Biomedical subjects

G Nakos

Publications and source records attributed to G Nakos.

At least 37 records · Page 2Linked to original sources

PubMed1997

Conditional evaluation of broncho-alveolar lavage in mechanically ventilated patients with suspected unilateral lobar pneumonia.

OBJECTIVE: In an attempt to improve our ability to diagnose the cause of ventilator-associated pneumonia (VAP), we explore the usefulness of the conditional evaluation of bronchoalveolar lavage (BAL) samples from the involved and non-involved areas in patients with suspected unilateral lobar VAP (UL-VAP). DESIGN: Prospective study. SETTING: University teaching hospital intensive care unit. PATIENTS: We studied 19 consecutive patients with suspected UL-VAP. MEASUREMENTS AND MAIN RESULTS: Nine of the 12 patients (47%) developed UL-VAP. There was a significant difference between the involved and non-involved areas in UL-VAP patients (P < 0.001) in respect of the quantitative bacterial cultures (QBCs) of BAL samples for each micro-organism, whereas there was no difference in patients without UL-VAP. When we applied the criterion of usual BAL (one micro-organism in concentrations > 10(5) colony-forming units per millilitre) for UL-VAP diagnosis, the sensitivity was 100%, the specificity 70%, the positive predictive value 75%, and the negative predictive value 100%. When we used the conditional evaluation of the BAL results for UL-VAP diagnosis, in the involved and non-involved areas, the sensitivity was 78%, the specificity 90%, the positive predictive value 87.5% and the negative predictive value 82%. A statistically significant difference was found when we compared the difference in QBCs between the BAL samples for each micro-organism, between the involved and non-involved areas in patients with and without VAP (P < 0.001). CONCLUSION: These data suggest that utilisation of the conditional evaluation of the QBCs of BAL samples improves significantly our ability to diagnose the cause of UL-VAP.

Adult↗

PubMed1996

Nitric oxide synthase I immunoreactivity and NOS-associated NADPHd histochemistry in the visceral epithelial cells of the intraplacental mouse yolk sac.

In the course of our studies on the local blood flow modulation in the NMRI-mouse placenta we have focussed on regulatory pathways involving recently appreciated gaseous messenger molecules nitric oxide (NO) and carbon monoxide (CO), which are generated by NO synthase (NOS) and heme oxygenase (HO)-2, respectively. The distribution of NOS was investigated by immunohistochemistry using an antiserum to the neuronal isoform (NOS-I) and by NADPH diaphorase (NADPHd) histochemistry, supplemented with procedures (permanganate and formaldehyde method) serving to enhance the specificity of the enzyme histochemical method for NOS visualization. HO-2 was demonstrated immunohistochemically. In addition, cyclic guanosine monophosphate (cGMP)-forming soluble guanylate cyclase (sGC) and dehydrogenases generating the NOS co-substrate NADPH were analysed either by immunohistochemistry or enzyme histochemistry. NOS-I immunostaining was observed in the intraplacental visceral yolk sac epithelial cells but not in the placenta and extraplacental visceral epithelial yolk sac cells. Co-localization of NOS-I immunolabeling and NOS-associated NADPHd was exclusively found in the intraplacental visceral epithelial cells, while NADPHd activity not associated to NOS was present in other placental and extraplacental cells additionally analysed for control reasons. HO-2 and sGC immunoreactivity could not be detected in the placenta including the intraplacental visceral epithelial cells but were expressed in several extraplacental cells. Dehydrogenases producing the NOS co-substrate NADPH were present in the intraplacental visceral epithelium as well as in other placental and extraplacental cells. Since the intraplacental visceral epithelial yolk sac layer closely accompanies large fetal blood vessels entering the placental labyrinth from the chorionic plate it may be assumed that NO, generated by the NADPH-consuming NOS-I in the intraplacental yolk sac epithelium, acts to regulate the blood flow by relaxing smooth muscle cells in the wall of these fetal vessels. The lack of immunoreactivity to the NO-effector molecule sGC may be due to methodological reasons. The absence of the HO-2/CO system suggests its insignificant role as a potential gas signaling pathway in the vascular smooth muscle system of the intraplacental visceral yolk sac of mice.

Animals↗

PubMed1996

Tracheal gas insufflation: catheter effectiveness determined by expiratory flush volume.

