Published ahead of print on October 5, 2006, doi:10.1164/rccm.200604-501OC
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1310-1318, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200604-501OC
Volume Reduction Surgery Impairs Immediate Postoperative Pulmonary Function in Canine Emphysema
Gordon Buduhan,
Lawrence Tan,
Krika Kasian and
Steven N. Mink
Departments of Surgery and Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Correspondence and requests for reprints should be addressed to Steven N. Mink, M.D., GF-221, Health Sciences Centre, Winnipeg, MB, R3E-0Z3 Canada. E-mail: minksn{at}cc.umanitoba.ca
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ABSTRACT
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Rationale: In severe pulmonary emphysema, lung volume reduction surgery (LVRS) improves pulmonary function over a 2-yr period in selected patients. However, the changes in lung function and maximal flow ( max) occurring immediately postoperatively are not clear and may contribute to the high morbidity observed. In the present study, we used a chronic canine model of upper lobe emphysema to address this question.
Methods: Bilateral upper lobe emphysema was produced by the intrabronchial administration of papain. Measurements were made before and immediately after LVRS was performed. A vacuum-assisted surgical system (VALR Surgical System; Spiration, Redmond, WA) that deploys a compression sleeve over portions of the disease tissue was used to produce LVRS. Changes in max were interpreted in terms of the wave-speed theory of flow limitation in which a pressure sensor was placed into the airway to determine the site of limitation and intrabronchial pressures.
Results: In the emphysema group, total lung capacity postemphysema increased to approximately 20% above the preemphysema value, whereas max was reduced as compared with a control group. After LVRS, tidal respiratory compliance and max decreased, whereas lung elastic recoil and frictional resistance increased in both the emphysema and control groups as compared with presurgery.
Conclusion: The acute effect of LVRS leads to an impairment in lung mechanical properties. These changes could contribute to ventilatory complications, including the difficulty of weaning patients from mechanical ventilation and the mortality observed from this procedure.
Key Words: chronic obstructive lung disease • maximum expiratory flow • tidal compliance • wave-speed theory of flow limitation
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AT A GLANCE COMMENTARY
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Scientific Knowledge on the Subject
Although most investigations have centered on the long-term effects of lung volume reduction surgery (LVRS) on pulmonary function where the effects have been beneficial, there is only limited information about the changes that evolve in the immediate postoperative period.
What This Study Adds to the Field
We show that the acute effect of LVRS in a canine model of upper lobe emphysema is to impair lung mechanics and maximal expiratory flow. This study points out that an acute impairment in pulmonary function post-LVRS may contribute to the respiratory compromise that frequently develops after this procedure is performed.
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In pulmonary emphysema, severe disease is characterized by shortness of breath on minimal exertion or at rest, as well as limited exercise tolerance (1). Medical therapy for emphysema remains limited (2). Although bronchodilator and steroid therapies are usually administered, the quality of life of patients with emphysema is poor. Over the last few years, lung volume reduction surgery (LVRS) has become a therapeutic option for the treatment of severe emphysema (3–6). In LVRS, the most severely diseased emphysematous regions of both lungs are resected to allow re-expansion of remaining healthy lung units. In the National Emphysema Treatment Trial (NETT), a significant survival advantage of this surgery was demonstrated among a subgroup of patients with predominantly upper lobe emphysema and low preoperative exercise capacity (4).
Although it has been observed that there is general improvement in expiratory flow and lung mechanics several months after LVRS (7–11), little work has been presented on the physiologic changes that occur immediately after surgery. The acute postoperative recovery period represents a time of high morbidity and mortality for patients with emphysema who have limited physiologic reserves (12). The physiologic changes that occur after LVRS may contribute to the development of respiratory failure, but the extent to which such changes occur is not well described. Barnas and colleagues (13) examined the effect of LVRS on lung and chest wall mechanical properties on patients immediately after surgery. They found that airway resistance increased and respiratory compliance decreased as compared with preoperative values. Such effects may contribute to an increase in work of breathing and respiratory failure postoperatively, but only limited measurements of respiratory mechanics were obtained in this study.
