bluuebunny/crossref_metadata_2025 huggingface dataset:
Gradient of fatty acids from blood plasma to skeletal muscle in dogs
Authors: Van der Vusse G. J. , Roemen T. H.
Published: December 2017

In anesthetized dogs, the amount of fatty acyl moieties in the fatty acid, triacylglycerol, and phospholipid fractions of arterial blood and biceps femoris muscle has been determined to delineate the presence of a fatty acid gradient from blood to skeletal muscle tissue, if any. The content of fatty acids in biceps femoris muscle was found to be very low (approximately 0.1% of total amount of unesterified and esterified fatty acyl moieties in the tissue sample). The ratio of the content of fatty acids (nmol/ml) in arterial plasma and the tissue level of fatty acids (nmol/g wet weight) was approximately 17. This finding supports the notion that a fatty acid gradient from the vascular compartment to the skeletal muscle fibers might be one of the driving forces of net extraction of fatty acids by skeletal muscle.
Allergen-induced hyperresponsiveness to bradykinin is more pronounced than that to methacholine
Authors: Berman A. R. , Togias A. G. , Skloot G. , Proud D.
Published: December 2017

Bradykinin reduces airflow in asthmatic patients via indirect mechanism(s), possibly involving sensory nerve stimulation and increased vascular permeability. We hypothesized that allergen inhalation, which affects reactivity of nerves and vessels, would differentially alter reactivity to bradykinin and the smooth muscle spasmogen methacholine. We compared reactivity to methacholine and bradykinin 1, 2, 4, 7, 11, and 14 days after allergen provocation in 12 atopic asthmatic patients with stable baseline reactivity to bradykinin. Maximal allergen-induced shifts from baseline in reactivity were 0.73 +/- 0.12 log unit for bradykinin compared with 0.27 +/- 0.13 log units for methacholine (P = 0.0005). Nine subjects showed significant increases in bradykinin reactivity, with four subjects increasing reactivity by > 1 log unit. Moreover, the maximal mean change in bradykinin reactivity occurred 2 days postallergen. Thus, allergen-induced changes in reactivity to bradykinin and methacholine differ in magnitude and time course. Bradykinin inhalational challenge provides a sensitive index of the airway's response to allergen.
Differential effect of ventrolateral medullary cooling on respiratory muscles of goats
Authors: Forster H. V. , Lowry T. F. , Ohtake P. J. , Pan L. G. , Korducki M. J. , Forster A. L.
Published: December 2017

The objective was to determine whether there is an inhomogeneous response of respiratory muscles during cooling-induced ventrolateral medullary (VLM) neuronal dysfunction in anesthetized and awake goats. Thermodes for cooling were chronically implanted on all or portions of rostral, intermediate, and caudal areas of the VLM of 16 adult goats. Electromyograms (EMGs) were obtained from chronically implanted wires in the diaphragm (di), transversus abdominis (TA), and triangularis sterni (TS) muscles. During some periods of cooling in 9 of 16 anesthetized airway-intubated goats, complete cessation of EMGdi coincided with a reduced yet sustained inspiratory flow. In six awake tracheotomized goats, VLM cooling decreased (P < 0.05) EMGdi duration and minute activity more than inspiratory duration and minute ventilation. Cooling thus decreased activation of the diaphragm more than activation of other respiratory muscles. On the other hand, during VLM cooling in 3 of 10 airway-intact awake goats, cessation of inspiratory flow coincided with sustained EMGdi, suggesting that cooling decreased stimulation of the upper airway muscles more than stimulation of the diaphragm. Finally, VLM cooling in a majority of goats decreased EMGTA and EMGTS more than EMGdi. We conclude that VLM neuronal dysfunction has a differential effect on respiratory muscles of adult anesthetized and awake goats.
Direct effects of inhaled nitric oxide on canine peripheral airways
Authors: Lindeman K. S. , Aryana A. , Hirshman C. A.
Published: December 2017

The effects of nitric oxide on peripheral airways in vivo, and whether these effects occur via direct or indirect mechanisms, are unknown. We studied effects of inhaled nitric oxide on histamine-constricted canine peripheral airways in the presence or absence of atropine and an inhibitor of guanylyl cyclase, methylene blue. Peripheral resistance (Rp) was measured by using a wedged-bronchoscope technique in anesthetized dogs. A stable baseline Rp was established. Histamine was infused intravenously, and increasing concentrations of nitric oxide (50–500 ppm) were delivered through the bronchoscope. In separate experiments, histamine was infused intravenously in the presence or absence of atropine (0.2 mg/kg iv) or methylene blue (20 mg/min iv). When Rp stabilized, nitric oxide (500 ppm) was delivered. Nitric oxide partially reversed histamine-induced bronchoconstriction in a dose-dependent fashion (maximum of 42 +/- 3% reduction at 500 ppm; n = 5; P < 0.01) that did not differ in the presence or absence of atropine. Methylene blue blocked the effect of nitric oxide on histamine-induced constriction (n = 6; P = 0.45). These findings suggest that high concentrations of nitric oxide produce small but significant bronchodilation of peripheral airways through a mechanism independent of the cholinergic neural pathway. The mechanism of action appears to involve activation of guanylyl cyclase.
Norepinephrine release in the rat frontal cortex under treadmill exercise: a study with microdialysis
Authors: Pagliari R. , Peyrin L.
Published: December 2017

