bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat debt during cold air exposure before and after cold water immersions
Authors: Tikuisis P. , McCracken D. H. , Radomski M. W.
Published: December 2017

Acclimation to cold can manifest itself in several different ways, insulative and metabolic being the most common. Bittel (J. Appl. Physiol. 62: 1627–1634, 1987) has demonstrated that heat debt, which encompasses both heat production and heat loss, can be used as a unitary index of acclimation. However, conflicting results are obtained if heat debt is calculated using a mean-weighted body temperature (Tb) vs. the change of body heat content through the integration of heat storage (S). The present study examines the determination of heat debt by three methods of calculation, the first based on Tb and the other two based on S where heat losses are measured in one and predicted in the other. Data were obtained from five healthy young males exposed to 10 degrees C air for 2 h on four different occasions. The first two exposures provided control data, while the last two were performed after 5 and 10 days, respectively, of daily immersions in 15 degrees C water to induce acclimation. The variability in response between the control exposures was as large as that among the other exposures. Although the method of calculation using Tb indicated that subjects were close to a thermal balance after 2 h of cold air exposure, this contrasted sharply with the result of the other two methods that indicated heat debt was still increasing steadily. The latter two methods are considered more accurate for transient heat debt calculation. Although cases of individual acclimation were found, these were different among the subjects, resulting in pooled responses that indicated no group acclimation by means of any of the three methods of calculation.(ABSTRACT TRUNCATED AT 250 WORDS)
Autonomic control of heart rate during exercise studied by heart rate variability spectral analysis
Authors: Yamamoto Y. , Hughson R. L. , Peterson J. C.
Published: December 2017

Spectral analysis of heart rate variability (HRV) might provide an index of relative sympathetic (SNS) and parasympathetic nervous system (PNS) activity during exercise. Eight subjects completed six 17-min submaximal exercise tests and one resting measurement in the upright sitting position. During submaximal tests, work rate (WR) was increased for the initial 3 min in a ramp fashion until it reached constant WRs of 20 W, or 30, 60, 90, 100, and 110% of the predetermined ventilatory threshold (Tvent). Ventilatory profile and alveolar gas exchange were monitored breath by breath, and beat-to-beat HRV was measured as R-R intervals of an electrocardiogram. Spectral analysis was applied to the HRV from 7 to 17 min. Low-frequency (0–0.15 Hz) and high-frequency (0.15–1.0 Hz) areas under power spectra (LO and HI, respectively) were calculated. The indicator of PNS activity (HI) decreased dramatically (P less than 0.05) when the subjects exercised compared with rest and continued to decrease until the intensity reached 60% Tvent. The indicator of SNS activity (LO/HI) remained unchanged up to 100% Tvent, whereas it increased abruptly (P less than 0.05) at 110% Tvent. The results suggested that (cardiac) PNS activity decreased progressively from rest to a WR equivalent to 60% Tvent, and SNS activity increased only when exercise intensity exceeded Tvent.
Optimizing athletic performance by influence curves
Authors: Fitz-Clarke J. R. , Morton R. H. , Banister E. W.
Published: December 2017

Recent application of modeling techniques to physical training has opened the possibility for prediction from training. Solution of the inverse problem, determining a training program to produce a desired performance at a specific time, is also possible and may yield strategies for achieving better training and tapering (complete or relative rest for a period before competition) regimens for competitive athletes. A mathematical technique derived from model theory is described in this paper that allows the design of an optimal strategy of physical preparation for an individual to do well in a single future competitive event or cluster of events. Simulation results, using default parameters of a training model, suggest that presently accepted forms of taper for competition may remain too rigorous and short in duration to achieve the best result possible from the training undertaken.
Multiple effects of BAY K 8644 and nifedipine on isolated diaphragmatic fibers in vitro
Authors: Viires N. , Pavlovic D. , Aubier M.
Published: December 2017

The dose-response effects of BAY K 8644 and nifedipine on diaphragmatic contractility were assessed in vitro. Isolated diaphragmatic fibers were obtained from rats and placed in an open-topped channel of a Plexiglas tissue chamber perfused with continuously flowing Krebs solution heated to 37 degrees C. Isometric twitch force, generated in response to 1-Hz supramaximal electrical stimulation (4 times/min), was measured with a highly sensitive photoelectric force transducer. Low doses of BAY K 8644 or nifedipine (10(-7) M) were without effect on twitch tension. For 10(-6) M, twitch tension increased by 10 +/- 1% (P less than 0.005) for both drugs. For 10(-5) M, twitch tension increased by 12 +/- 1% (P less than 0.05), and maximal contractures were observed (BAY K 8644 and nifedipine). Simultaneous drug administration did not reveal mutual antagonism as expected; instead the effects were additive, with twitch tension increasing by 30 +/- 2% (P less than 0.001) for 10(-5) M BAY K 8644 + nifedipine. Both BAY K 8644 and nifedipine altered twitch characteristics. In low-calcium media (0.5 mM) twitch potentiation produced by the two drugs was further enhanced (increasing 60% for 10(-5) M BAY K 8644 or nifedipine). Contractures, by contrast, were abolished. From these results it is difficult to reconcile a unique action of these drugs on calcium channels as is conventionally accepted.
Absence of exercise-induced MRI enhancement of skeletal muscle in McArdle's disease
Authors: Fleckenstein J. L. , Haller R. G. , Lewis S. F. , Archer B. T. , Barker B. R. , Payne J. , Parkey R. W. , Peshock R. M.
Published: December 2017