We previously developed a canine model of severe upper lobe emphysema to study the changes in pulmonary mechanics and maximal expiratory flow (max) that occur after LVRS (14). We produced severe upper lobe emphysema by the multiple instillations of the enzyme papain, which were administered over a period of approximately 6 mo. In this chronic canine model, we found that after 6 mo post-LVRS, there were increases in max and beneficial changes in lung mechanics that were comparable to those observed in human studies (14).
In the present study, we used this canine model to determine the acute effect of LVRS on pulmonary mechanics and max in which measurements were obtained immediately postoperatively. These changes in max were interpreted in terms of the wave-speed theory of flow limitation (see below), which appears to be the most rigorous in explaining flow limitation in normal and diseased lungs (15, 16). The objective of this study was to determine whether the physiologic changes observed could contribute to the development of respiratory failure in the immediate postoperative period after this procedure is performed.
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METHODS
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This study was approved by the University of Manitoba Central Animal Care Committee, and all animals involved in the study were treated in accordance with the "Guide for the Care and Use of Laboratory Animals" published by the U.S. National Institutes of Health (NIH Publication No. 85–23, revised 1996) (17).
Experimental Groups
A total of 17 healthy adult dogs (23–30 kg body weight) were used in the study (see Figure 1). The study consisted of four groups: two emphysema groups and two nonemphysema groups. Nine dogs were included in the two emphysema groups. Six of the nine dogs were randomized to have LVRS, whereas three dogs were randomized to an emphysema time control group. In the two nonemphysema control groups, of the eight dogs studied, five were randomized to LVRS, whereas three were included in the nonemphysema time control group.
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Figure 1. The protocol is shown indicating when pulmonary function tests (PFTs), measurements of maximal flow, and lung volume reduction surgery (LVRS) were performed.
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Emphysema Model
Upper lobe emphysema was induced as previously described by the intrabronchial instillations of papain (14, 18). The animal was anesthetized with intravenous pentobarbital (30 mg/kg) and placed on mechanical ventilation. Papain solution (2.5 ml of the enzyme, mixed in 25 ml normal saline solution; Sigma Chemical, St. Louis, MO) was administered under bronchoscopic visualization into one of the upper lobe segments. Approximately eight instillations were performed into each upper lobe over a 4-mo interval alternating between the upper lobes at 7- to 10-d intervals to produce severe upper lobe emphysema (see References 14 and 18).
Pulmonary Function Tests
Pulmonary function tests (PFTs) were performed by methods previously described (14, 18), at the intervals described in Figure 1, and at least 2 wk after the last dose of papain was given. From the PFT measurements, it was determined that severe emphysema was produced, defined by an increase in total lung capacity (TLC) of about 20%. In both the LVRS emphysema and nonemphysema groups, a final set of PFTs was performed immediately after surgery. In the nonsurgical emphysema and nonemphysema groups, PFTs were performed over the intervals depicted in Figure 1, because it was previously demonstrated that PFT measurements did not change in adult dogs with normal or emphysematous lungs over a 6-mo interval in previous studies (14, 18).
PFTs were performed with the animal anesthetized with pentobarbital (30 mg/kg), intubated with an endotracheal tube, mechanically ventilated (15 ml/kg), and placed in a volume displacement plethysmograph in the left lateral decubitus position (14). Lung volumes were measured by means of a Krogh spirometer (J. H. Emerson Co., Cambridge, MA), whereas flow was measured with a pneumotachygraph (Fleisch no. 4; Fleisch, Lausanne, Switzerland) (see Figure 2). An esophageal balloon was inserted with the tip approximately 5 cm from the gastroesophageal junction to measure pleural surface pressure (Ppl). Airway opening pressure (Pao) was measured from a lateral pressure tap placed in the endotracheal tube. Both the airway pressure tap and esophageal balloon catheter were connected to respective differential pressure transducers (MP-45; Validyne, Northridge, CA) by polyethylene catheters. Transducer outputs could be displayed as Pao, Ppl, or transpulmonary pressure (Ptp = Pao – Ppl). Signals for volume, flow, and pressure were displayed on a dual-beam oscilloscope (Tektronix, Inc., Beaverton, OR) and on an eight-channel recorder (Astro-Med, Inc., West Warwick, RI).