Used adjunctively during mechanical ventilation, tracheal gas insufflation (TGI) improves CO2 elimination, principally by decreasing effective anatomic dead space. Continuing lung deflation at end- expiration raises the end-expiratory C02 concentration within the proximal airway, and could theoretically reduce the efficiency of a given catheter flow. To test this possibility, we designed a series of experiments that examined the influence of TGI delivery patterns on the efficiency of CO2 elimination. Using a gating device, catheter flow was delivered selectively during desired portions of expiration. Paralyzed, ventilated dogs were studied at short and extended inspiratory time fractions (TI/TT) with inspiratory tidal volume and ventilator frequency held constant. The expiratory flush volume, not the pattern of gas delivery, determined the observed decline in PaCO2, provided that the end-expiratory period was included in the catheter flush period. Despite continuing end-expiratory lung deflation (extended TI/TT), catheter effectiveness remained the same at matched expiratory flush volumes. To determine if enhanced distal mixing at the higher catheter flows required during the extended TI/TT (to match expiratory flush volume) masked a decrease in efficiency, we repeated the experiment with a tip-inverted catheter. We again found that matched catheter delivered expiratory volumes were similarly effective. With or without ongoing lung deflation, the volume of gas flushed during the expiratory period determined the effectiveness of TGI, provided that inspired minute ventilation remains unchanged and end-expiration is included in the catheter flush period.

Analysis of Variance↗

PubMed1995

Species-independent expression of nitric oxide synthase in the sarcolemma region of visceral and somatic striated muscle fibers.

The expression and distribution of nitric oxide synthase (NOS) was studied by use of the newly designed specific histochemical NADPH diaphorase staining method and the indirect immunofluorescence technique employing an antiserum to brain NOS in visceral and somatic striated muscles of several mammalian species. Histochemical activity and immunoreactivity were located in the sarcolemma region of type I and II fibers of all muscles investigated. Visceral muscles were more strongly stained than somatic muscles. Furthermore, type II fibers, identified by staining of myosin adenosine triphosphatase activity after pre-incubation at alkaline pH, were more intensely labeled than type I fibers. In addition, NOS activity was detected in the area of the sarcolemma of intrafusal fibers. No obvious differences between species were observed. It was concluded that NOS of striated muscles probably makes up the richest and most important nitric oxide source in mammals.

Animals↗

PubMed1995

Respiratory effects of tracheal gas insufflation in spontaneously breathing COPD patients.

OBJECTIVE: To evaluate the effect of tracheal gas insufflation (TGI) in spontaneously breathing, intubated patients with chronic obstructive pulmonary disease (COPD) undergoing weaning from the mechanical ventilation. DESIGN: A prospective study in humans. SETTING: Polyvalent intensive care unit (14-bed ICU) in a 700-bed general university hospital. PATIENTS: Twelve patients with chronic obstructive pulmonary disease (COPD) who required intubation and mechanical ventilation were studied. All patients met standard criteria for weaning from mechanical ventilation. Seven patients (group 1) had been transorally intubated during episodes of acute respiratory failure. Five patients, all men (group 2), had previously undergone tracheostomy and had a transtracheal tube in place. INTERVENTIONS: Intratracheal, humidified, O2-mixture insufflation (TGI) was given via a catheter placed in distal or proximal position. Gas delivered through the intratracheal catheter was blended to match the fractional of inspired gas through the endotracheal tube. Continuous flows of 3 and 6 l/min in randomized order were used in each catheter position. Prior to data collection at each stage, an equilibration period of at least 30 min was observed, and thereafter blood gases were analyzed every 5 min. A new steady state was assumed to have been established when values of both PaCO2 and V CO2 changed by less than 5% between adjacent measurements. The last values of blood gases were taken as representative. The new steady state was confirmed within 35-50 min. Baseline measurements with zero Vcath were made at the beginning and end of the experiment. RESULTS: This study shows that VT, MV, PaCO2, and VD/VT are reduced in a flow-dependent manner when gas is delivered through an oral-tracheal tube (group 1). The distal catheter position was more effective than the proximal one. In contrast, when gas was delivered through tracheostomy (group 2), TGI was ineffective in the proximal position and less effective than in group 1 in distal position. CONCLUSION: Under the experimental conditions, tracheal gas insufflation decreased dead space, increased alveolar ventilation and possibly reduced work of breathing. From the preliminary data reported here, we believe that TGI may help patients experiencing difficulty during weaning.

