bluuebunny/crossref_metadata_2025 huggingface dataset:
Microvascular gas embolization clearance following perfluorocarbon administration
Authors: Eckmann David M. , Lomivorotov Vladimir N.
Published: March 2015

Effective treatment of vascular gas embolism may be possible with emulsified fluorocarbon compounds. We tested the hypothesis that a fluorocarbon emulsion delivered before gas embolization would enhance bubble motion through the vasculature, favoring more rapid clearance. Air microbubbles were injected into the rat cremaster microcirculation in six groups of rats receiving Perftoran, an emulsified fluorocarbon, or saline immediately before, 2 h before, or after bubble injection. Embolism dimensions and dynamics were observed by using intravital microscopy. Surface area at lodging was equal between groups. Bubbles having smaller volume embolized smaller diameter vessels in the Perftoran pretreatment groups. A higher incidence of bubble dislodgement and larger distal displacement occurred in these two groups, with a 36% decrease in the time to bubble clearance and restoration of blood flow. Intravascular emulsified fluorocarbon administration before gas embolization affected initial bubble conformation, increased bubble dislodgement, and resulted in bubble displacement further into the periphery of the microcirculation. These dynamic events did not occur if embolization preceded fluorocarbon administration.
Exercise hyperpnea in chronic heart failure: relationships to lung stiffness and expiratory flow limitation
Authors: Agostoni Piergiuseppe , Pellegrino Riccardo , Conca Cristina , Rodarte Joseph R. , Brusasco Vito
Published: March 2015

The changes in breathing pattern and lung mechanics in response to incremental exercise were compared in 14 subjects with chronic heart failure and 15 normal subjects. In chronic heart failure subjects, exercise hyperpnea was achieved by increasing breathing frequency more than tidal volume. The rate of increase in breathing frequency with carbon dioxide output was inversely correlated ( r = −0.61, P< 0.05) with dynamic lung compliance measured at rest, but not with static lung compliance either at rest or at maximum exercise. Although decrease in expiratory flow reserve near functional residual capacity in chronic heart failure occurred earlier with exercise than in the normal subjects ( P < 0.01), it was not correlated with changes in breathing pattern or occurrence of tachypnea. Tachypnea was achieved in chronic heart failure subjects with an increase in duty cycle because of a greater than normal decrease in expiratory time with exercise. We conclude that in chronic heart failure preexisting increase in lung stiffness plays a significant role in causing tachypnea during exercise. The results of the present study do not support the hypothesis that dynamic compression of the airways downstream from the flow-limiting segment occurring during exercise contributes to hyperpnea.
Lesions of rat skeletal muscle after local block of acetylcholinesterase and neuromuscular stimulation
Authors: Mense S. , Simons D. G. , Hoheisel U. , Quenzer B.
Published: March 2015

In skeletal muscle, a local increase of acetylcholine (ACh) in a few end plates has been hypothesized to cause the formation of contraction knots that can be found in myofascial trigger points. To test this hypothesis in rats, small amounts of an acetylcholinesterase inhibitor [diisopropylfluorophosphate (DFP)] were injected into the proximal half of the gastrocnemius muscle, and the muscle nerve was electrically stimulated for 30–60 min for induction of muscle twitches. The distal half of the muscle, which performed the same contractions, served as a control to assess the effects of the twitches without DFP. Sections of the muscle were evaluated for morphological changes in relation to the location of blocked end plates. Compared with the distal half of the muscle, the DFP-injected proximal half exhibited significantly higher numbers of abnormally contracted fibers (local contractures), torn fibers, and longitudinal stripes. DFP-injected animals in which the muscle nerve was not stimulated and that were allowed to survive for 24 h exhibited the same lesions but in smaller numbers. The data indicate that an increased concentration of ACh in a few end plates causes damage to muscle fibers. The results support the assumption that a dysfunctional end plate exhibiting increased release of ACh may be the starting point for regional abnormal contractions, which are thought to be essential for the formation of myofascial trigger points.
Temporary tracheal occlusion in fetal sheep with lung hypoplasia does not improve postnatal lung function
Authors: Davey Marcus G. , Hedrick Holly L. , Bouchard Sarah , Mendoza Julianne M. , Schwarz Uwe , Adzick N. Scott , Flake Alan W.
Published: March 2015

Prolonged fetal tracheal occlusion (TO) accelerates lung growth but leads to loss of alveolar epithelial type II (AE2) cells. In contrast, temporary TO leads to recovery of AE2 cells and their ability to produce surfactant. The aim of this study was to determine the effects of temporary TO in fetal sheep with lung hypoplasia on postnatal lung function, structure, and surfactant protein mRNA expression. Diaphragmatic hernia (DH) was created in 22 fetal sheep at 65 days of gestation. TO was performed between 110 days of gestation and full term (DH/TO, n = 7) and between 110 and 130 days of gestation (DH/TO+R, n = 6). Sham-operated fetuses ( n = 11) served as controls. Lambs were delivered at ∼139 days of gestation, and blood gas tensions were monitored over a 2-h resuscitation period. Temporary TO increased growth of the hypoplastic lung and restored surfactant protein mRNA expression and AE2 cell density but did not improve respiratory function above that of animals that underwent prolonged TO; DH/TO and DH/TO+R lambs were hypoxic and hypercapnic compared with Sham animals. Lung compliance remained low in DH/TO+R lambs, most likely as a consequence of the persistent increase in alveolar wall thickness in these animals.
Blood flow and muscle fatigue in SCI individuals during electrical stimulation
Authors: Olive Jennifer L. , Slade Jill M. , Dudley Gary A. , McCully Kevin K.
Published: March 2015