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Figure 2. Schematic drawing of the apparatus for tests of parameters of maximal expiratory flow. The lungs are inflated to total lung capacity and then the airway opened to a negative pressure reservoir to achieve maximal expiratory flow. Flow and airway pressure–volume curves, and flow and airway pressure–time curves were recorded during each forced deflation maneuver.
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Functional residual capacity (FRC) was obtained by means of the Dubois method (19). At end-expiration, the change in thoracic gas volume ( V) as the animal attempted to breathe against a closed upper airway was plotted against the change in airway opening pressure (Pao). FRC is equal to (V/Pao)P, where P = (atmospheric pressure – water vapor pressure). Expiratory reserve volume (ERV) was then obtained by means of withdrawing gas volume from the lungs to Ptp = –10 cm H2O by means of a 1-L-volume syringe. The lungs were then inflated to TLC (defined as Ptp = 30 cm H2O). Inspiratory capacity (IC) and residual volume (RV) were calculated by IC = TLC – FRC and RV = FRC – ERV, respectively. Two quasi-static deflation Ptp versus volume curves from TLC to RV were additionally obtained, after which the pressure–volume curves were photographed and the results averaged. FRC was then repeated following a standard volume history to Ptp = 30 cm H2O, and this value of FRC was used as the end-expiratory volume in the construction of the deflation pressure–volume curve determined in each condition.
After a standard volume history, lung compliance (CL), chest wall compliance (CCW), and respiratory system compliance (CRS) were calculated by dividing the change in volume by the change in appropriate pressures (C = V/P) during one complete inspiration–expiration tidal volume cycle on the ventilator. Airway resistance (RL) at FRC was calculated by an oscillation technique (20). At a frequency of 4 Hz and a flow rate of 1 L/s, RL was calculated by dividing the change in Ptp that was in phase with flow by flow (RL = Ptp/flow).
Measurements of Expiratory Flow Limitation
In addition to the assessment of max immediately post-LVRS, these measurements were performed 2 wk before surgery in the LVRS emphysema and LVRS control groups, as well as at comparable intervals in the nonsurgical, nonemphysema group to determine the reproducibility of these measurements in the latter group. In the nonsurgical, emphysema group, flow measurements were obtained only at the end of the study, because the emphysematous lesion has been shown to be unchanged over a 6-mo interval in this model (14) (see Figure 1).
With the animals anesthetized with pentobarbital anesthesia (30 mg/kg), a tracheotomy was performed and a large bore steel tracheostomy tube was secured into the airway. The animal was placed in the plethysmograph in the prone position to ensure accurate Ppl measurements (21–23). A Pitot-static tube (see Figure 2) was used to locate airway sites of flow limitation (i.e., choke points [CPs], see theory below) and to measure airway pressures as previously described (18). The Pitot-static tube measured 1.6 cm in length and 2.5 mm o.d. and was identical to that shown in Figure 17 in Reference 24. The lateral (Plat) and end-on (Pend) ports of the Pitot-static tube were connected to respective differential pressure transducers by polyethylene tubing (1.6-mm diameter, 65-cm length) from which corresponding pressures were measured. Plat and Pend were referenced relative to Ppl, in which Ppl was measured by the esophageal balloon technique (22, 23). These pressures are reported as transmural pressures (i.e., PlatTM and PendTM) in which Ppl has been subtracted. The Pitot-static tube was placed into the airway through a port in the steel tracheal tube under bronchoscopic visualization to ensure axial orientation (22, 23). The Pitot-static tube was initially placed into the trachea and then was advanced down the right mainstem bronchus into the right lower lobe bronchi to identify CPs at the different lung volumes, as previously reported (18, 22, 23) (see below).
During the forced expiratory maneuver, the lungs were inflated to TLC (Ptp = 30 cm H2O) and the airway was opened to a negative pressure reservoir (18). Forced expiratory flow–volume and pressure–volume curves were recorded on the oscilloscope and the graphical images were photographed. Quasi-static pressure–volume curves (Pel –VL) were produced by inflation of the lungs to TLC of 30 cm H2O after which they were slowly deflated (< 100 ml/s) to RV. Pel can be calculated from (Pao – Ppl) during conditions of this low flow rate.
