bluuebunny/crossref_metadata_2025 huggingface dataset:
Operation Everest II: neuromuscular performance under conditions of extreme simulated altitude
Authors: Garner S. H. , Sutton J. R. , Burse R. L. , McComas A. J. , Cymerman A. , Houston C. S.
Published: December 2017

The force output of the ankle dorsiflexors was studied during a 40-day simulated ascent of Mt. Everest in a hypobaric chamber; both electrically activated and maximal voluntary contractions (MVCs) were employed. The purpose of this study was to establish whether, under conditions of progressive chronic hypoxia, there was a decrease in muscle force output and/or increased fatigability. We also attempted to identify the main site of any failure, i.e., central nervous system, neuromuscular junction, or muscle fiber. Muscle twitch torque (Pt), tetanic torque (Po), MVC torque, and evoked muscle compound action potential (M wave) were monitored during 205-s exercise periods in five subjects at three simulated altitudes (760, 335, and 282 Torr). All three types of torque measurement were well preserved at the three altitudes. In some subjects, the responses to stimuli interpolated during repeated MVCs provided evidence of “central” fatigue at altitude. In addition, the rate of fatigue during 20-Hz electrical stimulation was greater (P less than 0.01) at altitude and there was increased fatigability of the twitch (P less than 0.025); however, the M wave amplitude was maintained. We conclude that central motor drive becomes more precarious at altitude and is associated with increased muscle fatigue at low excitation frequencies; the latter is the result, in part, of chronic hypoxia and occurs in the muscle fiber interior because no impairment in neuromuscular transmission could be demonstrated.
Neurogenesis, control, and functional significance of gasping
Authors: St John W. M.
Published: December 2017

Gasps are frequently the first and last breaths of life. Gasping, which is generated by intrinsic medullary mechanisms, differs fundamentally from other automatic ventilatory patterns. A region of the lateral tegmental field of the medulla is critical for the neurogenesis of the gasp but has no role in eupnea. Neuronal mechanisms in separate brain stem regions may be responsible for the neurogenesis of different ventilatory patterns. This hypothesis is supported by the recording of independent respiratory rhythms simultaneously from isolated brain stem segments. Data from fetal and neonatal animals also support gasping and eupnea being generated by separate mechanisms. Gasping may represent the output of a simple but rugged pattern generator that functions as a backup system until the control system for eupnea is developed. Pacemaker elements are hypothesized as underlying the onset of inspiratory activity in gasping. Similar elements, in a different brain stem region, may be responsible for the onset of the eupneic inspiration with neural circuits involving the pons, the medulla, and the spinal cord serving to shape efferent respiratory-modulated neural discharges.
Total and local impedances of the chest wall up to 10 Hz
Authors: Barnas G. M. , Yoshino K. , Fredberg J. , Kikuchi Y. , Loring S. H. , Mead J.
Published: December 2017

To understand how bical mechanical chest wall (CW) properties are related to those of the CW as a whole, we measured esophageal and gastric pressures, CW volume changes (measured with a head-out body plethysmograph), and anteroposterior and transverse CW diameter changes (measured with magnetometers attached to the surface) during sinusoidal forcing at the mouth (2.5% vital capacity, 0.5-10 Hz) in four healthy subjects. Total CW resistance decreased sharply as frequency rose to 3-4 Hz and remained relatively constant at higher frequencies. Total CW reactance became less negative with increasing frequency but showed no tendency to change sign. Above 2 Hz, diameters measured at different locations changed asynchronously between and within the rib cage and abdomen. “Local pathway impedances” (ratios of esophageal or gastric pressure to a rate of diameter change) showed frequency dependence similar to that of the total CW less than 3 Hz. Local pathway impedances increased during contraction of respiratory muscles acting on the pathway. We conclude that 1) total CW behavior is mainly a reflection of its individual local properties at less than or equal to 3 Hz, 2) local impedances within the rib cage or within the abdomen can change independently in some situations, and 3) asynchronies that develop within the CW during forcing greater than 3 Hz suggest that two compartments may be insufficient to describe CW properties from impedance measurements.
Effect of diaphragmatic contraction on intramuscular pressure and vascular impedance
Authors: Supinski G. S. , DiMarco A. F. , Altose M. D.
Published: December 2017

The purpose of the present study was to determine whether the diaphragm, like limb muscles, generates high levels of intramuscular pressure during contraction. Studies were performed on in situ diaphragm strips in 15 dogs. An isometric force transducer was used to measure strip tension, and intramuscular pressure was assessed using both wick and balloon catheter techniques. Tension and intramuscular pressures were recorded during a series of graded contractions elicited by electrically stimulating strips via intramuscular electrodes. Similar techniques were used to record the tension and intramuscular pressures developed during graded contractions of a limb muscle, the vastus medialis. Intramuscular pressure was linearly related to tension in both the diaphragm and vastus medialis. However, for a given level of tension development, vastus medialis pressures were two- to threefold greater than those developed within the diaphragm. For example, at a tension of 2 kg/cm2 vastus medialis and diaphragm intramuscular pressures were 105 +/- 11 and 25 +/- 4 mmHg, respectively, when assessed with wick catheters, and were 159 +/- 11 and 48 +/- 5 mmHg, respectively, when assessed by the balloon catheter technique. These differences may reflect the fact that thick rounded muscles, like the vastus, may be capable of generating higher intramuscular pressures than the thin sheetlike diaphragm. To determine whether intradiaphragmatic pressure swings were large enough to explain the vascular compression produced by contraction, we measured phrenic arterial impedance during contraction in nine animals. In these animals the inferior phrenic artery was cannulated and pump perfused at a constant flow rate. With contraction, phrenic arterial pressure rose; i.e., phrenic arterial impedance increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Xanthine oxidase is increased and contributes to paraquat-induced acute lung injury
Authors: Waintrub M. L. , Terada L. S. , Beehler C. J. , Anderson B. O. , Leff J. A. , Repine J. E.
Published: December 2017

