bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of work load on cutaneous vascular response to exercise
Authors: Smolander J. , Saalo J. , Korhonen O.
Published: December 2017

The purpose of the present study was to examine whether intensity of exercise affects skin blood flow response to exercise. For this purpose, six healthy men cycled, in a random order on different days, for 15 min at 50, 60, 70, 80, and 90% of their maximum oxygen consumption (VO2max) at a room temperature of 25 degrees C. At the end of exercise, esophageal temperature (Tes) averaged 37.4 +/- 0.2, 37.7 +/- 0.2, 37.9 +/- 0.2, 38.6 +/- 0.3, and 38.9 +/- 0.4 degrees C (SE) at the 50, 60, 70, 80, and 90% work loads, respectively. At the two highest work loads, no steady state was observed in Tes. Skin blood flow was estimated by measuring forearm blood flow (FBF) with strain-gauge plethysmography and by laser-Doppler flowmetry on the upper back. Both techniques showed that skin blood flow response to rising Tes was markedly reduced at the 90% work load compared with other work loads. At the end of exercise, FBF averaged 7.5 +/- 1.7, 10.7 +/- 3.1, 9.6 +/- 2.1, 11.3 +/- 2.6, and 5.4 +/- 1.3 (SE) ml.min-1.100 ml-1 (P less than 0.01) at the 50, 60, 70, 80, and 90% VO2max work loads, respectively. The corresponding values for Tes threshold for cutaneous vasodilation (FBF) were 37.42 +/- 0.16, 37.48 +/- 0.13, 37.59 +/- 0.13, 37.79 +/- 0.19, and 38.20 +/- 0.22 degrees C (P less than 0.05) at 50, 60, 70, 80, and 90% VO2max, respectively. In two subjects, no cutaneous vasodilation was observed at the 90% work load.(ABSTRACT TRUNCATED AT 250 WORDS)
Epithelium modulates the potency of vasoactive intestinal peptide in the guinea pig
Authors: Takubo T. , Banks K. , Martin J. G.
Published: December 2017

The purpose of the study was to evaluate the importance of the epithelium in determining the potency of exogenous vasoactive intestinal peptide (VIP) in inhibiting responses of isolated guinea pig trachea to vagal stimulation. Isolated innervated tracheal preparations (n = 56) were mounted in glass organ baths in Krebs-Henseleit (K-H) solution at 37 degrees C and gassed with 95% O2–5% CO2. The inside of the trachea was separately perfused with K-H solution at 1 ml/min. The vagal nerve trunks were stimulated (20 V, 1-ms pulses, 10-s trains) at low (0.5 Hz) and high frequency (15 Hz) alternately, and the contractile responses were measured as increases in intratracheal pressures. VIP (10(-8)-10(-7) M) inhibited responses to both high- and low-frequency stimulation. VIP was more potent in inhibiting contractions when administered to the outside than the inside surface of the trachea, and disruptionon of the epithelium abolished this difference. The endopeptidase inhibitors phosphoramidon and thiorphan (5 x 10(-6) M) potentiated the action of VIP. These data indicate that the epithelium reduces the efficacy of VIP. We suggest that the epithelium is a site of degradation of VIP by endopeptidase and may also be a diffusion barrier.
Longitudinal distribution of pulmonary vascular pressures as a function of postnatal age in rabbits
Authors: Fike C. D. , Kaplowitz M. R.
Published: December 2017

The major purpose of this study was to determine whether the longitudinal distribution of pulmonary vascular pressures changes with postnatal age in rabbits. Using the direct micropuncture technique, we measured pressures in 20- to 80-microns-diam arterioles and venules in isolated lungs of rabbits of different postnatal ages. To determine the contribution of vasomotor tone, we added the vasodilator papaverine to the perfusate of some lungs of each age group. We compared vascular pressures measured at blood flow rates chosen to approximate in vivo cardiac outputs. In untreated lungs, the resistance across 20- to 80-microns-diam microvessels decreased from 12- to 72-h-old (0.022 +/- 0.009 cmH2O.min.kg.ml-1) to 5- to 15-day-old rabbits (0.008 +/- 0.007 cmH2O.min.kg.ml-1) and remained at this lower level in adults (0.013 +/- 0.008 cmH2O.min.kg.ml-1). In contrast, in papaverine-treated lungs, the resistance across 20- to 80-microns-diam microvessels did not change between 12- to 72-h-old (0.007 +/- 0.005 cmH2O.min.kg.ml-1) and 5- to 15-day-old rabbits (0.005 +/- 0.002 cmH2O.min.kg.ml-1) but increased between 5- to 15-day-old and adult rabbits (0.014 +/- 0.007 cmH2O.min.kg.ml-1). Thus vasomotor tone contributed to the postnatal change in the distribution of vascular pressures across lungs of rabbits.
Intra- and extracellular pH of the brain in vivo studied by 31P-NMR during hyper- and hypocapnia
Authors: Portman M. A. , Lassen N. A. , Cooper T. G. , Sills A. M. , Potchen E. J.
Published: December 2017

Studies were performed to determine the pH relationships among the extracellular, intracellular, and arterial blood compartments in the brain in vivo. Resolution of the extracellular monophosphate resonance peak from the intracellular peak in 31P nuclear magnetic resonance (NMR) spectra of sheep brain with the calvarium intact enabled pH measurement in these respective compartments. Sheep were then subjected to both hyper- and hypoventilation, which resulted in a wide range of arterial PCO2 and pH values. Linear regression analysis of pH in these compartments yielded slopes of 0.56 +/- 0.05 for extracellular pH (pHe) vs. arterial pH, 0.43 +/- 0.078 for intracellular pH (pHi) vs. pHe, and 0.23 +/- 0.056 for pHi vs. arterial pH. These data indicate that CO2 buffering capacity is different and decreases from the intracellular to extracellular to arterial blood compartments. Separation of the extracellular space from the vascular space may be a function of the blood-brain barrier, which contributes to the buffering capability of the extracellular compartment. A marked decrease in the pH gradient between the extracellular and intracellular space occurs during hypercarbia and may influence mechanisms of central respiratory control.
Polycythemia and vascular remodeling in chronic hypoxic pulmonary hypertension in guinea pigs
Authors: Janssens S. P. , Thompson B. T. , Spence C. R. , Hales C. A.
Published: December 2017