After completion of maximal expiratory flow tests, the animal was removed from the plethysmograph and the steel tracheal tube was removed. After the initial set of maximum flow measurements, the tracheostomy incision was closed and the animal brought back to the recovery area. Intramuscular antibiotic injections (clindamycin 5 mg/kg and gentamycin 7 mg/kg) were given for 2 d after the surgery. After the final set of maximal flow measurements, the study was completed and the animal was killed.
LVRS with the VALR System
Approximately 2 wk after the initial maximal flow experiments, bilateral upper lobe LVRS was performed in which the animal was anesthetized with intravenous propofol and sufentanil (the respective loading doses were 7.5 mg/kg and 1.25 µg/kg, and the corresponding infusion rates were 0.18 mg · kg–1 · min–1 and 1 µg · kg–1 · min–1) (14). The animal was intubated with a 10-mm endotracheal tube. A median sternotomy was performed and the upper lobes were identified. A vacuum-assisted surgical system, the VALR system (VALR Surgical System; Spiration, Redmond, WA), was used to capture the targeted lung tissue within the upper lobe as previously reported (14) (see Figure 3). The VALR system was preferred over staples for its simple, fast application, absence of air leaks, and minimal complications previously demonstrated in this animal model (14).
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Figure 3. Top: The VALR Surgical System (Spiration, Redmond, WA) consists of an elastomer sleeve and introducer chamber. Middle: After application of vacuum pressure, targeted lung tissue is drawn into the elastomer sleeve, and when the system is deployed, the reinforced compression band has been secured at the base of the captured tissue. Bottom: The lung tissue within the sleeve has been resected, leaving the compression band that was further secured to the lung with suture.
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The VALR Surgical System consisted of a silicone compression sleeve loaded within a polycarbonate cylindric introducer. The compression sleeve has a compression band fitted with lugs at the proximal end within its inner circumference to facilitate secure placement once deployed. By means of a controlled vacuum pressure, targeted lung tissue was atraumatically suctioned up into the compression sleeve (see Figure 3; see Reference 14 for details). For the emphysematous animals, an attempt was made to capture the most diseased portions of the upper lobes. In the control nonemphysematous animals, approximately 75% of each upper lobe volume was resected. After completion of lung volume reduction, a chest tube was placed adjacent to the mediastinum to ensure complete evacuation of residual pleural fluid and air, and the sternum and chest wall closed with sutures. The chest tube was removed when there was no ongoing efflux of fluid and no air leak was observed.
After completion of LVRS, the steel tracheostomy tube was again inserted into the trachea as previously described. PFTs and maximal flow measurements were then performed in the plethysmograph as delineated for the initial study. After completion of the experiments, the animal was killed with lethal dose of pentobarbital and intracardiac injection of potassium chloride.
Wave-speed Theory of Flow Limitation and Analysis
Maximal flow was examined in terms of the wave-speed theory of flow limitation, which appears to be the most rigorous in explaining the mechanism of flow limitation in normal and diseased lungs (15, 16). This theory states that flow becomes limited when at a site within the airway, termed the "choke point" (CP), gas velocity is equal to the speed of propagation of pressure pulse waves along the airway wall. max is equal to (A*3/ qK)1/2, where A*, , q, and K are, respectively, airway cross-sectional area at the CP, gas density, correction factor for departure from blunt velocity profile (assumed = 1), and compliance at the CP. At a given lung volume (VL), the CP was located by means of pressure criteria previously described in which Plat at an airway site did not vary with reservoir pressure, whereas slightly downstream, variation occurred (18). Parameters of maximal expiratory flow (PlatTM, PendTM, Pel, max) were measured at three lung volumes: 70% (VC70), 50% (VC50), and 30% (VC30) of the VC determined at each of the measurement studies (see DISCUSSION).
