Free
Meeting Abstracts  |   November 1999
Respiratory Mechanics during Xenon Anesthesia in Pigs  : Comparison with Nitrous Oxide
Author Affiliations & Notes
  • Enrico Calzia, M.D.
    *
  • Wolfgang Stahl, M.D.
  • Thomas Handschuh, M.D.
  • Thomas Marx, M.D.
    *
  • Gebhardt Fröba, M.D.
    *
  • Stefan Bäder, Ph.D.
  • Michael Georgieff, M.D., Ph.D.
    §
  • Peter Radermacher, M.D., Ph.D.
  • * Staff Anesthetist. † Resident in Anesthesiology. ‡ Biomedical Engineer. § Professor and Chairman of Anesthesiology. ∥ Professor of Anesthesiology.
Article Information
Meeting Abstracts   |   November 1999
Respiratory Mechanics during Xenon Anesthesia in Pigs  : Comparison with Nitrous Oxide
Anesthesiology 11 1999, Vol.91, 1378. doi:
Anesthesiology 11 1999, Vol.91, 1378. doi:
XENON (Xe), because of its high density (ρxe= 5.9 kg/m3at 0°C and 1.013 bar) and viscosity (ηxe= 2.3 Pa/s at 25°C and 1 bar), may impair respiratory function when used as an inhaled anesthetic. A need for caution when using xenon in patients with lung disease has been suggested by previous studies of the effects of physical gas properties on pulmonary mechanics 1–5 and gas exchange, 6–13 which revealed that respiratory mechanics in particular are affected by density and viscosity of specific gas mixtures. For example, airway resistance (Raw) is markedly increased when breathing sulfur hexafluoride (SF6)–oxygen mixtures, 2,4 which are less viscous (ηSF6= 1.57) but more dense (ρSF6= 6.6) than air (ηair= 1.83, ρair= 1.29). Even with xenon ventilation, an increase in Rawrelated to the inspiratory xenon concentration has been found previously by Zhang et al.  14 During experimentally induced bronchoconstriction, however, these authors tested only a lower xenon concentration (50%), which did not produce any significant effect on respiratory mechanics or gas exchange. Furthermore, they performed their measurements in open-chest dogs;i.e.  , during conditions that are known to affect the impact of methacholine on Raw. 15 In contrast, gas exchange and lung mechanics improve in asthmatic patients during artificial ventilation with helium (He)–oxygen mixtures, 13 which have a low density (ρHe= 0.18) but a higher viscosity (ηHe= 1.97) when compared to nitrogen (N2, ρN2= 1.25, ηN2= 1.79) and nitrous oxide (N2O, ρN2O= 1.94, ηN2O= 1.46).
The aim of the current investigation was to study respiratory mechanics and gas exchange in anesthetized, closed-chest pigs during controlled positive pressure ventilation with an inspiratory mixture composed of either 70% xenon or 70% N2O + 30% oxygen or with a 70% nitrogen + 30% oxygen.
Materials and Methods 
Animals, Anesthesia Technique, and Animal Preparation 
The study design was approved by the institutional and federal animal care committee (Tuebingen, Germany). Eighteen pigs (mean body weight 41 ± 4 kg), randomly assigned to receive either N2O or xenon (n = 9 for each group), were anesthetized with pentobarbital sodium (Nembutal, Sanofi-Wintrop, Munich, Germany; 15 mg/kg induction dose, followed by a continuous infusion of 6–12 mg · kg−1· h−1) supplemented every 4 h and before any surgical or noxious stimuli by 0.3-mg intravenous boluses of buphrenorphine (Temgesic; Boehringer Mannheim, Mannheim, Germany) to prevent an increase in heart rate and blood pressure. The adequacy of this anesthetic procedure has been tested in previous experiments. 16 To eliminate any possible respiratory effort, the animals were paralyzed using alcuronium dichloride (Alloferin, Hoffmann–LaRoche, Basel, Switzerland; 0.25 mg/kg initial dose followed by a continuous application of 0.25 mg · kg−1· h−1) throughout the study period. Depth of anesthesia was controlled by hemodynamic variables and continuous electroencephalographic monitoring (Neurotrac; Interspec Inc., Conshohocken, PA). The spectral edge frequency was always below 15 Hz, and the median power frequency was 5–10 Hz.
After induction of anesthesia, the pigs were intubated with a cuffed endotracheal tube (8.5 mm ID), and their lungs were mechanically ventilated while in the supine position using a semiclosed circuit anesthesia machine (Cicero; Drägerwerk AG, Lübeck, Germany) with a carbon dioxide absorber placed in the inspiratory limb of the breathing circuit. A central venous catheter and a thermistor-tipped pulmonary artery flotation catheter (model 93A 754 7F; Baxter Healthcare, Irvine, CA) were placed through an external jugular vein into the superior vena cava and into a pulmonary artery, respectively, for drug infusion, monitoring, and data sampling of hemodynamics and gas exchange. A 4-French catheter was inserted into a femoral artery for hemodynamic monitoring and arterial blood gas sampling. Mixed venous and arterial blood samples were analyzed for oxygen tension (PO2) and carbon dioxide tension (PCO2), using an IL 1306 blood gas analyzer (Instrumentation Laboratory, Lexington, MA), and for arterial and mixed venous hemoglobin oxygen saturation (SaO2and SvO2) and total hemoglobin concentration by means of the Co-Oximeter IL 282 (Instrumentation Laboratory), which was precalibrated for pig blood.
