bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary hypertension and increased vasoreactivity caused by repeated indomethacin in sheep
Authors: Meyrick B. , Niedermeyer M. E. , Ogletree M. L. , Brigham K. L.
Published: December 2017

Six chronically catheterized awake sheep were given the cyclooxygenase inhibitor indomethacin (5 mg/kg) twice a day over a 3-wk period. Three sheep receiving vehicle alone served as controls. Pulmonary arterial, left atrial, and systemic arterial pressures, cardiac output, blood gases, and pH were measured biweekly. Pulmonary vasoreactivity to 12% O2 and an analogue of prostaglandin H2 (PGH2-A) was also assessed. As a percent of base line, indomethacin caused a doubling in pulmonary vascular resistance (3 wk = 190 +/- 26%, mean +/- SE) and a 50% increase in pulmonary arterial pressure (3 wk = 151 +/- 9%). Vasoreactivity to 12% O2 increased approximately fourfold during the 1st wk of treatment and then declined. Vasoreactivity to PGH2-A increased steadily, nearly doubling by 3 wk. Light-microscopic counts of peripheral lung biopsy tissue revealed marked sequestration of granulocytes. Morphometric techniques applied to lungs removed at autopsy and fixed with the pulmonary arteries distended with barium gelatin mixture showed a significant reduction in number of barium-filled peripheral arteries and reduction in their external diameter. We conclude that repeated administration of indomethacin alters pulmonary vasoreactivity and causes sustained pulmonary hypertension. Structural studies reveal peripheral lung inflammation and changes in the arterial circulation that are perhaps more consistent with maintained vasoconstriction than chronic pulmonary hypertension.
Pressor reflex evoked by muscular contraction: contributions by neuraxis levels
Authors: Iwamoto G. A. , Waldrop T. G. , Kaufman M. P. , Botterman B. R. , Rybicki K. J. , Mitchell J. H.
Published: December 2017

The pressor reflex evoked by muscular contraction (exercise pressor reflex) is one important model of cardiovascular adjustments during static exercise. The central nervous system (CNS) structures mediating this reflex have remained largely obscure. Therefore, we examined the contribution of selected levels of the neuraxis in mediating the pressor reflex evoked by muscular contraction from stimulation of ventral roots. Decerebrate cats exhibited larger pressor reflexes than those found in intact alpha-chloralose-anesthetized cats, a difference more apparent at low (5 Hz or repeated twitch) rather than at high (50 Hz or tetanic) stimulus frequencies. Although a depressor response to 5-Hz stimulation was observed in the intact anesthetized cats, it appeared to be primarily due to anesthetic level, since a depressor response was not observed in decerebrate animals (nonanesthetized). Cerebellectomy produced no changes in the reflexes of the decerebrate animal. Further transection of the neuraxis (caudal to the midcollicular level) attenuated the exercise pressor reflex. The spinal cat demonstrated slight evidence of exercise pressor reflex activity. These results provide clarification as to representation of this pressor reflex within the CNS and establish the reflex's characteristics at several levels of neuraxis integration.
Heat transfer pathways between fetal lamb and ewe
Authors: Gilbert R. D. , Schroder H. , Kawamura T. , Dale P. S. , Power G. G.
Published: December 2017

Heat produced by the fetus exists to the mother by one of two principal routes: by fetal-maternal exchange in the placenta or through the fetal skin to the amniotic fluid and uterine wall. We measured heat conductances along each pathway to estimate the fraction of total heat exiting each route. Thermistors were placed in the fetal aorta, two different sites in the amniotic fluid, and in a maternal artery. Five days after surgery we injected a total of 280 ml of ice-cold saline into the two separate amniotic fluid sites during a 45-s interval and measured the temperature response for the next hour. After one or two such injections the fetus was killed to cut off umbilical blood flow, and the experiment was repeated to measure the heat fluxes in the absence of placental heat exchange. Experimentally obtained temperature curves were compared with the predictions of a mathematical model. Heat conductances of the skin and uterine wall, as well as the fetal heat production, were estimated in the model using least-squares parameter optimization. In 10 fetal lambs, weighing 3.73 +/- 0.40 (SE) kg, total fetal heat production averaged 3.75 +/- 0.33 W X kg-1. The heat conductance of the uterine wall, 6.6 +/- 0.8 W X degrees C-1, was lower than that of the fetal skin, 10.2 +/- 1.0, and of the placenta, 25.7 +/- 2.9 W X degrees C-1, temperature gradient. We estimated that 84.5% of total fetal heat production exists by fetal-maternal exchange in the placenta with the remaining 15.5% exiting through the fetal skin.
Genesis of rhythmic respiratory activity in pons independent of medulla
Authors: St John W. M. , Bledsoe T. A.
Published: December 2017