To assess the role of glycogenolysis in mediating exercise-induced increases in muscle water as monitored by changes in muscle proton relaxation times on magnetic resonance imaging (MRI) and cross-sectional area (CSA), five patients with myophosphorylase deficiency (MPD) were compared with seven controls. Absolute and relative work loads were matched during ischemic handgrip and graded cycling, respectively. Relaxation times of active muscle did not increase after handgrip in MPD (T1: 1 +/- 14%, P greater than 0.1; T2: 4 +/- 4%, P greater than 0.1) but did in controls (T1: 59 +/- 30%, P less than 0.005; T2: 26 +/- 9%, P less than 0.005). The volume of exercised muscles, estimated by CSA, increased in both groups after handgrip (controls: 13.8 +/- 3.5%, n = 7, P less than 0.0001; MPD: 7.5 +/- 1.5%, n = 4, P less than 0.005), but the change was greater in controls (P less than 0.02). Ischemic handgrip in controls resulted in a large increase in finger flexor signal intensity (SI) on short tau-inversion recovery images (25 +/- 7%, n = 3; P less than 0.005 compared with preexercise) and a further increase with subsequent reflow (43 +/- 11%, n = 3; P less than 0.001 compared with rest); in MPD, SI did not increase. The ratio of active to inactive muscle SI did not increase from rest to maximal cycle exercise in MPD (0 +/- 20%, n = 2, P greater than 0.1) but did in normals (73 +/- 36%, n = 3; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Steady and oscillatory transnasal pressure-flow relationships in healthy adults
Authors: Sullivan K. J. , Chang H. K.
Published: December 2017

The influence of flow characteristics and gas physical properties on nasal resistance (NR) is difficult to ascertain with traditional rhinomanometric methods because the respiratory airflows used in these methods are largely uncontrolled. As an alternative, we used a novel method of rhinomanometry in which an externally generated flow is passed through the nasal passage via a mouthpiece. The transnasal pressure-flow relationships for both quasi-steady and oscillating flows and with different gases were obtained in five healthy adults with this method. For quasi-steady nasal flows the dimensionless pressure losses were largely independent of physical properties of the gas and a function of the Reynolds number (Re) of the flow. Values of NR for quasi-steady flows were largely independent of flow direction for Re up to roughly 3,000 in all five subjects and for Re up to roughly 19,000 in two of the five subjects. Airway collapse occurred in two subjects at Re greater than 3,000, suggesting that the nonrigid segments of the nasal passage contribute to the intersubject variations in NR at high flow rates. Pressure losses associated with oscillating flows measured at frequencies between 1 and 16 Hz were similar to steady flow losses provided that Re was less than roughly 3,000. For Re greater than 3,000 the oscillating flow resistances were affected by the phasic redistribution of flow into compliant segments of the nasal passage. These results indicate that, for flow rates and harmonic frequencies associated with breathing at rest, the nasal passage behaves as a rigid rough-walled pipe in which pressure losses are largely determined by forces relating to viscous friction and convective accelerations.
Site of action of hypertonic saline in the canine lung
Authors: Sly P. D. , Lanteri C. J.
Published: December 2017

The site of action of inhaled hypertonic saline was determined in 8- to 10-wk-old puppies by combining measurements of respiratory mechanics, made during mechanical ventilation and after midexpiratory flow interruptions, with direct measurements of alveolar pressure. Under both control conditions and after inhalation of 10% saline, we were able to partition lung mechanics into components representing the airways and tissue viscoelastic properties. Hypertonic saline challenge altered lung mechanics by increasing airway resistance and did not have any effect on elastic or viscoelastic properties of the lung.
Effects of hypoxia and cold acclimation on thermoregulation in the rat
Authors: Gautier H. , Bonora M. , M'Barek S. B. , Sinclair J. D.
Published: December 2017

The effects of hypoxia (inspired O2 fraction = 0.12) on thermoregulation and on the different sources of thermogenesis were studied in rats before and after periods of 1–4 wk of cold acclimation. Measurements of metabolic rate (VO2) and body temperature (Tb) were made at 5-min intervals, and shivering activity was recorded continuously in groups of rats subjected to three protocols. In protocol 1, rats were exposed to normoxia to an ambient temperature (Ta) of 5 degrees C for 2 h. In protocol 2, at Ta of 5 degrees C, rats were exposed for 30 min to normoxia, then for 45 min to hypoxia, and finally for 30 min to normoxia. In protocol 3, in the non-cold-acclimated (NCA) rats, Ta was decreased from 30 to 5 degrees C in steps of 5 degrees C and of 30-min duration while in cold-acclimated (CA) rats at 5 degrees C for 4-wk, Ta was increased from 5 to 30 degrees C in steps of 5 degrees C and of 30-min duration. Recordings were made in normoxia and in hypoxia on different days in the same animals. The results showed that 1) in NCA rats, cold exposure in normoxia induced increases in VO2 and shivering that were proportional to the decrease in Ta; 2) in CA rats in normoxia, for a given Ta, VO2 and Tb were higher than in NCA rats, whereas shivering was generally lower; and 3) in both NCA and CA rats, hypoxia induced a transient decrease in shivering and a sustained decrease in nonshivering thermogenesis associated with a marked decrease in Tb that was about the same in NCA and CA rats. We speculate that hypoxia acts on Tb control to produce a general inhibition of thermogenesis. Nonshivering thermogenesis is markedly sensitive to hypoxia, especially demonstrable in CA rats; a recovery or even an increase in shivering can compensate for the decrease in nonshivering thermogenesis.
Effect of hypovolemia on forearm vascular resistance control during exercise in the heat
Authors: Nishiyasu T. S. , Shi X. G. , Mack G. W. , Nadel E. R.
Published: December 2017