The Cicero anesthesia machine, which was modified to provide xenon application, performs mechanical ventilation by means of a motor-driven piston pump, which provides constant inspiratory flow. Ventilator settings throughout the experiment were as follows: tidal volume (VT)= 12–14 ml/kg (adjusted to achieve a PaCO2between 37 and 43 mmHg); frequency (f)= 12/min; inspiratory time (Ti)= 1.5 s; inspiration hold = 1 s; expiratory time (Te)= 2.5 s; and positive end-expiratory pressure (PEEP)= 5 cm H2O. The inspiratory oxygen fraction (FIO2) was kept constant at 30%, regardless of the inspiratory mixture actually used (N2O–oxygen, xenon–oxygen, or nitrogen–oxygen, see fig. 1) and was continuously measured in the inspiratory limb of the ventilator circuit by the machine-integrated oxygen monitor (a fuel cell sensor with an accuracy of ± 2%) calibrated before each experiment. Fresh gas supply of the anesthesia circuit was set to one half the minute ventilation throughout the experiment. Density and viscosity of the gas mixtures for the experimental conditions (37°C, 1 bar) were ρxe/O2= 3.95, ηxe/O2= 2.4, ρN2O/O2= 1.57, ηN2O/O2= 1.67, ρN2/O2= 1.13, and ηN2/O2= 1.93. Airway pressure (Paw) was measured through a port placed between the endotracheal tube and Y piece with a pressure transducer (142PC01G; Honeywell, Plymouth, MN) with a range of 70 cm H2O, a linearity of 0.75%, and a precision of 0.25%. Flow was measured with a heated pneumotachograph (Fleisch No. 2; Fleisch, Lausanne, Switzerland) connected to a differential pressure transducer (PC 500; PasCal, Schwerin, Germany) and calibrated for each gas mixture using a 1-l supersyringe. Expiratory PCO2was analyzed with the side-stream infrared carbon dioxide analyzer integrated in the anesthesia machine. Gas sampling rate was 200 ml/min, the delay between flow and carbon dioxide signal was corrected using values determined separately for gas mixtures containing 70% nitrogen, N2O, or xenon in 30% oxygen (DelayN2= 185 ms, DelayN2O = 175 ms and DelayXe= 240 ms. For recording Paw, Flow, and PCO2signals on a personal computer we used the DaqBoard 216 A/D converter system (IOtech, Cleveland, OH) and the data acquisition software DASYLab (Datalog, Mönchengladbach, Germany).
Study Design 
Measurements were performed at the end of three sequential 45-min periods of ventilation with either nitrogen–oxygen (periods 1 and 3 designated as control 1 and control 2) or anesthetic gas (xenon–oxygen or N2O–oxygen, depending on the random order of the experiment, period 2, designated as test-gas period) before and during methacholine infusion (fig. 1). At each point of measurement, we recorded the Paw, Flow, and PCO2signals for three sequential 2-min periods of continuous measure at a frequency of 100 Hz for subsequent off-line analysis. Additionally, we registered heart rate, mean arterial pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output. Methacholine infusion was started with a dosage of 10 μg · kg−1· min−1, which was increased stepwise (5–10 μg · kg−1· min−1) every 3–5 min, until Rawhad approximately doubled when compared to the value measured with baseline conditions before methacholine infusion. Then, the study protocol was repeated identically and analogous to the previous series of measurements.
Fig. 1. Both phases of our experiments,  i.e.  , before and during bronchoconstriction, were subdivided into three 45-min periods of ventilation with either control gas (70% nitrogen + 30% oxygen) or test gas (70% xenon or 70% N2O + 30% oxygen). Measurements were performed at the end of each period, as shown by the white dotted arrows in chronologic order. 
Fig. 1. Both phases of our experiments,  i.e.  , before and during bronchoconstriction, were subdivided into three 45-min periods of ventilation with either control gas (70% nitrogen + 30% oxygen) or test gas (70% xenon or 70% N2O + 30% oxygen). Measurements were performed at the end of each period, as shown by the white dotted arrows in chronologic order. 
Fig. 1. Both phases of our experiments,  i.e.  , before and during bronchoconstriction, were subdivided into three 45-min periods of ventilation with either control gas (70% nitrogen + 30% oxygen) or test gas (70% xenon or 70% N2O + 30% oxygen). Measurements were performed at the end of each period, as shown by the white dotted arrows in chronologic order. 
×
Calculations 
Pulmonary mechanics were assessed according to the method described by Bates et al.  17 The same technique was also used to separately determine the resistance of the endotracheal tube (Rtube) for each experimental gas mixture over a flow range between 0.1 and 1.0 l/s. For this purpose, the tip of the cuffed endotracheal tube was positioned at the distal end of an artificial trachea, which was connected to a 3-l bag.