We hypothesized that rhythmic respiratory-related activity could be generated in pons independent of medullary mechanisms. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, we recorded efferent activities of the phrenic nerve and mylohyoid branch of the trigeminal nerve. Following transections of the brain stem at the pontomedullary junction, the phrenic and trigeminal nerves discharged with independent rhythms. Spontaneous trigeminal discharges eventually ceased but were reestablished after strychnine, doxapram, and/or protriptyline were administered. In some animals having no spontaneous trigeminal discharges after transection, these discharges appeared, with a rhythm different from the phrenic, following administration of these agents. In other cats having no transections between pons and medulla, these pharmacological agents induced trigeminal and phrenic discharges after kainic acid had been injected into the entire dorsal and ventral medullary respiratory nuclei. Phrenic and trigeminal discharges were linked, indicating survival of bulbospinal neurons or presence of pontospinal units. We conclude that rhythms, similar to respiratory rhythm, can occur by mechanisms in isolated pons. Such mechanisms are hypothesized to be within the pneumotaxic center and may underlie the neurogenesis of eupnea.
Control of exercise hyperpnea during hypercapnia in humans
Authors: Poon C. S. , Greene J. G.
Published: December 2017

Previous studies have yielded conflicting results on the ventilatory response to CO2 during muscular exercise. To obviate possible experimental errors contributing to such variability, we have examined the CO2-exercise interaction in terms of the ventilatory response to exercise under conditions of controlled hypercapnia. Eight healthy male volunteers underwent a sequence of 5-min incremental treadmill exercise runs from rest up to a maximum CO2 output (VCO2) of approximately 1.5 l . min-1 in four successive steps. The arterial PCO2 (PaCO2) at rest was stabilized at the control level or up to 14 Torr above control by adding 0–6% CO2 to the inspired air. Arterial isocapnia (SD = 1.2 Torr) throughout each exercise run was maintained by continual adjustment of the inspired PCO2. At all PaCO2 levels the response in total ventilation (VE) was linearly related to exercise VCO2. Hypercapnia resulted in corresponding increases in both the slope (S) and zero intercept (V0) of the VE-VCO2 curve; these being directly proportional to the rise in PaCO2 (means +/- SE: delta S/ delta PaCO2, 2.73 +/- 0.28 Torr-1; delta V0/ delta PaCO2, 1.67 +/- 0.18 l . min-1 . Torr-1). Thus the ventilatory response to concomitant hypercapnia and exercise was characterized by a synergistic (additive plus multiplicative) effect, suggesting a positive interaction between these stimuli. The increased exercise sensitivity in hypercapnia is qualitatively consistent with the hypothesis that VE is controlled to minimize the conflicting challenges due to chemical drive and the mechanical work of breathing (Poon, C. S. In: Modelling and Control of Breathing, New York: Elsevier, 1983, p. 189–196).
Relation between electromyogram and force in fatigue
Authors: Kranz H. , Cassell J. F. , Inbar G. F.
Published: December 2017

The relationship between the surface electromyogram (SEMG) and force was examined during maximal voluntary contraction (MVC). Isometric MVC of elbow flexors were studied in 18 subjects who performed 27 trials, each consisting of six MVCs lasting 45 s at intervals of 30 s. There was a decrease in the median frequency (Fm) of the SEMG and of the compound action potentials (CAP) during MVC. The CAPs demonstrated that the fall in Fm was associated with a proportional increase in signal power, whereas CAP amplitude did not decrease, indicating intact neuromuscular transmission. The SEMG root-mean-square amplitude remained fairly constant, progressively deviating from force with time of contraction (r = 0.40). When SEMG amplitude was corrected for the Fm change, it tracked force more closely (r = 0.68), indicating a fall in motoneuron drive during MVC. The corrected SEMG was used to calculate the change in the generalized firing rate of motoneurons. The firing rate decreased 60% in the first and sixth contractions, tracked force closely, and corresponded to the firing rate fall seen in late adaptation of motoneurons (r = 0.90, P less than 0.001).
Convection- and diffusion-dependent ventilation maldistribution in normal subjects
Authors: Crawford A. B. , Makowska M. , Paiva M. , Engel L. A.
Published: December 2017

We performed multiple-breath N2 washouts (MBNW) with tidal volumes of 1 liter at 8–16 breaths/min and constant flow rates in six normal subjects. For each breath we computed the slope of the alveolar plateau, normalized by the mean expired N2 concentration (Sn), the Bohr dead space (VDB), an index analogous to the Fowler dead space (V50), and the normalized slope of phase II (S2). In four subjects helium (He) and sulfur hexafluoride (SF6) were washed out after equilibration with a 5% gas mixture of each tracer. The Sn for He and SF6 increased in consecutive breaths, but the difference (delta Sn) increased only over the first five breaths, remaining constant thereafter. In all six subjects Sn, VDB, and V50 increased progressively in consecutive breaths of the MBNW, the increase in Sn being the greatest, approximately 290% from the first to the 23–25th breath. In contrast, S2 was unchanged initially and decreased after the sixth breath. The results indicate that after the fifth breath the increase in Sn during a MBNW is diffusion independent and may constitute a sensitive index of convection-dependent inhomogeneity (CDI). Subtraction of this component from the first breath suggests that Sn in a single-breath washout is largely due to a diffusion-dependent mechanism. The latter may reflect an interaction of convection and diffusion within the lung periphery, whereas CDI may comprise ventilation inequality among larger units, subtended by more centrally located branch points.
Regional lung water and hematocrit determined by positron emission tomography
Authors: Schuster D. P. , Mintun M. A. , Green M. A. , Ter-Pogossian M. M.
Published: December 2017

