Lung volume reduction surgery for severe emphysema

BACKGROUND: We report mid-term results after 25 consecutive lung volume reduction operations (LVRS) for the treatment of severe dyspnea due to advanced emphysema. METHODS: Study design: patients were studied prospectively up to 12 months after surgery. Setting: preoperative evaluation, surgery and postoperative care took place in our university hospital. Patients: patient selection was based on severe dyspnea and airway obstruction despite optimal medical treatment, lung overinflation and completed rehabilitation programme. Patients with severe hypercarbia (PCO2>50 mmHg) were excluded. Nineteen rehabilitated patients who fulfilled our inclusion criteria but postponed or denied LVRS were followed up clinically. Interventions: LVRS was performed bilaterally in 22 patients (median sternotomy) and unilaterally in 3 patients (limited thoracotomy). Measures: Outcome was measured by dyspnea evaluation, 6-minute-walking distance and pulmonary function tests. RESULTS: Twelve months postoperatively dyspnea and mobility improved significantly (MRC score from 3.3+/-0.7 to 2.12+/-0.8, 6-min-walk from 251+/-190 to 477+/-189 m). These results were superior compared to the results of the conservatively treated patients. Significant improvement could also be documented in airway obstruction (FEV1 from 960+/-369 to 1438+/-610 ml) and overinflation (TLC from 133+/-14 to 118+/-21% predicted and RV from 280+/-56 to 186+/-59% predicted). CONCLUSIONS: LVRS is an effective and promising treatment option for selected patients with end-stage emphysema and could be offered as an alternative and / or bridge to lung transplantation.     

Two distinct anti-allergic drugs, amlexanox and cromolyn, bind to the same kinds of calcium binding proteins, except calmodulin, in bovine lung extract

Patients with COPD who fulfill the diagnostic criteria of chronic bronchitis have been shown to exhibit lower serum levels of complement components C3 and C4 than healthy subjects, and this may indicate sustained complement activation as a result of recurrent respiratory tract infections. Since activation of complement leads to influx of inflammatory cells into the lung parenchyma with subsequent release of elastases and oxidants that cause damage to elastic lung tissue, we postulated that there might be a quantitative relationship between complement consumption and degree of elastic tissue destruction. In this study, we tried to investigate possible correlations between serum levels of C3 and C4 and degree of emphysema among patients with COPD of the bronchitic type. We studied 20 patients with chronic bronchitis aged 68+/-1 years (mean+/-SEM) without significant fluctuations of serum C3 and C4 levels over a 3-month period by performing detailed lung function tests, recording of emphysema score in chest radiogram, and the incidence of infective exacerbations during the past 3 years. Measured C3 and C4 serum levels were 124+/-9 and 28.5+/-2 mg/dL, respectively, lower than the respective levels in control subjects (141+/-3 and 39+/-2 mg/dL, respectively). Significant correlations were observed between levels of C4 and (1) incidence of respiratory tract infections during the past 3 years (r=-0.747, p<0.001), (2) radiologic emphysema score (r=-0.936, p<0.001), and (3) various functional indexes, such as midexpiratory flow rate, percent of predicted (r=0.629, p<0.01), forced expiratory flow rate at 50% of vital capacity, percent of predicted (r=0.606, p<0.01), residual volume/total lung capacity ratio (r=-0.651, p<0.01), and the exponential constant of static pressure-volume curve (r=-0.606, p<0.01). These results suggest that patients with chronic bronchitis with the lowest levels of C4 are those experiencing more frequent respiratory infections, tend to have more signs indicative of emphysema in their chest radiograph, have a more prominent small airways dysfunction and gas trapping, and present a greater defect in lung elastic recoil.     