To determine the influence of hypovolemia on the control of forearm vascular resistance (FVR) during dynamic exercise, we studied five physically active men during 60 min of supine cycle ergometer exercise bouts at 35 degrees C in control (normovolemic) and hypovolemic conditions. Hypovolemia was achieved by 3 days of diuretic administration and resulted in an average decrease in plasma volume of 15.9%. Relative to normovolemia, hypovolemia caused an attenuation of the progressive rise in forearm blood flow (P less than 0.05) and an increase in heart rate (P less than 0.05) during exercise. Because mean arterial blood pressure during hypovolemic exercise was well maintained, the attenuation of forearm blood flow was due entirely to a relative increase in FVR. At the onset of dynamic exercise, FVR was increased significantly in control and hypovolemic conditions by 13.2 and 27.1 units, respectively. The increase in FVR was significantly different between control and hypovolemic conditions as well. We attributed the increased vasoconstrictor bias during hypovolemia to cardiopulmonary baroreceptor unloading and/or an increased sensitivity to cardiopulmonary baroreceptor unloading. We concluded that reduced blood flow to the periphery during exercise in the hypovolemic condition was caused entirely by an increase in vascular resistance, thereby preserving arterial blood pressure and adequate perfusion to the organs requiring increased flow.
Acoustic myography for investigating human skeletal muscle fatigue
Authors: Stokes M. J. , Dalton P. A.
Published: December 2017

Sounds produced during voluntary isometric contractions of the quadriceps muscle were studied by acoustic myography (AMG) in five healthy adults. With the subject seated, isometric force, surface electromyography (EMG), and AMG were recorded over rectus femoris, and the EMG and AMG signals were integrated (IEMG and IAMG). Contractions lasting 5 s each were performed at 10, 25, 50, 60, 75, and 100% of maximum voluntary contraction (MVC) force. Fatigue was then induced by repeated voluntary contractions (10 s on, 10 s off) at 75% MVC until only 40% MVC could be sustained. After 15 min of rest, the different force levels were again tested in relation to the fresh MVC. Both before and after fatiguing activity the relationships between force and IEMG [r = 0.99 +/- 0.01 (SD), n = 10] and force and IAMG (r = 0.98 +/- 0.02) were linear. After activity, however, the slopes of the regression lines for force and IEMG increased (P less than 0.01) but those for force and IAMG remained the same (P greater than 0.05). The present results clarify the relationship between AMG and isometric force in fatigued muscle without the problem of fatigue-induced tremor, which hampered previous studies of prolonged activity. This study contributes to the validation of AMG and shows that it is a potentially useful method for noninvasive assessment of force production and fatigue. Further studies to establish the origin of AMG activity are required before AMG can be accepted for use in neuromuscular physiology or rehabilitation.
Determinants of bronchoalveolar lavage cellularity in idiopathic pulmonary fibrosis
Authors: Schwartz D. A. , Helmers R. A. , Dayton C. S. , Merchant R. K. , Hunninghake G. W.
Published: December 2017

To investigate factors that determine bronchoalveolar lavage (BAL) cellularity in patients with idiopathic pulmonary fibrosis (IPF), we compared BAL cells in patients with IPF (n = 83) to both nonsmoking (n = 111) and smoking (n = 19) normal volunteers. Patients with IPF had higher concentrations of BAL total cells and alveolar macrophages than nonsmoking volunteers and more BAL neutrophils and eosinophils than normal volunteers regardless of smoking status. Among patients with IPF, the numbers of alveolar macrophages, neutrophils, or eosinophils were strongly associated with either smoking status or pack-years of cigarette smoking. In fact, after accounting for cigarette smoking, using multivariate analysis, the only additional factors that were found to be associated with BAL cellularity were age (macrophages and eosinophils) and the percent predicted forced expired volume in 1 s (neutrophils). Additional multivariate models failed to identify a significant relationship between BAL cellularity and either the type of immunosuppressive therapy or other physiological measures of lung function. We conclude that cigarette smoking strongly influences BAL cellularity in patients with IPF. These findings suggest that cigarette smoking may have a role in the pathogenesis of IPF or may adversely affect the prognosis in patients with IPF.
Effect of estradiol on tissue glycogen metabolism and lipid availability in exercised male rats
Authors: Kendrick Z. V. , Ellis G. S.
Published: December 2017