Cortical norepinephrine (NE) release and metabolism were studied by using chronic microdialysis in rats performing a treadmill exercise at 25 m/min with a 3% slope. Cortical microdialysates and peripheral blood were collected at rest, during 1- or 2-h treadmill running, and for 1 h after exercise. Microdialysate NE and its main metabolites, 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol, and plasma epinephrine (Epi) and NE were determined by high-performance liquid chromatography with electrochemical detection. The results show that treadmill running is able to stimulate concomitantly peripheral catecholamine secretion and central noradrenergic activity, i.e., NE turnover and release. The duration of the central activation and its prolongation over recovery period increases as the duration of the running increases. A positive correlation was found between the central noradrenergic activation and peripheral Epi secretion but not peripheral NE. These findings confirm and extend our previous observations in exercising men and give support to the hypothesis that the elevation of circulating Epi can be a relevant factor mediating, directly or indirectly, the exercise-induced central neurochemical, psychological, and cognitive changes.
Energy expenditure and substrate utilization in older women after strength training: 24-h calorimeter results
Authors: Treuth M. S. , Hunter G. R. , Weinsier R. L. , Kell S. H.
Published: December 2017

The purpose of this study was to examine the effects of strength training (ST) in healthy older women on 24-h energy expenditure (EE) and its components and on 24-h substrate utilization. Thirteen women (age 67 +/- 1 yr) exercised three times per week for 16 wk in a total body ST program. EE components and substrate utilization were determined for 24 h in an indirect room calorimeter before and after training. The ST invoked a 47% increase in upper body and a 66% increase in lower body strength (P < 0.001). Body weight, percent body fat, and fat-free mass did not change significantly; however, midthigh muscle area increased (55.2 +/- 3.1 vs. 60.4 +/- 2.3 cm2; P < 0.05). There are a significant increase in resting EE (5,017 +/- 218 vs. 5,473 +/- 213 kJ/day; P < 0.05) but no significant changes in sleeping EE (4,929 +/- 180 vs. 5,067 +/- 251 kJ/day), diet-induced thermogenesis (359 +/- 25 vs. 393 +/- 33 kJ/day), activity EE (682 +/- 84 vs. 381 +/- 117 kJ/day), or 24-h EE (6,054 +/- 188 vs. 6,247 +/- 243 kJ/day). The increase in resting EE was not significant after the increase in muscle area is taken into account. The 24-h nonprotein respiratory quotient decreased (0.90 +/- 0.01 vs. 0.82 +/- 0.01; P < 0.001), revealing a significant increase in 24-h fat oxidation (42 +/- 6 vs. 81 +/- 7 g/day) and a decrease in carbohydrate oxidation (180 +/- 14 vs. 113 +/- 10 g/day; both P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Succinate dehydrogenase activity of sexually dimorphic muscles of rats
Authors: Blanco C. E. , Micevych P. E. , Zhan W. Z. , Sieck G. C.
Published: December 2017

Muscles of the male rat perineum attaching to the penis are the ischiocavernosus, the medial bulbocavernosus (BC), and the dorsal BC, also known as the levator ani (LA). The BC and the LA muscles are innervated by a morphologically, neurochemically, and physiologically homogeneous pool of motoneurons, the spinal nucleus of BC (SNB). The purpose of the present study was to determine whether BC and LA muscle fibers constitute histochemically and biochemically homogeneous populations, reflecting the homogeneity of the innervating motoneuron pool. Histochemical fiber type was based on the pH lability of myofibrillar adenosinetriphosphatase. Activity of the mitochondrial enzyme succinate dehydrogenase (SDH) was determined by using a quantitative histochemical procedure. A nonsexually dimorphic, androgen-insensitive muscle, the medial gastrocnemius (MG), was used as control. The superficial regions of the MG, BC, and LA muscles were composed exclusively of type IIb muscle fibers, whereas the fiber type composition of the deep region of the MG was mixed: 28.3% type I, 20.6% type IIa, 40.1% type IIx, and 11.0% type IIb. The SDH activities of type IIb fibers in the deep region of the MG ranged from 1.20 to 9.00 (mean 3.72 +/- 0.40) mmol fumarate.liter tissue-1.min-1. Fiber SDH activities in the superficial region of the MG ranged from 0.04 to 2.70 (mean 1.20 +/- 0.21) mmol fumarate.liter tissue-1.min-1. In the BC muscle, the SDH activities of the type IIb fibers ranged from undetectable to 1.80 with a mean of 0.62 +/- 0.05 mmol fumarate.liter tissue-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Central and reflex neural control of genioglossus in subjects who underwent laryngectomy
Authors: Innes J. A. , Morrell M. J. , Kobayashi I. , Hamilton R. D. , Guz A.
Published: December 2017

Inspiratory activation of the genioglossus (GG) may occur by central drive or as a reflex to negative airway pressure. To distinguish between these, we studied seven laryngectomy patients who breathe via tracheal stomas. Negative pressure stimuli (-15 and -25 cmH2O for 500 ms) were applied 1) at functional residual capacity and 2) during early inspiration via (i) the upper airway (UA) and (ii) the tracheal stoma. Intraoral surface GG electromyogram was quantified, as described previously (R. L. Horner, J. A. Innes, K. Murphy, and A. Guz, J. Physiol. Lond. 436: 15-29, 1991). Phasic GG activity was also measured from an integrated electromyogram during spontaneous and inspiratory loaded breathing. Reflex GG activation occurred with negative UA pressure both at functional residual capacity and during inspiration (P < 0.001), but pressure stimuli at the stoma caused no significant activation (P = 0.07). Phasic inspiratory activation occurred in four patients at rest and in all seven patients during inspiratory loading (P < 0.02). These patients demonstrate 1) reflex activation of the GG by negative UA pressure without airflow or respiratory effort and 2) central inspiratory GG activation that is not mediated by negative airway pressure.
Exercise causes branched-chain oxoacid dehydrogenase dephosphorylation but not AMP deaminase binding
Authors: Rush J. W. , MacLean D. A. , Hultman E. , Graham T. E.
Published: December 2017