Two lines of investigation suggested that xanthine oxidase- (XO) derived O2 metabolites contribute to paraquat- (PQ) induced acute lung injury. First, PQ treatment increased lung XO activity and decreased lung xanthine dehydrogenase activity. Second, lung albumin uptake increased compared with control values in untreated XO-replete but not tungsten-treated XO-depleted lungs in rats treated with PQ.
Insensitivity of maximum expiratory flow to bronchodilation in normal dogs
Authors: Eng J. , Gomez A. , Mink S.
Published: December 2017

We examined the effects of the inhaled parasympatholytic agent atropine and the sympathomimetic agent salbutamol on partitioned frictional pressure (Pfr) losses to the site of flow limitation (choke point, CP) in dogs to see how changes brought about by these agents would affect maximum expiratory flow (Vmax) and response to breathing 80% He-20% O2 (delta Vmax) in terms of wave-speed theory of flow limitation. In open-chest dogs, a Pitot-static tube was advanced down the right lower lobe to locate CP, to determine CP lateral and end-on pressures (PE), and to partition the airway into peripheral (alveoli to sublobar) and central (sublobar to CP) segments. Measurements were obtained at approximately 50% vital capacity. After inhalation, CP locations were unchanged with both bronchodilating agents. After atropine inhalation, Pfr central was decreased by one-half compared with base line. Despite the decrease in Pfr central, however, Vmax failed to increase after atropine because of altered bronchial area pressure (BAP) behavior at the CP site. After salbutamol inhalation, Pfr peripheral was reduced by about one-half compared with base line. However, Vmax failed to increase, because this reduction was too small to significantly increase the CP pressure head (i.e., PE). delta Vmax was also insensitive to these agents. Our results show mechanisms by which small changes in Pfr, as well as the complex interaction of changes in Pfr and BAP, may limit the use of Vmax in detecting bronchodilation at different airway sites.
Cyclooxygenase inhibitors increase canine tracheal muscle response to parasympathetic stimuli in situ
Authors: Bethel R. A. , McClure C. L.
Published: December 2017

To determine whether cyclooxygenase inhibitors alter parasympathetic control of airway smooth muscle in situ, we pretreated anesthetized dogs with intravenous indomethacin, meclofenamate, or normal saline and measured the isometric contraction of tracheal muscle in response to electrical stimulation of the vagus nerves. Indomethacin and meclofenamate increase the response of airway smooth muscle to parasympathetic stimulation. In subsequent experiments to determine the site of action of cyclooxygenase inhibitors, we found that indomethacin does not alter the response of tracheal muscle to intra-arterial acetylcholine (a muscarinic agonist) but does augment the response to intra-arterial dimethylpiperaziniumiodide (a nicotinic agonist). Moreover, the response to parasympathetic stimulation after pretreatment with a combination of indomethacin and BW755C (a combined cyclooxygenase-lipoxygenase inhibitor) does not differ significantly from the response after indomethacin or meclofenamate alone. We conclude that cyclooxygenase inhibitors increase the sensitivity of the contractile response of tracheal smooth muscle to parasympathetic stimulation, that they exert their effect on the postganglionic parasympathetic neuron, and that their effect is prejunctional. The effect appears secondary to a decrease in cyclooxygenase products rather than to an increase in lipoxygenase products. These findings suggest that endogenous cyclooxygenase products may modulate parasympathetic control of airway smooth muscle in vivo. They may relate to the mechanisms that underlie airway hyperresponsiveness, by which mediators of inflammation modulate airway responsiveness and by which nonsteroidal anti-inflammatory drugs induce severe bronchoconstrictor responses in some persons who have asthma.
Substance P in the ventrolateral medulla oblongata regulates ventilatory responses
Authors: Chen Z. , Hedner J. , Hedner T.
Published: December 2017

Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.
Hypopharyngeal and neck cross-sectional changes monitored by inductive plethysmography
Authors: Liistro G. , Stanescu D. , Dooms G. , Veriter C. , Aubert-Tulkens G. , Rodenstein D.
Published: December 2017

We present a method to assess cross-sectional area (CSA) changes of the extrathoracic airways (EA) by using an inductive plethysmograph (IP) band placed around the upper part of the neck. Measurements of mouth pressure (Pm) (or flow rate, V) and neck CSA changes during respiratory efforts against a high (or infinite) resistance have shown a highly significant relationship between Pm changes (or V changes, respectively), reflecting CSA changes of the EA and CSA changes of the neck. Simultaneous measurements of CSA of the neck (by IP) and of EA (by computerized tomography) during sustained inspiratory and expiratory efforts against a closed airway showed a high correlation between changes in the former and latter structures. Changes in CSA of the neck were larger with positive than negative transmural pressures, in keeping with the known larger compliance of this airway during expiration. We found this method helpful to assess the behavior of the EA during obstructive apnea episodes, hypopneas, and snoring.
Alveolar pressure inhomogeneity during low-frequency oscillation of excised canine lobes
Authors: Warner D. O.
Published: December 2017

