically inflamed airways (ova/ova)], by assessing the impact of the addition of nonlinear terms (E2V2 and R2V˙‖V˙‖) on the goodness of model fit seen with Eq. 1 . Significant improvement in fit (51.85 ± 4.19%) was only seen in the ova/ova mice during bronchoconstriction when the E2V2alone was added. An improvement was also observed with addition of the E2V2 term in mice with both low and high lung volumes ventilated at baseline, suggesting a volume-dependent nonlinearity of E. We speculate that airway closure in the constricted ova/ova mice accentuated the volume-dependent nonlinearity by decreasing lung volume and overdistending the remaining lung.
Altered single cell force-velocity and power properties in exercise-trained rat myocardium
Authors: Diffee Gary M. , Chung Eunhee
Published: March 2015

Myocardial function is enhanced by endurance exercise training, but the cellular mechanisms underlying this improved function remain unclear. The ability of the myocardium to perform external work is a critical aspect of ventricular function, but previous studies of myocardial adaptation to exercise training have been limited to measurements of isometric tension or unloaded shortening velocity, conditions in which work output is zero. We measured force-velocity properties in single permeabilized myocyte preparations to determine the effect of exercise training on loaded shortening and power output. Female Sprague-Dawley rats were divided into sedentary control (C) and exercise trained (T) groups. T rats underwent 11 wk of progressive treadmill exercise. Myocytes were isolated from T and C hearts, chemically skinned, and attached to a force transducer. Shortening velocity was determined during loaded contractions at 15°C by using a force-clamp technique. Power output was calculated by multiplying force times velocity values. We found that unloaded shortening velocity was not significantly different in T vs. C myocytes (T = 1.43 muscle lengths/s, n = 46 myocytes; C = 1.12 muscle lengths/s, n = 43 myocytes). Training increased the velocity of loaded shortening and increased peak power output (peak power = 0.16 P/Po × muscle length/s for T myocytes; peak power = 0.10 P/Po× muscle length/s for C myocytes, where P/Po is relative tension). We found no effect of training on myosin heavy chain isoform content. These results suggest that training alters power output properties of single cardiac myocytes and that this adaptation may improve the work capacity of the myocardium.
Effects of nonspecific β-adrenergic stimulation and blockade on blood coagulation in hypertension
Authors: von Känel Roland , Dimsdale Joel E. , Adler Karen A. , Dillon Elaine , Perez Christy J. , Mills Paul J.
Published: March 2015

A hypercoagulable state might contribute to increased atherothrombotic risk in hypertension. The sympathetic nervous system is hyperactive in hypertension, and it regulates hemostatic function. We investigated the effect of nonspecific β-adrenergic stimulation (isoproterenol) and blockade (propranolol) on clotting diathesis in hypertension. Fifteen hypertensive and 21 normotensive subjects underwent isoproterenol infusion in two sequential, fixed-order doses of 20 and then 40 ng · kg−1 · min−1 for 15 min/dose. Thirteen subjects were double-blind studied after receiving placebo or propranolol (100 mg/day) for 5 days each. In hypertensive subjects, isoproterenol elicited a dose-dependent increase in plasma von Willebrand factor (vWF) antigen [ F(2,34) = 5.02; P = 0.032] and a decrease in D-dimer [ F(2,34) = 4.57; P = 0.040], whereas soluble tissue factor remained unchanged. Propranolol completely abolished the increase in vWF elicited by isoproterenol [ F(1,12) = 10.25; P = 0.008] but had no significant effect on tissue factor and D-dimer. In hypertension, vWF is readily released from endothelial cells by β-adrenergic stimulation, which might contribute to increased cardiovascular risk. However, β-adrenergic stimulation alone may not be sufficient to trigger fibrin formation in vivo.
Effect of extracellular Po 2 on the fall in intracellular Po 2 in contracting single myocytes
Authors: Kindig Casey A. , Howlett Richard A. , Hogan Michael C.
Published: March 2015