Our purpose was to measure blood flow and muscle fatigue in chronic, complete, spinal cord-injured (SCI) and able-bodied (AB) individuals during electrical stimulation. Electrical stimulation of the quadriceps muscles was used to elicit similar activated muscle mass. Blood flow was measured in the femoral artery by Doppler ultrasound. Muscle fatigue was significantly greater (three- to eightfold, P ≤ 0.001) in the SCI vs. the AB individuals. The magnitude of blood flow was not significantly different between groups. A prolonged half-time to peak blood flow at the beginning of exercise (fivefold, P = 0.001) and recovery of blood flow at the end of exercise (threefold, P = 0.009) was found in the SCI vs. the AB group. In conclusion, the magnitude of the muscle blood flow to electrical stimulation was not associated with increased muscle fatigue in SCI individuals. However, the prolonged time to peak blood flow may be an explanation for increased fatigue in SCI individuals.
Effect of acute exposure to 3,660 m altitude on orthostatic responses and tolerance
Authors: Blaber A. P. , Hartley T. , Pretorius P. J.
Published: March 2015

Orthostatic reflexes were examined at 375 m and after 60 min of exposure in a hypobaric chamber at 3,660 m using a 20-min 70° head-up tilt (HUT) test. Mean arterial blood pressure, R wave-R wave interval (RRI), and mean cerebral blood flow velocity (MFV) were examined with coarse-graining spectral analysis. Of 14 subjects, 7 at 375 m and 12 at 3,660 m were presyncopal. Immediately on arrival to high altitude, breathing frequency and MFV increased, and endtidal PCO2, RRI, RRI complexity, and the parasympathetic nervous system indicator decreased. MFV was similar in HUT at both altitudes. The sympathetic nervous system indicator increased with tilt at 3,660 m, whereas parasympathetic nervous system indicator decreased with tilt at both altitudes. Multiple regression analysis of supine variables from either 375 or 3,660 m and the time to presyncope at 3,660 m indicated that, after 1 h of exposure, increased presyncope at altitude was the result of 1) ineffective peripheral vasoconstriction, despite increased cardiac sympathetic nervous system activity with HUT, and 2) insufficient cerebral perfusion owing to cerebral vasoconstriction as the result of hypoxic hyperventilation-induced hypocapnia.
Wall stress misrepresents afterload in children and young adults with abnormal left ventricular geometry
Authors: Gentles Thomas L. , Colan Steven D.
Published: March 2015

Wall stress, although commonly used as an index of afterload, fails to take into account forces generated within the wall of the left ventricle (LV) that oppose systolic fiber shortening. Wall stress may, therefore, misrepresent fiber stress, the force resisting fiber shortening, particularly in the presence of an abnormal LV thickness-to-dimension ratio ( h/ D). M-mode LV echocardiograms were obtained from 207 patients with a wide range of values for LV mass and/or h/ D. Diagnoses were valvar aortic stenosis, coarctation repair, anthracycline treated, and severe aortic and/or mitral regurgitation. End-systolic wall stress (WSes) and fiber stress (FSes) were expressed as age-corrected Z scores relative to a normal population. The difference between WSes and FSes was extreme when h/ D was elevated or reduced [WSes Z score − FSes Z score = 0.14 × ( h/ D)−1.47 − 2.13; r = 0.78, P < 0.001], with WSes underestimating FSes when h/ D was increased and overestimating FSes when h/ D was decreased. Analyses of myocardial mechanics based on wall stress have limited validity in patients with abnormal ventricular geometry.
Effects of chronic sympathectomy on locally mediated cutaneous vasodilation in humans
Authors: Charkoudian Nisha , Eisenach John H. , Atkinson John L. D. , Fealey Robert D. , Joyner Michael J.
Published: March 2015

In human skin, the vasodilator response to local heating includes a sensory nerve-dependent peak followed by a nadir and then a slower, nitric oxide-mediated, endothelium-dependent vasodilation. To investigate whether chronic sympathectomy diminishes this endothelium-dependent vasodilation, we studied individuals who had previously undergone surgical T2 sympathectomy ( n = 9) and a group of healthy controls ( n = 8). We assessed the cutaneous vascular response (laser-Doppler) to 30 min of local warming to 42.5°C on the ventral forearm (no sympathetic innervation) and the lower legs (sympathetic nerves intact). Lower body negative pressure (LBNP) was measured to confirm sympathetic denervation. During local warming in sympathectomized individuals, vascular conductance reached an initial peak at both sites [achieving 1.73 ± 0.22 laser-Doppler units (LDU)/mmHg in the forearm and 1.92 ± 0.21 LDU/mmHg in the leg]. It then decreased to a nadir in the innervated leg [to 1.77 ± 0.23 LDU/mmHg ( P < 0.05)] but not in the sympathectomized arm (1.69 ± 0.21 LDU/mmHg; P > 0.10). The maximal vasodilation seen during the slower phase was not different between limbs or between groups. Furthermore, LBNP caused a 44% reduction in forearm vascular conductance (FVC) in control subjects, but FVC did not decrease significantly in sympathectomized individuals, confirming sympathetic denervation. These data indicate that endothelial function in human skin is largely preserved after sympathectomy. The altered pattern of the response suggests that the nitric oxide-dependent portion may be accelerated in sympathectomized limbs.
Assessment of exhaled nitric oxide kinetics in healthy infants
Authors: Martı́nez T. , Weist A. , Williams T. , Clem C. , Silkoff P. , Tepper R. S.
Published: March 2015