The responses of AMP deaminase (AMPD) and branched-chain oxoacid dehydrogenase (BCOAD) to moderate (70% maximal O2 consumption for 90 min) followed by intense (90% maximal O2 consumption to exhaustion) cycling exercise were evaluated in the active skeletal muscle of human subjects (n = 8). The exercise conditions invoke different energy demands and ammonia production rates. Active muscle and plasma ammonia concentrations continuously increased throughout moderate exercise in the absence of significant inosine 5-monophosphate accumulation. The free activity of AMPD decreased during moderate exercise (by approximately 25-35%), whereas myosin-bound activity did not change. BCOAD was significantly dephosphorylated (activated) at 5 min and was continuously dephosphorylated during moderate exercise (to a maximum of approximately 21%). Ammonia accumulation rate increased dramatically during the higher intensity exercise accompanied by inosine monophosphate accumulation of approximately 2 mmol/kg dry muscle. The higher intensity exercise caused no further changes in AMPD activity distribution or BCOAD dephosphorylation. Resting muscle percent bound AMPD was notably higher than values previously reported for rat muscle. Increases in percent bound AMPD during exercise were the result of decreases in the sum of free and bound activities and not increases in bound activity. The results of this study do not support a role for myosin binding in the activation of AMPD in human skeletal muscle.
Nitrogen narcosis attenuates shivering thermogenesis
Authors: Mekjavic I. B. , Savic S. A. , Eiken O.
Published: December 2017

Thermoregulatory responses of eight healthy subjects (six men and two women) were compared when they were head-out immersed in 15 degrees C water at both 1 and 6 ATA. Both trials were conducted in a hyperbaric chamber. During the immersions, esophageal temperature (T(es)) and skin temperature at two sites (chest and calf) were recorded at minute intervals. Oxygen uptake was determined at 5-min intervals with the Douglas bag method. The order of the two trials was alternated. The rate of T(es) cooling was greater during the 6-ATA trial [2.1 +/- 0.5 degrees C/h (SE)] than during the 1-ATA trial (1.3 +/- 0.5 degrees C/h; P < 0.01). Despite the greater rate of core cooling, and presumably a greater thermal drive for shivering, the oxygen uptake response for a similar decrement in T(es) was lower during exposure to 6 than to 1 ATA (P < 0.05). Also, for similar displacement in T(es), the subjects perceived the immersions at 6 ATA to be less cold than those at 1 ATA (P < 0.05). It is concluded that the development of hypothermia in compressed-air divers may be due, in large part, to the attenuation of heat production and cold perception. Most likely, the observed effects on the autonomic responses and thermal perception are due to an inhibitory action of hyperbaric nitrogen on central neural structures involved in temperature regulation.
Ovine fetal swallowing response to intracerebroventricular hypertonic saline
Authors: Ross M. G. , Kullama L. K. , Ogundipe A. , Chan K. , Ervin M. G.
Published: December 2017

In the near-term ovine fetus, systemic hyperosmolality stimulates dipsogenic responses. Putative systemic dipsogens (hypertonicity, angiotensin II) may initiate responses by stimulation of select cerebral circumventricular nuclei lacking a blood-brain barrier. To investigate whether central osmotic-dipsogenic mechanisms are functional in utero, fetal swallowing responses to intracerebroventricular (i.c.v.) hypertonic saline were examined. Five pregnant ewes with singleton fetuses (128 +/- 1 days gestation) were prepared with fetal lateral cerebral ventricle and vascular catheters, electrocortical (ECoG) electrodes, and electromyogram wires on the fetal thyrohyoid muscle, nuchal and thoracic esophagus, and diaphragm and studied for a minimum of 5 days postoperatively. After a 2-h basal period, fetuses received an i.c.v. infusion of artificial cerebrospinal fluid followed by successive 30-min infusions of hypertonic NaCl in artificial cerebrospinal fluid (500 and 700 mosmol/kgH2O). In response to the i.c.v. hypertonic NaCl infusions, fetal swallowing significantly increased (1.4 +/- 0.4 to 3.9 +/- 1.4 and 2.9 +/- 0.5 swallows/min low-voltage ECoG, respectively). Plasma arginine vasopressin levels increased, although the change was not statistically significant (9.1 to 24.2 pg/ml; P = 0.07), and there was no change in fetal plasma osmolality, sodium concentration, or ECoG activity. Together with previous studies, these results indicate that both central and systemic osmotic dipsogenic mechanisms are functional in utero.
Time-varying pulmonary arterial input impedance via wavelet decomposition
Authors: Li Z. , Grant B. J. , Lieber B. B.
Published: December 2017

Wavelet decomposition is proposed as a novel approach for determining pulmonary arterial input impedance throughout the breathing cycle. The canine pulmonary arterial input impedance was evaluated throughout the ventilatory cycle at 5, 10, and 15 cmH2O of positive end-expiratory pressure. The impedance spectrum was obtained by Fourier transformation of wavelets generated by decomposing the pulmonary arterial pressure and flow waveforms. With wavelet decomposition, each heart beat is viewed individually as a transient pulse rather than as an interval within a continuous function of pressure and flow. The advantage of using this approach is the ability to obtain stable estimates of input impedance spectra with high-frequency resolution over the entire frequency range with only a limited data set of pressure and flow decomposed to wavelets as short as singular extrapolated cardiac cycles. This method was used to define the changes of input impedance that occur during the ventilatory cycle. Results show that the impedance spectrum undergoes notable changes during the breathing cycle and demonstrate the utility of the proposed method.
Circulating endothelin-1 reduces splanchnic and renal blood flow and splanchnic glucose production in humans
Authors: Ahlborg G. , Weitzberg E. , Lundberg J. M.
Published: December 2017