The purpose of this investigation was to study the effects of altered extracellular Po 2 (Pe O2 ) on the intracellular Po 2(Pi O2 ) response to contractions in single skeletal muscle cells. Single myocytes ( n = 12) were dissected from lumbrical muscles of adult female Xenopus laevis and injected with 0.5 mM Pd- meso-tetra(4-carboxyphenyl)porphine for assessment of Pi O2 via phosphorescence quenching. At a Pe O2 of ∼20 (low), ∼40 (moderate), and ∼60 (high) Torr, tetanic contractions were induced at a frequency of 0.67 Hz for ∼2 min with a 5-min recovery between bouts (blocked order design). The Pi O2 response to contractions was characterized by a time delay followed by a monoexponential decline to steady-state (SS) values. The fall in Pi O2 to SS values was significantly greater at each progressively greater Pe O2 (all P < 0.05). The mean response time (time delay + time constant) was significantly faster in the low (35.2 ± 5.1 s; P < 0.05 vs. high) and moderate (43.3 ± 6.4 s; P < 0.05 vs. high) compared with high Pe O2 (61.8 ± 9.4 s) and was correlated positively ( r = 0.965) with the net fall in Pi O2 . However, the initial rate of change of Pi O2 (calculated as net fall in Pi O2 /time constant) was not different ( P > 0.05) among Pe O2 trials. These latter data suggest that, over the range of 20–60 Torr, Pe O2 does not play a deterministic role in setting the initial metabolic response to contractions in isolated frog myocytes. Additionally, these results suggest that oxidative phosphorylation in these myoglobin-free myocytes may be compromised by Pe O2 at values nearing 60 Torr.
Leg blood flow during submaximal cycle ergometry is not reduced in healthy older normally active men
Authors: Proctor David N. , Newcomer Sean C. , Koch Dennis W. , Le Khoi U. , MacLean David A. , Leuenberger Urs A.
Published: March 2015

The purpose of the present study was to test the hypothesis that leg blood flow responses during submaximal cycle ergometry are reduced with age in healthy normally active men. Eleven younger (20–25 yr) and eight older (62–73 yr) normotensive, nonendurance-trained men performed both graded and constant-load bouts of leg cycling at the same absolute and relative [% of peak O2 consumption (V˙o 2 peak)] exercise intensities while leg blood flow (femoral vein thermodilution), mean arterial pressure (MAP; radial artery), cardiac output (acetylene rebreathing), blood O2 content, and plasma catecholamines were measured. Leg blood flow responses at the same absolute submaximal power outputs (20–100 W) and at a fixed systemic O2 demand (1.1 l/min) did not differ between groups ( P = 0.14–0.19), despite lower absolute levels of cardiac output in the older men ( P < 0.05). MAP at the same absolute power outputs was 8–12 mmHg higher ( P < 0.05) in the older men, but calculated leg vascular conductance responses (leg blood flow/MAP) were identical in the two groups ( P > 0.9). At the same relative intensity (60% V˙o 2 peak), leg norepinephrine spillover rates were approximately twofold higher in the older men ( P = 0.38). Exercise-induced increases in leg arterial-venous O2difference were identical between groups ( P > 0.9) because both arterial and venous O2 contents were lower in the older vs. younger men. These results suggest that the ability to augment active limb blood flow and O2 extraction during submaximal large muscle mass exercise is not impaired but is well preserved with age in healthy men who are normally active.
Alterations in regional ventilation, perfusion, and shunt after smoke inhalation measured by PET
Authors: Willey-Courand Donna Beth , Harris R. Scott , Galletti Gaetano G. , Hales C. A. , Fischman Alan , Venegas Jose G.
Published: March 2015