The effect of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil-1.100 g body wt-1) on exercise performance, tissue glycogen utilization, and lipid availability was determined in male rats. In experiment 1, estradiol or oil was administered 1 h or 1–6 days before a treadmill run to exhaustion. No differences in body weight between oil- and estradiol-administered animals were observed during the 6-day treatment. Animals receiving estradiol for 3–6 days ran significantly longer and completed more work than oil-administered animals. Significant degradation of red and white vastus muscle, myocardial, and liver glycogen was observed in all animals run to exhaustion. In experiment 2, animals were administered estradiol for 5 days and then run for 2 h. The submaximal run for 2 h significantly reduced tissue glycogen content in red and white vastus muscle, heart, and liver of oil-administered animals. The latter effect was attenuated in both vastus muscles, liver, and myocardial tissues in the estradiol-administered animals. Estradiol administration significantly increased plasma fatty acids and lowered plasma lactate during the submaximal run. These data indicate that when body weight remained constant between groups of male rats, estradiol administration for 3–6 days increased exercise performance. Furthermore, estradiol administration for 5 days resulted in greater lipid availability and less tissue glycogen utilization during submaximal running for 2 h.
Role of vagal afferents in the control of abdominal expiratory muscle activity in the dog
Authors: Hollstien S. B. , Carl M. L. , Schelegle E. S. , Green J. F.
Published: December 2017

We examined the contribution of afferent vagal A- and C-fibers on abdominal expiratory muscle activity (EMA). In seven spontaneously breathing supine dogs anesthetized with alpha-chloralose we recorded the electromyogram of the external oblique muscle at various vagal temperatures before and after the induction of a pneumothorax. When myelinated fibers were blocked selectively by cooling the vagus nerves to 7 degrees C, EMA decreased to 40% of control (EMA at 39 degrees C). With further cooling to 0 degrees C, removing afferent vagal C-fiber activity, EMA returned to 72% of control. On rewarming the vagus nerves to 39 degrees C, we then induced a pneumothorax (27 ml/kg) that eliminated the EMA in all the dogs studied. Cooling the vagus nerves to 7 degrees C, during the pneumothorax, produced a slight though not significant increase in EMA. However, further cooling of the vagus nerves to 0 degrees C caused the EMA to return vigorously to 116% of control. In three dogs, intravenous infusion of a constant incrementally increasing dose of capsaicin, a C-fiber stimulant, decreased EMA in proportion to the dose delivered. These results suggest that EMA is modulated by a balance between excitatory vagal A-fiber activity, most likely from slowly adapting pulmonary stretch receptors, and inhibitory C-fiber activity, most likely from lung C-fibers.
Airways impedance during single breaths of foreign gases
Authors: Oostveen E. , Peslin R. , Duvivier C. , Rotger M. , Mead J.
Published: December 2017

The changes in airways resistance (Raw) and inertance (Iaw) during single inspirations of pure methane, helium, neon, and ethane at a flow of 0.1 l/s were measured in six healthy subjects by use of a forced-oscillation technique. Raw and Iaw were computed from respiratory transfer impedance obtained at a frequency of 20 Hz by applying pressure oscillations at the chest and measuring flow at the mouth with a bag-in-box system. Compared with the air data, the changes of Iaw after inhalation of 500 ml of gas averaged -41.1% with methane, -82.8% with helium, -25.8% with neon, and +4.8% with ethane. These changes were slightly less than the changes in gas density (-45%, -86%, -31%, and +5%, respectively). The inhaled volumes at which 50% of the changes had occurred (V50) did not differ significantly among gases and were approximately 100 ml. For Raw the data were more noisy than for Iaw; they were discarded in two subjects because of a strong and irreproducible volume dependence in air. Consistent differences were seen between the remaining subjects, one of whom exhibited a predominant viscosity dependence of Raw, one a predominant density dependence, and two an intermediate pattern. V50s were larger for Raw than for Iaw, indicating a more peripheral distribution of Raw. For Raw, V50s were lower with helium than with methane, in agreement with the notion that density-dependent resistance is located mainly in the large airways. The results suggest that some information on the serial distribution of Raw and Iaw may be derived from impedance measurements with foreign gases.
Fetal swallowing: response to graded maternal hypoxemia
Authors: Sherman D. J. , Ross M. G. , Day L. , Humme J. , Ervin M. G.
Published: December 2017

A computer-based system, incorporating electromyography (EMG) and esophageal fluid flow measurement, was used to determine fetal breathing and swallowing responses to graded maternal hypoxemia. Five chronically prepared ewes with singleton fetuses at a gestational age of 130 +/- 2 (SE) days were subjected to successive 30-min periods of mild and moderate hypoxemia (inspired O2 fraction = 0.16 and 0.13, respectively). Mild and moderate maternal hypoxemia evoked significant reductions in fetal arterial PO2 (21 +/- 1 to 17 +/- 1 and 13 +/- 1 Torr, respectively), while fetal arterial pH, hematocrit, plasma osmolality, heart rate, and mean blood pressure did not change. Moderate hypoxemia was associated with significant increases in fetal plasma arginine vasopressin and renin activity and significant reductions from basal values in percent time breathing (53 +/- 4 to 25 +/- 12%), percent time swallowing (11.5 +/- 3.1 to 1.3 +/- 0.7%), and volume swallowed (21.3 +/- 2.1 to 4.8 +/- 2.7 ml/30 min). Fetal swallowing activity was better correlated with arterial PO2 (r = 0.8) than breathing activity (r = 0.45). We conclude that fetal swallowing is suppressed during mild and moderate hypoxemia. It is suggested that several sites and/or mechanisms may account for the hypoxemic inhibition of fetal activities.
Hypoxic remodeling of the rat pulmonary arterial microcirculation assessed by microdissection
Authors: Davies P. , Reid L.
Published: December 2017