Chronic hypoxia increases pulmonary arterial pressure (PAP) as a result of vasoconstriction, polycythemia, and vascular remodeling with medial thickening. To determine whether preventing the polycythemia with repeated bleeding would diminish the pulmonary hypertension and remodeling, we compared hemodynamic and histological profiles in hypoxic bled (HB, n = 6) and hypoxic polycythemic guinea pigs (H, n = 6). After 10 days in hypoxia (10% O2), PAP was increased from 10 +/- 1 (SE) mmHg in room air controls (RA, n = 5) to 20 +/- 1 mmHg in H (P less than 0.05) but was lower in HB (15 +/- 1 mmHg, P less than 0.05 vs. H). Cardiac output and pulmonary artery vasoreactivity did not differ among groups. Total pulmonary vascular resistance increased from 0.072 +/- 0.011 mmHg.ml-1.min in RA to 0.131 mmHg.ml-1.min in H but was significantly lower in HB (0.109 +/- 0.006 mmHg.ml-1.min). Hematocrit increased with hypoxia (57 +/- 3% in H vs. 42 +/- 1% in RA, P less than 0.05), and bleeding prevented the increase (46 +/- 4% in HB, P less than 0.05 vs. H only). The proportion of thick-walled peripheral pulmonary vessels (53.2 +/- 2.9% in HB and 50.6 +/- 4.8% in H vs. 31.6 +/- 2.6% in RA, P less than 0.05) and the percent medial thickness of pulmonary arteries adjacent to alveolar ducts (7.2 +/- 0.6% in HB and 7.0 +/- 0.4% in H vs. 5.2 +/- 0.4% in RA, P less than 0.05) increased to a similar degree in both hypoxic groups. A similar tendency was present in larger bronchiolar vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of fatigue on maximal power output at different contraction velocities in humans
Authors: Beelen A. , Sargeant A. J.
Published: December 2017

The effect of fatigue as a result of a standard submaximal dynamic exercise on maximal short-term power output generated at different contraction velocities was studied in humans. Six subjects performed 25-s maximal efforts on an isokinetic cycle ergometer at five different pedaling rates (60, 75, 90, 105, and 120 rpm). Measurements of maximal power output were made under control conditions [after 6 min of cycling at 30% maximal O2 uptake (VO2max)] and after fatiguing exercise that consisted of 6 min of cycling at 90% VO2max with a pedaling rate of 90 rpm. Compared with control values, maximal peak power measured after fatiguing exercise was significantly reduced by 23 +/- 19, 28 +/- 11, and 25 +/- 11% at pedaling rates of 90, 105, and 120 rpm, respectively. Reductions in maximum peak power of 11 +/- 8 and 14 +/- 8% at 60 and 75 rpm, respectively, were not significant. The rate of decline in peak power during the 25-s control measurement was least at 60 rpm (5.1 +/- 2.3 W/s) and greatest at 120 rpm (26.3 +/- 13.9 W/s). After fatiguing exercise, the rate of decline in peak power at pedaling rates of 105 and 120 rpm decreased significantly from 21.5 +/- 9.0 and 26.3 +/- 13.9 W/s to 10.0 +/- 7.3 and 13.3 +/- 6.9 W/s, respectively. These experiments indicate that fatigue induced by submaximal dynamic exercise results in a velocity-dependent effect on muscle power. It is suggested that the reduced maximal power at the higher velocities was due to a selective effect of fatigue on the faster fatigue-sensitive fibers of the active muscle mass.
Effects of fitness, fatness, and age on men's responses to whole body cooling in air
Authors: Budd G. M. , Brotherhood J. R. , Hendrie A. L. , Jeffery S. E.
Published: December 2017

Simple and multiple regression analyses were used to assess the influence of 12 white men's fitness (aerobic capacity 44–58 ml O2.min-1.kg fat-free mass-1), fatness (mean skin-fold thickness 5–20 mm, body fat content 15–36%), and age (26–52 yr) on their thermal, metabolic, cardiovascular, and subjective responses to 2 h of whole body cooling, nude, in air at 10 degrees C. Fitter men had slower heart rates, and fatter men had higher blood pressures. Fitness had no effect (P greater than 0.39) on any measured response to cold. Fatness was associated (P less than 0.01) with reduced heat loss, heat production, and mean skin temperature; unchanged heat debt; and increased tissue insulation. Age had the opposite effects. When the confounding effects of fatness were held constant by multiple regression, older men responded to cold as though they were 1 mm of skinfold thickness leaner for each 3–4 yr of age. We conclude that aging, even between the relatively youthful ages of 26 and 52 yr, is accompanied by a progressive weakening of the vasoconstrictor response to cold.
Spectral content of forced expiratory wheezes during air, He, and SF6 breathing in normal humans
Authors: Shabtai-Musih Y. , Grotberg J. B. , Gavriely N.
Published: December 2017