Regional changes in ventilation and perfusion occurring in the early hours after smoke inhalation injury were evaluated through the use of positron emission tomography. Five lambs were imaged before and 1, 2, and 4 h after receiving 100 breaths of cotton smoke. Utilizing a recently developed model of13N tracer kinetics (3), we evaluated changes in ventilation, perfusion, shunt, and regional gas content in nondependent, middle, and dependent lung zones. The data demonstrated a progressive development of regional shunt in dependent (dorsal) regions in which perfusion remained the highest throughout the study. These findings, together with decreasing regional ventilation and fractional gas content in the dependent regions, correlated with decreasing arterial PaO2values over the course of the study. A negative correlation between regional shunt fraction and regional gas content in dependent and middle regions suggests that shunt was caused by progressive alveolar derecruitment or flooding.
Selected Contribution: Circadian rhythm of tumor necrosis factor-α uptake into mouse spinal cord
Authors: Pan Weihong , Cornélissen Germaine , Halberg Franz , Kastin Abba J.
Published: March 2015

Circadian variations in the actions of tumor necrosis factor-α (TNF-α) have been observed. Because a saturable transport system at the blood-brain barrier mediates most of the influx of TNF-α from blood to the central nervous system (CNS), the circadian variation of the CNS effects of TNF-α could be related to changes in this transport system. Accordingly, we measured the uptake of intravenously injected TNF-α into various CNS regions at different times and compared these measurements with the uptake into a peripheral control (muscle). We found that the spinal cord, but not the brain, showed a circadian rhythm in the uptake of TNF-α. This pattern is similar to that of leptin but different from that of interleukin-1. The circadian rhythm of the influx of TNF-α into this region of the CNS suggests a functional role for the spinal cord in the physiological actions of TNF-α.
Acetaminophen does not affect 24-h body temperature or sleep in the luteal phase of the menstrual cycle
Authors: Baker Fiona C. , Driver Helen S. , Paiker Janice , Rogers Geoffrey G. , Mitchell Duncan
Published: March 2015

Body temperature and sleep change in association with increased progesterone in the luteal phase of the menstrual cycle in young women. The mechanism by which progesterone raises body temperature is not known but may involve prostaglandins, inducing a thermoregulatory adjustment similar to that of fever. Prostaglandins also are involved in sleep regulation and potentially could mediate changes in sleep during the menstrual cycle. We investigated the possible role of central prostaglandins in mediating menstrual-associated 24-h temperature and sleep changes by inhibiting prostaglandin synthesis with a therapeutic dose of the centrally acting cyclooxygenase inhibitor acetaminophen in the luteal and follicular phases of the menstrual cycle in young women. Body temperature was raised, and nocturnal amplitude was blunted, in the luteal phase compared with the follicular phase. Acetaminophen had no effect on the body temperature profile in either menstrual cycle phase. Prostaglandins, therefore, are unlikely to mediate the upward shift of body temperature in the luteal phase. Sleep changed during the menstrual cycle: on the placebo night in the luteal phase the women had less rapid eye movement sleep and more slow-wave sleep than in the follicular phase. Acetaminophen did not alter sleep architecture or subjective sleep quality. Prostaglandin inhibition with acetaminophen, therefore, had no effect on the increase in body temperature or on sleep in the midluteal phase of the menstrual cycle in young women, making it unlikely that central prostaglandin synthesis underlies these luteal events.
Invited Review: Integration of human sleep-wake regulation and circadian rhythmicity
Authors: Dijk Derk-Jan , Lockley Steven W.
Published: March 2015

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.
H1-receptor antagonist, tripelennamine, does not affect arterial hypoxemia in exercising Thoroughbreds
Authors: Manohar Murli , Goetz Thomas E. , Humphrey Sarah , Depuy Tracy
Published: March 2015