The effect of minimal changes in circulating plasma endothelin-1 (ET-1) was studied in 12 healthy subjects receiving either 60 min of ET-1 (0.2 pmol.kg-1.min-1) or physiological saline intravenously. Blood was drawn from arterial, renal, and central hepatic vein catheters. Arterial ET-1-like immunoreactivity (ET-1-LI) increased from 4.7 +/- 0.4 (SE) to 8.6 +/- 1.0 pmol/l during ET-1 infusion. After 10 min, plasma ET-1-LI had increased to 6.12 +/- 0.29 pmol/l. For comparison the plasma ET-1-LI level was 12.9 +/- 4.2 pmol/in five patients with sepsis syndrome. Mean arterial blood pressure rose from 92 +/- 3 to 99 +/- 4 mmHg. Estimated splanchnic and renal blood flows fell by 18 +/- 5 and 10 +/- 3%, respectively, and splanchnic glucose production fell by 42 +/- 6% within 10 min of the ET-1 infusion and differed compared with corresponding control values. Only estimated splanchnic blood flow had increased 60 min after the ET-1 infusion. No change in splanchnic uptake of lactate or glycerol was seen. In conclusion, we suggest that circulating ET-1 with small or no demonstrable change in plasma concentration interferes with vasoactivity and splanchnic glycogenolyses in health and possibly pathophysiological conditions.
Alterations in uteroplacental blood flow precede hypertension in preeclampsia at high altitude
Authors: Zamudio S. , Palmer S. K. , Dahms T. E. , Berman J. C. , Young D. A. , Moore L. G.
Published: December 2017

High-altitude residence during pregnancy is associated with an increased incidence of preeclampsia. To determine whether uteroplacental blood flow was reduced and pelvic blood flow distribution altered before the onset of hypertension, we measured common iliac (CI), uterine (UA), and external iliac (EI) artery flow velocities (FV), indexes of flow distribution, and blood volume (BV) at week 12, 24, and 36 of pregnancy and 6 mo postpartum in 23 normotensive, 7 preeclamptic, 5 transiently hypertensive, and 3 chronically hypertensive residents of 3,100 m. Normotensive women had a progressive increase in CIFV and UAFV, decrease in EIFV, redistribution of CIFV from the EI to the UA, and increase in BV with advancing pregnancy. Preeclamptic women attained maximal UAFV and redistribution of CIFV from the EI to the UA well before the onset of hypertension and, unlike normotensive women, showed no further increases near term. Plasma volume increment with pregnancy related to the fall in the EIFV/CIFV ratio. Transiently hypertensive women resembled normotensive subjects in the parameters measured, whereas chronically hypertensive subjects resembled preeclamptic subjects. We concluded that preeclamptic vs. normotensive pregnant residents of high altitude had less redistribution of CI flow to the UA and no increase in UA blood flow near term. That these differences were present before the onset of hypertension supports the concept that preeclampsia is characterized by an incomplete vascular adjustment to pregnancy.
Limitations of the efficacy of hemoglobin-based oxygen-carrying solutions
Authors: Lee R. , Neya K. , Svizzero T. A. , Vlahakes G. J.
Published: December 2017

Improvements in hemoglobin-based oxygen-carrying (HBOCs) solutions have overcome the toxicities that plagued earlier efforts. However, limitations of the efficacy of HBOCs are emerging. The potential limitations of an HBOC were studied in an ovine model (n = 6) of exchange transfusion. Hemodynamic, oxygen transport, and hemoglobin kinetic parameters were examined during isovolumic blood exchange to a final hematocrit of 3.2 +/- 0.7% and a plasma hemoglobin concentration of 8.1 +/- 0.4 g/dl while sheep were awake and breathing room air. However, the infusion of HBOC was associated with immediate increases in systemic and pulmonary arterial pressures. Despite hemodilution with HBOC, systemic and pulmonary vascular resistance increased 43.9% (P < 0.001) and 204.2% (P < 0.001), respectively, after HBOC infusion. After blood exchange, the plasma hemoglobin level exhibited a circulatory half-life of 52.7 +/- 18.0 h. The formation of methemoglobin was significant, accounting for 33.0 +/- 7.1% of the total circulating plasma hemoglobin at 24 h; the half-life of HBOC capable of carrying oxygen was 30.1 +/- 5.4 h. This relatively short period of oxygen-carrying efficacy and the observed vasoconstriction properties may constrain the potential applications of HBOC solutions.
Intrinsic myocardial function and oxidative stress after exhaustive exercise
Authors: Seward S. W. , Seiler K. S. , Starnes J. W.
Published: December 2017

The purposes of this study were to determine the effect of an exhaustive running bout on intrinsic myocardial function by using the isolated working rat heart and to determine whether exhaustive exercise resulted in measurable oxidative stress in the myocardium. Untrained familiarized male rats were run at 18 m/min on a 0% grade until exhausted. Run time to exhaustion was approximately 75 min. Postexhaustion isolated heart measurements of cardiac output, rate-pressure product at low and high workloads, maximum left ventricular pressure, or 50-min performance at 85% of peak rate-pressure product were not different from those of nonexercised perfused control hearts. Exhaustive exercise resulted in a significant decline (174 vs. 224 nmol/g wet wt; P < 0.05) in nonprotein nonglutathione sulfhydryls, a thiol fraction indicative of oxidative stress. However, the magnitude of this measure of oxidative stress appears insufficient to cause alterations in intrinsic myocardial performance. We conclude that healthy untrained rats subjected to exhaustive exercise fail to demonstrate accumulation of a functionally significant level of myocardial oxidative stress.
Does the anatomic makeup of parenchymal lung strips affect oscillatory mechanics during induced constriction?
Authors: Salerno F. G. , Dallaire M. , Ludwig M. S.
Published: December 2017