The two prerequisites for using the occlusion technique described by Bates et al.  , 17 namely, continuous inspiratory flow and sudden flow interruption at the end of inspiration, are met during volume-controlled ventilation with the CICERO anesthesia machine. In contrast to previous investigations using this technique, the sudden flow interruption is not obtained by occluding the inspiratory valve, as occurs when using intensive care unit ventilators, but by the sudden arrest of the piston pump. Nevertheless, a square flow pattern is achieved regardless of the interruption mode. According to previous descriptions of this occlusion technique, we determined the peak airway pressure (Pmax), and the airway pressures registered both immediately after end-inspiratory flow interruption (P1) and after an occlusion period of 6 s (P2) from each occluded breath. By subtraction of the pressure component imposed by the resistance of the endotracheal tube (calculated by multiplying Rtubeand inspiratory flow) from Pmaxwe obtained an estimation of the peak pressure within the trachea (Pmax′). The correction proposed by Bates et al.  , 18 which consists of extrapolating the pre- and postocclusion pressure signals to the point in time when the inspiratory valve is semiclosed, was used for determining Pmaxand P1, to account for the finite time of flow interruption. For this purpose, the postocclusion pressure decay, which is caused by the stress relaxation of the lung tissue and by gas redistribution, was analyzed with a logarithmic function determined by the least-squares fit technique as described by Marquardt. 19 This logarithmic fit was back-extrapolated to the time of flow interruption to obtain P1. Inspiratory resistance was then determined as Rminand Rmaxby the equations MATH 1MATH 2Because Rminequals the sum of Rawand Rtube, Rawwas obtained by subtraction of Rtubefrom Rmin. ΔR was then calculated as MATH 3The total inspiratory pressure drop over the bronchial tree (ΔP) was calculated for each gas mixture as MATH 4and the ΔP ratio of two different gas mixtures x and y was calculated as ΔPx/ΔPy.
Static and dynamic compliances (Cstand Cdyn) were calculated by the equations MATH 5MATH 6where PEEPiis the intrinsic positive end-expiratory pressure, determined by the end-expiratory occlusion maneuver, i.e.  , Paw10 s after occlusion. Representative original Pawand Flow curves registered during baseline conditions and during methacholine infusion, which further explain these calculations, are shown in figures 2A and B, respectively.
Fig. 2. (  A  ) Original airway pressure (Paw) and flow curves registered during control conditions (inspiratory gas mixture composed by 70% nitrogen and 30% oxygen, no methacholine infusion). Note the rectangular flow pattern that results from the constant inspiratory flow and the simultaneous linear increase in Paw. After inspiratory flow decreases sharply to zero at the end of inspiration, a sudden drop is observed in the Pawtracing. According to Bates  et al.  ,  18 peak airway pressure (Pmax) is determined by linear extrapolation of the Pawsignal preceding flow interruption up to the point in time when flow has reached one half the inspiratory value (this point is indicated by the vertical dotted line). Correspondingly, P1is determined by back extrapolation of the logarithmic postocclusion pressure decay to the same point. The preinterruption linear and postinterruption logarithmic fit are shown superimposed to the corresponding parts of the Pawcurve. P2was determined as the Pawafter 6 s of flow interruption. (  B  ) Pawand flow curves registered in the same animal during methacholine infusion. Inspiratory flow pattern remain unchanged, but the Pawincreased more steeply and the postinterruption pressure drop, as well as the decay, from P1to P2is more pronounced. 
Fig. 2. (  A  ) Original airway pressure (Paw) and flow curves registered during control conditions (inspiratory gas mixture composed by 70% nitrogen and 30% oxygen, no methacholine infusion). Note the rectangular flow pattern that results from the constant inspiratory flow and the simultaneous linear increase in Paw. After inspiratory flow decreases sharply to zero at the end of inspiration, a sudden drop is observed in the Pawtracing. According to Bates  et al.  ,  18peak airway pressure (Pmax) is determined by linear extrapolation of the Pawsignal preceding flow interruption up to the point in time when flow has reached one half the inspiratory value (this point is indicated by the vertical dotted line). Correspondingly, P1is determined by back extrapolation of the logarithmic postocclusion pressure decay to the same point. The preinterruption linear and postinterruption logarithmic fit are shown superimposed to the corresponding parts of the Pawcurve. P2was determined as the Pawafter 6 s of flow interruption. (  B  ) Pawand flow curves registered in the same animal during methacholine infusion. Inspiratory flow pattern remain unchanged, but the Pawincreased more steeply and the postinterruption pressure drop, as well as the decay, from P1to P2is more pronounced. 
Fig. 2. (  A  ) Original airway pressure (Paw) and flow curves registered during control conditions (inspiratory gas mixture composed by 70% nitrogen and 30% oxygen, no methacholine infusion). Note the rectangular flow pattern that results from the constant inspiratory flow and the simultaneous linear increase in Paw. After inspiratory flow decreases sharply to zero at the end of inspiration, a sudden drop is observed in the Pawtracing. According to Bates  et al.  ,  18 peak airway pressure (Pmax) is determined by linear extrapolation of the Pawsignal preceding flow interruption up to the point in time when flow has reached one half the inspiratory value (this point is indicated by the vertical dotted line). Correspondingly, P1is determined by back extrapolation of the logarithmic postocclusion pressure decay to the same point. The preinterruption linear and postinterruption logarithmic fit are shown superimposed to the corresponding parts of the Pawcurve. P2was determined as the Pawafter 6 s of flow interruption. (  B  ) Pawand flow curves registered in the same animal during methacholine infusion. Inspiratory flow pattern remain unchanged, but the Pawincreased more steeply and the postinterruption pressure drop, as well as the decay, from P1to P2is more pronounced. 