It has been suggested that pulmonary injury and inflammation-induced histamine release from airway mast cells may contribute to exercise-induced arterial hypoxemia (EIAH). Because stress failure of pulmonary capillaries and EIAH are routinely observed in exercising horses, we examined whether preexercise administration of an H1-receptor antagonist may mitigate EIAH. Two sets of experiments, placebo (saline) and antihistaminic (tripelennamine HCl at 1.10 mg/kg iv, 15 min preexercise) studies, were carried out on seven healthy, exercise-trained Thoroughbred horses in random order 7 days apart. Arterial and mixed venous blood-gas and pH measurements were made at rest before and after saline or drug administration and during incremental exercise leading to maximal exertion at 14 m/s on 3.5% uphill grade for 120 s. Galloping at this workload elicited maximal heart rate and induced exercise-induced pulmonary hemorrhage in all horses in both treatments, thereby indicating that capillary stress failure-related pulmonary injury had occurred. In both treatments, EIAH, desaturation of hemoglobin, hypercapnia, and acidosis of a similar magnitude developed during maximal exertion, and statistically significant differences between the placebo and antihistaminic studies could not be demonstrated. The failure of the H1-receptor antagonist to modify EIAH significantly suggests that pulmonary injury-induced histamine release may not play a major role in bringing about EIAH in Thoroughbred horses.
Exercise and T-lymphocyte function: a comparison of proliferation in PBMC and NK cell-depleted PBMC culture
Authors: Green Katherine J. , Rowbottom David G. , Mackinnon Laurel T.
Published: March 2015

This study utilized recently developed microbead technology to remove natural killer (NK) cells from peripheral blood mononuclear cell (PBMC) preparations to determine the effect of acute exercise on T-lymphocyte function, independent of changes in lymphocyte subpopulations. Twelve well-trained male runners completed a 60-min exercise trial at 95% ventilatory threshold and a no-exercise control trial. Six blood samples were taken at each session: before exercise, midexercise, immediately after exercise, and 30, 60, and 90 min after exercise. Isolated PBMC and NK cell-depleted PBMC were stimulated with the mitogen phytohemagglutinin. Cellular proliferation was assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye uptake. In the PBMC cultures, there was a significantly lower mitogen response to phytohemagglutinin in exercise compared with the control condition immediately postexercise. There were no significant differences between the control and exercise conditions in NK cell-depleted PBMC cultures or in the responses adjusted for the percentage of CD3 cells. The present findings do not support the view that T-lymphocyte function is reduced after exercise.
Canine model of nasal congestion and allergic rhinitis
Authors: Tiniakov Ruslan L. , Tiniakova Olga P. , McLeod Robbie L. , Hey John A. , Yeates Donovan B.
Published: March 2015

The ragweed- and histamine-induced decreases in nasal patency in cohorts of ragweed-sensitized and nonsensitized dogs were assessed. The volume of nasal airways (VNA) was assessed by acoustic rhinometry and resistance to airflow (RNA) by anterior rhinomanometry. Histamine delivered to the nasal passages of five dogs caused a rapid and prolonged increase in RNA (0.75 ± 0.26 to 3.56 ± 0.50 cmH2O · l−1 · min), an effect that was reversed by intranasal delivery of aerosolized phenylephrine. Ragweed challenge in five ragweed-sensitized dogs increased RNA from 0.16 ± 0.02 to 0.53 ± 0.07 cmH2O · l−1 · min and decreased VNA from 12.5 ± 1.9 to 3.9 ± 0.3 cm3, whereas administration of saline aerosol neither increased RNA nor decreased VNA. Prior administration of d-pseudoephedrine (30 mg po) attenuated the ragweed-induced increase in RNA and decrease in VNA. Ragweed challenge changed neither RNA nor VNA in four nonsensitized dogs. Mediator-induced nasal congestion and allergen-induced allergic rhinitis in ragweed-sensitized dogs, which exhibit symptoms similar to human disease, can be used in the evaluation of safety and efficacy of antiallergic activity of potential drugs.
Age-specific modification of local cutaneous vasodilation by capsaicin-sensitive primary afferents
Authors: Munce Thayne A. , Kenney W. Larry
Published: March 2015