Exhaled nitric oxide (Fe NO) measurements provide a noninvasive approach to the evaluation of airway inflammation. Flow-independent NO exchange parameters [airway NO transfer factor (DNO) and airway wall NO concentration (CwNO)] can be estimated from Fe NO measurements at low flows and may elucidate mechanisms of disturbances in NO exchange. We measured Fe NO in sedated infants by using an adaptation of a raised lung volume rapid thoracic compression technique that creates forced expiration through a mass-flow controller that lasts 5–10 s, at a constant preset flow. We measured Fe NO at expired flows of 50, 25, and 15 ml/s in five healthy infants (7–31 mo). Median Fe NO increased [24, 40, and 60 parts per billion (ppb)] with decreasing expiratory flows (50, 25, and 15 ml/s). Group median (range) for DNO and CwNO were 12.7 (3.2–37) × 10−3nl · s−1 · ppb−1and 108.9 (49–385) ppb, respectively, similar to values reported in healthy adults. Exhaled NO is flow dependent; flow-independent parameters of exhaled NO kinetics can be assessed in infants and are similar to values described in adults.
Invited Review: Regulation of mammalian circadian clock genes
Authors: Albrecht Urs
Published: March 2015

The circadian clock is a self-sustaining oscillator that has a period of ∼24 h and controls many physiological and behavioral systems. This clock can synchronize itself to changing environmental conditions to optimize an organisms performance. The underlying circadian rhythms are generated by periodic activation of transcription by a set of clock genes. Besides their own regulation, clock genes can influence biochemical processes by modulating specific genes of biochemical pathways. Developments in the last few years using genetics and molecular biological tools have led to a new understanding of the molecular basis of the circadian clock in mammals. In this mini-review, I will summarize these advances that have led us to begin understanding the mammalian circadian clock at the molecular level.
Mechanical properties of the passive pharynx in Vietnamese pot-bellied pigs. I. Statics
Authors: Tuck Stephanie A. , Remmers John E.
Published: March 2015

The static mechanical properties of the passive pharynx were investigated in Vietnamese pot-bellied pigs by using an isolated upper airway preparation. During general anesthesia and neuromuscular blockade, cross-sectional area ( A) of the pharynx was measured while airway pressure (Paw) was held at various pressures in the absence of airflow. The static A-Paw relationship was measured during application of 0, 1, and 2 cm of caudal tracheal displacement. Relative to humans, closing pressures (Pclose) of the pig pharynx were very low (−15 to −35 cmH2O). Tracheal displacement significantly decreased compliance of the hypopharynx (from 0.074 ± 0.02 cm2/cmH2O with no displacement to 0.052 ± 0.01 cm2/cmH2O with 2 cm of displacement) and decreased Pclose of the oropharynx (from −18.2 ± 9.9 cmH2O to −24.1 ± 10.5 and −28.7 ± 12.3 cmH2O with 1 and 2 cm of displacement, respectively). Tracheal displacement did not affect A of the pharyngeal segments. In conclusion, tracheal displacement decreased collapsibility of the passive pharynx. The pharynx of the pot-bellied pig is structurally more resistant to collapse than the human pharynx.
Carotid body denervation effect on cytochrome oxidase activity in pre-Bötzinger complex of developing rats
Authors: Liu Qiuli , Kim Judy , Cinotte Jamye , Homolka Patricia , Wong-Riley Margaret T. T.
Published: March 2015

Previously, we found that the rat pre-Bötzinger complex (PBC) exhibited reduced cytochrome oxidase (CO) activity on postnatal days (P) 3–4 and especially on P12, with a concomitant decrease in glutamate and N-methyl-d-aspartate receptor subunit 1, and an increase in GABA, GABAB, glycine recptor, and glutamate subunit 2. We hypothesized that the PBC would be more affected by carotid body denervation (CBD) during the two critical windows than at other times. Pairs of CBD and sham animals at each postnatal day from P2 to P14 and at P21 were operated on and survived for 3 days. Brain stems were processed for CO and neurokinin-1 receptor for the identification of PBC. Results indicate that CBD caused a significant loss in body weight in all animals and a reduction in PBC somal size when the surgery was between P2 and P7. CBD also induced a significant decrease in CO activity of the PBC in most animals and a distinct delay, as well as prolongation of the maturational process, especially when induced close to P3 and P11–P13.
Inflammatory cells in rat skeletal muscle are elevated after electrically stimulated contractions
Authors: McLoughlin Thomas J. , Mylona Eleni , Hornberger Troy A. , Esser Karyn A. , Pizza Francis X.
Published: March 2015

We determined the effect of muscle contractions resulting from high-frequency electrical stimulation (HFES) on inflammatory cells in rat tibialis anterior (TA), plantaris (Pln), and soleus (Sol) muscles at 6, 24, and 72 h post-HFES. A minimum of four and a maximum of seven rats were analyzed at each time point. HFES, applied to the sciatic nerve, caused the Sol and Pln to contract concentrically and the TA to contract eccentrically. Neutrophils were higher ( P < 0.05) at 6 and 24 h after HFES in the Sol, Pln, and TA muscles relative to control muscles. ED1+macrophages in the Pln were elevated at 6 and 24 h after HFES and were also elevated in the Sol and TA after HFES relative to controls. ED2+macrophages in the Sol and TA were elevated at 24 and 72 h after HFES, respectively, and were also elevated in the Pln after HFES relative to controls. In contrast to the TA muscles, the Pln and Sol muscles showed no gross histological abnormalities. Collectively, these data indicate that both eccentric and concentric contractions can increase inflammatory cells in muscle, regardless of whether overt histological signs of injury are apparent.
Acute hypoxia prolongs the apnea induced by right atrial injection of capsaicin
Authors: Xu Fadi , Gu Qi-Hai , Zhou Tongrong , Lee Lu-Yuan
Published: March 2015