The effect of gas density on the spectral content of forced expiratory wheezes was studied in the search for additional information on the mechanism of generation of respiratory wheezes. Five normal adults performed forced vital capacity maneuvers through four or five orifice resistors (0.4–1.92 cm ID) after breathing air, 80% He-20% O2, or 80% SF6–20% O2. Tracheal lung sounds, flow, volume, and airway opening (Pao) and esophageal (Pes) pressures were measured during duplicate runs for each orifice and gas. Wheezes were detected in running spectra of lung sounds by use of a frequency domain peak detection algorithm. The wheeze spectrograms were presented along side expiratory flow rate and transpulmonary pressure (Ptp = Pao - Pes) as function of volume. The frequencies and patterns of wheeze spectrograms were evaluated for gas density effects. We found that air, He, and SF6 had similar wheeze spectrograms. Both wheeze frequency and patterns (as function of volume) did not exhibit consistent changes with gas density. Speech tone, however, was substantially affected in the usual pattern. These observations support the hypothesis that airway wall vibratory motion, rather than gas phase oscillations, is the source of acoustic energy of wheezes.
Anesthesia alters pulmonary vasoregulation by angiotensin II and captopril
Authors: Nyhan D. P. , Chen B. B. , Fehr D. M. , Rock P. , Murray P. A.
Published: December 2017

We investigated the effects of an intravenous (pentobarbital sodium) and inhalational (halothane) general anesthetic on the pulmonary vascular responses to angiotensin II and angiotensin-converting enzyme inhibition (CEI). Multipoint pulmonary vascular pressure-flow (P/Q) plots were generated in conscious pentobarbital- (30 mg/kg iv) and halothane-anesthetized (approximately 1.2% end-tidal) dogs in the intact (no drug) condition, during angiotensin II administration (60 ng.kg-1.min-1 iv), and during CEI (captopril 1 mg/kg plus 1 mg.kg-1.h-1 iv). In conscious dogs, angiotensin II increased (P less than 0.001) the pulmonary vascular pressure gradient [pulmonary arterial pressure--pulmonary arterial wedge pressure (PAP-PAWP)] over the empirically measured range of Q; i.e., angiotensin II caused pulmonary vasoconstriction. Pulmonary vasoconstriction (P less than 0.01) in response to angiotensin II was also observed during pentobarbital sodium anesthesia. In contrast, angiotensin II had no effect on the P/Q relationship during halothane anesthesia. In conscious dogs, CEI decreased (P less than 0.001) PAP-PAWP over the empirically measured range of Q; i.e., CEI caused pulmonary vasodilation. However, CEI caused pulmonary vasoconstriction (P less than 0.02) during pentobarbital sodium and had no effect on the P/Q relationship during halothane. Thus, compared with the conscious state, the pulmonary vasoconstrictor response to angiotensin II is unchanged or abolished, and the pulmonary vasodilator response to CEI is reversed to vasoconstriction or abolished during pentobarbital sodium and halothane anesthesia, respectively.
Increased pulmonary vascular filtration pressure does not alter lung liquid secretion in fetal sheep
Authors: Carlton D. P. , Cummings J. J. , Poulain F. R. , Bland R. D.
Published: December 2017

The purpose of this study was to determine whether an increase in pulmonary vascular filtration pressure affects net production of liquid within the lumen of the fetal lung. We studied 14 chronically catheterized fetal lambs [130 +/- 3 (SD) days gestation] before, during, and after a 4-h rapid (500 ml/h) intravenous infusion of isotonic saline. In seven fetuses we measured pulmonary arterial and left atrial pressures, lung lymph flow, and protein osmotic pressures in plasma and lymph. In eight lambs with a chronically implanted tracheal loop cannula, we measured the change in luminal lung liquid volume over time by progressive dilution of tracheally instilled 125I-albumin, which stays within the lung lumen. Saline infusion increased pulmonary vascular pressures by 2–3 mmHg and decreased the plasma-lymph difference in protein osmotic pressure by 1 mmHg. Lung lymph flow increased from 1.9 +/- 0.6 to 3.9 +/- 1.2 (SD) ml/h; net production of luminal lung liquid did not change (12 +/- 5 to 12 +/- 6 ml/h). Thus an increase in net fluid filtration pressure in the pulmonary circulation, which was sufficient to double lung lymph flow, had no significant effect on luminal lung liquid secretion in fetal sheep.
Physiological effects of tapering in highly trained athletes
Authors: Shepley B. , MacDougall J. D. , Cipriano N. , Sutton J. R. , Tarnopolsky M. A. , Coates G.
Published: December 2017

This study examined some of the physiological and performance effects of three different tapers in highly trained athletes. After 8 wk of training, nine male middle-distance runners were randomly assigned to one of three different 7-day tapers: a high-intensity low-volume taper (HIT), a low-intensity moderate-volume taper (LIT), or a rest-only taper (ROT). After the first taper, subjects resumed training for 4 wk and performed a second taper and then resumed training for 4 wk and completed the remaining taper, so that each subject underwent all three tapers. Performance was measured before and after each taper by a treadmill run to fatigue at a velocity equivalent each subject's best 1,500-m time. Voluntary isometric strength and evoked contractile properties of the quadriceps were measured before and after each taper, as were muscle glycogen concentration and citrate synthase activity (from needle biopsies) and total blood and red cell volume by 125I and 51Cr tagging. Maximal O2 consumption was unaffected by all three tapers, but running time to fatigue increased significantly after HIT (+22%). It was unaffected by LIT (+6%) and ROT (-3%) procedure. Citrate synthase activity increased significantly with HIT and decreased significantly with ROT. Muscle glycogen concentration increased significantly after ROT and HIT, and strength increased after all three tapers. Total blood volume increased significantly after HIT and decreased after ROT.(ABSTRACT TRUNCATED AT 250 WORDS)
Phase resetting of the respiratory cycle before and after unilateral pontine lesion in cat
Authors: Oku Y. , Dick T. E.
Published: December 2017