×
The carbon dioxide expirograms were analyzed for the alveolar carbon dioxide slope (SCO2), which was calculated according to Fletcher et al.  20 and Meyer et al.  21,22 by linear fit of the expiratory PCO2plotted as a function of expired volume plot between 70 and 95% of expiration, which yields the change of PCO2normalized for mixed expired PCO2per unit of expired volume. In addition, series dead space was computed using the method described by Fletcher et al.  20 The expired volume was calculated by integration of the flow signal.
Dead space ventilation (VD/VT) and venous admixture (QS/QT) were calculated from blood gas data and mixed expired carbon dioxide pressure (PECO2) using the standard equations MATH 7MATH 8where CaO2and CvO2are the arterial and mixed venous oxygen content, respectively, and CcO2is the capillary oxygen content derived from the alveolar PO2(PAO2) calculated by the simplified alveolar gas equation 23 as MATH 9where PBis the barometric pressure, PH2Ois water–vapor pressure, FIO2is the inspiratory oxygen concentration, and RQ is the respiratory quotient assumed to be 0.8. Arterial to alveolar oxygen difference was then calculated as PAO2− PaO2.
Statistical Analysis 
All data are presented as mean ± SD. After normal distribution was confirmed by the Kolmogorov-Smirnov test, a two-way analysis of variance of repeated measures of one repeated factor, followed, when significant, by the Tukey test, was used to compare the data obtained within both groups (repeated factor) during the nitrogen–control periods and during the phases of xenon and N2O ventilation, before and after methacholine, respectively, and to further compare the differences between the two groups (not repeated factor) during xenon and N2O inhalation. Statistical significance was assumed at P  < 0.05.
Results 
The results of our experiments are summarized in figure 3and in tables 1 and 2. In each group, the first animal had to be discarded from statistical analysis because of a lethal complication during induction of bronchoconstriction in one case (N2O group) and because of insufficient effect of methacholine in the second case (xenon group). Comparing the data obtained during the two control periods of each series, i.e.  , the periods of nitrogen–oxygen ventilation before and after each test gas period, we found a statistically significant decrease in Cstand Cdynand increases in Pmax, P1, P2, and Pmeanin the N2O group during methacholine infusion only. There were no statistically significant differences between the two controls for any of the other conditions. The effects of methacholine infusion were validated by comparing the data related to airway pressure and resistance before and during bronchoconstriction during the nitrogen–oxygen control periods: all these values (except for Rtube) significantly increased during methacholine infusion (P  < 0.01); Cstand Cdynsimultaneously decreased (P  < 0.01). The methacholine dosage necessary for induction of bronchoconstriction was similar in both groups (40.5 ± 42.2 μg · kg−1· min−1in the xenon group and 36.1 ± 10.4 μg · kg−1· min−1in the N2O group). The large SD in the xenon group is caused by two single animals that required a relatively high (143.4 μg · kg−1· min−1) and low (12 μg · kg−1· min−1) dosage, respectively.
Fig. 3. The charts show the results concerning airway resistance (Raw) and peak airway pressure (Pmax) with all experimental conditions. Data are mean ± SD, X = significant difference between xenon–oxygen and nitrogen–oxygen. The white bars indicate the values obtained during nitrogen–oxygen ventilation, the dark ones those during xenon–oxygen or N2O–oxygen ventilation, respectively. Note that during xenon–oxygen ventilation Rawwas significantly higher both before and during bronchoconstriction when compared to the corresponding nitrogen–oxygen controls. A statistically significant increase in Paw, however, was found during xenon–oxygen ventilation during bronchoconstriction only. 
Fig. 3. The charts show the results concerning airway resistance (Raw) and peak airway pressure (Pmax) with all experimental conditions. Data are mean ± SD, X = significant difference between xenon–oxygen and nitrogen–oxygen. The white bars indicate the values obtained during nitrogen–oxygen ventilation, the dark ones those during xenon–oxygen or N2O–oxygen ventilation, respectively. Note that during xenon–oxygen ventilation Rawwas significantly higher both before and during bronchoconstriction when compared to the corresponding nitrogen–oxygen controls. A statistically significant increase in Paw, however, was found during xenon–oxygen ventilation during bronchoconstriction only. 
Fig. 3. The charts show the results concerning airway resistance (Raw) and peak airway pressure (Pmax) with all experimental conditions. Data are mean ± SD, X = significant difference between xenon–oxygen and nitrogen–oxygen. The white bars indicate the values obtained during nitrogen–oxygen ventilation, the dark ones those during xenon–oxygen or N2O–oxygen ventilation, respectively. Note that during xenon–oxygen ventilation Rawwas significantly higher both before and during bronchoconstriction when compared to the corresponding nitrogen–oxygen controls. A statistically significant increase in Paw, however, was found during xenon–oxygen ventilation during bronchoconstriction only. 
×
Table 1. Respiratory Mechanics Values at Each Point of Measurement 
Image not available
Table 1. Respiratory Mechanics Values at Each Point of Measurement 
×
Table 2. Gas Exchange with Each Study Condition 
Image not available
Table 2. Gas Exchange with Each Study Condition 
×
Substitution of xenon for nitrogen significantly increased Rmin, Rmax, Raw, and Rtubebefore and during methacholine infusion (P  < 0.01). These parameters also were increased when comparing the xenon and N2O group with both study conditions (P  < 0.01). In contrast, they were not affected when nitrogen was replaced by N2O. During methacholine-induced bronchoconstriction Pmaxand Pmeanwere significantly higher with xenon–oxygen ventilation when compared to the nitrogen–oxygen controls (P  < 0.01). In contrast, there were no statistically significant differences in Pmaxor Pmeanduring xenon–oxygen and nitrogen–oxygen ventilation before bronchoconstriction or during N2O–oxygen and nitrogen–oxygen ventilation during baseline conditions and during bronchoconstriction. During bronchoconstriction, Pmean, but not Pmax, was significantly higher with xenon–oxygen when compared to the N2O group (P  < 0.01). In the xenon group, but not in the N2O group, the ΔP ratio was higher during bronchoconstriction when compared to baseline.