To quantify the inhomogeneity of alveolar pressures (PA) during cyclic changes in lung volume similar to those present during spontaneous breathing, inhomogeneity of PA was measured with an alveolar capsule technique in six excised canine lungs. The lungs were ventilated by a quasi-sinusoidal pump with a constant end-expiratory lung volume and tidal volumes of 10, 20, and 40% of vital capacity at breathing frequencies ranging from 5 to 45 breaths/min. Inhomogeneity of PA was quantified as the sample standard deviation of pressures measured in three capsules. A component of inhomogeneity in phase with flow and a smaller component out of phase with flow were present. The in-phase component increased approximately linearly with flow. The ratio of inhomogeneity to flow was smaller at large tidal volumes and, at the two higher tidal volumes studied, the ratio was greater during inspiration than during expiration. If these data are interpreted in terms of a simple circuit model, this degree of inhomogeneity implies an approximately twofold variation in regional time constants. Despite these considerable differences in time constants, the absolute amount of inhomogeneity as defined by the sample standard deviation of the three PA's was small (maximum 0.57 +/- 0.32 cmH2O at the highest breathing frequency and tidal volume) because airway resistance in the canine lung was small.
A statistical model of the VA/Q distribution
Authors: Lim L. L.
Published: December 2017

A “blocks model” is proposed to model the distribution of the ventilation-perfusion ratio (VA/Q distribution). This model is developed from statistical principles and enables the estimated VA/Q distribution to be interpreted in a straightforward and intuitive manner. Estimation of parameters of the blocks model uses a constrained weighted least-squares procedure. Although developed initially to estimate VA/Q distributions from data generated by the multiple inert gas elimination technique (P. D. Wagner, H. A. Saltzman, and J. B. West, J. Appl. Physiol. 36: 588-599, 1974), the blocks method is applicable to any problem in which the unknown distribution is related to the data through an ill-posed integral equation and is particularly suited for problems in which the data are scarce. The method is illustrated with several examples--hypothetical data representing a wide range of VA/Q distributions as well as some real data.
Linkage between parasternals and external intercostals during resting breathing
Authors: De Troyer A. , Farkas G. A.
Published: December 2017

To assess the mechanical coupling between the parasternal and external intercostals in the cranial portion of the rib cage, we measured the respiratory changes in length and the electromyograms of the two muscles in the same third or fourth intercostal space in 24 spontaneously breathing dogs. We found that 1) the amount of inspiratory shortening of the external intercostal was considerably smaller than the amount of shortening of the parasternal; 2) after selective denervation of the parasternal, the inspiratory shortening of both the parasternal and the external intercostal was almost abolished; 3) on the other hand, after selective denervation of the external intercostal, the inspiratory shortening of the parasternal was unchanged, and the inspiratory shortening of the external intercostal was reduced but not suppressed; and 4) this persistent shortening of the external intercostal was reversed into a clear-cut inspiratory lengthening when the parasternal was subsequently denervated. We conclude that in the dog 1) the inspiratory contraction of the external intercostals in the cranial portion of the rib cage is agonistic in nature as is the contraction of the parasternals; 2) during resting breathing, however, the changes in length of these external intercostals are largely determined by the action of the parasternals. These observations are consistent with the idea that in the dog, the parasternals play a larger role than the external intercostals in elevating the ribs during resting inspiratio
Plasma catecholamines in the aorta and the phrenicoabdominal vein in exercising dogs
Authors: Beliveau L. , Peronnet F. , Trudeau F. , Brisson G. , Nadeau R.
Published: December 2017

Plasma epinephrine and norepinephrine concentrations were measured in the aorta and phrenicoabdominal vein in five dogs at rest and during short-duration mild- and moderate-intensity exercise and during prolonged mild-intensity exercise. Plasma epinephrine and norepinephrine concentrations increased with exercise in both the aorta and the phrenicoabdominal vein. Plasma epinephrine concentration was much higher in the phrenicoabdominal vein than in the aorta (24-43 times). Plasma epinephrine concentrations in the aorta and phrenicoabdominal vein were significantly correlated (r = 0.88). This confirms that peripheral epinephrine concentration is a reliable index of the activity of the adrenal medulla during exercise. The epinephrine-to-norepinephrine ratio in the phrenicoabdominal vein was stable (4:1) throughout the experimental protocol, suggesting that the proportion of the two amines released by the adrenal medulla did not vary through this range of adrenal activity in dogs.
Effects of exercise on insulin-induced hypoglycemia
Authors: Arogyasami J. , Conlee R. K. , Booth C. L. , Diaz R. , Gregory T. , Sephton S. , Wilson G. I. , Winder W. W.
Published: December 2017