From the Pitot-static tube pressures, the difference between Plat and Pend is proportional to the kinetic energy of gas passing through cross-sectional area (A*) and is termed "convective acceleration" (Pca) (18, 22, 23). Pca was calculated by the Bernoulli equation where Pca = q(max/A*)2/2 and where is the gas density (1.12 x 10–3 g/cm3) and q is assumed to be equal to 1. Frictional pressure losses (Pfr) from alveoli to the CP were calculated by Pfr = Pel – PendTM, where Pel is the average elastic recoil pressure at a given lung volume obtained from the quasi-static Pel–VL curve. For a given VL, frictional airway resistance (Rfr) to the CP was calculated from Rfr = Pfr/max. In normal lungs, lobar emptying was considered to be homogenous (25), and A* could be calculated from the Bernoulli equation whether CPs were identified in central or more upstream airways. In the emphysema groups, lobar emptying would not be homogeneous, and thus the flow subtended by the Pitot-static tube in upstream airways could not be assumed to be uniform among comparably sized airways. In the emphysema group, therefore, A* could only be determined when the CP was identified in the trachea, because max would represent total flow. After LVRS, because the emphysematous regions were removed, homogeneous emptying was again assumed and A* could be calculated whether CPs were identified in the trachea or more upstream airways. Similarly, Rfr could also only be calculated when flow was homogeneous, and the considerations outlined for A* also hold for Rfr. Finally, in some cases, parameters could not be obtained at all lung volumes, particularly at the lowest volume, because the catheter became plugged.
Statistics
Statistical analyses included a three-way (between–within–within) analysis of variance (ANOVA), a two-way (between–within) ANOVA, and a two-way (within–within analysis) and paired t test. A Student-Newman-Keul's multiple comparison test was used when multiple comparisons were obtained. Results were reported as mean (± SD).
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RESULTS
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Pre-LVRS
In the two emphysema groups (i.e., LVRS and non-LVRS groups), after papain administration, TLC increased by approximately 20% as compared with pre-emphysema, and RV and FRC showed similar findings (see Table 1). In this model of heterogeneous upper lobe emphysema, the postemphysema pressure–volume curve was shifted upward and to the left and only slightly rotated as compared with the pre-emphysema curve (see Figure 4). Pel in the emphysematous groups did not differ as compared with those found in the nonemphysematous control groups at 70, 50, and 30% VC, because a parallel shift in the curves was observed (see Table 2; see DISCUSSION).
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Figure 4. Volume–pressure curves are shown for the emphysema and control LVRS groups. Emphysema caused a predominant upward shift in the curve as compared with the pre-emphysema curve. In both the emphysema and control groups, after LVRS the curve was shifted downward and rotated to the right as compared with the pre-LVRS curve.
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In Figure 5 (left panel), max in a control dog is shown to remain constant over most of the VC and then falls abruptly at approximately 30% VC. On the other hand, in the emphysematous dog, max is shown to peak at the high lung volumes and then gradually decreases at the low lung volumes. On the mean, max in the emphysema groups was significantly less as compared with the control groups (see Table 2).
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Figure 5. In the control dog (left panel), maximal flow remains high until approximately 20–30% VC and then decreases sharply. In the emphysema dog (right panel), maximal flow decreases gradually after peak flow is reached.
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CP locations were analyzed in which a location in the trachea was described as location 1, a location at the carina described as location 2, and so forth (18). A schematic of the canine tracheobronchial tree is shown in Figure 6. On the mean, CPs in the nonemphysema control groups were identified at the level of the trachea at 70% VC, at the level of the mainstem bronchus at 50% VC, and at the level of the lobar bronchus at 30% VC. In the emphysema groups, CPs at the two high lung volumes were generally found more upstream at the lobar bronchus. At 30% VC, CPs in both emphysema and control groups were similarly located at lobar bronchi.
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Figure 6. Mean choke-point (CP) locations in the two control (n = 8) and emphysema (n = 9) groups before LVRS. In this schematic of the canine tracheal bronchial tree, the trachea is location 1 (see numbers to the right of airway designation), the carina is location 2, the location at the entrance to the right upper lobe is location 3, and so forth. In general, CPs in the control group were located centrally at high and mid-lung volumes, whereas CPs in the emphysema groups were located more peripherally. In the emphysema groups, mean (± SD) locations were 4.7 ± 3.9, 6.1 ± 4.0, and 7.6 ± 1.8 versus 2.3 ± 1.2, 3.4 ± 2.1, and 6.6 ± 2.8 in the control groups (p = 0.06 between groups). RLL = right lower lobe; RML = right middle lobe; RUL = right upper lobe.