Parenchymal tissue strips have been used to investigate the mechanical behavior of the lung parenchyma. We questioned whether the relative amounts of alveolar, blood vessel, and bronchial walls would be important when the contractile response of parenchymal strips from Sprague-Dawley rats was studied. One group of strips was cut from the subpleural edge and another from between 1 and 3 mm proximal to the pleura. Strips were suspended in an organ bath filled with Krebs solution (37 degrees C, pH 7.4) bubbled with 95% O2–5% CO2. Resting tension (T) was set at 1.1 g, and sinusoidal oscillations of 2.5% resting length at a frequency of 1 Hz were applied. Measurements of length and T were recorded during baseline conditions and after acetylcholine (10(-3) M) was added to the bath. Elastance, resistance, and hysteresivity (the ratio of the energy dissipated to that conserved) were calculated. Strips were fixed in Formalin at a T of 1 g, histological sections were prepared, and the fractional areas of alveolar, blood vessel, and bronchial walls were measured by using point counting. Significant differences were found between the two groups of strips in the acetylcholine response and anatomic makeup. The magnitude of the changes of all the mechanical parameters were correlated with the volume proportions of the different anatomic constituents when all the strips were plotted together but not when the subpleural strips were considered alone. We conclude that subpleural parenchymal strips are a sound model of parenchymal lung behavior. When more proximal strips are studied, the amount of bronchial wall may play an important role in determining the hysteretic response.
Individual differences in relationship between upper airway resistance and ventilation during sleep onset
Authors: Kay A. , Trinder J. , Kim Y.
Published: December 2017

Sleep-induced hypoventilation is caused partly by inadequate compensation for elevated upper airway resistance (UAR). Some evidence suggests that the effect of UAR on ventilation may vary among individuals. The relationship between minute ventilation (VI) and UAR was examined in 26 healthy young men (average of 10.12 sleep onsets). Variables were analyzed over transitions between wakefulness (defined by alpha electroencephalographic activity) and sleep (theta electroencephalographic activity). Transitions to sleep were associated with increases in UAR in synchrony with reductions in VI, and equally rapid opposite changes occurred with awakenings. The relationship between the magnitudes of the changes in VI and UAR at transitions varied among subjects, accounting for 30% of the variance for alpha-to-theta transitions and 50% of the variance for theta-to-alpha transitions. Results indicated that, although ventilatory changes during sleep onset are partly a consequence of changes in UAR, alterations in UAR do not account fully for alterations in VI. Other factors that may contribute to ventilatory instability during sleep onset include state-related fluctuations in drive to the primary respiratory muscles and variability in compensatory mechanisms.
Cocaine alters myosin isoform expression in the rat soleus
Authors: Prevost M. C. , Nelson A. G. , Kelly K. P. , Han D. H. , Conlee R. K.
Published: December 2017

The purpose of this study was to determine whether chronic cocaine administration alters the expression of myosin isoforms in the rat soleus. Forty-five adult Sprague-Dawley rats were divided into three groups: chronic cocaine (n = 15), 12.5 mg/kg cocaine-HCl injected intraperitoneally twice daily for 14 days and one injection of cocaine (12.5 mg/kg ip) on day 15; acute cocaine (n = 15), saline injections twice daily for 14 days and one injection of cocaine (12.5 mg/kg ip) on day 15; and chronic saline (n = 15), saline injections twice daily for 14 days and one saline injection on day 15. Myosin isoform content of the soleus (native and heavy chains) was identified by electrophoresis. The solei samples from the chronic saline and acute cocaine animals contained slow myosin only. However, solei samples from the chronic cocaine group contained slow myosin and two to three other myosin isoforms and the associated heavy chains IIa and IIx. Therefore, chronic cocaine administration causes in the rat soleus a shift in myosin expression from slow isoforms to fast isoforms.
Influence of background vagal C-fiber activity on eupneic breathing pattern in anesthetized dogs
Authors: Schelegle E. S. , Mansoor J. K. , Green J. F.
Published: December 2017

In 19 dogs anesthetized with xylazine and alpha-chloralose, we examined the influence of background vagal C-fiber activity on the breathing pattern using a modified perineural capsaicin treatment. In seven dogs, we tested the efficacy of this treatment by recording compound action potentials before and after capsaicin application. In the remaining 12 dogs, we examined the effect of vagal perineural capsaicin on the Hering-Breuer expiratory facilitatory inflation reflex, pulmonary chemoreflex, and breathing pattern (tidal volume and expiratory and inspiratory times). Neither the peak height nor integral of the A wave of the compound action potential was significantly affected. However, the peak height and integral of the C wave of the compound action potential were significantly affected. However, the peak height and integral of the C wave of the compound action potential were significantly reduced. The myelinated fiber-initiated Hering-Breuer reflex remained intact after perineural capsaicin, but the C-fiber-initiated pulmonary chemoreflex was abolished. Perineural capsaicin increased tidal volume (0.399 +/- 0.031 to 0.498 +/- 0.058 liter; P < 0.05), expiratory time (3.62 +/- 0.31 to 4.82 +/- 0.68 s; P < 0.05), inspiratory time (1.49 +/- 0.12 to 1.72 +/- 0.17 s; P < 0.10) and total time per breath (5.11 +/- 1.08 to 6.54 +/- 0.82 s; P < 0.05). We conclude that background vagal C-fiber activity exerts an inhibitory effect on tidal volume and an excitatory effect on breathing frequency.
Muscle blood flow in cats: comparison of microdialysis ethanol technique with direct measurement
Authors: Hickner R. C. , Ekelund U. , Mellander S. , Ungerstedt U. , Henriksson J.
Published: December 2017