The purpose of this study was to determine the effect of exercise on the rate of onset of hypoglycemia induced by infusion of excess insulin (0.8 mU.min-1.100 g-1). Rats were either fasted overnight (FS) or fed ad libitum (FD). FS rats were killed after 5, 10, or 15 min of infusion at rest or after running on the treadmill at 21 m/min and 15% grade. FD rats were killed after 10, 20, or 40 min of infusion at rest or after exercise. Rats were also killed 15 min postexercise for FS and 60 or 120 min postexercise for FD with continued insulin infusion. The progressive decline in blood glucose was not altered by exercise in the FS rats. FD rats showed a significant difference due to exercise only after 40 min (rest 4.2 +/- 0.3 mM, exercise 3.2 +/- 0.2 mM). A significant postexercise repletion of glycogen was observed in red vastus and soleus muscles of FD rats despite the decreasing blood glucose values. These data indicate that exercise accelerates the rate of development of hypoglycemia in FD rats. In the FS rats, where the rate of decline in blood glucose was greater, exercise had no effect on the time course of development of hypoglycemia.
Sympathetic secretory response to hypercapnic acidosis in swine
Authors: Brofman J. D. , Leff A. R. , Munoz N. M. , Kirchhoff C. , White S. R.
Published: December 2017

We studied the effect of graded acute hypercapnic acidosis (HA) on sympathetic neural activation in 15 juvenile farm swine in vivo. In seven animals with acute HA, plasma norepinephrine (NE) concentration increased progressively from 189 +/- 34 to 483 +/- 80 pg/ml (P less than 0.04) as arterial CO2 partial pressure (PaCO2) increased in steps from 40 to 80 Torr (pH 7.17 +/- 0.01). Plasma epinephrine (EPI) concentration increased from 30 +/- 15 to 125 +/- 66 pg/ml (P = NS) over the same change in PaCO2. At PaCO2 of 110 Torr, plasma NE increased 3.4-fold above maximal basal concentrations; plasma EPI was 1.8-fold greater than basal under the same conditions. With HA, systemic vascular resistance (SVR) decreased from 1,748 +/- 110 to 1,392 +/- 145 dyn.s.cm-5 (P less than 0.0002), cardiac output (CO) increased from 3.4 +/- 0.3 to 4.3 +/- 0.3 l/min (P less than 0.01), and heart rate (HR) increased from 117 +/- 11 to 154 +/- 17 beats/min (P less than 0.03). To demonstrate that catecholamine secretion was related directly to acidosis caused by an increase in PaCO2, HCO3- was infused in eight other swine to buffer extracellular acute HA (pH 7.37 +/- 0.01 at PaCO2 of 80 Torr). Buffering attenuated the increase in plasma NE, which remained within the normal range at PaCO2 of 80 Torr. The decrease in SVR and increases in CO and HR also were also attenuated by HCO3- buffering of HA. We demonstrate the effects of graded acute HA on endogenous secretion of catecholamine and on the associated hemodynamic responses in swine.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurement of phase I volume breath by breath in spontaneously breathing guinea pigs
Authors: Gaertner T. , Barnikol W. K.
Published: December 2017

A new method to determine phase I volume in tracheotomized spontaneously breathing guinea pigs is presented. Measurements were performed in three animals weighing 567-896 g. In simultaneous tracings of tidal volume (VT) and expiratory profiles of endogenous gases (PO2 or PCO2), the phase I volume of each breath was determined graphically as the volume expired up to the end of phase I of the expirogram. The mean phase I volume of different animals ranged from 0.29 to 0.43 ml with an arithmetic dispersion between 0.014 and 0.021 ml. Spontaneous sighs sometimes with doubling of the VT caused a significant rise of phase I volume up to 50% of the normal values. The linear regression curve was calculated for corresponding VT's and phase I volumes. The VT gradient of the phase I volume as the slope of this curve ranged from 0.108 to 0.217 ml/ml VT. The results of the new procedure, which works also with humans and rabbits, are discussed in respect to improvement of the characterization of the bronchial system. Compared with the human system, the VT gradient of the guinea pig is four times greater. By not being affected by disorders in pulmonary gas exchange, the phase I volume determined as described is a new suitable quantity to specifically assess actions and reactions of the bronchial system.
Sensitivity analysis of respiratory parameter uncertainties: impact of criterion function form and constraints
Authors: Lutchen K. R.
Published: December 2017

A sensitivity analysis based on weighted least-squares regression is presented to evaluate alternative methods for fitting lumped-parameter models to respiratory impedance data. The goal is to maintain parameter accuracy simultaneously with practical experiment design. The analysis focuses on predicting parameter uncertainties using a linearized approximation for joint confidence regions. Applications are with four-element parallel and viscoelastic models for 0.125- to 4-Hz data and a six-element model with separate tissue and airway properties for input and transfer impedance data from 2-64 Hz. The criterion function form was evaluated by comparing parameter uncertainties when data are fit as magnitude and phase, dynamic resistance and compliance, or real and imaginary parts of input impedance. The proper choice of weighting can make all three criterion variables comparable. For the six-element model, parameter uncertainties were predicted when both input impedance and transfer impedance are acquired and fit simultaneously. A fit to both data sets from 4 to 64 Hz could reduce parameter estimate uncertainties considerably from those achievable by fitting either alone. For the four-element models, use of an independent, but noisy, measure of static compliance was assessed as a constraint on model parameters. This may allow acceptable parameter uncertainties for a minimum frequency of 0.275-0.375 Hz rather than 0.125 Hz. This reduces data acquisition requirements from a 16- to a 5.33- to 8-s breath holding period. These results are approximations, and the impact of using the linearized approximation for the confidence regions is discussed.
Central nervous effects of CRF and angiotensin II on cardiac output in conscious rats
Authors: Overton J. M. , Davis-Gorman G. , Fisher L. A.
Published: December 2017