We have measured with positron emission tomography (PET) the regional distribution of extravascular lung water (EVLW) and hematocrit (HctL) in normal supine dogs. H2(15)O and C15O were used as total lung water (TLW) and intravascular water (IVW) compartment labels, respectively. An additional plasma volume label (68Ga-transferrin) was used to determine regional HctL. EVLW was calculated as the difference between TLW and IVW. In 13 dogs, EVLW was relatively constant along a gravity-dependent vertical gradient, although values in the most anterior regions were statistically less (P less than 0.05) than those in more posterior ones. The average value for EVLW (13 dogs) was 14.4 +/- 2.5 ml H2O/100 ml lung. When EVLW was compared with IVW on a regional basis, the EVLW/IVW ratio decreased significantly in a gravity-dependent direction from 1.95 +/- 0.28 to 0.88 +/- 0.18. In 7 dogs, no significant difference between HctL and systemic hematocrit (average ratio 1.01 +/- 0.08) was found nor was any significant variation of HctL within the lung detected. Thus, in contrast to gravimetric techniques, a hematocrit correction does not appear to be necessary when regional EVLW is studied by PET.
Cardiac response to submaximal exercise in dogs susceptible to sudden cardiac death
Authors: Billman G. E. , Schwartz P. J. , Gagnol J. P. , Stone H. L.
Published: December 2017

The hemodynamic response to submaximal exercise was investigated in 38 mongrel dogs with healed anterior wall myocardial infarctions. The dogs were chronically instrumented to measure heart rate (HR), left ventricular pressure (LVP), LVP rate of change, and coronary blood flow. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise. Nineteen dogs had ventricular fibrillation (susceptible) while 19 animals did not (resistant) during this test. The cardiac response to submaximal exercise was markedly different between the two groups. The susceptible dogs exhibited a significantly higher HR and left ventricular end-diastolic pressure (LVEDP) but a significantly lower left ventricular systolic pressure (LVSP) in response to exercise than did the resistant animals. (For example, response to 6.4 kph at 8% grade; HR, susceptible 201.4 +/- 5.1 beats/min vs. resistant 176.2 +/- 5.6 beats/min; LVEDP, susceptible 19.4 +/- 1.1 mmHg vs. resistant 12.3 +/- 1.7 mmHg; LVSP, susceptible 136.9 +/- 7.9 mmHg vs. resistant 154.6 +/- 9.8 mmHg.) beta-Adrenergic receptor blockade with propranolol reduced the difference noted in the HR response but exacerbated the LVP differences (response to 6.4 kph at 8% grade; HR, susceptible 163.4 +/- 4.7 mmHg vs. resistant 150.3 +/- 6.4 mmHg; LVEDP susceptible 28.4 +/- 2.1 mmHg vs. resistant 19.6 +/- 3.0 mmHg; LVSP, susceptible 122.2 +/- 8.1 mmHg vs. resistant 142.8 +/- 10.7 mmHg). These data indicate that the animals particularly vulnerable to ventricular fibrillation also exhibit a greater degree of left ventricular dysfunction and an increased sympathetic efferent activity.
Elevated diaphragm electromyogram during neonatal hypoxic ventilatory depression
Authors: LaFramboise W. A. , Woodrum D. E.
Published: December 2017

Diaphragmatic electromyogram (EMG) was obtained in eight 48-h-old unanesthetized monkeys while breathing air and then either of two different hypoxic gas mixtures (12 or 8% O2 in N2) for 5 min. Minute ventilation (VI) rose significantly above control levels by 1 min of hypoxemia while animals were breathing either of the hypoxic gas mixtures as tidal volume (VT) and slope and rate moving average EMG increased. The relative gains in VI were associated with comparable increases in diaphragmatic neural activity per minute (EMG/min = peak EMG X frequency) during this early phase of hypoxemia. VI subsequently fell to control levels (inspired O2 fraction = 12%, arterial PO2 = 23 +/- 3 Torr) or significantly below (inspired O2 fraction = 8%, arterial PO2 = 18 +/- 0.4 Torr) by 5 min of hypoxemia, secondary to changes in VT. Despite the decline in VI, slope and rate moving average EMG, and EMG/min remained statistically above control values by 5 min of hypoxemia, although there was a trend for EMG/min to decrease slightly from the 1-min peak response. These findings demonstrate that hypoxic-induced depression of neural input to the diaphragm is not independently responsible for the biphasic nature of the newborn ventilatory response, although it cannot be ruled out as a contributor. The fall in inspiratory volumes despite constant elevated EMG activity suggests the presence of a change in respiratory mechanics and/or an impairment in diaphragmatic contractile function without offsetting neural compensatory activity.
Effect of head-down tilt on basal plasma norepinephrine and renin activity in humans
Authors: Goldsmith S. R. , Francis G. S. , Cohn J. N.
Published: December 2017

The effects of loading cardiopulmonary baroreceptors on basal norepinephrine and renin activity were studied in six normal subjects. Loading of cardiopulmonary baroreceptors was accomplished by a 60-min 30 degrees head-down tilt with small supplemental saline infusions. Central venous pressure was measured continuously by intrathoracic catheter; arterial pressure was measured indirectly by cuff. During the tilt, central venous pressure increased from 5.1 +/- 1.3 to 8.9 +/- 1.7 mmHg (P less than 0.001), whereas arterial pressure was unchanged. Plasma norepinephrine (185 +/- 85 pg/ml) and plasma renin activity (3.9 +/- 5.7 ng . ml-1 . h-1) did not change. Moderate sustained loading of cardiopulmonary baroreceptors is therefore without effect on unstressed plasma norepinephrine and renin activity in normal humans, suggesting that the tonic inhibitory effects of these receptors on these neurohumoral control systems are not readily increased in the basal state.
Effects of hyperoxia on DNA synthesis in cultured porcine aortic endothelial cells
Authors: Clement A. , Hubscher U. , Junod A. F.
Published: December 2017