A quantitative validation of the microdialysis ethanol technique was performed in cat gastrocnemius muscle. Six to eight microdialysis probes were inserted into the isolated muscle preparation and perfused (0.5–10.0 microliters/min) with Krebs-Henseleit buffer containing between 5 and 1,000 mmol/l ethanol. Skeletal muscle blood flow was held constant in the range of 4–99 ml.100 g-1.min-1 by a servo-controlled roller pump and was determined with the microdialysis ethanol technique as well as by timed collection of venous outflow. The ethanol concentration outflow-to-inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium) decreased in a nonlinear fashion when microdialysis perfusion flow rates of 0.5 and 1.0 microliter/min were employed. However, a linear decrease was found between 4 and approximately 45 ml.100 g-1.min-1 (r = -0.92 to -0.99). The lower outflow-to-inflow ratio was at 4 ml.100 g-1.min-1 (i.e., due to a low probe perfusion flow rate or a large dialysis membrane), the greater the sensitivity of the method was. It is concluded that this nonradioactive technique provides a simple and valid method for determining nutritive blood flow in skeletal muscle.
Running performance and cardiovascular capacity are not impaired in creatine-depleted rats
Authors: Adams G. R. , Bodell P. W. , Baldwin K. M.
Published: December 2017

Several published reports have indicated that derangement of the phosphocreatine/creatine (Cr) energy-buffering system via Cr analogue feeding results in cardiomyopathy when cardiac performance is assessed in vitro. The present study was designed to examine indexes of cardiac performance in rats that have been chronically Cr depleted. Adult (180 +/- 4 g) rats were assigned to a normal diet (ND) (n = 8) or a Cr-depletion diet (CD) group (n = 10). After 61 +/- 1 days of ad libitum feeding, measurements of steady-state exercise O2 consumption were made. Hemodynamic indexes were then assessed during incremental running to peak sustained levels. Rats were then killed and the left ventricle was excised. In the CD group Cr was depleted 82% and V1 isomyosin decreased while V2 increased. O2 consumption during steady-state running was not different in CD rats. The respiratory exchange ratios of CD rats reflected a bias toward fat utilization during the latter stages of prolonged exercise. The exercise heart rates and peak systolic blood pressures of CD rats were slightly lower than those of ND rats. Both negative and positive rates of left ventricular pressure development were significantly reduced at all running speeds in the CD rats. CD rats were capable of exercise performance equal to that of ND animals. The hemodynamic and metabolic data suggest that the adaptations seen in the CD animals may be similar to those reported after endurance training. These results indicate that chronic Cr depletion does not impair either the circulatory or exercise capacity of rodents.
Effect of analyzer on determination of mixed venous PCO2 and cardiac output during exercise
Authors: Hornby L. , Coates A. L. , Lands L. C.
Published: December 2017

Cardiac output (CO) during exercise can be determined noninvasively by using the indirect Fick CO2-rebreathing technique. CO2 measurements for this technique are usually performed with an infrared analyzer (IA) or mass spectrometer (MS). However, IA CO2 measurements are susceptible to underreading in the face of high O2 concentrations because of collision broadening. We compared an IA (Ametek model CD-3A) with a MS (Marquette model MGA-1100) to see the effect this would have on mixed venous PCO2 (PVCO2) and CO measurements. After calibration with room air and a gas mixture of 5% CO2–12% O2–83% N2, both devices were tested with three different gas mixtures of CO2 in O2. For each gas mixture, IA gave lower CO2 values than did the MS (4.1% CO2: IA, 3.85 +/- 0.01% and MS, 4.13 +/- 0.01%; 9.2% CO2: IA, 8.44 +/- 0.07% and MS, 9.19 +/- 0.01%; 13.8% CO2: IA, 12.57 +/- 0.15% and MS, 13.82 +/- 0.01%). Warming and humidifying the gases did not alter the results. The IA gave lower values than did the MS for eight other medical gases in lower concentrations of O2 (40–50%). Equilibrium and exponential rebreathing procedures were performed. Values determined by the IA were > 10% higher than those determined by the MS for both rebreathing methods. We conclude that all IAs must be checked for collision broadening if they are to be used in environments where the concentration of O2 is > 21%. If collision broadening is present, then either a special high O2-CO2 calibration curve must be constructed, or the IA should not be used for both arterial PCO2 and PVCO2 estimates because it may produce erroneously low PVCO2 values, with resultant overestimation of CO.
Bronchoscopic determination of ozone uptake in humans
Authors: Gerrity T. R. , Biscardi F. , Strong A. , Garlington A. R. , Brown J. S. , Bromberg P. A.
Published: December 2017