Studies were performed to determine whether the central nervous system actions of corticotropin-releasing factor (CRF) and angiotensin II (ANG II) on systemic arterial pressure are mediated, in part, through changes in cardiac output (CO). Changes in CO after intracerebroventricular administration of ANG II and CRF were assessed in conscious unrestrained rats bearing pulsed Doppler flow probes on the ascending aorta. Intracerebroventricular injection of CRF (0.15 nmol) increased arterial pressure (15-20 mmHg), heart rate (70-100 beats/min), and CO (25-35%) without significantly affecting total peripheral resistance. Intracerebroventricular injection of ANG II (0.1 nmol) produced similar elevations of arterial pressure (15-20 mmHg). However, the ANG II-induced pressor response was attended by significant decreases in heart rate (20 beats/min) and CO (10-15%) and significant increases in total peripheral resistance (30-40%). The results of these studies demonstrate that CO, as assessed by pulsed Doppler flow probe methodology, may be influenced significantly and differentially by central nervous system administration of CRF and ANG II.
A comparison of changes in esophageal pressure and regional juxtacardiac pressures
Authors: Smiseth O. A. , Veddeng O.
Published: December 2017

The relationship between esophageal pressure and juxtacardiac pressures was studied during positive end-expiratory pressure (PEEP) ventilation applied to both lungs or selectively to one lung. The experiments were performed in eight anesthetized dogs with balloon catheters in the esophagus and in the left and right pericardial and overlying pleural cavities and with an open-ended liquid-filled catheter in the pleural cavity. Bilateral PEEP (10, 20, and 30 cmH2O) caused progressive and similar increments in left and right pleural pressure. Selective PEEP, however, increased ipsilateral pleural balloon pressure more than contralateral pressure. The increase in ipsilateral pleural balloon pressure markedly exceeded the increase in esophageal pressure. There was a small increase in pleural open-ended catheter pressure that approximated the increase in esophageal pressure. During selective PEEP, pericardial balloon pressure remained uniform because of a decrease in ipsilateral pericardial transmural pressure. In conclusion, selective PEEP caused nonuniform increments in regional pleural balloon pressure. Left and right pericardial balloon pressure, however, increased uniformly with selective PEEP because of reduced ipsilateral pericardial transmural pressure. The esophageal balloon did not reflect the marked regional increments in pleural balloon pressure with selective PEEP and consistently underestimated the changes in pleural balloon pressure with general PEEP.
Tracheal blood flow during spontaneous and mechanical ventilation of dry gases in sheep
Authors: White D. A. , Parsons G. H.
Published: December 2017

Tracheal blood flow increases greater than twofold in response to eucapnic hyperventilation of dry gas in anesthetized sheep. To determine whether this occurs at normal minute ventilation, we studied sheep in which tracheal blood flow was measured in response to humid and dry gas ventilation while 1) awake and spontaneously breathing and 2) anesthetized and intubated during isocapnic mechanical ventilation. In additional sheep, three tracheal mucosal temperatures were measured during humid and dry gas mechanical ventilation to measure airway tissue cooling. Tracheal blood flow was determined by use of a left atrial injection of 15-microns-diam radiolabeled microspheres. Previously implanted flow probes on the pulmonary artery and the common bronchial artery allowed continuous recording of cardiac output and bronchial blood flow. Tracheal blood flow in awake spontaneously breathing sheep was 10.8 +/- 5.6 (SD) ml.min-1.100 g wet wt-1 while humid gas was breathed, and it was unchanged with dry gas. In contrast, isocapnic ventilation of intubated animals with dry gas resulted in a 10-fold increase in blood flow to the most proximal two-ring tracheal segment compared with that seen while humid gases were spontaneously ventilated [101 +/- 75 vs. 11 +/- 6 (SD) ml.min-1.100 g-1, P less than 0.05]. Despite a 10-fold increase in proximal tracheal blood flow, there was no response in distal tracheal and bronchial blood flow, as indicated by no change in the common bronchial artery blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary blood volume and edema in postpneumonectomy lung growth in rats
Authors: Doerschuk C. M. , Sekhon H. S.
Published: December 2017

After pneumonectomy in young animals, the contralateral lung undergoes compensatory growth and generally attains the same weight and air space volume as both lungs in age-matched controls. In this study, we determined the contribution of lung edema and increased blood volume to the weight gain in rats. Three weeks after pneumonectomy (n = 18) or sham pneumonectomy (n = 17), the pulmonary blood volume and the extravascular water and albumin were evaluated by use of 51Cr-labeled erythrocytes and 125I-labeled albumin. The air space volume, blood-free lung weights, and DNA and protein content were also compared. The data show that the total pulmonary blood volumes and the blood volume per gram of blood-free dry lung were similar in pneumonectomized and age-matched sham controls. The total extravascular albumin and the extravascular albumin per gram of blood-free dry lung were also similar as well as the extravascular lung water, wet-to-dry weight ratios, DNA and protein content, and air space volumes. These data indicate that the increased weight of the postpneumonectomy lung was due to cellular and stromal proliferation. The blood volume and interstitial fluid increased in proportion to the increase in lung parenchyma. Neither vascular congestion nor increased extravascular protein and water contributed to the observed weight gain.
Membrane and cellular properties in oscillating networks: implications for respiration
Authors: Dekin M. S. , Haddad G. G.
Published: December 2017