Generally, PEEPiwas low and did not change significantly when replacing nitrogen with xenon or with N2O, regardless of the experimental condition, but increased during bronchoconstriction when compared to baseline conditions.
Regardless of the inspiratory gas mixture, pulmonary gas exchange was impaired during methacholine infusion, as shown by the lower PaO2, the higher PaCO2, the QS/QT, the alveolar–arterial difference in partial pressure of oxygen (PAO2− PaO2), and the total dead space (VDtot) when compared to baseline conditions (table 2). However, before, and during, bronchoconstriction, gas exchange parameters did not differ between the xenon–oxygen and N2O–oxygen groups, or between nitrogen–oxygen controls and either test gas. In both groups, SCO2was higher with bronchoconstriction when compared to baseline conditions but did not differ between control and test–gas ventilation.
No changes in hemodynamic variables were induced by the different gases used in our experiment, whereas metacholine infusion, when compared to the baseline conditions before bronchoconstriction, significantly decreased mean arterial pressure, concomitant with a simultaneous increase in mean pulmonary artery pressure in both groups. There were no statistically significant differences regarding heart rate, central venous pressure, pulmonary artery occlusion pressure between baseline conditions, and bronchoconstriction. During xenon ventilation, but not during N2O ventilation, cardiac output decreased significantly with bronchoconstriction.
Discussion 
The aim of this investigation was to compare pulmonary mechanics and gas exchange in mechanically ventilated pigs during xenon–oxygen and N2O–oxygen anesthesia before and during continuous intravenous methacholine. The main result was that Rawand pressure increased during xenon–oxygen ventilation. In terms of absolute values, these changes were moderate before methacholine infusion, as suggested by the unchanged Pmax, despite the increased resistance, but more pronounced during intravenous methacholine.
Lung Mechanics 
Our results agree with previous data regarding the effect of physical gas properties on respiratory mechanics. 2,4 They also confirm data regarding pulmonary resistance in dogs during 70% xenon and 70% N2O anesthesia, previously published by Zhang et al.  14; however, in our study, the relative change in Rawproduced by xenon was more pronounced (1.54 before and 1.88 during bronchoconstriction compared to 1.35 as measured by Zhang et al.  14). With inspiratory xenon concentrations of 50%, as tested by these authors during methacholine-induced bronchoconstriction, they did not find any significant difference between xenon and nitrogen or N2O. The discrepancy in our data during bronchoconstriction may be caused by the maintenance of the anesthetic concentration at 70% even during this condition. This is crucial for xenon because, due to the particularly high density and viscosity of this noble gas, the effects of a xenon–oxygen mixture on respiratory mechanics are markedly sensitive to changes of the inspired xenon concentration. Moreover, it must be taken into account that baseline Rawvalues measured by Zhang et al.  14 in dogs were lower when compared to our data, suggesting larger airway dimensions in this species. Finally, Zhang et al.  14 performed their measurements in open-chest animals, a condition that affects the response to methacholine. 15 
According to the theoretical approaches proposed by Pedley et al.  , 24,25 Olson et al.,  26 and Jaffrin and Kesic, 27 which were more recently reviewed by Pedley and Drazen, 28 both the high viscosity and the density of xenon are probably responsible for the results of our experiment. Briefly, these authors applied laws of fluid mechanics to complex systems of branching tubes such as the bronchial airways. Their model calculations showed how gas flow, despite laminar throughout the bronchial system, is disturbed at branching sites, resulting in blunted flow velocity profiles. A specific distance (called “entrance length”), which depends on airway diameter and the Reynold number (and hence on viscosity and density of the gas mixture), has to be covered by the bulk flow at each generation of the bronchial tree until the typical parabolic velocity profile of fully developed laminar flow is reestablished. Because this is an energy-consuming process, previous predictions of total pressure drop over the bronchial system based on the assumption of overall fully developed laminar flow, 29 which only depends on the viscosity of the inspiratory gas mixture, resulted in underestimation of experimental data. 30,31 This is also the case for our results insofar as both ratios ηXe/O2N2/O2(1.25 at 37°C) and ηN2O/O2N2/O2(0.87 at 37°C) were lower than ΔPXe/O2/ΔPN2/O2(1.55 before and 1.90 during bronchoconstriction) and ΔPN2O/O2/ΔPN2/O2(1.23 before and 1.16 during bronchoconstriction). In contrast, ΔP ratios calculated according to Pedley et al.,  25 i.e.  , ΔPx/ΔPy=(ρxx)1/2/(ρyy)1/2, which yields theoretical values for ΔPXe/O2/ΔPN2/O2= 2.08 and for ΔPN2O/O2/ΔPN2/O2= 1.1, more closely approximated the measured ΔPXe/O2/ΔPN2/O2and ΔPN2O/O2/ΔPN2/O2ratios. However, ΔPXe/O2/ΔPN2/O2before methacholine infusion was overestimated by Pedley's formula. According to Ingram and Pedley 32 and Wood et al.  , 4 the presence of flow conditions equivalent to fully developed laminar flow in the more peripheral sections of the bronchial system (bronchial diameters < 4 mm) partially may have caused this overestimation. These flow conditions are not explained by the theory of Pedley et al.  25 and tend to reduce the measured pressure drop over the distal airways when compared to the predicted values, in particular by the use of high-density gases. We can exclude an airway narrowing effect of xenon as a possible further cause of the increased Rawobserved in our experiment when considering the data for ΔR, Cst, and Cdyn: neither of these changed with respect to the different inspiratory gas mixtures as one would expect if airway smooth muscle tone was raised.