Acute Disease↗

PubMed1995

Demonstration of nitric oxide synthase (NOS) in marmosets by NADPH diaphorase (NADPH-d) histochemistry and NOS immunoreactivity.

Since species interdiversity often prevents the extrapolation of laboratory rodent data to man and similar problems may exist for nitric oxide synthase (NOS), NADPH-d activity and immunohistochemistry of NOS were investigated in the New World monkey Callithrix jacchus (marmoset), which has been shown to be close to the human situation in many respects. Using the NADPHd reaction with beta-NADPH and nitroblue tetrazolium (NBT) on acetone-chloroform pretreated cryosections, NBT formazan was found in many neural and non-neural (e.g. diverse epithelia, striated muscle fibers, vascular endothelium) cells in numerous tissues and organs. Prefixation with formaldehyde lowered the number of NADPH-d active sites and the amount of formazan with the exception of neuronal NADPH-d as did incubation of fresh or acetone-chloroform-pretreated sections for NADPH-d in the presence of 0.5% formaldehyde. When 1% formaldehyde or 0.5 mM permanganate were used significant amounts of formazan appeared only in central and peripheral neurons, vasal endothelial cells, small intestinal enterocytes, plasma membrane region of striated muscle fibers as well as arteriolar cells in the kidney; except for enterocytes, these observations were confirmed by NOS-immunohistochemistry which revealed in addition reactive cells in the thymus and intestinal lamina propria.

Acetone↗

PubMed1995

Hydrogen peroxide (H2O2) production by monoamine oxidase in rat tissues using endogenous catecholamines as substrates. A comparison of catalytic monoamine oxidase histochemistry and recently published catechol-O-methyltransferase immunohistochemistry.

Histochemical studies on hydrogen peroxide (H2O2) production by monoamine oxidase (MAOX) using xenobiotic (foreign) catecholamines such as tryptamine or tyramine as substrates may not reveal the true H2O2-production capacity of this enzyme and the potential co-localization and cooperation of MAOX with catechol-O-methyltransferase (COMT), the other catecholamine-degrading enzyme. Therefore, in the present study the catecholamine hormones adrenaline (epinephrine) and noradrenaline (norepinephrine) and the catecholamine neurotransmitter noradrenaline as well as the COMT metabolites metanephrine and normetanephrine, which are likely to be the more important MAOX substrates, were used for MAOX visualization in many rat tissues with a cerium-diaminobenzidine-H2O2-Co method. Adrenaline and noradrenaline were autooxidized by Ce3+ and could not be employed; with metanephrine or normetanephrine as substrates MAOX produced considerable amounts of H2O2 in many cells and tissues. Comparisons with immunohistochemical COMT-data for rats from the literature show that MAOX and COMT are co-localized or not. Therefore, different from our current knowledge in rats COMT and MAOX either co-operate in catecholamine degradation or they degrade the respective catecholamines alone.

Animals↗

PubMed1995

Visualization of hydrogen peroxide (H2O2)-production from histamine.

The cellular and intracellular metabolization sites of the tissue hormone and paracrine compound histamine as a source for the indirect and potentially toxic or physiological mediator molecule H2O2 are not yet known. Therefore, in the present study, histamine was used as the substrate in a cerium-diaminobenzidine-H2O2-Co procedure to visualize for the first time the oxidative deamination and H2O2-production sites of this amine in various laboratory animals. Diamine oxidase (DAOX) was shown to be the responsible enzyme. With the exception of marmosets, all species could deaminate histamine oxidatively and form H2O2. In most species, H2O2 was produced by DAOX from histamine in small intestinal enterocytes; in rats H2O2 was generated in all vascular and non-vascular smooth muscle cells; in guinea-pigs only smooth muscle cells in the digestive tract and uterus and in addition the cardiac and gastric capillary endothelium and hepatic sinusoidal endothelium produced H2O2. Furthermore, in some species H2O2 was generated by DAOX with histamine as the substrate in certain renal, adrenal and splenic cell types. While H2O2-production in enterocytes may derive from luminal-borne histamine, i.e., from histamine of foreign origin, the formation of H2O2 in the other cells suggests endogenous (mast cell, basophilborne) histamine as the substrate and H2O2 source.