Because of a number of major advances in the past one to two decades, there is little doubt that the inherent cellular and membrane properties of neurons in an oscillating network play an important role in shaping the output of that network. There are a number of such examples in vertebrate and invertebrate systems. In this review, we present some of the newer methods that have been used in the identification of membrane properties and detail some cellular studies performed in both vertebrate (locomotion and sleep/waking rhythms) and invertebrate network systems (escape swimming in Tritonia diomedia and pyloric rhythm in Panulirus interruptus). Studies examining the cellular or membrane properties of respiratory neurons have been scarce until recently. The importance of these properties in dictating respiratory rhythm generation and output in the mature and immature animal is not yet known; however, we put this issue in perspective by building a parallel between mammalian respiration and other vertebrate networks that have been better investigated and characterized.
Effect of left atrial pressure on bronchial vascular hemodynamics
Authors: Wagner E. M. , Mitzner W. A.
Published: December 2017

We studied the bronchial vascular response to downstream pressure elevation by increasing left atrial pressure (Pla) and mean airway pressure (Paw) with positive end-expiratory pressure (PEEP). In seven pentobarbital-anesthetized ventilated sheep, we cannulated and perfused the bronchial branch of the bronchoesophageal artery. Steady-state bronchial artery pressure- (Pba) flow (Qba) relationships were obtained as Pla was increased by inflating a balloon catheter in the left atrium. Bronchial vascular resistance (BVR), determined by the inverse slope of the Pba-Qba relationship, increased significantly from 3.2 +/- 0.3 (SE) mmHg.ml-1.min-1 at a Pla of 2.9 +/- 0.7 mmHg to 5.1 +/- 0.5 mmHg.ml-1.min-1 at a Pla of 20.1 +/- 2.0 mmHg (P = 0.0007). Under control Qba (23.3 +/- 1.2 ml/min), these changes in BVR represent a 3.6 +/- 0.7-mmHg increase in Pba per mmHg increase in Pla. The zero-flow pressure increased 1.3 +/- 0.2 mmHg/mmHg increase in Pla. After infusion of papaverine, a smooth muscle paralytic agent, directly into the bronchial artery, BVR decreased significantly to 1.3 +/- 0.7 mmHg.ml-1.min-1 (P = 0.0004). Under these dilated conditions, BVR was unaltered by increases in Pla. After papaverine administration, Pba increased 0.9 +/- 0.1 and 1.2 +/- 0.1 mmHg/mmHg increase in Pla during control and zero-flow conditions, respectively. Thus the effect of Pla elevation on BVR appears to be dependent on active smooth muscle responses. Paw elevation had similar effects on Pba. Under control Qba, Pba increased 2.2 +/- 0.4 mmHg/mmHg increase in Paw.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of continuous low-frequency pacing on immature canine diaphragm
Authors: Marzocchi M. , Brouillette R. T. , Klemka-Walden L. M. , Heller S. L. , Weese-Mayer D. E. , Brozanski B. S. , Caliendo J. , Daood M. , Ilbawi M. N. , Hunt C. E.
Published: December 2017

Although diaphragm pacing has been shown to be a practical method of supporting ventilation in children, its usefulness has been limited because of concern that continuous (24 h/day) diaphragm pacing would fatigue and damage the diaphragm. We examined the functional and structural effects of continuous low-frequency diaphragm pacing on the left hemidiaphragm of five immature dogs aged 65 +/- 2 (SD) days at onset of pacing. Stimulus parameters approximated those required to pace infants: frequency 11.1 Hz, inspiratory time 810 ms, and respiratory rate 20 breaths/min. Animals were paced 24 h/day for 24-28 days. Paced tidal volumes and airway occlusion pressures were unchanged at low (less than 15 Hz) stimulus frequencies but were reduced at high (greater than 20 Hz) stimulus frequencies. Although histologically the paced hemidiaphragms appeared normal, histochemical studies showed a conversion from a mixture of type I (54%) and type II (46%) fibers to a uniform population of type I fibers with high oxidative enzyme activity. Transformation of muscle type was also demonstrated by pyrophosphate gel electrophoresis; fast and slow isomyosin bands were noted in control specimens, whereas only slow isomyosin was identified in paced specimens. Thus, in immature dogs, continuous low-frequency pacing affects both function and structure of the diaphragm.
Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans
Authors: Hampson N. B. , Camporesi E. M. , Stolp B. W. , Moon R. E. , Shook J. E. , Griebel J. A. , Piantadosi C. A.
Published: December 2017