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Pfr was calculated from Pel – PendTM. With CPs located at a more downstream site in the control groups, Pfr to CP values were significantly higher than values measured in the emphysema groups (see Table 2). However, in those experiments in which CPs were similarly identified in the trachea, frictional resistance to CP was not different between the emphysema and control groups. At 70% VC, where CPs were identified in trachea in the control groups and in about half of the animals in the emphysema groups, A* in the emphysema groups averaged 1.5 cm2, which was significantly less than that found in the control groups, where A* averaged approximately 2.5 cm2. In addition, in the control groups, PlatTM at the tracheal CP site had a greater negative value (–8.4 ± 0.7 vs. –4.3 ± 3.8 cm H2O) than that found in the emphysema groups, even though A* was smaller in the emphysema groups.
Post-LVRS
After LVRS was performed in the emphysema group, TLC, VC, and IC returned to near pre-emphysema values (see Table 3), whereas FRC and RV remained unchanged as compared with pre-LVRS values. The fact that RV remained unchanged postsurgery, whereas TLC decreased indicates that gas trapping as demonstrated by RV/TLC increased postoperatively. In addition, respiratory system compliance decreased postsurgery, which was predominantly due to a decrease in tidal chest wall compliance. In the control group, similar changes in lung volumes and mechanics were observed after surgery, and evidence of gas trapping and reduced tidal respiratory compliance was also found.
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TABLE 3. LUNG VOLUMES AND TIDAL COMPLIANCES PRE– AND POST–LUNG VOLUME REDUCTION SURGERY IN THE EMPHYSEMA AND CONTROL GROUPS
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In both the emphysema and control groups, the pressure–volume curves obtained after LVRS were shifted downward and rotated to the right as compared with the respective presurgery curves (see Figure 4). For similar fractions of the VC, Pel after LVRS generally increased in both the emphysematous and control groups as compared with pre-LVRS, particularly in the emphysema group (see Table 4). Despite the increase in Pel after LVRS, max generally decreased in both groups as compared with pre-LVRS values, reaching statistical significance at 70% VC in the emphysema group and 30% VC in the control group (see Table 4).
In both the emphysema and control groups, LVRS was associated with a tendency for Pfr to increase, whereas Rfr significantly increased as compared with presurgery (see Table 4). PendTM values in the emphysema group were higher than those found in the control group, but there was no effect of LVRS on this parameter. After LVRS, on the mean, CP movement was small and was nonsignificantly different between groups (see Table 5). There was also no effect of LVRS on A* in the two groups (see Table 4).
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TABLE 5. CHANGE IN CHOKE-POINT AIRWAY LOCATIONS PRE– VERSUS POST–LUNG VOLUME REDUCTION SURGERY IN THE EMPHYSEMA AND CONTROL GROUPS
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Time Control Non-LVRS Groups
Three emphysematous and three nonemphysematous dogs were monitored over the interval of the study in which the results showed that parameters of maximum flow at the end of the study in the non–LVRS-treated animals were comparable to those found before surgery in the LVRS groups. Moreover, in the three nonemphysematous dogs, max and CP variables were repeated to determine whether the parameters could be reproducibly obtained, and these were very similar on the two occasions (see online supplement).
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DISCUSSION
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In this study, we show that after LVRS was performed, tidal respiratory compliance and max decreased, whereas lung elastic recoil and frictional resistance increased in both the emphysema and control groups as compared with presurgery. In contrast to a previous study in which lung function and max improved after 6 mo post-LVRS (14), the acute effect of LVRS led to an impairment in lung mechanical properties. These changes could contribute to the ventilatory complications including the difficulty of weaning patients from mechanical ventilation and the mortality observed from this procedure.
The findings of emphysema per se on parameters of expiratory flow limitation on lung volumes were similar to those previously reported (18). However, in contrast to what was observed in a diffuse emphysema model, we found in this upper lobe model that Pel did not decrease compared with values measured in nonemphysematous lungs. This can be ascribed to the more localized nature of the lesion in which the effect of papain on lung elastic recoil was less apparent as compared with the diffuse model, and because the major physiologic effect of papain is to increase air trapping rather than to decrease elasticity.