Amine Oxidase (Copper-Containing)↗

PubMed1995

A modified method allows for correlation between NADPH-diaphorase histochemistry and immunohistochemistry for the demonstration of neuronal nitric oxide synthase (nNOS).

Results obtained with the conventional nitro blue tetrazolium salt method for the visualization of the NADPH-diaphorase (NADPH-d) activity of nitric oxide synthase (NOS) are not specific for this particular enzyme, since this activity represents only a fraction of the total cellular NADPH-d pool. Therefore, the standard NADPH-d procedure was modified by performing the incubation in the presence of formaldehyde. Parallel application of the modified NADPH-d staining technique and the indirect immunofluorescence using an antibody against the neuronal isoenzyme (nNOS) on rat, mouse and guinea-pig tissues showed a correlation between histochemical and immunocytochemical staining. It can thus be concluded that the modified NADPH-d procedure allows for a more specific detection of the histochemical nNOS activity than the conventional method.

Animals↗

PubMed1994

Tracheal gas insufflation reduces the tidal volume while PaCO2 is maintained constant.

OBJECTIVE: The aims of the present study were two-fold: first, to confirm the effect of tracheal gas insufflation (TGI) throughout the respiratory cycle on alveolar ventilation at various catheter flows and constant total inspired VT as an adjunct to conventional volume cycled mechanical ventilation in patients with acute lung injury; second, to test the efficacy of TGI in the reduction of toal VT, peak and mean airway pressure while maintaining PaCO2 in its baseline value. The hemodynamic effect and the consequences on oxygenation as result of the reduction of VT, were also estimated. DESIGN: Prospective study of patients with acute lung injury requiring mechanical ventilation. SETTING: 12 bedded, adult polyvalent intensive care unit in a teaching hospital. PATIENTS: 7 paralyzed and sedated patients with acute respiratory failure were studied. All patients were clinically and hemodynamically stable without fluctuation of the body temperature. All patients were orally intubated with cuffed endotracheal tubes, and mechanically ventilated with a standard circuit of known compliance. INTERVENTIONS: Continuous flows (4 and 6 l/min) were delivered through a catheter positioned 1 cm above carina while tidal volume or PaCO2 were maintained constant at their baseline value. RESULTS: In this study a modest level of TGI significantly enhanced CO2 elimination in patients with acute respiratory failure. Improved ventilatory efficiency resulted from the functional reduction of dead space during TGI allowing the same PaCO2 to be maintained at the same frequency with lower tidal volume and lower airway pressure requirement. Tidal volume, peak and mean airway pressure decreased linearly with catheter flow, without significant changes in oxygenation, while PaCO2 remained stable. CONCLUSION: The results of this study suggest that TGI may be an useful adjunct mode of mechanical ventilation that limits alveolar pressure and minute ventilation requirements.

Acute Disease↗

PubMed1994

When NADPH diaphorase (NADPHd) works in the presence of formaldehyde, the enzyme appears to visualize selectively cells with constitutive nitric oxide synthase (NOS).

The NADPH diaphorase (NADPHd) reaction for nitric oxide synthase (NOS) visualization suffers from the circumstance that the diaphorase activity of NOS represents only part of the total diaphorase activity, and so far all efforts to make the reaction more specific for routine studies failed. The present investigation describes a simple procedure for mouse tissue, which allows the selective staining primarily of neurons, vascular endothelial cells and macula densa cells, those cells where constitutive NOS has been described reliably. In this method unfixed cryosections and 0.5-1% phosphate-buffered formaldehyde containing 0.5 mg NADPH/1 ml and 1 mg nitro BT/1 ml are used. Compared to strong prefixation with formaldehyde after which many additional cells are still positive for NADPHd, presence of formaldehyde in the incubation medium obviously allows the selective reaction of NOS-positive cells. In conclusion, compared with the original technique a more specific method for the visualization of the NADPHd activity of NOS appears to be available now and can be used for NOS studies in all kinds of mammalian species.

Amino Acid Oxidoreductases↗

PubMed1994

Light microscopic visualization of diamine oxidase using a cerium method.