The different effect of xenon on Rawand airway pressure is caused by the fact that airway pressure is determined by both a resistive and an elastic component. During xenon anesthesia resistance, consequently, the resistive pressure component only, was increased, but not compliance.
Gas Exchange and Hemodynamics 
In contrast to respiratory mechanics, xenon and N2O did not affect gas exchange or hemodynamics. Even the methacholine-induced deterioration in gas exchange, as documented by the PaO2; Qs/QT; PAO2− PaO2; PaCO2; and VD/VT, was of similar degree, regardless of the composition of the inspiratory gas. In addition, the SCO2was unaffected by the different inspiratory gas mixtures, suggesting that the properties of the gas species used in our experiment did not significantly affect the VA/Q distribution in the lung. The alveolar slope of the expired PCO2is considered as an indicator of the nonhomogenous VA/Q distribution. 21 Interpreting this test, however, is particularly difficult, because the alveolar PCO2slope is determined by both the series and the parallel nonhomogeneity of the VA/Q ratio, 22 and these two components cannot be analyzed separately.
Our gas exchange data agree fairly well with previously published investigations of the effects of gas mixtures with different physical properties on VA/Q matching. In fact, in three of these studies, 7,10,11 PAO2− PaO2even decreased with increasing gas density, but the changes were only subtle and probably of no clinical relevance. In contrast, in two other studies, PAO2− PaO2was uninfluenced or even slightly increased with higher gas density. In line with these results, investigations by Schumacker et al.  12 and Schulz et al.  33 showed only a slight relation between gas density and intrapulmonary gas distribution, gas distribution being more homogeneous in high-density atmospheres.
In summary, airway mechanics in pigs are affected during xenon anesthesia. This response is moderate with baseline conditions but more pronounced during bronchoconstriction. The results of our findings, however, probably assume only minor importance for the general anesthetic use of xenon for the following reasons:(1) during mechanical ventilation, as usual during general anesthesia, the ventilator but not the patient has to overcome the increased inspiratory resistance caused by the high density and viscosity of xenon. (2) The consequent effects on airway pressure are probably of minor relevance because they are negligible in healthy conditions and only moderate during bronchoconstriction. Furthermore, the increment in airway pressure is likely to be less accentuated in more peripheral lung regions and to disappear at the alveolar level because it is caused by the physical properties of xenon but not by an increase in airway muscle tone that would narrow the airway diameter and increase lung compliance. (3) Gas exchange does not deteriorate during xenon anesthesia, and, therefore, xenon is unlikely to impair oxygenation even during bronchoconstriction.
References 
References 
McIlroy MB, Mead J, Selverstone NJ, Radford EP: Measurement of lung tissue viscous resistance using gases of equal kinematic viscosity. J Appl Physiol 1954; 7:485—90
Drazen JM, Loring SH, Ingram RH. Distribution of pulmonary resistance: Effects of gas density, viscosity and flow rate. J Appl Physiol 1976; 41:388—95
Forkert L, Wood LDH, Cherniak RM: Effect of gas density on dynamic pulmonary compliance. J Appl Physiol 1975; 39:906—10
Wood LDH, Engel LH, Griffin P, Despas P, Macklem PT: Effect of gas physical properties and flow on lower pulmonary resistance. J Appl Physiol 1976; 41:234–44
Behnke AR, Yarbrough OD: Respiratory resistance, oil-water solubility, and mental effects of argon compared with helium and nitrogen. Am J Physiol 1939; 126:409–15
Christopherson SK, Hlastala MP: Pulmonary gas exchange during altered density gas breathing. J Appl Physiol 1982; 52:221–25
Gledhill N, Froese AB, Buick FJ, Bryan AC: VA/Q inhomogeneity and AaDO2in man during exercise: Effects of SF6breathing. J Appl Physiol 1978; 45:512–5
Nemery B, Nullens W, Veriter C, Brasseur L, Frans A: Effects of gas density on pulmonary gas exchange of normal man at rest and during exercise. Pflügers Arch 1983; 397:57–61
Saltzman HA, Salzano JV, Blenkarn GD, Kylstra JA: Effects of pressure on ventilation and gas exchange in man. J Appl Physiol 1971; 30:443–9
Wood LDH, Bryan AC, Bau SK, Wenig TR, Levison H: Effect of increased gas density on pulmonary gas exchange in man. J Appl Physiol 1976; 41:206–10