The mode of action of hyperoxia on the inhibition of DNA synthesis from thymidine (dThd) was studied in primary cultures of porcine aortic endothelial cells (EC) at confluence. A significant effect of hyperoxia on dThd uptake was detected only after a 48-h exposure to 95% O2. On the other hand, decrease in dThd kinase activity was already observed after a 12-h exposure, and the time course of its reduction followed closely that of the inhibition of dThd incorporation into DNA. The incorporation of dThd triphosphate into DNA in permeabilized EC was unaffected by hyperoxia. Determination of DNA alpha- and beta-polymerase activities showed that hyperoxia reduced the activity of the alpha-polymerase and increased that of the beta-polymerase. We conclude that most of the O2 effects on DNA synthesis from dThd can be attributed to dThd kinase inhibition. The increased activity of DNA beta-polymerase, an enzyme involved in DNA repair, also supports the view that hyperoxia could damage DNA.
Evaluation of factors affecting relationship between transcutaneous PO2 and probe temperature
Authors: Gronlund J.
Published: December 2017

Several studies on transcutaneous O2 probes have shown that the transcutaneous PO2 increases to approximately 80% of the arterial PO2 when the probe is heated to 44 degrees C. It is not known whether this result reflects near-complete thermic arterialization or rather other factors such as the temperature-linked right shift of the hemoglobin O2-binding curve. In many clinical applications of transcutaneous probes the use of 44 degrees C is a major disadvantage because of the risk of skin burns. The development of new probes operating at lower temperatures is hampered by the lack of data on the temperature dependence of the factors influencing the relationship between the transcutaneous PO2 and the probe temperature. The present study attempts to estimate the temperature dependence of 1) the degree of arterialization of the blood in the skin capillaries, 2) the PO2 difference across the epidermis caused by the diffusion gradient and the epidermal O2 consumption, and 3) the arteriovenous saturation difference over the skin capillaries. The estimation is based on simultaneously measured transcutaneous PO2, PCO2, and argon partial pressure (PAr) values at seven different probe temperatures. The transcutaneous PCO2 is assumed equal to the mean capillary PCO2, which is used to calculate the mean capillary PO2 by the aid of a skin model. The O2 diffusion gradient is estimated from the transcutaneous PAr, and the PO2 difference caused by the epidermal O2 consumption is set equal to the difference between the mean capillary and transcutaneous PO2 less the partial pressure difference caused by the diffusion gradient. The degree of arterialization was found to be 53% at 38 degrees C and 65% at 44 degrees C. The partial pressure difference caused by the epidermal O2 consumption decreased from 33 Torr at 38 degrees C to 6 Torr at 44 degrees C. The PO2 difference across the epidermis caused by the diffusion gradient was 7 Torr at 38 degrees C and 5 Torr at 44 degrees C. The arteriovenous saturation difference fell from 31% at 38 degrees C to 12% at 44 degrees C.
Effect of increases in lung volume on clearance of aerosolized solute from human lungs
Authors: Marks J. D. , Luce J. M. , Lazar N. M. , Wu J. N. , Lipavsky A. , Murray J. F.
Published: December 2017

To study the effect of increases in lung volume on solute uptake, we measured clearance of 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosol (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH2O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.
A study of the variability in the febrile responses of rabbits to endogenous pyrogen
Authors: Stitt J. T.
Published: December 2017

The range of body temperature increases elicited by a standard dose of endogenous pyrogen (0.5 ml/kg iv) was examined in a population of 26 male New Zealand White rabbits. Although the mean maximum increase in rectal temperature was 0.88 +/- 0.06 degree C (SE), individual responses varied from 0.4 degree to 1.5 degree C. Three representative animals that responded to the standard dose of pyrogen with small, intermediate, and large febrile responses were selected and challenged with the same dose of pyrogen on eight separate occasions, and the variability of these responses was examined. There was little variability within the characteristic responses of any particular animal to the repeated challenges. The variability of the febrile responses elicited by both intravenous and intracerebroventricular administration of the same pyrogen was examined and compared using another group of 11 rabbits. The variability in response to the intravenous route was similar to that found in the larger population, whereas the variation in response to the intracerebroventricular route was smaller, and all 11 animals had fevers that were greater than 1 degrees C. It is concluded that the variability of the febrile responses of rabbits to intravenous pyrogen was due to differences between individual sensitivities of animals to the intravenously administered pyrogen. This difference in sensitivity may be due to a difference in the amount of pyrogen that reaches the putative receptor sites, or to a difference in the density or effectiveness of receptor sites in translating the pyrogenic stimulus into a fever response.
Longitudinal dispersion of gases measured in a model of the bronchial airways
Authors: van der Kooij A. M. , Luijendijk S. C.
Published: December 2017