Inspiratory central drive is augmented by acute hypoxia that leads to a hyperventilation, but it is inhibited by capsaicin (Cap)-induced stimulation of pulmonary C fibers (PCFs) that produces an expiratory apnea. We hypothesized that acute hypoxia should shorten or eliminate the Cap-induced apnea. The ventilatory responses to bolus injection of Cap (0.2–0.5 μg) into the right atrium before and during acute hypoxia (10% O2for ∼1 min; Hypoxia+Cap) were compared in anesthetized and spontaneously breathing rats. We found that Cap injection during acute hypoxia produced an extremely long-lasting apnea (69.67 ± 11.97 s) that was 16-fold longer than the apnea induced by Cap alone (expiratory duration = 4.37 ± 0.53 s; P< 0.01). A similar prolonged apnea was also observed during hypoxia in anesthetized guinea pigs. Bilateral vagotomy abolished apneic responses to Cap both before and during hypoxia. Subsequent recording of single-fiber activity of PCFs (PCFA) showed that acute hypoxia did not significantly affect baseline PCFAbut that it doubled PCFAresponses to Cap via increasing both the firing rate (3.34 ± 0.76 to 7.65 ± 1.32 impulses/s; P < 0.05) and burst duration (1.12 ± 0.18 to 2.32 ± 0.31 s; P < 0.05). These results suggest that acute hypoxia augments PCF-mediated inspiratory inhibition and thereby leads to an extremely long-lasting apnea. This interaction is partially due to hypoxic sensitization of PCF response to Cap.
Effects of expiratory muscle work on muscle sympathetic nerve activity
Authors: Derchak P. Alexander , Sheel A. William , Morgan Barbara J. , Dempsey Jerome A.
Published: March 2015

We hypothesized that contractions of the expiratory muscles carried out to the point of task failure would cause an increase in muscle sympathetic nerve activity (MSNA). We measured MSNA directly in six healthy men during resisted expiration (60% maximal expiratory pressure) leading to task failure with long [breathing frequency (fb) = 15 breaths/min; expiratory time (Te)/total respiratory cycle duration (Tt) = 0.7] and short (fb = 30 breaths/min; Te/Tt = 0.4) Te. Both of these types of expiratory muscle contractions elicited time-dependent increases in MSNA burst frequency that averaged +139 and +239%, respectively, above baseline at end exercise. The increased MSNA coincided with increases in mean arterial pressure (MAP) for both the long-Te (+28 ± 6 mmHg) and short-Te (+22 ± 14 mmHg) trials. Neither MSNA nor MAP changed when the breathing patterns and increased tidal volume of the task failure trials were mimicked without resistance or task failure. Furthermore, very high levels of expiratory motor output (95% maximal expiratory pressure; fb = 12 breaths/min; Te/Tt = 0.35) and high rates of expiratory flow and expiratory muscle shortening without task failure (no resistance; fb = 45 breaths/min; Te/Tt = 0.4; tidal volume = 1.9 × eupnea) had no effect on MSNA or MAP. Within-breath analysis of the short-expiration trials showed augmented MSNA at the onset of and throughout expiration that was consistent with an influence of high levels of central expiratory motor output. Thus high-intensity contractions of expiratory muscles to the point of task failure caused a time-dependent sympathoexcitation; these effects on MSNA were similar in their time dependency to those caused by high-intensity rhythmic contractions of the diaphragm and forearm muscles taken to the point of task failure. The evidence suggests that these effects are mediated primarily via a muscle metaboreflex with a minor, variable contribution from augmented central expiratory motor output.
Blood extraction from lancet wounds using vacuum combined with skin stretching
Authors: Cunningham David D. , Henning Timothy P. , Shain Eric B. , Young Douglas F. , Hannig Jurgen , Barua Eric , Lee Raphael C.
Published: March 2015

Key factors and practical limits of blood extraction from lancet wounds on body sites other than the finger were determined by testing a large number of conditions. During these tests, the pain associated with lancing alternate body sites was rated as less painful than a fingerstick 98% of the time. Vacuum combined with skin stretching was effective in extracting an adequate volume of blood from the forearm for glucose testing, up to an average of 16 μl in 30 s. The amount of blood extracted increases with the application of heat or vacuum before lancing, the level of vacuum, the depth of lancing, the time of collection, and the amount of skin stretching. Vacuum and skin stretching led to significant increases, up to fivefold in the perfusion of blood in the skin as measured by laser Doppler. Our observations suggest that vacuum combined with skin stretching increases blood extraction at alternate sites by increasing the lancet wound opening, increasing the blood available for extraction by vasodilatation, and reducing the venous return of blood through capillaries.
Contractile properties of rat single muscle fibers and myosin and troponin isoform expression after hypergravity
Authors: Stevens Laurence , Bozzo Cyril , Nemirovskaya Tatiana , Montel Valerie , Falempin Maurice , Mounier Yvonne
Published: March 2015