The pontine respiratory group (PRG) facilitates the mechanism for terminating the inspiratory phase but may influence other phases in the respiratory cycle as well. We determined the effects of PRG lesions on the response of the respiratory cycle to superior laryngeal nerve stimulation delivered in each phase of the cycle in decerebrate, vagotomized, paralyzed, and ventilated cats (n = 6). We measured the duration of inspiration (TI) and expiration (TE) for three breaths before and in the perturbed breath and TI for three breaths after the perturbation. The delay to next inspiration was plotted against the phase at which the stimulus was delivered. Before lesioning, premature inspiratory termination was followed by phase-dependent shortening of TE. After lesioning, premature inspiratory termination did not systematically change the following TE. Breath-by-breath variability (measured 50 breaths) increased and stimulus after-effects (prolonged TI in the subsequent cycle) were augmented following lesions. These data indicate that the PRG plays an important role in the control of TE after perturbation and in the stability of the respiratory central pattern generator.
Influence of flow on pulmonary vascular surface area inferred from blue dextran efflux data
Authors: Nelin L. D. , Roerig D. L. , Rickaby D. A. , Linehan J. H. , Dawson C. A.
Published: December 2017

Blue dextran (BD), which binds to proteins on the pulmonary endothelial surface and to plasma albumin, was used in isolated perfused dog lung lobe experiments to address the question: do changes in perfusate flow rate cause changes in perfused vascular surface area? When BD was added to a protein-free perfusate under zone 3 conditions at a high flow rate (15.8 +/- 0.7 ml/s), it was adsorbed by the endothelial surface. Then by changing the perfusate entering the lobe to an albumin-containing perfusate, the BD was eluted from the perfused surface by competitive binding to the perfusate albumin. The amount of BD eluted was measured in three experiments. In experiment 1, elution of the BD by the perfusate albumin was initiated after a balloon had been inflated within the lobar arterial tree to occlude a portion of the lobar vascular bed containing BD. Then the balloon was deflated, permitting albumin perfusate to perfuse the previously occluded part of the lobe. In experiment 2, BD elution began at a flow rate of 3 +/- 0.1 ml/s under zone 3 conditions and continued after the high-flow zone 3 conditions were reestablished. In experiment 3, the BD elution began at a flow rate of 4.2 +/- 0.7 ml/s under zone 2 conditions and continued after the high-flow zone 3 conditions were reestablished. Balloon inflation reduced the amount of BD recovered by 43%, demonstrating that a decrease in perfused vascular surface area could decrease BD recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
Nocturnal variations in human lower leg subcutaneous blood flow related to sleep stages
Authors: Sindrup J. H. , Kastrup J. , Madsen P. L. , Christensen H. , Jorgensen B. , Wildschiodtz G.
Published: December 2017

Nocturnal subcutaneous adipose tissue blood flow rate was measured in the lower legs of 10 normal human subjects together with systemic arterial blood pressure, heart rate, and registration of sleep stages under ambulatory conditions. The 133Xe washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used for measurement of blood flow rates. The sleep recordings were performed with a portable computerized sleep analysis system. In accordance with the results of previous studies, a hyperemic blood flow rate phase (mean increase 140%) for 100 min was observed approximately 60 min after the subjects went to bed. The moment of onset of the hyperemic phase was closely related to the moment of onset of the first episode of deep sleep (stages 3 and 4). There was a significant (P < 0.01) overrepresentation of deep sleep in the hyperemic phase compared with adjacent phases, and rapid-eye-movement sleep predominantly occurred in the latter part of the night, when the subcutaneous blood flow rate was stable. The results of the present study are in accordance with current theories of the interrelationship between the thermoregulatory and the arousal state control systems and, thus, might suggest that the nightly subcutaneous hyperemia represents a thermoregulatory effector mechanism.
Changes in human muscle protein synthesis after resistance exercise
Authors: Chesley A. , MacDougall J. D. , Tarnopolsky M. A. , Atkinson S. A. , Smith K.
Published: December 2017

The purpose of this study was to investigate the magnitude and time course for changes in muscle protein synthesis (MPS) after a single bout of resistance exercise. Two groups of six male subjects performed heavy resistance exercise with the elbow flexors of one arm while the opposite arm served as a control. MPS from exercised (ex) and control (con) biceps brachii was assessed 4 (group A) and 24 h (group B) postexercise by the increment in L-[1–13C]leucine incorporation into muscle biopsy samples. In addition, RNA capacity and RNA activity were determined to assess whether transcriptional and/or translational processes affected MPS. MPS was significantly elevated in biceps of the ex compared with the con arms of both groups (group A, ex 0.1007 +/- 0.0330 vs. con 0.067 +/- 0.0204%/h; group B ex 0.0944 +/- 0.0363 vs. con 0.0452 +/- 0.0126%/h). RNA capacity was unchanged in the ex biceps of both groups relative to the con biceps, whereas RNA activity was significantly elevated in the ex biceps of both groups (group A, ex 0.19 +/- 0.10 vs. con 0.12 +/- 0.05 micrograms protein.h-1.microgram-1 total RNA; group B, ex 0.18 +/- 0.06 vs. con 0.08 +/- 0.02 micrograms protein.h-1.microgram-1 total RNA). The results indicate that a single bout of heavy resistance exercise can increase biceps MPS for up to 24 h postexercise. In addition, these increases appear to be due to changes in posttranscriptional events.
Mechanical properties of human bronchial smooth muscle in vitro
Authors: Ishida K. , Pare P. D. , Hards J. , Schellenberg R. R.
Published: December 2017