Age-related changes in neurogenic vasodilation mediated by sensory nerves may alter local skin blood flow (SkBF) responses in older individuals. The purpose of this study was to determine the age-specific modification of cutaneous vasodilation by capsaicin-sensitive primary afferent (CSPA) nerves during local heating. Nine young (18-30 yr), eight middle-aged (40-55 yr), and eight older (65-80 yr) healthy men participated in the experiments. Two local-heating protocols (rapid and slow) were performed before and after 1 wk of capsaicin pretreatment (CP), used to desensitize CSPAs. All temperatures were below those that elicit pain. SkBF was measured with a laser-Doppler imager and indexed to percentage of maximal cutaneous vascular conductance (%CVCmax). CP caused a significant reduction in %CVCmax in the middle-aged and older groups during slow heating ( P < 0.05), without affecting %CVCmax in the young group. During rapid heating, CP significantly reduced (53.9 ± 4.4 vs. 74.4 ± 7.4% CVCmax, P < 0.05), but did not abolish, the initial sensory nerve-mediated rise in SkBF in the young group. No significant effects of CP on SkBF were observed during rapid heating in the middle-aged or older groups. These results indicate that, with advanced age, CSPA activity is more important to the maximal SkBF response during prolonged local heating, whereas it has a reduced role in the initial SkBF peak elicited by rapid local heating. In summary, CSPA activity contributes modestly to the overall SkBF response to local heating in an age-specific manner.
Spinal stiffness changes throughout the respiratory cycle
Authors: Shirley D , Hodges P. W. , Eriksson A. E. M. , Gandevia S. C.
Published: March 2015

Posteroanterior stiffness of the lumbar spine is influenced by factors, including trunk muscle activity and intra-abdominal pressure (IAP). Because these factors vary with breathing, this study investigated whether stiffness is modulated in a cyclical manner with respiration. A further aim was to investigate the relationship between stiffness and IAP or abdominal and paraspinal muscle activity. Stiffness was measured from force-displacement responses of a posteroanterior force applied over the spinous process of L2and L4. Recordings were made of IAP and electromyographic activity from L4/L2erector spinae, abdominal muscles, and chest wall. Stiffness was measured with the lung volume held at the extremes of tidal volume and at greater and lesser volumes. Stiffness at L4and L2increased above base-level values at functional residual capacity (L214.9 N/mm and L415.3 N/mm) with both inspiratory and expiratory efforts. The increase was related to the respiratory effort and was greatest during maximum expiration (L224.9 N/mm and L423.9 N/mm). The results indicate that changes in trunk muscle activity and IAP with respiratory efforts modulate spinal stiffness. In addition, the diaphragm may augment spinal stiffness via attachment of its crural fibers to the lumbar vertebrae.
Na+-K+-ATPase α2-gene and skeletal muscle characteristics in response to long-term overfeeding
Authors: Ukkola Olavi , Joanisse Denis R. , Tremblay Angelo , Bouchard Claude
Published: March 2015

The role of Na+-K+-ATPase α2-gene BglII polymorphism in the changes of skeletal muscle metabolic properties after a 100-day overfeeding protocol conducted with 12 pairs of monozygotic twins is reported. The activities of oxoglutarate dehydrogenase (OGDH) and phosphofructokinase (PFK) were determined from muscle biopsies. A larger increase in the total fat mass (127 vs. 61%) ( P < 0.05) and low-density lipoprotein cholesterol (20 vs. 0.7%) ( P = 0.05) in 8.0/8.0-kb [3.3-kb negative (−); n = 7 pairs] than in 8.0/3.3 + 3.3/3.3-kb [3.3-kb positive (+); n = 5 pairs] subjects was observed. OGDH activity decreased in 3.3-kb−(−15%), whereas PFK (+26%) as well as the PFK-to-OGDH ratio (90%) increased. In contrast, among 3.3-kb+, OGDH increased (+54%) together with a decrease in PFK (−1%) and PFK-to-OGDH ratio (−5%). These changes were significantly different between genotypes ( Pfrom <0.05 to 0.01). In conclusion, fat mass, low-density lipoprotein cholesterol, and skeletal muscle glycolytic-to-oxidative enzyme ratio increased more in the α2-gene 3.3-kb−subjects with overfeeding, suggesting more unfavorable metabolic changes compared with the 3.3-kb+subjects.