Worth H, Takahashi H, Wilmer H, Piiper J: Pulmonary gas exchange in dogs ventilated with mixtures of oxygen with various inert gases. Respir Physiol 1976; 28:1–15
Schumacker PT, Samsel RW, Sznajder JI, Wood LD, Solway J: Gas density dependence of regional VA/Vand VA/Qinequality during constant-flow ventilation. J Appl Physiol 1989; 66 (4):1722–9
Gluck EH, Onorato DJ, Castriotta R: Helium-oxygen mixtures in intubated patients with status asthmaticus and respiratory acidosis. Chest 1990; 98:693–8
Zhang P, Ohara A, Mashimo T, Imanaka H, Uchiyama A, Yoshiya I: Pulmonary resistance in dogs: A comparison of xenon with nitrous oxide. Can J Anaesth 1995; 42:547–53
Suki B, Petak F, Adamicza A, Daroczy B, Lutchen KR, Hantos Z: Airway and tissue constrictions are greater in closed than in open-chest conditions. Respir Physiol 1997; 108:129–41
Šantak B, Radermacher P, Iber T, Adler J, Wachter U, Vassilev D, Georgieff M, Vogt J: In vivo Quantification of Endotoxin-induced Nitric Oxide Production in Pigs from Na15NO3-infusion. Br J Pharmacol 1997; 122:1605–10
Bates JHT, Rossi A, Milic-Emili J: Analysis of the behavior of the respiratory system with constant inspiratory flow. J Appl Physiol 1985; 58:1840–8
Bates JHT, Hunter IW, Sly PD, Okubo S, Filiatrault S, Milic-Emili J: Effect of valve closure time on the determination of respiratory resistance by flow interruption. Med Biol Eng Comput 1987; 25:136–40
Marquardt DW: An algorithm for least-squares estimation of nonlinear parameters. J Soc Ind Appl Math 1963; 11:431–41
Fletcher R, Jonson B, Cumming G, Brew J: The concept of deadspace with special reference to the single breath test for carbon dioxide. Br J Anaesth 1981; 53:77–88
Meyer M, Mohr M, Schulz H, Piiper J: Sloping alveolar plateaus of CO2, O2, and intravenously infused C2H2and CHClF2in the dog. Respir Physiol 1990; 81:137–52
Meyer M, Schuster KD, Schulz H, Mohr M, Piiper J: Alveolar Slope and dead space of He and SF6in dogs: Comparison of airway and venous loading. J Appl Physiol 1990; 69:937–44
Martin L: Abbreviating the alveolar gas equation: An argument for simplicity. Respir Care 1986; 31:40–4
Pedley TJ, Schroter RC, Sudlow MF: Energy losses and pressure drop in models of human airways. Respir Physiol 1970; 9:371–86
Pedley TJ, Schroter RC, Sudlow MF: The prediction of pressure drop and variation of resistance within the human bronchial airways. Respir Physiol 1970; 9:387–405
Jaffrin MY, Kesic P: Airway resistance: A fluid mechanical approach. J Appl Physiol 1974; 36:354–61
Olson DE, Dart GA, Filley GF: Pressure drop and fluid flow regime of air inspired into the human lung. J Appl Physiol 1970; 28:482–94
Pedley TJ, Drazen JM: Aerodynamic theory, Handbook of Physiology, Section 3: The Respiratory System, 3rd edition. Edited by Fishman AP, Macklem PT, Mead J, Geiger SR. Bethesda, Williams & Wilkins, 1986, pp 41–54
Horsfield K, Cumming G: Functional consequences of airway morphology. J Appl Physiol 1968; 24:384–90
Ferris BG, Mead J, Opie LH: Partitioning of respiratory flow resistance in man. J Appl Physiol 1964; 19:653–8
Hyatt RE, Wilcox RE: The pressure-flow relationships of the intrathoracic airway in man. J Clin Invest 1963; 42:29–39
Ingram RH, Pedley TJ: Pressure-flow relationships in the lungs, Handbook of Physiology, Section 3: The Respiratory System, 3rd edition. Edited by Fishman AP, Macklem PT, Mead J, Geiger SR. Bethesda, Williams & Wilkins, 1986, pp 277–93
Schulz H, Schulz A, Eder G, Heyder J: Influence of gas composition on convective and diffusive intrapulmonary gas transport. Exp Lung Res 1995; 21:853–76
Fig. 1. Both phases of our experiments,  i.e.  , before and during bronchoconstriction, were subdivided into three 45-min periods of ventilation with either control gas (70% nitrogen + 30% oxygen) or test gas (70% xenon or 70% N2O + 30% oxygen). Measurements were performed at the end of each period, as shown by the white dotted arrows in chronologic order. 
Fig. 1. Both phases of our experiments,  i.e.  , before and during bronchoconstriction, were subdivided into three 45-min periods of ventilation with either control gas (70% nitrogen + 30% oxygen) or test gas (70% xenon or 70% N2O + 30% oxygen). Measurements were performed at the end of each period, as shown by the white dotted arrows in chronologic order. 
Fig. 1. Both phases of our experiments,  i.e.  , before and during bronchoconstriction, were subdivided into three 45-min periods of ventilation with either control gas (70% nitrogen + 30% oxygen) or test gas (70% xenon or 70% N2O + 30% oxygen). Measurements were performed at the end of each period, as shown by the white dotted arrows in chronologic order. 