The in vitro mechanical properties of smooth muscle strips from 10 human main stem bronchi obtained immediately after pneumonectomy were evaluated. Maximal active isometric and isotonic responses were obtained at varying lengths by use of electrical field stimulation (EFS). At the length (Lmax) producing maximal force (Pmax), resting tension was very high (60.0 +/- 8.8% Pmax). Maximal fractional muscle shortening was 25.0 +/- 9.0% at a length of 75% Lmax, whereas less shortening occurred at Lmax (12.2 +/- 2.7%). The addition of increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening but increased tension generation of muscle strips stimulated by EFS. Morphometric analysis revealed that muscle accounted for 8.7 +/- 1.5% of the total cross-sectional tissue area. Evaluation of two human tracheal smooth muscle preparations revealed mechanics similar to the bronchial preparations. Passive tension at Lmax was 10-fold greater and maximal active shortening was threefold less than that previously demonstrated for porcine trachealis by us of the same apparatus. We attribute the limited shortening of human bronchial and tracheal smooth muscle to the larger load presumably provided by a connective tissue parallel elastic component within the evaluated tissues, which must be overcome for shortening to occur. We suggest that a decrease in airway wall elastance could increase smooth muscle shortening, leading to excessive responses to contractile agonists, as seen in airway hyperresponsiveness.
Immune responses and increased training of the elite athlete
Authors: Verde T. J. , Thomas S. G. , Moore R. W. , Shek P. , Shephard R. J.
Published: December 2017

Ten elite male runners (age, 29.8 +/- 1.7 yr; maximum oxygen consumption, 65.3 +/- 4.9 ml.kg-1.min-1; 10-km times, 31 min 43 s +/- 1 min 46 s) deliberately increased training schedules by an average of 38% for 3 wk. Resting heart rate and maximal oxygen intake were unchanged, but the heart rate response to acute exercise was decreased. Following heavy training, blood samples taken at rest showed trends to a decreased helper/suppressor cell ratio, an increased phytohemagglutinin (PHA)- and concanavalin (ConA)-stimulated lymphocyte proliferation, and a decreased production of immunoglobulins IgG and IgM. Whereas PHA-stimulated lymphocyte proliferation was initially unchanged by acute exercise, after 3 wk of heavy training the same acute exercise caused an 18% suppression of proliferation. Acute exercise following heavy training did not alter pokeweed-stimulated IgG or IgM synthesis. There was no correlation between changes in lymphocyte subpopulations, helper/suppressor ratios, and mitogen-induced cellular proliferation. The immune system of endurance-trained athletes at rest seemed to tolerate the stress of heavy training, but superimposition of a bout of acute exercise on the chronic stress of heavy training resulted in immunosuppression, which was transient and most likely not of clinical significance.
Regulating ATP turnover rates over broad dynamic work ranges in skeletal muscles
Authors: Hochachka P. W. , Matheson G. O.
Published: December 2017

It has long been appreciated that rates of ATP utilization and production need to be extremely closely balanced. To put it in molecular rather than molar terms, in human muscle engaged in a 15-min work protocol, approximately 3.3 x 10(20) ATP/g are used and resynthesized at approximately 100 times the resting cycling rates before fatigue, during which time only a 20–25% decrease in the ATP pool is sustained. Analysis of how such remarkable regulatory precision is achieved suggests that in resting muscle myosin behaves as a latent catalyst whose full catalytic potential 1) is realized with the arrival of an activator signal (Ca2+) and 2) is tempered with reaction products; such proactive control, initiated at ATP utilization, sets the required flux through ATP-producing pathways. For any given enzyme step in ATP-producing pathways, reaction velocity (v) becomes the independent parameter, with substrate concentration ([S], the dependent parameter) being adjusted accordingly. Because the dynamic range for muscles (change from resting to maximum ATP turnover rates) can exceed 100-fold, in many studies of working muscle the percent change in ATP turnover rate exceeds (sometimes by very large margins) the percent change in [S]. These observations are not easily explained by current metabolic regulation models but are consistent with pathway enzymes behaving as latent catalysts in resting muscle. In this view, the unmasking of such latent catalytic potential is the main explanation for how large changes in v can be achieved with modest (sometimes immeasurable) changes in [S].(ABSTRACT TRUNCATED AT 250 WORDS)
T wave changes in humans and dogs during experimental dives
Authors: Joulia F. , Barthelemy P. , Guerrero F. , Jammes Y.
Published: December 2017

Electrocardiogram (ECG) analysis was performed in three human divers studied at 21 and 23.5 ATA while they breathed various gas mixtures containing H2 and/or He (COMEX HYDRA IX experiment) and in five dogs exposed to 91 ATA of He-O2 or He-N2-O2. In all cases, the O2 partial pressure was slightly higher than its physiological value. These human and animal studies reveal that elevated pressure of different inert gases did not change the resting heart rate or its respiratory fluctuation. However, the T wave amplitude increased in proportion to the gas density in the three divers; this was also found in four of the five dogs studied. Changes in peak T wave configurations were also observed in the dog experiments. Positional changes in QRS or T vectors cannot explain these T wave changes.
Effect of PEEP on the mechanics of the respiratory system in ARDS patients
Authors: Eissa N. T. , Ranieri V. M. , Corbeil C. , Chasse M. , Braidy J. , Milic-Emili J.
Published: December 2017