We investigated the longitudinal dispersion of helium (He), methane, acetylene, butane, sulfur hexafluoride, and octafluorocyclobutane (C4F8) in a clear plastic model of the human bronchial airways. The dimensions of the seven airway generations (0–6) of the model were chosen to be equal to those given by Weibel's model A (Morphometry of the Human Lung; New York: Academic, 1963). Total volume of the model amounts to 52 ml. A small bolus of each of the tracer gases was injected within 1 ms into a constant airflow at the inlet of the model, and the bolus dispersion curve was measured at the outlet by means of a mass spectrometer. Both inspirations and expirations were simulated; the four selected values of the flow rate (V) for each simulation were 0.25, 0.5, 1, and 2 1/s, respectively. The measured bolus dispersion curves were corrected for the response characteristics of the mass spectrometer. In this way, the basal shape of the dispersion curve could be shown to be Gaussian. No significant changes in the standard deviation (sigma v) (Ultman et al., J. Appl. Physiol. 44: 297–303, 1978) of each tracer gas are found for the V values applied. sigma v increases significantly (approximately 50%), however, between the lightest (He) and the heaviest (C4F8) tracer gas used. The mean sigma v values of the 24 results (4 V values and 6 tracer gases) obtained for inspirations and expirations are 15.3 and 13.6 ml, respectively.
Physiological determinants of nocturnal arterial oxygenation in patients with obstructive sleep apnea
Authors: Bradley T. D. , Martinez D. , Rutherford R. , Lue F. , Grossman R. F. , Moldofsky H. , Zamel N. , Phillipson E. A.
Published: December 2017

Among patients with similar degrees of obstructive sleep apnea (OSA) there is considerable variability in the degree of associated nocturnal hypoxemia. The factors responsible for this variability have not been clearly defined. Therefore we studied 44 patients with OSA to identify the physiological determinants of nocturnal arterial O2 saturation (SaO2). All patients underwent pulmonary function testing, arterial blood gas analysis, and overnight polysomnography. Mean nocturnal SaO2 ranged from 96 to 66% and apnea-hypopnea index from 11 to 128 per hour of sleep. Several anthropometric, respiratory physiological, and polysomnographic variables that could be expected to influence nocturnal SaO2 were entered into a stepwise multiple linear regression analysis, with mean nocturnal SaO2 as the dependent variable. Three variables [awake supine arterial PO2 (PaO2), expiratory reserve volume, and percentage of sleep time spent in apnea] were found to correlate strongly with mean nocturnal SaO2 (multiple R, 0.854; P less than 0.0001) and accounted for 73% of its variability among patients. Body weight, other lung volumes, and airflow rates influenced awake PaO2 and expiratory reserve volume but had no independent influence on nocturnal SaO2. In a further group of 15 patients with OSA a high correlation was obtained between measured nocturnal SaO2 and that predicted by the model (r = 0.87; P less than 0.001). We conclude that derangements of pulmonary mechanics and awake PaO2 (generally attributable to obesity and diffuse airway obstruction) are of major importance in establishing the severity of nocturnal hypoxemia in patients with OSA.
Thermoregulatory and blood responses during exercise at graded hypohydration levels
Authors: Sawka M. N. , Young A. J. , Francesconi R. P. , Muza S. R. , Pandolf K. B.
Published: December 2017

We studied the effects of graded hypohydration levels on thermoregulatory and blood responses during exercise in the heat. Eight heat-acclimated male subjects attempted four heat-stress tests (HSTs). One HST was attempted during euhydration, and three HSTs were attempted while the subjects were hypohydrated by 3, 5, and 7% of their body weight. Hypohydration was achieved by an exercise-heat regimen on the day prior to each HST. After 30 min of rest in a 20 degrees C antechamber the HST consisted of a 140-min exposure (4 repeats of 10 min rest and 25 min treadmill walking) in a hot-dry (49 degrees C, 20% relative humidity) environment. The following observations were made: 1) a low-to-moderate hypohydration level primarily reduced plasma volume with little effect on plasma osmolality, whereas a more severe hypohydration level resulted in no further plasma volume reduction but a large increment in plasma osmolality; 2) core temperature and heart rate responses increased with severity of hypohydration; 3) sweating rate responses for a given rectal temperature were systematically decreased with severity of hypohydration; and 4) the reduction in sweating rate was more strongly associated with plasma hyperosmolality than hypovolemia. In conclusion, an individual's thermal strain increases linearly with the severity of hypohydration during exercise in the heat, and plasma hyperosmolality influences the reduction in sweating more profoundly than hypovolemia.
Incompatibility of endurance- and strength-training modes of exercise
Authors: Dudley G. A. , Djamil R.
Published: December 2017

Twenty-two male and female subjects trained for 7 wk for endurance (group E), for strength (group IS), or for both strength and endurance (group C) to evaluate the effect of concurrent performance of both modes of training on the in vivo force-velocity relationship of human muscle and on aerobic power. Endurance training consisted of five 5-min sessions three times a week on cycle ergometer with a work load that approached the subject's peak cycle-ergometer O2 uptake (peak CE VO2). Strength training consisted of two 30-s sets of maximal knee extensions per day performed on an isokinetic dynamometer three times a week at a velocity of 4.19 rad X s-1. Group C performed the same training as groups IS and E, alternating days of strength and endurance training. Subjects (groups C and IS) were tested pre- and posttraining for maximal knee-extension torque at a specific joint angle (0.52 rad below horizontal) for seven specific angular velocities (0, 0.84, 1.68, 2.81, 3.35, 4.19, and 5.03 rad X s-1). Groups C and E were tested for peak CE VO2 pretraining, at 14-day intervals, and posttraining. Group IS showed significant increases in angle-specific maximal torque at velocities up to and including the training speed (4.19 rad X s-1). Group C showed increases (P less than 0.05) at velocities of 0, 0.84, and 1.68 rad X s-1 only. Peak CE VO2, when expressed in relative or absolute terms, increased (P less than 0.05) approximately 18% for both groups E and C.
Exercise training and "ventilation threshold" in elderly
Authors: Thomas S. G. , Cunningham D. A. , Thompson J. , Rechnitzer P. A.
Published: December 2017