The effects of mild hypoxia on brain oxyhemoglobin, cytochrome a,a3 redox status, and cerebral blood volume were studied using near-infrared spectroscopy in eight healthy volunteers. Incremental hypoxia reaching 70% arterial O2 saturation was produced in normocapnia [end-tidal PCO2 (PETCO2) 36.9 +/- 2.6 to 34.9 +/- 3.4 Torr] or hypocapnia (PETCO2 32.8 +/- 0.6 to 23.7 +/- 0.6 Torr) by an 8-min rebreathing technique and regulation of inspired CO2. Normocapnic hypoxia was characterized by progressive reductions in arterial PO2 (PaO2, 89.1 +/- 3.5 to 34.1 +/- 0.1 Torr) with stable PETCO2, arterial PCO2 (PaCO2), and arterial pH and resulted in increases in heart rate (35%) systolic blood pressure (14%), and minute ventilation (5-fold). Hypocapnic hypoxia resulted in progressively decreasing PaO2 (100.2 +/- 3.6 to 28.9 +/- 0.1 Torr), with progressive reduction in PaCO2 (39.0 +/- 1.6 to 27.3 +/- 1.9 Torr), and an increase in arterial pH (7.41 +/- 0.02 to 7.53 +/- 0.03), heart rate (61%), and ventilation (3-fold). In the brain, hypoxia resulted in a steady decline of cerebral oxyhemoglobin content and a decrease in oxidized cytochrome a,a3. Significantly greater loss of oxidized cytochrome a,a3 occurred for a given decrease in oxyhemoglobin during hypocapnic hypoxia relative to normocapnic hypoxia. Total blood volume response during hypoxia also was significantly attenuated by hypocapnia, because the increase in volume was only half that of normocapnic subjects. We conclude that cytochrome a,a3 oxidation level in vivo decreases at mild levels of hypoxia. PaCO is an important determinant of brain oxygenation, because it modulates ventilatory, cardiovascular, and cerebral O2 delivery responses to hypoxia.
Cardiogenic oscillations in He and SF6 expirograms during airway and venous loading
Authors: Meyer M. , Lewis S. M. , Mohr M. , Schulz H. , Schuster K. D. , Piiper J.
Published: December 2017

Cardiogenic oscillations in the expired partial pressure profiles of two inert gases (He and SF6) were monitored in seven anesthetized paralyzed mechanically ventilated dogs. He and SF6 were administered either intravenously by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)] or by washin into lung gas [airway loading (AL)]. The single-breath expirograms obtained during constant-flow expiration after inspiration of test gas-free air displayed distinct and regular cardiogenic oscillations. The relative oscillation amplitude (ROA), calculated as oscillation amplitude divided by mixed expired-inspired partial pressure difference, was in the range of 1-8%. The ROA for both He and SF6 was approximately 4.2 times higher in VL than in AL, which indicated that among lung units that emptied sequentially in the cardiac cycle, the effects of alveolar ventilation-perfusion (VA/Q) inequality were more pronounced than those of alveolar ventilation-alveolar volume (VA/VA) inequality. In AL, He and SF6 oscillations were 180 degrees out of phase compared with CO2 and O2 oscillations and with He and SF6 oscillations in VL, which suggests that regions with low VA/VA had high VA/Q and very low Q/VA. The ROA was practically unaffected by breath holding in both AL and VL, which indicates that there was little diffusive or convective (cardiogenic) mixing between the lung units that were responsible for cardiogenic oscillations. The ROA was consistently higher for He than for SF6, and the He-to-SF6 ratio was independent of route of test gas loading, averaging 1.6 in both AL and VL. This result may be explained by laminar Taylor dispersion, whereby oscillations generated in peripheral lung regions are dissipated in inverse proportion to diffusion coefficient during transit through the proximal (larger) airways.
Effect of LY171883 on endotoxin-induced lung injury in pigs
Authors: Olson N. C. , Kruse-Elliott K. T. , Johnson L.
Published: December 2017

We evaluated the role of sulfidopeptide leukotrienes as mediators of endotoxin-induced respiratory failure in pigs. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h followed by 2 micrograms.kg-1.h-1 for 3 h in the presence and absence of LY171883, a specific leukotriene D4 (LTD4)/LTE4 receptor antagonist. Endotoxin caused hemoconcentration, granulocytopenia, decreased cardiac index, systemic hypotension, pulmonary hypertension, increased pulmonary vascular resistance, bronchoconstriction, hypoxemia, increased permeability of the alveolar-capillary membrane, pulmonary edema, and increased plasma concentrations of thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha), and 6-keto-PGF1 alpha. LY171883 did not modify endotoxin-induced cardiopulmonary and hematologic abnormalities, except for a modest attenuation of pulmonary hypertension (at 1 h) and increased pulmonary vascular resistance (at 1-2 h). Ex vivo stimulation of whole blood with calcium ionophore caused large increases in plasma concentrations of TxB2, PGF2 alpha, and LTB4. These increases were not significantly modified in blood derived from pigs treated with LY171883, indicating no inhibition of cyclooxygenase or 5-lipoxygenase. We conclude that LTD4 and LTE4 are not important mediators of endotoxin-induced lung injury in anesthetized pigs, although they may contribute modestly to pulmonary vasoconstriction.
Vagal innervation of guinea pig bronchial smooth muscle
Authors: Undem B. J. , Myers A. C. , Barthlow H. , Weinreich D.
Published: December 2017