In patients with adult respiratory distress syndrome (ARDS) we studied the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics. We used the technique of rapid airway occlusion during constant flow (V) inflation to partition the total respiratory system resistance (Rrs) into the interrupter resistance (Rint,rs) and the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities. We also measured static (Est,rs) and dynamic (Edyn,rs) elastance of the respiratory system. The procedure was carried out in nine ARDS patients at different inspiratory V and inflation volumes (delta V) at PEEP of 0, 5, 10, and 15 cmH2O. We found that during baseline ventilation (delta V = 0.7 liter and V = 1 l/s), Est,rs, Edyn,rs, and Rint,rs did not change significantly with PEEP, whereas delta Rrs and Rrs increased significantly only with PEEP of 15 cmH2O. The increase of delta Rrs and Rrs with PEEP was positively correlated with the concomitant changes in end-expiratory lung volume (P < 0.001). At all levels of PEEP, under iso-delta V conditions, delta Rrs decreased with increasing V, whereas at a fixed V, delta Rrs increased with increasing delta V. A four-parameter model of the respiratory system failed to fully describe respiratory dynamics in the ARDS patients, probably due to nonlinearities.
Stroke volume and cardiac output decrease at termination of obstructive apneas
Authors: Garpestad E. , Katayama H. , Parker J. A. , Ringler J. , Lilly J. , Yasuda T. , Moore R. H. , Strauss H. W. , Weiss J. W.
Published: December 2017

Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations of systemic arterial pressure that occur in association with changes in respiration and changes in sleep state. To investigate cardiac function during the cycle of obstruction (apnea) and resumption of ventilation (recovery), we continuously measured left ventricular stroke volume (LVSV) and mean arterial blood pressure (MAP) during non-rapid-eye-movement sleep in six males with severe OSA (apnea/hypopnea index > or = 30 events/h associated with oxygen saturation < 82%). LVSV was assessed continuously using an ambulatory ventricular function monitor (VEST; Capintec). The apnea-recovery cycle was divided into three phases: 1) early apnea (EA), 2) late apnea (LA), and 3) recovery (Rec). In all subjects recovery was associated with an abrupt decrease in LVSV [54.0 +/- 14.5 (SD) ml] compared with either EA (91.4 +/- 14.7 ml; P < 0.001) or LA (77.1 +/- 15.2 ml; P < 0.005). Although heart rate increased with recovery, the increase was not sufficient to compensate for the decrease in LVSV so that cardiac output (CO) fell (EA: 6,247 +/- 739 ml/min; LA: 5,741 +/- 1,094 ml/min; Rec: 4,601 +/- 1,249 ml/min; EA vs. Rec, P < 0.01; LA vs. Rec, P < 0.025). Recovery was also associated with a significant increase in MAP. We speculate that such abrupt decreases in LVSV and CO at apnea termination, occurring coincident with the nadir of oxygen saturation, may further compromise tissue oxygen delivery.
Postnatal expression of myosin isoforms in an expiratory muscle--external abdominal oblique
Authors: Watchko J. F. , Daood M. J. , Vazquez R. L. , Brozanski B. S. , LaFramboise W. A. , Guthrie R. D. , Sieck G. C.
Published: December 2017

We studied the postnatal expression of heavy-chain (MHC) and native myosin isoforms in an expiratory abdominal muscle of the rat, the external abdominal oblique (EO). Moreover, we contrasted EO myosin expression with that of the costal diaphragm (DIA) to draw inspiratory vs. expiratory muscle comparisons during development. Examination of MHC gels demonstrated a mature phenotype of slow and adult fast myosin isoforms at an earlier age in the EO (day 60) than in the DIA [day > 115 (adult)]. The mature MHC phenotype of the EO was characterized by a preponderance of MHC 2B, whereas the DIA was characterized by approximately equal portions of MHC slow, MHC 2A, and MHC 2X. During early postnatal development, there was a delay in the expression of MHC 2A in the EO compared with the DIA. However, MHC 2B, expressed later in development in both muscles, was noted in the EO before the DIA. We conclude that 1) the EO mature myosin phenotype is characterized by a preponderance of fast myosin isoforms and 2) the EO and DIA muscles are subject to different temporal patterns of isoform expression during postnatal development.
Analysis of respiratory neuronal activity in fetal sheep
Authors: Ioffe S. , Jansen A. H. , Chernick V.
Published: December 2017

We developed a new method to monitor fetal medullary respiratory neurons utilizing a two-stage approach. At 129–133 days of gestation, sheep were anesthetized, and a window was placed over the area of the fourth ventricle. After a recovery period of 3–5 days, the fetus was exteriorized into a saline bath under maternal spinal anesthesia, and the head was connected rigidly to a stereotaxic frame. Microelectrodes were inserted into the area of the nucleus tractus solitarius during rapid-eye-movement sleep, and extracellular recordings of 223 respiratory neurons were analyzed: 76% were inspiratory, 9% expiratory, and 15% phase spanning, as classified by visual and computer correlation to diaphragmatic activity. More detailed analysis of 100 neurons was done to assess the respiratory component (eta 2) by use of a modification of the method developed by Orem and Dick (J. Neurophysiol, 50: 1098–1107, 1983). With use of cohorts of 25 breaths, fetal respiratory neurons were found to frequently change their phase relationship to diaphragmatic activity. The eta 2 statistic of fetal respiratory neurons was not a stable characteristic but changed over time. This could be a reflection of an immature central respiratory system before birth or the lack of major sensory inputs.
TNF-alpha augments pulmonary vasoconstriction via the inhibition of nitrovasodilator activity
Authors: Johnson A. , Ferro T. J.
Published: December 2017