Artery segments were microdissected from distal acini of the rat lung and studied by light and electron microscopy. Morphometric methods were used to quantify the structure of the wall at defined levels within the normal axial pathway and to determine the changes after 5 and 7 days of whole-animal exposure to hypobaric hypoxia at an inspiratory O2 fraction of 0.1. In the normal lung, at the level of the terminal bronchiolus, the artery wall comprised up to six layers of smooth muscle cells (SMCs). At the respiratory bronchiolar level, however, the wall contained fewer than two layers of SMCs with a consistently circumferential orientation. By the second-generation alveolar ducts (AD2), the medial layer was lost, replaced by subendothelial precursor smooth muscle cells (PCs) resembling intermediate cells. At this and the next level (AD3), the PC layer was often circumferentially discontinuous. Regression analysis of the morphometric data suggested, however, that the smallest AD3 artery is likely to have a layer of PCs but with virtually no measurable separation between them and the endothelium. The mean maximum radial diameter of SMCs decreased along the axial pathway with a significant difference between diameters at terminal bronchiolus and AD2 levels; yet the diameter of endothelial cells remained the same. After 7 days of hypoxia, no change was noted in the number of smooth muscle layers, but at the AD2 level the relative area of media in the total wall increased. This was due in part to hypertrophy of PCs, as evidenced by an increase in their mean maximum radial diameter.(ABSTRACT TRUNCATED AT 250 WORDS)
TNF but not IL-1 in dogs causes lethal lung injury and multiple organ dysfunction similar to human sepsis
Authors: Eichacker P. Q. , Hoffman W. D. , Farese A. , Banks S. M. , Kuo G. C. , MacVittie T. J. , Natanson C.
Published: December 2017

We compared the early and late pulmonary effects of human recombinant tumor necrosis factor (TNF) and interleukin 1 (IL-1) challenges in awake dogs with chronic tracheostomies. Serial blood gas analysis, bronchoalveolar lavage (BAL) with cell and protein analysis, intravascular catheter hemodynamics, and radionuclide left ventricular ejection fractions (LVEF) were determined before and after infusion of TNF (60 micrograms/kg body wt, n = 8), IL-1 (1,000 micrograms/kg body wt, n = 6), or heat-inactivated IL-1 (n = 6, controls). Controls given heat-inactivated IL-1 had no changes (P = NS) in any pulmonary parameter throughout the study. Animals given IL-1 had a transient increase (P less than 0.05) in BAL neutrophil concentration 1 day after infusion but no other changes (P = NS) in pulmonary function throughout the study. Animals given TNF had early (0–4 h) decreases (P less than 0.05) in arterial PO2, increases (P less than 0.05) in physiological shunt fraction and alveolar-to-arterial PO2 gradient, and a high mortality rate (50%). In TNF animals, volume challenges at 4 h were associated (P less than 0.05) with death and noncardiogenic pulmonary edema. In TNF survivors, hypoxemia persisted for 2–3 days and was associated with increases (P less than 0.05) in alveolar protein and neutrophil concentration on days 1 and 3, respectively, which in survivors returned to near normal over 6–21 days. Animals challenged with TNF and not IL-1 had reversible depression of LVEF similar in time course to abnormalities in arterial PO2. In this study, TNF (but not IL-1) challenges were lethal and produced acute pulmonary dysfunction sustained over days (reversible in survivors) that was similar to that seen in human septic shock. The ability of TNF to induce pulmonary injury similar to bacterial shock suggests that TNF is a key mediator of sepsis-induced lung injury. Furthermore, because TNF challenge induced both sustained pulmonary and cardiac injury, TNF may be a common pathway for the multiple organ dysfunction that occurs during septic shock.
Physiological consequences of intermittent exercise during compensable and uncompensable heat stress
Authors: Kraning K. K. , Gonzalez R. R.
Published: December 2017

Time-weighted averaging is a traditional method used in heat stress analyses to approximate, in terms of a single continuous level of heat production, the rate of heat production from complex intermittent exercise patterns. Physiological responses during intermittent and continuous exercise were studied in four subjects exposed to heat stress in which evaporation was either free or severely restricted. Intermittent work consisted of repeated 10-min exercise-rest patterns. Continuous work was at the time-weighted average of intermittent exercise: 3.3 mets. When heat stress was uncompensable, intermittent work induced more physiological strain than continuous work: endurance time was 14 min less (P less than 0.05); core temperature at 60 min was 0.40 degrees C higher (P less than 0.05); and, after 30 min of exposure, the rate of core temperature rise was 33% greater. The difference in the rate of heat storage was not satisfactorily explained by a discrepancy in the average rate of heat production or in the calculated rate of surface heat loss. Alternatively, the results may be partially explained by interruptions in the usual rate of heat transport via the cutaneous circulation. These interruptions may be caused by nonthermal factors associated with postural and work load transitions. Although the mechanisms are not totally understood, it is clear that application of the time-weighted averaging method can lead to erroneous overprediction of endurance time and should be applied with discretion.
Kinetic measurements of gas exchange in the intact pulmonary microcirculation
Authors: Klocke R. A.
Published: December 2017