The effects of 19 days of hypergravity (HG) were investigated on the biochemical and physiological properties of the slow soleus muscle and its fast agonist, the plantaris. HG was induced by rotational centrifugation that led to a 2-G gravity level. The HG rats were characterized by a slower body growth than control, whereas the soleus muscle mass was increased by 15%. Using electrophoretic techniques, we showed that the distribution of myosin heavy chain and troponin T isoforms was not modified after HG in both soleus and plantaris. In contrast, the isoform expression pattern of two troponin subunits, troponin I and troponin C, was changed in a slow-to-fast manner only in the soleus. From tension-pCa relationships, changes in Ca2+activation threshold by 0.18 pCa unit indicated a decrease in Ca2+sensitivity and an increase in the slope of the curve, attesting to a higher cooperativity along the thin filament after HG. Comparison of our HG data with previous results in microgravity conditions indicated that muscle characteristics, except muscle mass, did not evolve linearly from 0 to 2 G.
Invited Review: Developmental plasticity in respiratory control
Authors: Carroll John L.
Published: March 2015

Development of the mammalian respiratory control system begins early in gestation and does not achieve mature form until weeks or months after birth. A relatively long gestation and period of postnatal maturation allows for prolonged pre- and postnatal interactions with the environment, including experiences such as episodic or chronic hypoxia, hyperoxia, and drug or toxin exposures. Developmental plasticity occurs when such experiences, during critical periods of maturation, result in long-term alterations in the structure or function of the respiratory control neural network. A critical period is a time window during development devoted to structural and/or functional shaping of the neural systems subserving respiratory control. Experience during the critical period can disrupt and alter developmental trajectory, whereas the same experience before or after has little or no effect. One of the clearest examples to date is blunting of the adult ventilatory response to acute hypoxia challenge by early postnatal hyperoxia exposure in the newborn. Developmental plasticity in neural respiratory control development can occur at multiple sites during formation of brain stem neuronal networks and chemoafferent pathways, at multiple times during development, by multiple mechanisms. Past concepts of respiratory control system maturation as rigidly predetermined by a genetic blueprint have now yielded to a different view in which extremely complex interactions between genes, transcriptional factors, growth factors, and other gene products shape the respiratory control system, and experience plays a key role in guiding normal respiratory control development. Early-life experiences may also lead to maladaptive changes in respiratory control. Pathological conditions as well as normal phenotypic diversity in mature respiratory control may have their roots, at least in part, in developmental plasticity.
Effects of muscle metaboreceptor stimulation on cutaneous blood flow from glabrous and nonglabrous skin in mildly heated humans
Authors: Kondo Narihiko , Yanagimoto Shuji , Nishiyasu Takeshi , Crandall Craig G.
Published: March 2015

Given differences in sympathetic innervation to glabrous and nonglabrous skin, we tested the hypothesis that muscle metaboreceptor regulation of cutaneous vascular conductance (CVC) differs between these skin regions. Subjects ( n = 21) performed isometric handgrip exercise (IHG; 50% maximal voluntary contraction for 60 s), followed by 2 min of postexercise ischemia. Throughout IHG and postexercise ischemia, CVC was measured from glabrous (palm) and nonglabrous (forearm and chest) regions contralateral to the exercising arm. These procedures were conducted after the subjects had been exposed to an ambient temperature of 35°C and a relative humidity of 50% for 60 min. These thermal conditions were intended to cause slight increases in cutaneous blood flow via sympathetic withdrawal. Esophageal, sublingual, and mean skin temperatures did not change markedly during IHG or postexercise ischemia. During IHG, forearm CVC did not change, chest CVC increased slightly, and palm CVC decreased substantially (from 100 to 34.8 ± 3.5%; P = 0.001). During muscle metaboreceptor stimulation due to postexercise ischemia, CVC from nonglabrous regions returned to preexercise baselines, whereas CVC at the palm remained below preexercise baseline (68.2 ± 4.2%; P = 0.001 relative to preexercise baseline). These results indicate that in mildly heated humans muscle metaboreflex stimulation is capable of modulating CVC in glabrous, but not in nonglabrous, skin.
Mechanisms of aortic smooth muscle hyporeactivity after prolonged hypoxia in rats
Authors: Zacour Mary E. , Teoh Hwee , Halayko Andrew J. , Ward Michael E.
Published: March 2015

The aim of this study was to determine whether the effects of hypoxia on aortic contractility reflect a decrease in smooth muscle activation [phosphorylation of the 20-kDa myosin regulatory light chain (LC20)], the capacity for myofibrillar ATP hydrolysis (mATPase activity), or both. Our results indicate that, in endothelium-denuded aortic rings from rats exposed to hypoxia for 48 h (inspired O2concentratio n = 10%), contractions to phenylephrine and potassium chloride (KCl) are impaired compared with rings from normoxic rats. The proportion of phosphorylated to total LC20during aortic contraction induced by 10−5M phenylephrine was reduced after hypoxia (51.4 ± 5.4% in normoxic control rats vs. 32.5 ± 4.7% in hypoxic rats, P < 0.01). Aortic mATPase activity was also decreased (maximum ATPase rate = 29.6 ± 3.4 and 20.7 ± 3.7 nmol · min−1· mg protein−1in control and hypoxic rats, respectively, P < 0.05). Neither proliferation nor dedifferentiation of aortic smooth muscle was evident in this model; immunostaining for smooth muscle expression of the proliferating cell nuclear antigen was negative and smooth muscle-specific isoforms of myosin heavy chains, h-caldesmon, and calponin were increased, not decreased, after hypoxic exposure. Decreased aortic reactivity after hypoxia is associated with both impairment of smooth muscle activation and diminished capacity of the actomyosin complex, once activated, to hydrolyze ATP. These changes cannot be attributed to smooth muscle dedifferentiation or to reduced contractile protein expression.
Time course of changes in lipoprotein lipase activity in rat skeletal muscles during denervation-reinnervation
Authors: Z˙ernicka E. , Smol E. , Langfort J. , Górecka M.
Published: March 2015