We tested the hypothesis that tumor necrosis factor-alpha (TNF-alpha) increases pulmonary vasoconstriction by decreases in nitric oxide- (NO) dependent vasodilation. Lungs were isolated from guinea pigs 18 h after intraperitoneal injection of either TNF-alpha (1.60 x 10(5) U/kg) or control. U-46619 (365 mM/min) caused increases in pulmonary arterial and capillary pressures, pulmonary arterial and venous resistances, and lung weight. TNF-alpha augmented the U-46619-induced increases in pulmonary arterial and capillary pressures, pulmonary arterial and venous resistances, and lung weight. Methylene blue (1 microM), which inhibits the activation of soluble guanylate cyclase by NO, had an effect similar to TNF-alpha on the pulmonary response to U-46619 alone but was not additive to the effect of TNF-alpha. NG-monomethyl-L-arginine (270 microM), an inhibitor of NO generation, also enhanced the response to U-46619. Lung effluent levels of nitrite, the oxidation product of NO, were reduced after treatment with either TNF-alpha or NG-monomethyl-L-arginine compared with U-46619 alone. In addition, lungs isolated after TNF-alpha treatment showed decreased vasodilation in response to acetylcholine (10(-8)-10(-5) M) compared with control; however, vasodilation in response to L-arginine (10 mM) and nitroprusside (10(-6.3) and 10(-6) M), agents that promote NO release, was not decreased in TNF-alpha-treated lungs. The data indicate that TNF-alpha induces an increase in vascular constriction in response to U-46619 and a decrease in vasodilation in response to acetylcholine. The mechanism for the TNF-alpha-induced alteration in pulmonary vascular reactivity may be decreased generation of NO.
OKY-046 prevents increases in LTB4 and pulmonary edema in phorbol ester-induced lung injury in dogs
Authors: Sprague R. S. , Stephenson A. H. , Lonigro A. J.
Published: December 2017

Thromboxanes (Txs) were implicated as possible participants in the altered microvascular permeability of acute lung injury when the Tx synthase inhibitor, OKY-046, was reported to prevent pulmonary edema induced by phorbol myristate acetate (PMA). Recently, however, we found that OKY-046, at a dose just sufficient to block Tx synthesis in intact dogs, did not prevent PMA-induced pulmonary edema but rather merely reduced it modestly. The present study was designed to explore other mechanisms whereby OKY-046 might prevent PMA-induced pulmonary edema. The finding that 5-lipoxygenase (5-LO) metabolites of arachidonic acid were increased within the lung after PMA administration, coupled with the report that OKY-046 inhibited slow-reacting substance of anaphylaxis formation, permitted formulation of the hypothesis that OKY-046, at a dose in excess of that required to inhibit Tx synthesis, inhibits the formation of a product(s) of 5-LO and, thereby, prevents edema formation. In vehicle-pretreated pentobarbital-anesthetized male mongrel dogs (n = 4), PMA (20 micrograms/kg i.v.) increased pulmonary vascular resistance (PVR) from 4.4 +/- 0.3 to 26.3 +/- 8.8 mmHg.l-1 x min (P < 0.01) and extravascular lung water from 6.7 +/- 0.5 to 19.1 +/- 6.2 ml/kg body wt (P < 0.05). Concomitantly, both TxB2 and leukotriene B4 (LTB4) were significantly increased in the lung. Pretreatment with OKY-046 (100 mg/kg i.v., n = 8) prevented PMA-induced increases in TxB2, LTB4, and pulmonary edema formation but did not prevent the increase in PVR.(ABSTRACT TRUNCATED AT 250 WORDS)
Histamine decreases left ventricular contractility in normal human subjects
Authors: Cooper D. J. , Thompson C. R. , Walley K. R. , Gillis R. P. , Wolinski-Walley P. E. , Schellenberg R. R.
Published: December 2017

To determine whether histamine alters human left ventricular contractility we measured heart rate, calibrated carotid arterial pressure, and left ventricular dimensions (echocardiogram) in nine healthy volunteers. We assessed baseline contractility using the end-systolic pressure-dimension relationship and the end-systolic meridional wall stress-rate-corrected velocity of circumferential fiber shortening relationship determined over a wide range of afterloads using phenylephrine and nitroprusside infusions. We then infused histamine for 3–5 min at a dose predetermined to decrease mean arterial pressure by 20%, both before and after H1 receptor antagonist pretreatment (diphenhydramine 50 mg i.v.). Histamine decreased end-systolic pressure but, unlike an equally hypotensive infusion of nitroprusside, did not decrease end-systolic dimension or increase fractional shortening. Histamine also decreased velocity of circumferential fiber shortening at the same end-systolic meridional wall stress as controls (P < 0.05). These effects of histamine were inhibited by H1 antagonist pretreatment. We conclude that the dominant effect of histamine on the human heart is to decrease left ventricular contractility and that this decrease in contractility is dependent, at least partially, on H1-receptor activation.
Effects of ventilation inhomogeneity on DLcoSB-3EQ in normal subjects
Authors: Cotton D. J. , Prabhu M. B. , Mink J. T. , Graham B. L.
Published: December 2017

In patients with airflow obstruction, we found that ventilation inhomogeneity during vital capacity single-breath maneuvers was associated with decreases in the three-equation single-breath CO diffusing capacity of the lung (DLcoSB-3EQ) when breath-hold time (tBH) decreased. We postulated that this was due to a significant resistance to diffusive gas mixing within the gas phase of the lung. In this study, we hypothesized that this phenomenon might also occur in normal subjects if the breathing cycle were altered from traditional vital capacity maneuvers to those that increase ventilation inhomogeneity. In 10 normal subjects, we examined the tBH dependence of both DLcoSB-3EQ and the distribution of ventilation, measured by the mixing efficiency and the normalized phase III slope for helium. Preinspiratory lung volume (V0) was increased by keeping the maximum end-inspiratory lung volume (Vmax) constant or by increasing V0 and Vmax. When V0 increased while Vmax was kept constant, we found that the tBH-independent and the tBH-dependent components of ventilation inhomogeneity increased, but DLcoSB-3EQ was independent of V0 and tBH. Increasing V0 and Vmax did not change ventilation inhomogeneity at a tBH of 0 s, but the tBH-dependent component decreased. DLcoSB-3EQ, although independent of tBH, increased slightly with increases in Vmax. We conclude that in normal subjects increases in ventilation inhomogeneity with increases in V0 do not result in DLcoSB-3EQ becoming tBH dependent.
Topography of cat medullary ventral surface hypoxic acidification
Authors: Xu F. , Sato M. , Spellman M. J. , Mitchell R. A. , Severinghaus J. W.
Published: December 2017