The kinetics of gas exchange are monitored in an isolated perfused lung preparation contained within a plethysmograph. The lungs are perfused with buffer, and there is no gas exchange until a 2.0-ml bolus of reactant is injected into the perfusion system. Subsequent gas exchange produces a pressure transient that is related to the corresponding volume of exchanged gas. The observed rate of volume change is the result of two separate processes: 1) the rate of gas exchange during transit through the capillary bed and 2) the distribution of vascular transit times between the point of injection and the capillary bed. The latter is assessed by a control injection containing a dissolved inert gas that is liberated in the alveoli as the bolus enters the capillary bed. Analysis of the experimental curves permits the separation of these two processes. A model of exchange kinetics indicates that this method has the capability of measuring kinetic events occurring during gas exchange in the microcirculation under physiological conditions.
Tissue-specific regulation of inflammation
Authors: Colten H. R.
Published: December 2017

Proteins of the complement system are important effectors and modulators of inflammation. The complement cascade is triggered by microbes, tissue debris, and specific antibodies. Serum complement proteins are derived primarily from liver, but extrahepatic complement synthesis is important in homeostasis and in local host defenses. Tissue-specific regulation of expression of complement genes is governed by mechanisms similar to those that regulate other “acute phase reactants.” That is, tissue injury or infection elicit changes in expression of these acute phase proteins, which, although variable in kinetics, magnitude, and direction, are a consequence of an elaborate system of cell-to-cell communication. This communication is mediated via a complex network of cytokines, including the interferons, interleukins, several growth factors, and sex hormones. The cell biological and molecular biological details of these mechanisms are now under active investigation. An understanding in molecular terms of the balance between proinflammatory and counterregulatory forces on complement gene expression should provide new insight into the functions of complement and the design of novel therapies for disorders of inflammation.
Effects of selective sleep deprivation on ventilation during recovery sleep in normal humans
Authors: Neilly J. B. , Kribbs N. B. , Maislin G. , Pack A. I.
Published: December 2017

To assess the effects of selective sleep loss on ventilation during recovery sleep, we deprived 10 healthy young adult humans of rapid-eye-movement (REM) sleep for 48 h and compared ventilation measured during the recovery night with that measured during the baseline night. At a later date we repeated the study using awakenings during non-rapid-eye-movement (NREM) sleep at the same frequency as in REM sleep deprivation. Neither intervention produced significant changes in average minute ventilation during presleep wakefulness, NREM sleep, or the first REM sleep period. By contrast, both interventions resulted in an increased frequency of breaths, in which ventilation was reduced below the range for tonic REM sleep, and in an increased number of longer episodes, in which ventilation was reduced during the first REM sleep period on the recovery night. The changes after REM sleep deprivation were largely due to an increase in the duration of the REM sleep period with an increase in the total phasic activity and, to a lesser extent, to changes in the relationship between ventilatory components and phasic eye movements. The changes in ventilation after partial NREM sleep deprivation were associated with more pronounced changes in the relationship between specific ventilatory components and eye movement density, whereas no change was observed in the composition of the first REM sleep period. These findings demonstrate that sleep deprivation leads to changes in ventilation during subsequent REM sleep.
5-aminolevulinic acid-induced alterations of oxidative metabolism in sedentary and exercise-trained rats
Authors: Pereira B. , Curi R. , Kokubun E. , Bechara E. J.
Published: December 2017

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.
Microvascular pressure profile in intact in situ lung
Authors: Negrini D. , Gonano C. , Miserocchi G.
Published: December 2017

We measured the microvascular pressure profile in lungs physiologically expanded in the pleural space at functional residual capacity. In 29 anesthetized rabbits a caudal intercostal space was cleared of its external and internal muscles. A small area of endothoracic fascia was surgically thinned, exposing the parietal pleura through which pulmonary vessels were clearly detectable under stereomicroscopic view. Pulmonary microvascular pressure was measured with glass micropipettes connected to a servo-null system. During the pressure measurements the animal was kept apneic and 50% humidified oxygen was delivered in the trachea. Pulmonary arterial and left atrial pressures were 22.3 +/- 1.5 and 1.6 +/- 1.5 (SD) cmH2O, respectively. The segmental pulmonary vascular pressure drop expressed as a percentage of the pulmonary arterial to left atrial pressure was approximately 33% from pulmonary artery to approximately 130-microns-diam arterioles, 4.5% from approximately 130- to approximately 60-microns-diam arterioles, approximately 46% from approximately 60-microns-diam arterioles to approximately 30-microns-diam venules, approximately 9.5% from 30- to 150-microns-diam venules, and approximately 7% for the remaining venous segment. Pulmonary capillary pressure was estimated at approximately 9 cmH2O.
Ventilation-perfusion relationships in isolated blood-free perfused rabbit lungs
Authors: Walmrath D. , Konig R. , Ernst C. , Bruckner H. , Grimminger F. , Seeger W.
Published: December 2017