The effects of denervation-reinnervation after sciatic nerve crush on the activity of extracellular and intracellular lipoprotein lipase (LPL) were examined in the soleus and red portion of gastrocnemius muscles. The activity of both LPL fractions was decreased in the two muscles within 24 h after the nerve crush and remained reduced for up to 2 wk. During the reinnervation period, LPL activity was still reduced in the soleus and started to increase only on the 40th day. In the red gastrocnemius, LPL activity increased progressively with reinnervation, exceeding control values on the 30th day postcrush. The LPL activity in the soleus from the contralateral to denervated hindlimb was also affected, being increased on the postoperation day and then gradually decreased during the following days. In conclusion, the time course of changes in muscle LPL activity after nerve crush confirmed the predominant role of nerve conduction in controlling muscle potential to take up free fatty acids derived from the plasma triacylglycerols. However, other factors, such as muscle fiber composition and the fiber transformation, should also be considered in this aspect of the denervation-reinnervation process. Moreover, it was found that denervation of muscles from one hindlimb may influence LPL activity in muscles from the contralateral leg.
Selected Contribution: Role of IL-6 in LPS-induced nuclear STAT3 translocation in sensory circumventricular organs during fever in rats
Authors: Harré Eva-Maria , Roth Joachim , Pehl Ulrich , Kueth Matthias , Gerstberger Rüdiger , Hübschle Thomas
Published: March 2015

Interleukin-6 (IL-6) is regarded as an endogenous mediator of lipopolysaccharide (LPS)-induced fever. IL-6 is thought to act on the brain at sites that lack a blood-brain barrier, the circumventricular organs (CVOs). Cells that are activated by IL-6 respond with nuclear translocation of the signal transducer and activator of transcription 3 molecule (STAT3) and can be detected by immunohistochemistry. We investigated whether the LPS-induced release of IL-6 into the systemic circulation was accompanied by a nuclear STAT3 translocation within the sensory CVOs. Treatment with LPS (100 μg/kg) led to a slight (1 h) and then a strong increase (2–8 h) in plasma IL-6 levels, which started to decline at the end of the febrile response. Administration of both pyrogens LPS and IL-6 (45 μg/kg) induced a febrile response with IL-6, causing a rather moderate fever compared with the LPS-induced fever. Nuclear STAT3 translocation in response to LPS was observed within the vascular organ of the lamina terminalis (OVLT) and the subfornical organ (SFO) 2 h after LPS treatment. To investigate whether this effect was mediated by IL-6, the cytokine itself was systemically applied and indeed an identical pattern of nuclear STAT3 translocation was observed. However, nuclear STAT3 translocation already occurred 1 h after IL-6 application and proved to be less effective compared with LPS treatment when analyzing OVLT and SFO cell numbers that showed nuclear STAT3 immunoreactivity after the respective pyrogen treatment. Our observations represent the first molecular evidence for an IL-6-induced STAT3-mediated genomic activation of OVLT and SFO cells and support the proposed role of these brain areas as sensory structures for humoral signals created by the activated immune system and resulting in the generation of fever.
Shear stress depends on vascular territory: comparison between common carotid and brachial artery
Authors: Dammers Ruben , Stifft Frank , Tordoir Jan H. M. , Hameleers Jeroen M. M. , Hoeks Arnold P. G. , Kitslaar Peter J. E. H. M.
Published: March 2015

Shear stress (SS) is thought to be constant throughout the vascular system. Evidence for this supposition is scarce, however. To verify this hypothesis in vivo, we assessed common carotid (CCA) and brachial artery (BA) peak and mean wall shear rate (SR) noninvasively in 10 healthy volunteers (23.7 ± 3.4 yr) with an ultrasound SR estimation system. SS was estimated from SR and calculated whole blood viscosity. SR was higher ( P < 0.05) in the CCA (mean: 359 ± 111 s−1; peak: 1,047 ± 345 s−1) than in the BA (mean: 95 ± 24 s−1; peak: 770 ± 170 s−1). Whole blood viscosity was higher in the BA than in the CCA (5.1 ± 0.7 vs. 3.3 ± 0.6 mPa · s; P < 0.001). Peak SS did not differ between the CCA and the BA, whereas mean SS was significantly higher in the CCA (1.15 ± 0.21 Pa) than in the BA (0.48 ± 0.15 Pa; P < 0.001). These results demonstrate that BA SS strongly deviates from CCA SS in vivo.
Mechanical ventilation-induced oxidative stress in the diaphragm
Authors: Zergeroglu Murat A. , McKenzie Michael J. , Shanely R. Andrew , Van Gammeren Darin , DeRuisseau Keith C. , Powers Scott K.
Published: March 2015