Measurements of ozone uptake efficiency in the human respiratory tract provide critical information toward understanding ozone dose-response characteristics. We measured ozone uptake efficiency by different regions of the respiratory tract between the mouth and bronchus intermedius in 10 healthy, resting, nonsmoking male and female subjects. The distal end of a bronchoscope was sequentially positioned at the bronchus intermedius (BI), main carina (CAR), upper trachea, and above the vocal cords. Ozone concentration was measured continuously at each sight using a rapid-responding ozone analyzer. During sampling subjects breathed through a mouthpiece connected to a pneumotachograph at a paced rate of 12 breaths/min. Integration of the product of the flow and ozone concentrations during inspiration and expiration provided the ozone mass passing each anatomic location during each phase of respiration. On inspiration the uptake efficiencies of ozone by structures between the mouth and each location j (Em-j) were 0.176 +/- 0.037 (SE), 0.271 +/- 0.024, 0.355 +/- 0.030, and 0.325 +/- 0.031 for above the vocal cords, upper trachea, CAR, and BI, respectively. A significant effect of location on Em-j was found by analysis of variance (P < 0.0002). Pairwise comparisons showed that Em-j increased as the lung penetration increased except between CAR and BI, which was not significantly different.
Partitioning of airway and lung tissue properties: comparison of in situ and open-chest conditions
Authors: Suki B. , Petak F. , Adamicza A. , Hantos Z. , Lutchen K. R.
Published: December 2017

The purpose of this study was to investigate under physiological breathing conditions whether airway and lung tissue properties are different in situ and in open-chest conditions. We measured lung input impedance in dogs from 0.2 to 8 Hz with an optimal ventilator waveform at four tidal volumes (VT; from 75 to 450 ml) in intact animals using an esophageal balloon as well as after opening the chest. The lung impedance from both conditions was partitioned into airway and tissue compartments as characterized by airway resistance and inertance (Iaw) and tissue damping (G) and elastance (H) parameters respectively. All parameters except Iaw depended to some extent on VT. The in situ tissue G and H slightly decreased with VT while in the open-chest condition; G decreased and H increased slightly with VT. We found small but significant differences between the mechanical properties of the airway and lung tissues in situ and in open-chest conditions. Over the total population, the G, airway resistance, and Iaw parameters were 13% (not significant), 35% (P < 0.001), and 31% (P < 0.001) smaller, respectively, in situ than in the open-chest condition. However, the H was 15% larger in situ (P < 0.001). Although we cannot completely rule out certain artifacts, these differences most likely reflect real alterations in the lung due to the different configurations and possible differences in the distribution of pleural pressures in the two conditions. The G being smaller and E being larger in situ resulted in hysteresivity (G/H) 36% smaller in situ (P < 0.001).
Hypoxia, hypercapnia, and hypertension: their effects on pulsatile cerebral blood flow
Authors: Curran-Everett D. , Zhang Y. , Jones R. H. , Jones M. D.
Published: December 2017

Pulsatile cerebral blood flow reflects characteristics of arterial blood pressure as well as the structure and mechanical properties of the cerebrovascular network. Although the effects of changes in systemic blood gases and blood pressure on mean cerebral flow are established, their effects on pulsatile cerebral blood flow are unknown. These studies assessed the effects of hypoxia-hypercapnia (combined; both arterial PO2 and PCO2 approximately 55 Torr) and acute hypertension (+30–35 mmHg by aortic occlusion) on pulsatile cerebral blood flow in ketamine-anesthetized rabbits. We characterized the relationship between pulsatile systemic blood pressure (Millar catheter) and cerebral cortical capillary blood-flow (laser-Doppler) by calculating the transfer function, a frequency-domain expression that relates amplitudes and phase angles of flow output to those of the pressure input. During hypoxia-hypercapnia, mean flow increased 17% (P < 0.001), but the amplitude and contour of pulsatile cortical blood flow were unchanged (P > 0.10). Although aortic occlusion, during hypoxia-hypercapnia as well as during normoxia-normocapnia, increased systemic pulse pressure by 40%, the amplitude of cortical flow pulsations was unaffected. Changes in dynamic properties of the cerebral vasculature (P < 0.0001 by analysis of the transfer function) minimized alterations in pulsatile cortical blood flow and thus intrabeat vessel wall stress during acute hypertension; on the basis of analysis of an electrical analogue, we propose that these changes reflect alterations in both resistance and compliance.
Regional adaptations of rabbit diaphragm muscle fibers to unilateral denervation
Authors: Zhan W. Z. , Farkas G. A. , Schroeder M. A. , Gosselin L. E. , Sieck G. C.
Published: December 2017

We hypothesized that adaptations of the rabbit diaphragm (Dia) after unilateral denervation (DNV) result from removal of a neural influence rather than from passive stress. Length changes of midcostal and sternal Dia regions were measured before and after DNV by using sonomicrometry. Midcostal fibers passively lengthened after DNV, whereas sternal fibers shortened. In both regions, these length changes were associated with minimal stress, as estimated from passive force-length relationships. Morphological and contractile adaptions of midcostal and sternal Dia regions were examined after 1 and 4 wk of DNV. In both Dia regions, type I fibers progressively hypertrophied, whereas type IIb fibers atrophied. After DNV, changes in isometric contraction were similar in both Dia regions. Twitch contraction and half-relaxation times increased, force-frequency relationships shifted leftward, and maximum tetanic force decreased. We conclude that passive length changes and mechanical stress are not the main determinants of the morphological and contractile adaptations of the Dia after unilateral DNV but that these adaptations result from DNV itself.
Temporal heterogeneity of regional pulmonary perfusion is spatially clustered
Authors: Glenny R. W. , Polissar N. L. , McKinney S. , Robertson H. T.
Published: December 2017