The topographic relationship between previously identified medullary ventral surface respiratory chemosensitive regions and brain surface extracellular fluid (ECF) acid production during acute hypoxia was explored in anesthetized, paralyzed, and artificially ventilated cats. Glass pH electrodes (0.8-mm diam, sheathed in stainless steel tubing) were mounted in mechanical contact with surfaces of medullary surface or adjacent pyramids, pons, spinal cord, or parietal cortex. Isocapnic hypoxia of 5 min [at arterial O2 saturation (SaO2) = 48 +/- 10%] reduced pH over rostral (Mitchell) and caudal (Loeschcke) areas by 0.12 +/- 0.09 and 0.07 +/- 0.04, respectively (n = 10, P < 0.05). Change in pH (delta pH) was proportional to desaturation with slopes 100 delta pH/delta SaO2 of 0.45 (rostral) and 0.20 (caudal) (R = 0.91 and 0.88, respectively). pH drop usually began within 3 min of hypoxia, became stable between 5 and 15 min, began to rise within 2 min of reoxygenation, and returned to control within 10 min. During equally hypoxic tests, intermediate area (Schlafke), pons, and spinal cord surfaces showed no significant acid shift. Parietal cortex ECF pH dropped more slowly but steadily by 0.079 +/- 0.034 during 20 min at SaO2 = 50% after a small but significant initial alkaline shift, and acidification of cortical surface continued for > 5 min after reoxygenation. We conclude that medullary ventral chemosensitive regions produce more lactic acid during hypoxia than neighboring brain surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrolyte and fluid transport across the mature alveolar epithelium
Authors: Saumon G. , Basset G.
Published: December 2017

The lungs must be kept "dry" for efficient gas exchange. The mechanisms that contribute to clear alveoli from fetal lung fluid at birth are still present during adult life and allow recovery from alveolar flooding. It has recently been shown with the use of different approaches in vitro, as well as in vivo, that alveolar epithelium performs solute-coupled fluid transport. Fluid absorption from alveoli occurs chiefly as a result of active transepithelial Na+ transport. The mechanisms of Na+ transport have been partly elucidated; Na+ enters alveolar cells through apical Na+ channels and Na(+)-coupled solute transporters and is pumped out at the basolateral membrane by a Na(+)-K(+)-adenosinetriphosphatase (ATPase). Transepithelial Na+ transport and fluid absorption are stimulated by beta-adrenergic agonists, with adenosine 3',5'-cyclic monophosphate being the likely intracellular second messenger. K+ is probably secreted into alveoli because its concentration in the epithelial lining fluid is larger than expected for passive distribution. K+ channels have been described that, in conjunction with Na(+)-K(+)-ATP-ase, might provide pathways for active transport. Active proton secretion or bicarbonate absorption have been reported, which may explain the low pH of the alveolar epithelial lining fluid. It is probable that active solute transports are the main determinants of epithelial lining fluid depth and composition. A challenge for the future is to understand how this homeostasis is achieved.
Cytochrome oxidase in muscle of endurance-trained rats: subunit mRNA contents and heme synthesis
Authors: Town G. P. , Essig D. A.
Published: December 2017

Endurance training leads to an increase in the content of individual mitochondrial hemeproteins in skeletal muscle. To deduce the control mechanisms involved, cytochrome oxidase (COX) activity was compared with 1) the content of COX subunits III and IV and 2) 5-aminolevulinate synthase (ALAS) activity and mRNA content. In the plantaris muscle of female rats run daily for up to 28 days, ALAS activity was elevated 100% (P < 0.01) after 3 days and remained 150 and 125% higher (P < 0.001) after 7 and 28 days of running, respectively, than control. COX activity was also increased, but not until day 7 (40%; P < 0.05), and reached a maximal value 80% higher than control (P < 0.001) in the 28-day group. Compared with control, the content of COX subunit III and IV and ALAS mRNAs was not significantly changed by the training. The increased activities of COX and ALAS appear to be regulated by translational or posttranslational steps in the protein expression pathway. The induction of ALAS before COX suggests that the increased activity of COX may require increased synthesis of heme.
Changes in respiratory mechanics with age
Authors: Lanteri C. J. , Sly P. D.
Published: December 2017

A cross-sectional survey involving 51 children, ranging in age from 3 wk to 15 yr, was performed to examine the changes in respiratory mechanics with age in mechanically ventilated children, using both a single-compartment model of the respiratory system and a more sophisticated two-compartment model. Children were studied while under anesthesia for urological surgery and were considered to have normal lungs. They were paralyzed and mechanically ventilated throughout measurements. Respiratory mechanics were measured during ventilation by applying a single-compartment model and by using multilinear regression to calculate dynamic compliance and respiratory system resistance (Rrs). We then used the interrupter technique, which allowed us to partition Rrs into airway resistance and a tissue viscoelastic component known as Pdif. A static volume-pressure curve was constructed from multiple occlusions made at different lung volumes throughout expiration, and static compliance was determined. Rrs and airway resistance decreased as height increased. There was a progressive increase in respiratory system compliance with height. Pdif fell in the first 2 yr of life and then subsequently increased after the age of approximately 5 yr.