The multiple inert gas elimination technique (MIGET) was applied to blood-free perfused isolated rabbit lungs. Commonly accepted criteria for reliability of the method were found to be fulfilled in this model. Ventilation-perfusion (VA/Q) distributions in isolated control lungs corresponded to those repeatedly detected under physiological conditions. In particular, a narrow unimodal dispersion of perfusate flow was observed: perfusion of low-VA/Q areas ranged below 1% and shunt flow approximately 2–3%; perfusion of high-VA/Q regions was not detected. Gas flow was characterized by narrow dispersion in the midrange-VA/Q areas. Application of a low level of PEEP (1 cmH2O) reduced shunt flow to less than 1%, and low-VA/Q areas were no longer noted. By using this PEEP-level, stable gas exchange conditions were maintained for greater than 5 h of extracorporeal perfusion. Graded embolization with small air bubbles caused a typical rightward shift (to higher VA/Q ratios) of mean ventilation, associated with the appearance of high-VA/Q regions and an increase in dead space ventilation. Mean perfusion was shifted leftward, and shunt flow was approximately doubled. Whole lung lavage with saline for washout of surfactant evoked a progressive manifold increase in shunt flow, accompanied by a moderate rise of perfusate flow to low-VA/Q areas. We conclude that the MIGET can be applied to isolated blood-free perfused rabbit lungs for assessment of gas exchange and that typical patterns of VA/Q mismatch are reproduced in this model.
Adenosine stimulates breathing in fetal sheep with brain stem section
Authors: Koos B. J. , Chao A. , Doany W.
Published: December 2017

Breathing responses to adenosine were determined in 12 chronically catheterized fetal sheep (greater than 0.8 term) in which hypoxic inhibition of breathing had been eliminated by brain stem section. The caudal extent of transection varied from the rostral midbrain to the pontomedullary junction. Isocapnic hypoxia [delta arterial PO2 (PaO2) of -12 Torr] doubled the incidence and depth of breathing activity and increased the incidence of eye movements. Intra-arterial infusion of adenosine (0.30 +/- 0.03 mg.min-1.kg fetal wt-1) increased the incidence and amplitude of breathing without affecting blood gases. Adenosine did not significantly alter the incidence of eye activity. Intra-arterial injection of oligomycin (120 +/- 26 micrograms/kg fetal wt), an inhibitor of mitochondrial oxidative phosphorylation, also stimulated breathing activity. In four fetuses with brain stem section, peripheral arterial chemodenervation blunted the stimulatory effects of hypoxia on breathing activity and abolished altogether the excitatory effects of adenosine. It is concluded that 1) hypoxia and adenosine likely inhibit breathing in normal fetuses by affecting similar areas of the brain stem and 2) in fetuses with brain section, hypoxic hyperpnea depends on peripheral and central mechanisms, whereas adenosine stimulates breathing via the peripheral arterial chemoreceptors.
Identification of a subsurface area in the ventral medulla sensitive to local changes in PCO2
Authors: Issa F. G. , Remmers J. E.
Published: December 2017

The exact location of the central respiratory chemoreceptors sensitive to changes in PCO2 has not yet been determined. To avoid the confounding effects of the cerebral circulation, we used the in vitro brain stem-spinal cord of neonatal rats (1–5 days old) to identify areas within 500 microns of the ventral surface of the medulla where changes in PCO2 evoked a sudden increase in the rate of respiratory neural activity. The preparation was superfused with mock cerebrospinal fluid (CSF) while maintained at constant temperature (26 +/- 1 degrees C) and pH (7.34). Respiratory frequency increased linearly with decreases in superfusate pH (r2 = 0.92, P less than 0.001), indicating that the respiratory circuitry for the detection of CO2 and stimulation of breathing was intact in this preparation. The search for central chemoreceptors was performed with a specially designed micropipette that allowed microejection of 2–10 nl of mock CSF equilibrated with different CO2-O2 gas mixtures. The pipette was advanced in 50- to 100-microns steps by use of a microdrive to a maximum depth of 500 microns from the surface of the ventral medulla. Depending on the location of the micropipette, ejection of CO2-acidified mock CSF at depths of 100–350 microns below the ventral surface of the medulla stimulated neural respiratory output. Using this response as an indication of the location of central respiratory chemoreceptors, we found that chemoreceptive elements were located in a column in the ventromedial medulla extending from the hypoglossal rootlets caudally to an area 0.75 mm caudal to VI nerve in the rostral medulla.(ABSTRACT TRUNCATED AT 250 WORDS)
Catecholamines and regional hemodynamics during isovolemic hemodilution in anesthetized pigs
Authors: Van Woerkens E. C. , Trouwborst A. , Duncker D. J. , Koning M. M. , Boomsma F. , Verdouw P. D.
Published: December 2017