×
Fig. 2. (  A  ) Original airway pressure (Paw) and flow curves registered during control conditions (inspiratory gas mixture composed by 70% nitrogen and 30% oxygen, no methacholine infusion). Note the rectangular flow pattern that results from the constant inspiratory flow and the simultaneous linear increase in Paw. After inspiratory flow decreases sharply to zero at the end of inspiration, a sudden drop is observed in the Pawtracing. According to Bates  et al.  ,  18 peak airway pressure (Pmax) is determined by linear extrapolation of the Pawsignal preceding flow interruption up to the point in time when flow has reached one half the inspiratory value (this point is indicated by the vertical dotted line). Correspondingly, P1is determined by back extrapolation of the logarithmic postocclusion pressure decay to the same point. The preinterruption linear and postinterruption logarithmic fit are shown superimposed to the corresponding parts of the Pawcurve. P2was determined as the Pawafter 6 s of flow interruption. (  B  ) Pawand flow curves registered in the same animal during methacholine infusion. Inspiratory flow pattern remain unchanged, but the Pawincreased more steeply and the postinterruption pressure drop, as well as the decay, from P1to P2is more pronounced. 
Fig. 2. (  A  ) Original airway pressure (Paw) and flow curves registered during control conditions (inspiratory gas mixture composed by 70% nitrogen and 30% oxygen, no methacholine infusion). Note the rectangular flow pattern that results from the constant inspiratory flow and the simultaneous linear increase in Paw. After inspiratory flow decreases sharply to zero at the end of inspiration, a sudden drop is observed in the Pawtracing. According to Bates  et al.  ,  18peak airway pressure (Pmax) is determined by linear extrapolation of the Pawsignal preceding flow interruption up to the point in time when flow has reached one half the inspiratory value (this point is indicated by the vertical dotted line). Correspondingly, P1is determined by back extrapolation of the logarithmic postocclusion pressure decay to the same point. The preinterruption linear and postinterruption logarithmic fit are shown superimposed to the corresponding parts of the Pawcurve. P2was determined as the Pawafter 6 s of flow interruption. (  B  ) Pawand flow curves registered in the same animal during methacholine infusion. Inspiratory flow pattern remain unchanged, but the Pawincreased more steeply and the postinterruption pressure drop, as well as the decay, from P1to P2is more pronounced. 
Fig. 2. (  A  ) Original airway pressure (Paw) and flow curves registered during control conditions (inspiratory gas mixture composed by 70% nitrogen and 30% oxygen, no methacholine infusion). Note the rectangular flow pattern that results from the constant inspiratory flow and the simultaneous linear increase in Paw. After inspiratory flow decreases sharply to zero at the end of inspiration, a sudden drop is observed in the Pawtracing. According to Bates  et al.  ,  18 peak airway pressure (Pmax) is determined by linear extrapolation of the Pawsignal preceding flow interruption up to the point in time when flow has reached one half the inspiratory value (this point is indicated by the vertical dotted line). Correspondingly, P1is determined by back extrapolation of the logarithmic postocclusion pressure decay to the same point. The preinterruption linear and postinterruption logarithmic fit are shown superimposed to the corresponding parts of the Pawcurve. P2was determined as the Pawafter 6 s of flow interruption. (  B  ) Pawand flow curves registered in the same animal during methacholine infusion. Inspiratory flow pattern remain unchanged, but the Pawincreased more steeply and the postinterruption pressure drop, as well as the decay, from P1to P2is more pronounced. 
×
Fig. 3. The charts show the results concerning airway resistance (Raw) and peak airway pressure (Pmax) with all experimental conditions. Data are mean ± SD, X = significant difference between xenon–oxygen and nitrogen–oxygen. The white bars indicate the values obtained during nitrogen–oxygen ventilation, the dark ones those during xenon–oxygen or N2O–oxygen ventilation, respectively. Note that during xenon–oxygen ventilation Rawwas significantly higher both before and during bronchoconstriction when compared to the corresponding nitrogen–oxygen controls. A statistically significant increase in Paw, however, was found during xenon–oxygen ventilation during bronchoconstriction only. 
Fig. 3. The charts show the results concerning airway resistance (Raw) and peak airway pressure (Pmax) with all experimental conditions. Data are mean ± SD, X = significant difference between xenon–oxygen and nitrogen–oxygen. The white bars indicate the values obtained during nitrogen–oxygen ventilation, the dark ones those during xenon–oxygen or N2O–oxygen ventilation, respectively. Note that during xenon–oxygen ventilation Rawwas significantly higher both before and during bronchoconstriction when compared to the corresponding nitrogen–oxygen controls. A statistically significant increase in Paw, however, was found during xenon–oxygen ventilation during bronchoconstriction only. 
Fig. 3. The charts show the results concerning airway resistance (Raw) and peak airway pressure (Pmax) with all experimental conditions. Data are mean ± SD, X = significant difference between xenon–oxygen and nitrogen–oxygen. The white bars indicate the values obtained during nitrogen–oxygen ventilation, the dark ones those during xenon–oxygen or N2O–oxygen ventilation, respectively. Note that during xenon–oxygen ventilation Rawwas significantly higher both before and during bronchoconstriction when compared to the corresponding nitrogen–oxygen controls. A statistically significant increase in Paw, however, was found during xenon–oxygen ventilation during bronchoconstriction only. 
×
Table 1. Respiratory Mechanics Values at Each Point of Measurement 
Image not available
Table 1. Respiratory Mechanics Values at Each Point of Measurement 
×
Table 2. Gas Exchange with Each Study Condition 
Image not available
Table 2. Gas Exchange with Each Study Condition 
×