Dynamic exercise training of the elderly increases maximal O2 uptake (VO2max); however, the effects of training on the ventilation threshold (VET) have not been studied. VET was identified as the final point before the ventilatory equivalent for O2 (VE/VO2) increased, without an increase in the ventilatory equivalent for CO2 (VE/VCO2). Inactive elderly males (mean age, 62 yr) were randomly assigned to a control (C, n = 44) or activity (A, n = 45) group. VO2max and VET were determined from an incremental treadmill test. Initial VO2max was not different between the C (2.34 +/- 0.42 l X min-1) and A (2.28 +/- 0.44 l X min-1) groups, nor was there a significant difference in the VO2 at the VET (C = 1.39 +/- 0.26 l X min-1; A = 1.31 +/- 0.23 l X min-1). The activity group trained for 30 min/day, 3 days/wk at an intensity of approximately 65–80% of VO2max. After 1 yr of training the activity group exhibited an 18% increase in VO2max (A = 2.70 +/- 0.54 l X min-1), but the change in VET was not significant (A = 1.39 +/- 0.28 l X min-1). There was no significant change in VO2max (C = 2.45 +/- 0.68 l X min-1) or VET (C = 1.38 +/- 0.31 l X min-1) in the control group. VET/VO2max declined significantly in the activity group (from 58 to 52% of VO2max). Change in VET/VO2max with training was not correlated with the initial VO2max value. We conclude that increases in aerobic capacity are more readily effected than alterations of the VET in elderly subjects.
Separation of factors responsible for change in breathing pattern induced by instrumentation
Authors: Perez W. , Tobin M. J.
Published: December 2017

Employment of mouthpiece and noseclips (MP + NC) has repeatedly been shown to increase tidal volume (VT), but its effect on respiratory frequency (f) and its subsets is controversial. The mechanisms accounting for this alteration in breathing pattern are poorly understood and may include stimulation of oral or nasal sensory receptors or alteration in the route of breathing. In this study we demonstrated that use of a MP + NC, compared with nonobtrusive measurement with a calibrated respiratory inductive plethysmograph, alters the majority of the volume and time indexes of breathing pattern, with increases in minute ventilation (P less than 0.01), VT (P less than 0.001), inspiratory time (TI, P less than 0.05), expiratory time (TE, P less than 0.05), mean inspiratory flow (P less than 0.05), and mean expiratory flow (P less than 0.05) and a decrease in f(P less than 0.05). Separating the potential mechanisms we found that when the respiratory route was not altered, independent oral stimulation (using an occluded MP) or nasal stimulation (by applying paper clips to the alae nasi) did not change the breathing pattern. In contrast, obligatory oral breathing without additional stimulation of the oral or nasal sensory receptors caused increases in VT (P less than 0.05), TI (P less than 0.05), and TE (P less than 0.01) and a fall in f(P less than 0.05). Heating and humidifying the inspired air did not prevent the alteration in breathing pattern with a MP. Thus change in the respiratory route is the major determinant of the alteration in breathing pattern with a MP + NC.
Effects of hemodynamic edema formation on peripheral vs. central airway mechanics
Authors: Ishii M. , Matsumoto N. , Fuyuki T. , Hida W. , Ichinose M. , Inoue H. , Takishima T.
Published: December 2017

The mechanisms governing increased central (Rc) and peripheral airway resistance (Rp) during hemodynamic edema formation were studied in anesthetized dogs. Rc and Rp were measured by forced oscillation at 1 Hz by use of a retrograde catheter to partition resistance and a pleural capsule to detect alveolar pressure. After elevation of left atrial pressure to 30 cmH2O by inflation of the left atrial balloon, Rc gradually increased an average of 60% above control in approximately 100 min. Vagotomy had a small influence on the change. On the other hand, Rp with vagus nerves intact increased triphasically: first, it increased transiently by 160% above the control value within 15–20 min before returning to near base line. It then increased gradually for approximately 40 min and finally rose sharply up to five times the control value after approximately 100 min. With vagi cut, the initial phase disappeared, but the second gradual and final rapid phases were not affected. Several sequential mechanisms of increased Rp can be proposed: 1) transient bronchoconstriction mediated by vagal reflex; 2) gradual formation of peribronchial edema; and 3) a sharp increase in airway fluid and formation of bronchial froth. In addition, narrowing of the airways by vascular engorgement may have contributed to the increase of Rp throughout all stages.
Renin-angiotensin system: oral contraception and exercise in healthy female subjects
Authors: Huisveld I. A. , Derkx F. M. , Bouma B. N. , Erich W. B. , Schalekamp M. A.
Published: December 2017