Prolonged mechanical ventilation (MV) results in oxidative damage in the diaphragm; however, it is unclear whether this MV-induced oxidative injury occurs rapidly or develops slowly over time. Furthermore, it is unknown whether both soluble (cytosolic) and insoluble (myofibrillar) proteins are equally susceptible to oxidation during MV. These experiments tested two hypotheses: 1) MV-induced oxidative injury in the diaphragm occurs within the first 6 h after the initiation of MV; and 2) MV is associated with oxidative modification of both soluble and insoluble proteins. Adult Sprague-Dawley rats were randomly divided into one of seven experimental groups: 1) control ( n = 8); 2) 3-h MV ( n = 8); 3) 6-h MV ( n = 6); 4) 18-h MV ( n = 8); 5) 3-h anesthesia-spontaneous breathing ( n = 8); 6) 6-h anesthesia-spontaneous breathing ( n = 6); and 7) 18-h anesthesia-spontaneous breathing ( n = 8). Markers of oxidative injury in the diaphragm included the measurement of reactive (protein) carbonyl derivatives (RCD) and total lipid hydroperoxides. Three hours of MV did not result in oxidative injury in the diaphragm. In contrast, both 6 and 18 h of MV promoted oxidative injury in the diaphragm, as indicated by increases in both protein RCD and lipid hydroperoxides. Electrophoretic separation of soluble and insoluble proteins indicated that the MV-induced accumulation of RCD was limited to insoluble proteins with molecular masses of ∼200, 120, 80, and 40 kDa. We conclude that MV results in a rapid onset of oxidative injury in the diaphragm and that insoluble proteins are primary targets of MV-induced protein oxidation.
Skeletal muscle adaptations in response to voluntary wheel running in myosin heavy chain null mice
Authors: Harrison B. C. , Bell M. L. , Allen D. L. , Byrnes W. C. , Leinwand L. A.
Published: March 2015

10.1152/ japplphysiol.00832.2001.—To examine the effects of gene inactivation on the plasticity of skeletal muscle, mice null for a specific myosin heavy chain (MHC) isoform were subjected to a voluntary wheel-running paradigm. Despite reduced running performance compared with nontransgenic C57BL/6 mice (NTG), both MHC IIb and MHC IId/x null animals exhibited increased muscle fiber size and muscle oxidative capacity with wheel running. In the MHC IIb null animals, there was no significant change in the percentage of muscle fibers expressing a particular MHC isoform with voluntary wheel running at any time point. In MHC IId/x null mice, wheel running produced a significant increase in the percentage of fibers expressing MHC IIa and MHC I and a significant decrease in the percentage of fibers expressing MHC IIb. Muscle pathology was not affected by wheel running for either MHC null strain. In summary, despite their phenotypes, MHC null mice do engage in voluntary wheel running. Although this wheel-running activity is lessened compared with NTG, there is evidence of distinct patterns of muscle adaptation in both null strains.
Effects of volatile anesthetics on elastic stiffness in isometrically contracting ferret ventricular myocardium
Authors: Bartunek Anna E. , Claes Victor A. , Housmans Philippe R.
Published: March 2015

The effects of halothane, isoflurane, and sevoflurane on elastic stiffness, which reflects the degree of cross-bridge attachment, were studied in intact cardiac muscle. Electrically stimulated (0.25 Hz, 25°C), isometrically twitching right ventricular ferret papillary muscles ( n = 15) at optimal length ( L max) were subjected to sinusoidal length oscillations (40 Hz, 0.25– 0.50% of L maxpeak to peak). The amplitude and phase relationship with the resulting force oscillations was decomposed into elastic and viscous components of total stiffness in real time. Increasing extracellular Ca2+ concentration in the presence of anesthetics to produce peak force equal to control increased elastic stiffness during relaxation, which suggests a direct effect of halothane and sevoflurane on cross bridges.
Selected Contribution: Variation and heritability for the adaptational response to exercise in genetically heterogeneous rats
Authors: Troxell Michael Lee , Britton Steven Loyal , Koch Lauren Gerard
Published: March 2015

Adaptational response to aerobic exercise was artificially selected for across one generation in a founder population of 20 female and 20 male genetically heterogeneous rats (N:NIH). Selection for low and high response was based on the change in treadmill running capacity, assessed by meters (m) run to exhaustion before and after 24 days of modest treadmill running. The training response of the founder population averaged +222 m, with wide variation from a negative gain (−) of −110 m to a positive gain (+) of +430 m. Six pairs of the lowest (+13 m) and highest (+327 m) responders were mated. Mean response to training of the low-line (+242 m) offspring did not differ from the founder. The high-selected line gained 383 m from training, +161 m above the founder population. Narrow sense heritability estimated from regression of offspring on midparent values for response to training was 0.43 ( P< 0.007). One generation of selection resulted in a 58% divide between the low and high lines. Selectively bred models of both intrinsic (untrained) and adaptation response can be useful in resolving the genetic basis of variation in aerobic capacity.
Central dopamine modulates anapyrexia but not hyperventilation induced by hypoxia
Authors: Barros Renata C. H. , Branco Luiz G. S.
Published: March 2015

Hypoxia causes hyperventilation and decreases body temperature (Tb) and metabolism [O2 consumption (V˙o 2)]. Because dopamine (DA) is released centrally in response to peripheral chemoreceptor stimulation, we tested the hypothesis that central DA mediates the ventilatory, thermal, and metabolic responses to hypoxia. Thus we predicted that injection of haloperidol (a DA D2-receptor antagonist) into the third ventricle would augment hyperventilation and attenuate the drop in Tb and V˙o 2 in conscious rats. We measured ventilation, Tb, andV˙o 2 before and after intracerebroventricular injection of haloperidol or vehicle (5% DMSO in saline), followed by a 30-min period of hypoxia exposure. Haloperidol did not change Tb orV˙o 2 during normoxia; however, breathing frequency was decreased. During hypoxia, haloperidol significantly attenuated the falls in Tb andV˙o 2, although hyperventilation persisted. The present study shows that central DA participates in the thermal and metabolic responses to hypoxia without affecting hyperventilation, showing that DA is not a common mediator of this interaction.
Pressure (≤4 ATA) increases membrane conductance and firing rate in the rat solitary complex
Authors: Mulkey Daniel K. , Henderson Richard A. , Putnam Robert W. , Dean Jay B.
Published: March 2015