The effects of stepwise isovolemic hemodilution on systemic and regional hemodynamics, oxygen flux, and circulating catecholamines were studied in six pigs anesthetized with midazolam and fentanyl. Reduction of the hematocrit from 28 to 9% resulted in doubling of the cardiac output, mainly due to an increase in stroke volume. Regional blood flows, measured using the radioactive microsphere technique, showed an increase in blood flow to all organs except liver (hepatic artery fraction) and adrenals, with a redistribution of cardiac output in favor of heart and brain (increase in blood flow 420 and 170%, respectively). Oxygen flux to most organs did not decrease until hematocrit decreased to 9%, while total body oxygen consumption was well maintained. Left ventricular oxygen consumption increased, but because left ventricular blood flow also increased, left ventricular extraction ratio did not increase. Circulating catecholamines did not play any role in these regulatory mechanisms.
Forearm endurance training attenuates sympathetic nerve response to isometric handgrip in normal humans
Authors: Somers V. K. , Leo K. C. , Shields R. , Clary M. , Mark A. L.
Published: December 2017

Recent evidence indicates that muscle ischemia and activation of the muscle chemoreflex are the principal stimuli to sympathetic nerve activity (SNA) during isometric exercise. We postulated that physical training would decrease muscle chemoreflex stimulation during isometric exercise and thereby attenuate the SNA response to exercise. We investigated the effects of 6 wk of unilateral handgrip endurance training on the responses to isometric handgrip (IHG: 33% of maximal voluntary contraction maintained for 2 min). In eight normal subjects the right arm underwent exercise training and the left arm sham training. We measured muscle SNA (peroneal nerve), heart rate, and blood pressure during IHG before vs. after endurance training (right arm) and sham training (left arm). Maximum work to fatigue (an index of training efficacy) was increased by 1,146% in the endurance-trained arm and by only 40% in the sham-trained arm. During isometric exercise of the right arm, SNA increased by 111 +/- 27% (SE) before training and by only 38 +/- 9% after training (P less than 0.05). Endurance training did not significantly affect the heart rate and blood pressure responses to IHG. We also measured the SNA response to 2 min of forearm ischemia after IHG in five subjects. Endurance training also attenuated the SNA response to postexercise forearm ischemia (P = 0.057). Sham training did not significantly affect the SNA responses to IHG or forearm ischemia. We conclude that endurance training decreases muscle chemoreflex stimulation during isometric exercise and thereby attenuates the sympathetic nerve response to IHG.
Ibuprofen reduces ethchlorvynol lung injury: possible role of blood flow distribution
Authors: Yagi K. , Baudendistel L. J. , Dahms T. E.
Published: December 2017

The role of cyclooxygenase products in acute lung injury was determined by pretreatment of dogs with ibuprofen before injury with intravenous ethchlovynol (ECV). In animals given ECV only, lung injury resulted in extravascular lung water of 18.9 ml/kg after 2 h, which was significantly higher than the 14.8 ml/kg in the group pretreated with ibuprofen. The comparison of gravimetric and indicator-dilution measurements of edema fluid indicates that edema fluid could not be reliably detected after treatment with ibuprofen because of diversion of flow from injured areas. Venous admixture increased from 6% at baseline to 32% 120 min after ECV in the vehicle-pretreated group compared with an increase from 4% at baseline to 7% in the ibuprofen-pretreated group. The regression analysis of the relationship between venous admixture and extravascular lung water indicated that, at any level of edema, venous admixture was significantly less in the group treated with ibuprofen than in the untreated group. Measurement of plasma and bronchoalveolar lavage fluid indicated that ibuprofen inhibited cyclooxygenase activity without affecting lipoxygenase activity. These results suggest that in intact dogs ibuprofen has a protective effect on both pulmonary gas transfer and pulmonary edema formation in ECV-injured lungs, which is consistent with limiting blood flow to injured segments of the lung.
Effect of hyaluronidase on interstitial cuff and pressure response in liquid-inflated rabbit lung
Authors: Li J. , Lai-Fook S. J. , Conhaim R. L.
Published: December 2017

The sequential pattern of perivascular interstitial cuff growth was studied in liquid-inflated rabbit lungs. Degassed isolated lungs were immersed in a saline bath and inflated to 5 cmH2O transpulmonary pressure with a 3% albumin solution or 3% albumin solution containing hyaluronidase. After inflation times varying between 1 and 7 h, the lungs were frozen in liquid N2. From blocks cut from the frozen lungs, interstitial cuff cross-sectional area was measured as a function of vessel size. No cuffs were observed around vessels less than 0.1 mm diam. At all inflation times, only approximately 50% of vessels less than 0.5 mm diam had cuffs, whereas virtually all vessels greater than 0.5 mm diam had cuffs. Cuff-to-vessel area ratio increased with inflation time, reaching a maximum of 1.0–1.4 by 5 h. The time constant of cuff growth was 1 h for the albumin-inflated lungs and was independent of vessel size. The time constant was reduced by 60% in the hyaluronidase-inflated lungs. The time constant for the response in perivascular interstitial pressure measured by micropuncture near the lung hilum was 2.5 h for albumin-inflated lungs and 1.2 h for hyaluronidase-inflated lungs. Electrical analog models were used to fit the experimental data of cuff growth and to determine interstitial liquid resistance. Interstitial resistance for the albumin-inflated rabbit lungs was 2- and 24-fold greater than values estimated previously for sheep and dog lungs, respectively.