In terms of forced expiration, because, before surgery, Pel values in the emphysema and control groups (see Table 2) were not different at the three lung volumes examined, the mechanism of the decrease in max observed in emphysema must be related either to an increase in Pfr or to a more compliant airway. We found that Pfr values were lower and not higher in the emphysema groups, but nevertheless, this finding must be considered in the context of different CP locations between the emphysema and control groups and the higher flows observed in the control groups. In the control groups, we identified CPs at 70 and 50% VC slightly downstream to those determined in the emphysema groups, and a longer airway to the CP would be associated with greater Pfr in the control groups. At 30% VC, where CPs in both the emphysema and control groups were identified at lobar bronchi, we found that Pfr values, if anything, were still lower in the emphysema groups. Thus, an increase in Pfr does not appear to explain the reduction in max found in this emphysema model. Furthermore, although we identified CP locations in emphysematous canine lungs in relatively large airways, this proximal location would be similar to that found in humans with emphysema (26).
The mechanism of the decrease in max found in this emphysema model appears best explained by an alteration in bronchial pressure airway behavior. In pulmonary emphysema, as parenchymal destruction occurs, a more compliant airway may develop as a result of a loss of bronchial tethering and/or due to a decrease in longitudinal tension (27, 28). In the emphysema groups, when CPs were identified in central airways, A* was lower than that found in the control groups, even though PlatTM was more positive in the emphysema groups. This would be consistent with a change in bronchial pressure-area behavior limiting flow at a lower max in the emphysema groups.
In terms of the wave-speed equation, A* and K determine max where K is airway compliance at the CP. Although we did not measure K in the present study, it was generally decreased in this emphysema model in our previous study (18). In the present study, the K found in the emphysema groups can be estimated relative to the value in the control groups by means of the wave-speed equation in which the ratio of the variables max and A* (see Table 2) is compared between the emphysema and control groups. When K in the emphysema groups is expressed relative to that found in the control groups in terms of the wave-speed equation, K would be lower in the emphysema groups and would therefore not contribute to the decrease in max observed in this model. Of note, the finding of a decrease in K and the conclusion that an increase in airway compliance limited flow at a lower max in the emphysema groups are not contradictory to one another. K does not reflect pressure-area behavior of the airway per se, but the compliance of the CP airway at given lateral pressure, because the pressure-area behavior of the airway is curvilinear.
After LVRS, TLC decreased by approximately 20% as compared with presurgery in both the emphysema and control groups. Although we observed significant reductions in TLC, the results show that FRC and RV were not reduced, and in some cases remained slightly higher as compared with the presurgery values. The ratio of RV/TLC increased in both groups. Thus, after acute LVRS, there was air trapping observed that led to a relatively higher RV and FRC than was expected. In addition, post-LVRS, the static deflation volume–pressure curves were shifted downward and rotated to the right as compared with presurgery in both the emphysema and control groups. In the control group, although removal of normal lung units would be expected to reduce TLC, Pel measured at the same fractions of VC should be the same pre- versus postsurgery, because overall elasticity of the remaining units would be unchanged between conditions. However, in both the control and emphysema groups, for similar fractions of the VC, Pel generally increased after surgery. The mechanism of the increase in Pel after LVRS was probably multifactorial. In one aspect, because air trapping relatively increased after surgery, as indicated by the higher RV/TLC, airway closure may have occurred at a higher fraction of the VC, decreasing the number of lung units contributing to the expirate during deflation. In addition, an increase in Pel could reflect altered properties of the alveolar units themselves, resulting from changes in surfactant related to manipulation of the lung tissue and/or the high oxygen concentrations used during the procedure.
Nevertheless, an increase in Pel would be expected to lead to a higher max post-LVRS, because an increase in Pel would ordinarily increase the pressure head (i.e., PendTM: end-on pressure) at the CP, thereby resulting in a higher A* and hence a higher max (15, 16). However, PendTM did not systematically increase, and on the mean, the net effect was an unchanged PendTM in both groups. The lack of an increase in PendTM post-LVRS indicates that there was a greater dissipation of frictional pressure losses to CP, because Pel – Pfr = PendTM. In Table 4, this was generally the case, because Pfr appeared to increase post-LVRS and frictional resistance to CP was generally higher post-LVRS in both groups. Airway obstruction was likely responsible for the unchanged FRC and RV leading to the relative air trapping observed, as well as to the increase in frictional resistance that occurred. The mechanism of airway obstruction could be related to bronchoconstriction secondary to handling of the parenchyma, to compression of the airways as a consequence of changes in lobar geometry when the chest wall was closed, or to airway secretions. In addition, it is possible that torsion of the airways may have occurred, increasing resistance when the chest wall was closed. Furthermore, although RL as determined by the oscillatory technique did not increase post-LVRS, whereas Rfr as determined by the Pitot-static measurements generally increased, we think that this finding is related to the greater sensitivity of the Rfr measurement in the assessment of airway function.