We isolated the guinea pig right bronchus with the vagus nerves intact and evaluated the changes in isometric tension of the smooth muscle in response to nerve stimulation. Brief (10-s) trains of electrical field stimulation or vagus nerve stimulation caused a biphasic contraction: the "first phase" sensitive to atropine and the "second phase" sensitive to capsaicin. The two phases could be dissociated by adjusting the stimulus intensity; greater stimulus intensities (pulse durations or voltage) were required to evoke the capsaicin-sensitive phase. When stimulated at 30-min intervals, the magnitude of both phases of the contractions declined over a 2-h period of repeated stimulation; however, this was prevented by indomethacin. Stimulation of the left vagus nerve resulted in a monophasic contraction of the right bronchus, with little evidence of a capsaicin-sensitive phase. Blocking neurotransmission through the bronchial ganglion, as monitored by intracellular recording techniques, abolished the first-phase contraction but had no effect on the capsaicin-sensitive phase. Selective blockade of muscarinic M1 receptors had no effect on vagus nerve-mediated contractions. The results demonstrate that the left and right vagus nerves carry preganglionic fibers to the right bronchial ganglion. The right but not the left vagus nerve also carries capsaicin-sensitive afferent fibers that, when stimulated, result in a persistent contraction of the right bronchus. Finally, we provide functional and electrophysiological evidence supporting the hypothesis that capsaicin-sensitive afferent neurons communicate with postganglionic motoneurons within the bronchus.
Effect of exercise conditioning on excitation-contraction coupling in aged rats
Authors: Gwathmey J. K. , Slawsky M. T. , Perreault C. L. , Briggs G. M. , Morgan J. P. , Wei J. Y.
Published: December 2017

We studied aged (24-26 mo) Fischer 344 rats after they underwent 8 wk of moderate exercise conditioning. Right ventricular papillary muscles were loaded with the calcium indicator aequorin. Electrophysiological recordings were also performed. Time to peak isometric tension in muscles from exercised aged rats (EAR) was shorter than in those from unexercised aged rats (UAR) (126 +/- 7 vs. 167 +/- 7 ms; P less than 0.01). Time to 50% relaxation from peak isometric tension was also shorter in EAR than in UAR (88 +/- 3 vs. 119 +/- 12 ms; P less than 0.05). There was a trend toward decrease in time to peak light and a significant decrease in time to 50% decline from peak light (33 +/- 4 ms in EAR vs. 59 +/- 17 ms in UAR; P = 0.001). Action potential amplitude was smaller in EAR than in UAR (67 +/- 4 vs. 82 +/- 3 mV; P = 0.003); however, action potential duration was longer (137 +/- 6 ms in EAR vs. 100 +/- 10 ms in UAR; P = 0.005). Right ventricular-to-body weight ratios revealed no evidence of hypertrophy in EAR compared with UAR. Cardiac tissue norepinephrine content was significantly greater in EAR than in UAR (1,212 +/- 25 vs. 630 +/- 105 ng/tissue; P = 0.02). In summary, exercise reversed the age-related prolongation of isometric contraction and associated intracellular calcium transient in the aged rat while it prolonged the transmembrane action potential. In addition, exercise in aged rats resulted in an increase in cardiac norepinephrine content.
Effect of synchronous increase in intrathoracic pressure on cardiac performance during acute endotoxemia
Authors: Guimond J. G. , Pinsky M. R. , Matuschak G. M.
Published: December 2017

In the anesthetized closed-chest canine model of Gram-negative endotoxemia (n = 10), we tested the hypothesis that the effect of cardiac cycle-specific intrathoracic pressure pulses delivered by a heart rate-(HR) synchronized high-frequency jet ventilator (sync HFJV) on systolic ventricular performance is dependent on the level of preload. To control for HFJV frequency, hemodynamic responses were also measured at fixed frequency within 15% of HR (async HFJV). Biventricular stroke volumes (SV) were measured by electromagnetic flow probes. Measurements were made before (baseline) and 30 min after infusion of 1 mg/kg Escherichia coli endotoxin (serotype 055:B5) and then after 2 mg/kg propranolol at both low (less than 10 mmHg) left ventricular filling pressure (LVFP) and high (greater than 10 mmHg) LVFP. Ventricular function curves, aortic pressure-flow (P-Q) relationships, and venous return (VR) curves were analyzed. We found that endotoxin did not alter VR curves but shifted the aortic P-Q curves to the left with pressure on the x-axis (P less than 0.05). Volume loading increased SV (P less than 0.01) because of a rightward shift of the VR curve. No specific differences occurred with either sync or async HFJV during endotoxin, presumably because of preserved VR and shifted aortic P-Q. The lack of cardiac cycle-specific effects of ITP appears to be due to the selective endotoxin-induced changes in peripheral vasomotor tone that counterbalance any depressed myocardial contractility.
A very low dead space pneumotachograph for ventilatory measurements in newborns
Authors: Vallinis P. , Davis G. M. , Coates A. L.
Published: December 2017

In premature and full-term neonates, technical limitations hamper the measurements of pulmonary mechanics. Current commercially available pneumotachographs (PNT) either increase the dead space, causing hyperventilation, or increase resistance, thus altering the mechanics of breathing. We modified a previously described low dead space PNT for infants to increase the linear range and frequency response. The mean resistance of the new PNT was 2.44 cmH2O.1-1.s compared with 2.65 cmH2O.1-1.s for the Fleisch no. 0 PNT. The added dead space over the standard endotracheal connector was 0.6 ml compared with 4.7 ml for the Fleisch PNT. Like the Fleisch PNT, the flow resistance was linear from 0 to 15 l/min. In response to a sinusoidal waveform, the new PNT had a phase angle of 21 degrees at 5 Hz and 50 degrees at 16 Hz compared with 19 degrees and 43 degrees, respectively, for the Fleisch PNT. The change in attenuation for both systems was zero until 20 Hz. In summary, the new PNT is lightweight and provides accuracy and low resistance with a very small dead space.