Diamine oxidase (DAOX) can be localized in the light microscope using immunohistochemistry, but a reliable procedure for detecting the activity of the enzyme does not exist. A method was thus developed in which cerium ions trap H2O2, generated by DAOX, and a diaminobenzidine-H2O2-Co sequence serves for the visualization of the primary reaction product cerium perhydroxide. With this method and diamine substrates cadaverine or putrescine, or polyamine substrates spermidine or spermine as substrates, DAOX was localized species-independently but substrate-dependently in the basolateral cytoplasm and/or plasma membrane of small intestinal enterocytes of rats, mice and gerbils. Less, or even no, final reaction product was seen in these cells of guinea-pigs and marmosets. Colonic enterocytes were positive for DAOX solely in gerbils. Furthermore, species-dependent diamine oxidase was present in special cells of the mouse and guinea-pig kidney, immune organs and liver of rats and gerbils, marmoset placenta and in decidual cells of the human, rat and mouse placenta.

Amine Oxidase (Copper-Containing)↗

PubMed1994

Light microscopic visualization of semicarbazide-sensitive amine oxidase (benzylamine oxidase) using a cerium method.

Light microscopic histochemical studies to visualize semicarbazide-sensitive and H2O2-generating amine oxidase (SSAOX, benzylamine oxidase, BAOX; EC 1.4.3.6?) are usually performed with the coupled peroxidatic oxidation technique of Ryder et al. [25]. For methodological reasons this procedure has its limitations and was therefore replaced by a more reliable and easier to perform cerium-DAB-H2O2-Co technique. With this method SSAOX was studied in many organs of various laboratory rodents and marmosets and in human placenta. Independent of the species the enzyme was present mostly in the plasma membrane of nearly all vascular and non-vascular smooth muscle cells. However, there was a species-dependence of SSOX activity; the highest amounts of stain were found in gerbils and marmosets. In addition, the enzyme was found in these two species in the capillary endothelium of some extra-nervous tissues. The plasma membrane localization of SSAOX and plasma membrane-associated H2O2 production suggest a functional role for the enzyme different from that of other amine oxidases which appear to be primarily involved in intracellular amine detoxification or degradation.

Animals↗

PubMed1993

Haemodynamics and gas exchange in liver cirrhosis: the effect of orally administered almitrine bismesylate.

The present study was conducted to analyse the effect on haemodynamics and to evaluate the role of hypoxic pulmonary vasoconstriction (HPV) in cirrhotic patients with hypoxaemia using almitrine bismesylate, an agent which increases the response of HPV. Six male patients, mean age of 51 years, with hepatic cirrhosis and associated hypoxaemia were studied. All patients had normal lung and cardiac function tests. When the patients were clinically stable, right heart and radial artery catheterization were performed. Data from the pulmonary artery catheter and blood gases were obtained before and after 4 days of oral almitrine bismesylate. The results indicated that these cirrhotics were in a mild hyperdynamic circulatory state. The cardiac output (CO), cardiac index (CI), oxygen delivery (DO2), and oxygen consumption (VO2) were elevated while the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were low. Almitrine significantly increased PVR (P < 0.05) and mean pulmonary artery pressure (mPAP) (P < 0.01). In addition, almitrine improved alveolar arterial oxygen content difference [D(A-a)O2] (P < 0.01) and shunt fraction (Qva/QT) (P < 0.01). The PaCO2 and PaO2 increased slightly but this was not statistically significant. In conclusion, in our group of patients with hepatic cirrhosis, four days of treatment with almitrine improved their gas exchange. The data suggest a weak HPV response in this group of cirrhotics; that response may be enhanced by almitrine.

Administration, Oral↗

PubMed1993

Light microscopic visualization of monoamine oxidase using a cerium method.

H2O2-generating monoamine oxidase can be visualized in the light microscope with tetrazolium, metal salt (ferricyanide) and coupled peroxidatic oxidation methods. Due to methodological draw-backs these procedures do no allow satisfactory results. In search for an alternative method a light microscopic cerium procedure was designed in which the primary reaction product, cerium perhydroxide, serves for the generation of amplified and intensified diaminobenzidine brown. With this cerium-diaminobenzidine-H2O2-Co method monoamine oxidase was visualized more easily and reliably and with higher sensitivity and more precise localization than with the other techniques. At present this method is considered to be the procedure of choice and was used to re-investigate and investigate the distribution of monoamine oxidase in rats, mice, gerbils, guinea-pigs, marmosets, monkeys and man. In these species many cells and tissues showed monoamine oxidase activity where the enzyme has not yet been found before and the structures with already known monoamine oxidase activity showed an improved localization.