This study investigates temporal changes in regional pulmonary perfusion. Five dogs were studied with five or six different radiolabeled microspheres being injected via a central vein over 30 s every 20 min. The lungs of each animal were cubed into 1.9 cm3 pieces with spatial coordinates noted for each piece. Within individual pieces, the coefficient of variation of regional perfusion over time was 17.2 +/- 6.8% (SD) and across dogs accounted for 7.26 +/- 5.7% of total perfusion heterogeneity. Temporal variability or “twinkling” was not random. When lung pieces with similar temporal flow patterns were grouped together (regardless of spatial location), groups were more tightly clustered in space than expected by chance. Statistical clustering methods revealed regulation of blood flow on a large scale (lobar arteries), and fractal analyses suggested regulation existed on a smaller scale (arterioles). We conclude that regional pulmonary perfusion is heterogeneous over time in a nonrandom pattern and that pieces clustered by temporal patterns of perfusion are neighbors in the spatial domain.
Hypoxic respiratory responses attenuated by ablation of the cerebellum or fastigial nuclei
Authors: Xu F. , Owen J. , Frazier D. T.
Published: December 2017

The general contribution of the cerebellum to hypoxic respiratory responses and the special role of the fastigial nucleus (FN) in the hypoxic respiratory reflex mediated via peripheral chemoreceptors were investigated in anesthetized and spontaneously breathing cats. Seven cats were exposed to isocapnic progressive hypoxia before and after cerebellectomy by decreasing the fractional concentration of end-tidal O2 (FETO2) from 15 +/- 0.3% to 7% while maintaining the pressure of end-tidal CO2 at a constant level of approximately 30 mmHg. Five additional cats inhaled five breaths of pure N2 (transient hypoxia) and received sodium cyanide (50 micrograms iv) before and after thermal lesions of the bilateral FN. The results showed that cerebellectomy or FN lesions failed to alter the respiratory variables (minute ventilation, tidal volume, respiratory frequency, and the peak of integrated diaphragm activity) during eupneic breathing. However, cerebellectomy significantly attenuated minute ventilation (FETO2 < or = 13%) and the peak of integrated diaphragm activity (FETO2 < or = 10%) compared with control. During progressive hypoxia, changes in respiratory frequency were noted earlier (FETO2 < or = 13%) than changes in tidal volume (FETO2 < or = 10%). Similarly, bilateral lesions of the FN resulted in a profound reduction in these respiratory responses to transient hypoxia and sodium cyanide. We conclude that the cerebellum can facilitate the respiratory response to hypoxia and that the FN is an important region in the modulation of the hypoxic respiratory responses, presumably via its effects on inputs from peripheral chemoreceptors.
Effects of posture on respiratory mechanics in obesity
Authors: Yap J. C. , Watson R. A. , Gilbey S. , Pride N. B.
Published: December 2017

Increased abdominal mass in obesity should enhance normal gravitational effects on supine respiratory mechanics. We have examined respiratory impedance (forced oscillation over 4–26 Hz applied at the mouth during tidal breathing), maximum inspiratory and expiratory mouth pressures (MIP and MEP), and maximum effort flow-volume curves seated and supine in seven obese subjects (O) (mean age 51 yr, body mass index 43.6 kg/m2) and seven control subjects (C) (mean age 50 yr, body mass index 21.8 kg/m2). Seated mean total lung capacity was smaller in O than in C (82 vs. 100% of predicted); ratio of functional residual capacity (FRC) to total lung capacity averaged 43% in O and 61% in C (P < 0.01). Total respiratory resistance (Rrs) at 6 Hz seated was higher in O (4.6 cmH2O.l-1.s) than in C (2.2 cmH2O.l-1.s; P < 0.001); total respiratory reactance (Xrs) at 6 Hz was lower in O than in C. In C, on changing to the supine posture, mean Rrs at 6 Hz rose to 2.9 cmH2O.l-1.s, FRC fell by 0.68 liter, and Xrs at 6 Hz showed a small fall. In O, despite no further fall in FRC, supine Rrs at 6 Hz increased to 7.3 cmH2O.l-1.s, and marked frequency dependency of Rrs and falls in Xrs developed. Seated, MIP and MEP in C and O were similar; supine there were small falls in MEP and maximum expiratory flow in O. The site and mechanism of the increase in supine Rrs and reduction in supine Xrs and the mechanism maintaining supine FRC in obesity all need further investigation.
Modulation by dexamethasone of phospholipase A2 activities in endotoxemic guinea pigs
Authors: De Castro C. M. , Bureau M. F. , Nahori M. A. , Dumarey C. H. , Vargaftig B. B. , Bachelet M.
Published: December 2017

One hour after lipopolysaccharide (LPS) administration (intravenous) in guinea pigs, alveolar macrophages are primed for an ex vivo increased secretion of arachidonic acid metabolites from the cyclooxygenase and the lipoxygenase pathways, with challenge by a second stimulus. At the same time, maximal levels of tumor necrosis factor-alpha (TNF-alpha) are observed in the circulation and in the bronchoalveolar lavage fluid. An extracellular form of phospholipase A2, corresponding probably to the low-molecular-mass type II enzyme, known to accumulate in inflammatory exudates, appears later in the serum of guinea pigs, to reach maximal levels 6 h after the LPS. Unlike the intracellular enzyme, extracellular phospholipase A2 is not increased by LPS in alveolar macrophages or in bronchoalveolar lavage fluids. After 24 h, at the time when neither TNF-alpha nor extracellular phospholipase A2 is present and priming of macrophages is over, maximal neutrophil infiltration is observed in the alveolar space of LPS-treated guinea pigs. Dexamethasone administered repeatedly during 3 days (subcutaneous) before the LPS challenge prevented both early events such as the macrophage priming and the TNF-alpha appearance and later events such as extracellular phospholipase A2 release and neutrophil recruitment.