The effect of oral contraception and of exercise on the renin-angiotensin system was studied in 20 highly trained athletes, of whom 10 were ingesting oral contraceptives (users) and 10 were not (nonusers), and in 24 sedentary age-matched healthy female subjects, of whom 13 were users and 11 were nonusers. No training-related effects were observed with the exception of renin substrate, which was significantly higher in the athletes. The plasma concentrations of active renin and of trypsin-activatable prorenin were significantly lower in the subjects taking oral contraceptives. Renin substrate, however, was significantly higher in the oral contraceptives group. No difference in plasma renin activity (PRA) was observed between users and nonusers. The results demonstrate the well-known estrogen-induced stimulation of renin substrate synthesis by the liver and suggest a decreased secretion of renin by the kidney. Exhaustive exercise of short duration, performed by the trained athletes only, stimulated the renin-angiotensin system. An increase in PRA and in active renin concentration was observed. The prorenin concentration did not change significantly. The magnitude of the exercise-induced changes was considerably influenced by oral contraceptive medication. Nonusers showed a significantly greater increase in PRA and active renin and total renin concentration than users. Renin substrate decreased significantly during exercise in the nonusers only. These results demonstrate that oral contraceptives have a suppressive effect on renin secretion at rest, an effect that becomes more prominent during exercise, i.e., physiological stimulation.
Effects of catecholamines on lactic acid output during progressive working contractions
Authors: Stainsby W. N. , Sumners C. , Eitzman P. D.
Published: December 2017

Epinephrine and norepinephrine together (E + NE) and epinephrine (E) alone were infused intravenously in stepwise increasing doses during progressive isotonic tetanic contractions. The goal was to mimic, for in situ dog skeletal muscle, the concentrations of these catecholamines in the blood and the contractions during progressive exercise. The concentrations of lactate and O2 in arterial and muscle venous blood, the arterial plasma concentration of E and NE, PO2 in arterial and muscle venous blood, and the venous outflow were measured. The infusions caused a rise in plasma E and NE like those seen in progressive exercise. Compared with no-infusion controls, the E + NE infusions and the E alone infusion resulted in significant increases in maximal lactic acid output by the muscles during the contractions from 0.24 mumol X g-1 X min-1 in the controls to 0.44 and 0.54 mumol X g-1 X min-1 during E + NE and E alone infusions, respectively. The venous O2 concentrations and partial pressures were not reduced by the infusions. Both infusions resulted in a rise of arterial lactate concentration that could not be accounted for by the lactic acid output of the contracting muscles. The E alone infusions were associated with a rise in maximal O2 uptake during the contractions. Since the effects of the E + NE and E alone infusions were similar, it was suggested that E is more active than NE. It was suggested that E also increased lactic acid production in tissues other than the working muscles.
Effects of raised body temperature on reasoning, memory, and mood
Authors: Holland R. L. , Sayers J. A. , Keatinge W. R. , Davis H. M. , Peswani R.
Published: December 2017

Volunteers' body core temperatures were raised to 38.80–39.05 degrees C within a few minutes by immersion in water at 41 degrees C. Tests were then made with the subjects insulated and cooling slowly. Control immersions were made in water at 37 degrees C when core temperatures remained at 36.60–37.40 degrees C. Neither memory registration nor recall of memories registered an hour earlier, nor immediate ability to recall digit spans forward or backward was affected by the increase in core temperature. The increase in temperature did not have any significant effect on accuracy of performance of verbal logic problems or of two-digit subtractions. However, the increase in core temperature was associated with a significant increase in the speed of performance of the tests, by 11 and 10%, respectively. The warm immersions also induced a significant decrease in alertness and an increase in irritability as assessed subjectively by the volunteers; control immersions had no such effects.
Lung volume dependence of esophageal pressure in the neck
Authors: Brown I. G. , McClean P. A. , Webster P. M. , Hoffstein V. , Zamel N.
Published: December 2017

There is conflicting evidence in the literature regarding tissue pressure in the neck. We studied esophageal pressure along cervical and intrathoracic esophageal segments in six healthy men to determine extramural pressure for the cervical and intrathoracic airways. A balloon catheter system with a 1.5-cm-long balloon was used to measure intraesophageal pressures. It was positioned at 2-cm intervals, starting 10 cm above the cardiac sphincter and ending at the cricopharyngeal sphincter. We found that esophageal pressures became more negative as the balloon catheter moved from intrathoracic to cervical segments, until the level of the cricopharyngeal sphincter was reached. At total lung capacity, esophageal pressures were -10.5 +/- 2.9 (SE) cmH2O in the lower esophagus, -18.9 +/- 3.0 just within the thorax, and -21.3 +/- 2.73 within 2 cm of the cricopharyngeal sphincter. The variation in mouth minus esophageal pressure with lung volume was similar in cervical and thoracic segments. We conclude that the subatmospheric tissue pressure applied to the posterior membrane of the cervical trachea results in part from transmission of apical pleural pressure into the neck. Transmural pressure for cervical and thoracic tracheal segments is therefore similar.
Ventilatory responses of hamsters and rats to hypoxia and hypercapnia
Authors: Walker B. R. , Adams E. M. , Voelkel N. F.
Published: December 2017