Neuronal sensitivity to pressure, barosensitivity, is illustrated by high-pressure nervous syndrome, which manifests as increased central nervous system excitability when heliox or trimix is breathed at >15 atmospheres absolute (ATA). We have tested the hypothesis that smaller levels of pressure (≤4 ATA) also increase neuronal excitability. The effect of hyperbaric helium, which mimics increased hydrostatic pressure, was determined on putative CO2/H+-chemoreceptor neurons in the solitary complex in rat brain stem slices by intracellular recording. Pressure stimulated firing rate in 31% of neurons (barosensitivity) and decreased input resistance. Barosensitivity was retained during synaptic blockade and was unaffected by antioxidants. Barosensitivity was distributed among CO2/H+-chemosensitive and -insensitive neurons; in CO2/H+-chemosensitive neurons, pressure did not significantly reduce neuronal chemosensitivity. We conclude that moderate pressure stimulates certain solitary complex neurons by a mechanism that possibly involves an increased cation conductance, but that does not involve free radicals. Neuronal barosensitivity to ≤4 ATA may represent a physiological adaptive response to increased pressure or a pathophysiological response that is the early manifestation of high-pressure nervous syndrome.
Mechanical ventilation results in progressive contractile dysfunction in the diaphragm
Authors: Powers Scott K. , Shanely R. Andrew , Coombes Jeff S. , Koesterer Thomas J. , McKenzie Michael , Van Gammeren Darin , Cicale Michael , Dodd Stephen L.
Published: March 2015

These experiments tested the hypothesis that a relatively short duration of controlled mechanical ventilation (MV) will impair diaphragmatic maximal specific force generation (specific Po) and that this force deficit will be exacerbated with increased time on the ventilator. To test this postulate, adult Sprague-Dawley rats were randomly divided into one of six experimental groups: 1) control ( n = 12); 2) 12 h of MV ( n = 4); 3) 18 h of MV ( n = 4); 4) 18 h of anesthesia and spontaneous breathing ( n = 4); 5) 24 h of MV ( n = 7); and 6) 24 h of anesthesia and spontaneous breathing ( n = 4). MV animals were anesthetized, tracheostomized, and ventilated with room air. Animals in the control group were acutely anesthetized but were not exposed to MV. Animals in two spontaneous breathing groups were anesthetized and breathed spontaneously for either 18 or 24 h. No differences ( P > 0.05) existed in diaphragmatic specific Pobetween control and the two spontaneous breathing groups. In contrast, compared with control, all durations of MV resulted in a reduction ( P < 0.05) in diaphragmatic specific tension at stimulation frequencies ranging from 15 to 160 Hz. Furthermore, the MV-induced decrease in diaphragmatic specific Powas time dependent, with specific Pobeing ∼18 and ∼46% lower ( P < 0.05) in animals mechanically ventilated for 12 and 24 h, respectively. These data support the hypothesis that relatively short-term MV impairs diaphragmatic contractile function and that the magnitude of MV-induced force deficit increases with time on the ventilator.
Increased vascular resistance in paralyzed legs after spinal cord injury is reversible by training
Authors: Hopman Maria T. E. , Groothuis Jan T. , Flendrie Marcel , Gerrits Karin H. L. , Houtman Sibrand
Published: March 2015

The purpose of the present study was to determine the effect of a spinal cord injury (SCI) on resting vascular resistance in paralyzed legs in humans. To accomplish this goal, we measured blood pressure and resting flow above and below the lesion (by using venous occlusion plethysmography) in 11 patients with SCI and in 10 healthy controls (C). Relative vascular resistance was calculated as mean arterial pressure in millimeters of mercury divided by the arterial blood flow in milliliters per minute per 100 milliliters of tissue. Arterial blood flow in the sympathetically deprived and paralyzed legs of SCI was significantly lower than leg blood flow in C. Because mean arterial pressure showed no differences between both groups, leg vascular resistance in SCI was significantly higher than in C. Within the SCI group, arterial blood flow was significantly higher and vascular resistance significantly lower in the arms than in the legs. To distinguish between the effect of loss of central neural control vs. deconditioning, a group of nine SCI patients was trained for 6 wk and showed a 30% increase in leg blood flow with unchanged blood pressure levels, indicating a marked reduction in vascular resistance. In conclusion, vascular resistance is increased in the paralyzed legs of individuals with SCI and is reversible by training.
Physiological characterization of variability in response to lung volume reduction surgery
Authors: Ingenito Edward P. , Loring Stephen H. , Moy Marilyn L. , Mentzer Steven J. , Swanson Scott J. , Reilly John J.
Published: March 2015

This paper examines potential physiological mechanisms responsible for improvement after lung volume reduction surgery (LVRS). In 25 patients (63 ± 9 yr; 11 men, 14 women), spirometry [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)], lung volumes [residual volume (RV) and total lung capacity (TLC)], small airway resistance, recoil pressures, and respiratory muscle contractility (RMC) were measured before and 4–6 mo after LVRS. Data were interpreted to assess how changes in each component of lung mechanics affect overall function. Among responders (ΔFEV1 ≥ 12%; 150 ml), improvement was primarily due to an increase in FVC, not to FEV1-to-FVC ratio. Among nonresponders, FEV1, FVC, and RV/TLC did not change after surgery, although recoil pressure increased in both groups. Both groups experienced a reduction in RMC after LVRS. In conclusion, LVRS improves function in emphysema by resizing the lung relative to the chest wall by reducing RV. LVRS does not change airway resistance but decreases RMC, which attenuates the potential benefits of LVRS that are generated by reducing RV/TLC. Among nonresponders, recoil pressure increased out of proportion to reduced volume, such that no increase in vital capacity or improvement in FEV1 occurred.