Animals↗

PubMed1993

Effect of catheter flow direction on CO2 removal during tracheal gas insufflation in dogs.

Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination by replacing CO2 in the anatomic dead space proximal to the catheter tip with fresh gas during expiration. Turbulence generated by gas exiting the catheter tip may also contribute to alveolar ventilation. To separate distal (turbulence-related) and proximal (washout of dead space) effects of TGI, we compared the efficacy of a straight and an inverted catheter during continuous and expiratory TGI in six mechanically ventilated dogs. We reasoned that the inverted catheter cannot improve CO2 elimination from more distal conducting airways. During continuous TGI with the straight catheter, arterial PCO2 (PaCO2) decreased significantly from baseline (without TGI) of 56 +/- 10 Torr to 38 +/- 8, 36 +/- 8, and 35 +/- 8 Torr at catheter flow rates (Vcath) of 5, 10, and 15 l/min, respectively. For the same conditions, PaCO2 was always higher (P < 0.001) with the inverted catheter (42 +/- 10, 41 +/- 10, and 41 +/- 10 Torr). PaCO2 was lower with the straight (40 +/- 9 Torr) than with the inverted catheter (44 +/- 10 Torr, P < 0.001) during TGI delivered only during expiration at a Vcath of 10 l/min. End-expiratory lung volume relative to baseline increased during continuous, but not during expiratory, TGI and was significantly greater with the straight than with the inverted catheter (P < 0.0001). Our data confirm that the primary mechanism of TGI is expiratory washout of the proximal anatomic dead space but also suggest a minor contribution of turbulence beyond the tip of the straight catheter.

Animals↗

PubMed1993

Tracheal gas insufflation augments CO2 clearance during mechanical ventilation.

A technique that improves the efficiency of alveolar ventilation should decrease the pressure required and reduce the potential for lung injury during mechanical ventilation. Alveolar ventilation may be improved by replacing a portion of the anatomic dead space with fresh gas via an intratracheal catheter. We studied the effect of intratracheal gas insufflation as an adjunct to volume cycled ventilation in eight sedated, paralyzed patients with a variety of lung disorders. Continuous flows of 2, 4, and 6 L/min were delivered through a catheter positioned 1 or 10 cm above the carina. Carbon dioxide production, inspiratory minute ventilation, and peak and mean airway pressures did not change over the range of flows tested. PaCO2 and dead space volume/tidal volume decreased significantly as joint functions of catheter flow and position (p < 0.001). The highest catheter flow (6 L/min) and most distal catheter position (1 cm above the carina) were the most effective combination tested, averaging a 15% reduction in PaCO2 (range 9 to 23%). Certain characteristics of the expiratory capnogram were helpful in predicting the observed reduction in PaCO2. Tracheal gas insufflation may eventually prove a useful adjunct to a pressure-targeted strategy of ventilatory management (in either volume-cycled or pressure controlled modes), particularly when the total dead space is heavily influenced by its anatomic component.

Adult↗

PubMed1993

Modes of tracheal gas insufflation. Comparison of continuous and phase-specific gas injection in normal dogs.

Tracheal gas insufflation (TGI) improves the efficiency of CO2 elimination accomplished by conventional mechanical ventilation, primarily by reducing the anatomic (series) dead space volume. Dead space proximal to the catheter tip can be reduced by two methods. Fresh gas introduced at the carinal level during inspiration may effectively "bypass" the upper airway. Alternatively, proximal dead space can be "washed out" with fresh gas during expiration to reduce CO2 rebreathing. We examined these two modes of TGI-aided dead space reduction in nine paralyzed normal dogs receiving conventional mechanical ventilation and compared these results to those obtained with a catheter that delivered fresh gas continuously at the same flow rate, thereby accomplishing both bypass and washout. Total inspired tidal volume and cycling frequency were held constant. Differences in CO2 elimination efficiency among the TGI modes were flow dependent. Continuous catheter flow at 5 or 10 L/min reduced PaCO2 and physiologic dead space fraction (VD/VT) more than either proximal bypass or end-expiratory washout (p < 0.001). At the same catheter flow settings expiratory washout tended to improve VD/VT more than did inspiratory bypass. Under the conditions tested, constant tracheal insufflation of fresh gas improves alveolar ventilation by mechanisms that include, but are not limited to, a functional reduction in the dead space proximal to the catheter tip.

Analysis of Variance↗