As a fossorial species the hamster differs in its natural habitat from the rat. Experiments were performed to determine possible differences between the ventilatory responses of awake hamsters and rats to acute exposure to hypoxic and hypercapnic environments. Ventilation was measured with the barometric method while the animals were conscious and unrestrained in a sealed plethysmograph. Tidal volume (VT), respiratory frequency (f), and inspiratory (TI) and expiratory (TE) time measurements were made while the animals breathed normoxic (30% O2), hypercapnic (5% CO2), or hypoxic (10% O2) gases. Arterial blood gases were also measured in both species while exposed to each of these atmospheric conditions. During inhalation of normoxic gas, the VT/100 g was greater and f was lower in the hamster than in the rat. Overall minute ventilation (VE/100 g) in the hamster was less than in the rat, which was reflected in the lower PO2 and higher PCO2 of the hamster arterial blood. When exposed to hypercapnia, the hamster increased VE/100 g solely through VT; however, the VE/100 g increase was significantly less than in the rat. In response to hypoxia, the hamster and rat increased VE/100 g by similar amounts; however, the hamster VE/100 g increase was through f alone, whereas the rat increased both VT/100 g and f. Mean airflow rates (VT/TI) were no different in the hamster or rat in each gas environment; therefore most of the ventilatory responses were the result of changes in TI and TE and respiratory duty cycle (TI/TT).
Dependence of diaphragmatic length on lung volume and thoracoabdominal configuration
Authors: Loring S. H. , Mead J. , Griscom N. T.
Published: December 2017

Changes in lung volume can be partitioned into volume displacements of the rib cage and abdomen. Abdominal displacements are often used as estimates of diaphragmatic displacements and changes in lengthening of diaphragmatic muscle. We used X-rays, ultrasound, and linear measurements of thoracic and abdominal diameters to estimate relationships among lung volume, thoracoabdominal configuration and diaphragmatic length, and we found that diaphragmatic length was strongly dependent on rib cage as well as abdominal displacement. In three subjects, the diaphragm shortened 57–85% as much during a breath made without abdominal displacement as during a normal breath in which the abdominal wall moved outward with the rib cage. We conclude that changes in diaphragmatic length can be estimated from surface measurements without radiation and that the length of the diaphragm cannot be estimated from displacements of the abdominal wall alone.
Endogenous plasma proteins in edematous lungs and alveolar fluid in rabbits
Authors: Pavlin D. J. , Haschke R. , Nessly M. L. , Cheney F. W.
Published: December 2017

In this study, we compared two methods of differentiating hydrostatic and permeability types of pulmonary edema. The first method entailed measurement of protein concentrations directly in samples of alveolar fluid (AF); the second method was an indirect technique in which protein concentration in extravascular extracellular water (EVECW) was calculated on the basis of separate measurements of the quantity of protein in the lung and the volume of EVECW. The concentration of albumin (Alb) and gamma-G-globulin was measured in EVECW and alveolar fluid in excised edematous rabbit lungs. Edema was caused by elevation of left ventricular end-diastolic pressure to 25 Torr (hydrostatic edema, HE) or by intravenous oleic acid, 0.09 ml/kg (permeability edema, PE). The volume of distribution of Na+ was utilized as a measure of EVECW in the lung. Protein concentration in EVECW and AF relative to plasma (EV/PL and AF/PL, respectively) was compared in the two types of edema. The EV/PL was 0.61 +/- 0.12 (SD) for Alb in He compared with 1.18 +/- 0.47 in PE (P less than 0.02). The AF/PL was 0.54 +/- 0.12 and 1.25 +/- 0.33 in HE and PE, respectively (P less than 0.001). There was good correlation between EV/PL and AF/PL for Alb (r = 0.74, P less than 0.001) but not for gamma-G-globulin. Thus EV/PL for Alb, AF/PL for Alb, and gamma-G-globulin all differentiated hydrostatic from permeability edema.
Dry air-induced constriction in lung periphery: a canine model of exercise-induced asthma
Authors: Freed A. N. , Bromberger-Barnea B. , Menkes H. A.
Published: December 2017

We studied the effects of the flow of dry air on collateral tone in the lung periphery. A bronchoscope was wedged in sublobar segments of anesthetized dogs, and measurements of collateral resistance (Rcs) were recorded before and after flow was increased from 200 to 2,000 ml/min for a 5-min period. Five minutes after exposure was completed, Rcs increased by an average of 117 +/- 25.2% (SE) over control. Maximum Rcs occurred 5 min after the challenge was concluded and required 48 +/- 10.5 min to return to base line. When flow rate was held constant and exposure period varied, Rcs increased with increased stimulus duration. With exposure times held constant, the response of the collateral system was positively associated with changes in stimulus strength (flow rate). No refractory period was observed with repetitive challenges. Finally, when dry air (delivered at 22 degrees C) and conditioned air (i.e., delivered at 28 degrees C; relative humidity = 80%) challenges were alternated in the same wedged segment, dry air produced a mean increase in Rcs of 93.2%, whereas challenge with warm moist air increased Rcs only 33.5%. Regardless of which challenge was presented first, dry air consistently produced a greater constrictor response. This response is similar to that observed in cold air- and exercise-induced asthma and indicates that the lung periphery in dogs, like larger airways in asthmatic subjects, has the potential to increase tone when exposed to dry air. Peripheral airways in dogs thus constitute a model that can be used for the investigation of exercise-induced asthma.