Accordingly, the net consequence of LVRS on max will be dependent on the extent to which the increases in Pel and Pfr offset one another at each lung volume. These changes resulted in a decrease in max at the highest lung volume in the emphysema group and to a decrease in max at the lowest lung volume in the control group. Although one might have expected a decrease in A* post-LVRS to account for an accompanying decrease in max, such a decrease in A* would be small, and was not observed in the present study. Moreover, with removal of similar amounts of lung tissue, the emphysema group still had smaller flows and cross-sectional areas than in the control group, and this aspect needs to be addressed. This may reflect the fact that papain-induced changes were not localized to the upper lobes, and that there were emphysematous changes in the other lobes as well. Another explanation might be that not all the emphysematous lung from the upper lobes was removed after surgery. In addition, as compared with the control group, there may have been greater increases in Pfr post-LVRS in the emphysema group that were not detected by our analysis.
After LVRS, a decrease in tidal compliance of the respiratory system was also observed in both the emphysema and control groups, which resulted primarily from a reduction in chest wall compliance. This decrease in chest wall compliance was probably related to upward movement of the diaphragm into the chest cavity that made the pressure–volume behavior of the chest wall and diaphragm stiffer as compared with presurgery values. In clinical practice, a decrease in tidal compliance of the respiratory system would lead to an increase in the work of breathing and would contribute to a difficult weaning process after LVRS is performed.
Another factor to consider in this study is that we examined parameters of flow limitation at the same fractions of VC rather than at the same absolute lung volumes between pre-LVRS and post-LVRS conditions. We performed the present analysis because it is the one most commonly used in clinical medicine (7). Although such an approach may have affected interpretation of the findings, when we analyzed the results at the same absolute lung volume from TLC pre- versus post-LVRS, the conclusions were the same and showed that max similarly decreased immediately after LVRS in this emphysema model, despite an increase in Pel (see data in Table E1 of the online supplement).
Although most investigators have centered on the long-term effects of LVRS on lung mechanics and max (3, 4), there is only limited information about changes that evolve in the immediate postoperative period. The effects of acute LVRS differ from those previously reported in a chronic study in which there was an improvement in lung mechanics and maximal flows post-LVRS over 1- and 6-mo intervals (14). There are many reasons why a patient who undergoes LVRS might develop respiratory failure immediately after surgery, which include, among others, complications of retained secretions and infection. The present study points out that an acute impairment in lung mechanics may also contribute to the respiratory compromise that frequently occurs. Although the application of animal models to the human condition must be interpreted cautiously, the present study concludes that the beneficial effects of LVRS may not be observed immediately. Over time, remodeling leads to more beneficial effects of this treatment on lung mechanics.
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Acknowledgments
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The authors thank Dr. Xavier González and other members of Spiration, Inc. for their role in providing materials and training for these experiments. Without their generous support, this project could not have been completed.
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FOOTNOTES
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Supported by the Manitoba Medical Services Foundation.
This article has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org
Originally Published in Press as DOI: 10.1164/rccm.200604-501OC on October 5, 2006
Conflict of Interest Statement: G.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. K.K. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. S.N.M. received $160,000 between 2000 and 2004 from Spiration, Inc. ($40,000/yr), as a research grant for participation in the development of volume reduction techniques in experimental models.
Received in original form April 8, 2006;
accepted in final form October 5, 2006
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K. F. Rabe, B. Beghe, F. Luppi, and L. M. Fabbri
Update in Chronic Obstructive Pulmonary Disease 2006
Am. J. Respir. Crit. Care Med.,
June 15, 2007;
175(12):
1222 - 1232.
[Full Text]
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