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

Serum angiotensin converting enzyme activity in pulmonary diseases: correlation with lung function parameters

Serum angiotensin converting enzyme activity (ACE), plasma renin activity (PRA), blood pressure (BP), blood pH, blood gases and lung function parameters were measured in patients with emphysema, extrinsic and intrinsic asthma, malignant pulmonary neoplasms, active sarcoidosis and healthy adults. Serum ACE activity was significantly higher in sarcoidosis (250.22+/-34.18 U/L); in small cell carcinoma of lung (155.10+/-38.25 U/L); emphysema (149.82+/-18.31 U/L); extrinsic asthma (141.22+/-25.30 U/L) and lower in intrinsic asthma (98.12+/-15.11 U/L) and squamous cell carcinoma of lung (97.294+/-18.85 U/L) when compared with that of control subjects (108.20+/-13.15 U/L). PRA and BP values of the patients with sarcoidosis, emphysema and small cell carcinoma were markedly elevated and sACE activity was found to be correlated with PRA and mean BP in the same diagnostic groups. sACE activity, PRA and BP of smokers were higher than those of non-smokers in control subjects and in patients with emphysema, extrinsic asthma and small cell carcinoma of lung. Oxygen tensions of the patients with emphysema , extrinsic asthma and small cell carcinoma of lung were found to be significantly decreased. Negative correlations between the sACE activity and oxygen tension (r= -0.68) and between the sACE activity and lung function parameters (r= -0.69 ) were found in these diagnostic groups suggesting that increased sACE level might appeared as a response to chronic hypoxia in the patients with emphysema, extrinsic asthma and small cell carcinoma of lung.     

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.     

Hamstrings and psoas lengths during normal and crouch gait: implications for muscle-tendon surgery

OBJECTIVE: To study the relative contribution of the lung and the chest wall on the total respiratory system mechanics, gas exchange, and work of breathing in sedated-paralyzed normal subjects and morbidly obese patients, in the postoperative period. SETTING: Policlinico Hospital, University of Milan, Italy. METHODS: In ten normal subjects (normal) and ten morbidly obese patients (obese), we partitioned the total respiratory mechanics (rs) into its lung (L) and chest wall (w) components using the esophageal balloon technique together with airway occlusion technique, during constant flow inflation. We measured, after abdominal surgery, static respiratory system compliance (Cst,rs), lung compliance (Cst,L), chest wall compliance (Cst,w), total lung (Rmax,L) and chest wall (Rmax,w) resistance. Rmax,L includes airway (Rmin,L) and "additional" lung resistance (DR,L). DR,L represents the component due to viscoelastic phenomena of the lung tissue and time constant inequalities (pendelluft). Functional residual capacity (FRC) was measured by helium dilution technique. RESULTS: We found that morbidly obese patients compared with normal subjects are characterized by the following: (1) reduced Cst,rs (p < 0.01), due to lower Cst,L (55.3 +/- 15.3 mL x cm H2O-1 vs 106.6 +/- 31.7 mL x cm H2O-1; p < 0.01) and Cst,w (112.4 +/- 47.4 mL x cm H2O-1 vs 190.7 +/- 45.1 mL x cm H2O-1; p < 0.01); (2) increased Rmin,L (4.7 +/- 3.1 mL x cm H2O x L-1 x s; vs 1.0 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01) and DR,L (4.9 +/- 2.6 mL x cm H2O x L-1 x s; vs 1.5 +/- 0.8 mL x cm H2O x L-1 x s; p < 0.01); (3) reduced FRC (0.665 +/- 0.191 L vs 1.691 +/- 0.325 L; p < 0.01); (4) increased work performed to inflate both the lung (0.91 +/- 0.25 J/L vs 0.34 +/- 0.08 J/L; p < 0.01) and the chest wall (0.39 +/- 0.13 J/L vs 0.18 +/- 0.04 J/L; p < 0.01); and (5) a reduced pulmonary oxygenation index (PaO2/PAO2 ratio). CONCLUSION: Sedated-paralyzed morbidly obese patients, compared with normal subjects, are characterized by marked derangements in lung and chest wall mechanics and reduced lung volume after abdominal surgery. These alterations may account for impaired arterial oxygenation in the postoperative period.     

Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer

STUDY OBJECTIVE: To determine the impact of preoperative resting hypercapnia on patient outcome after bilateral lung volume reduction surgery (LVRS). METHODS: We prospectively examined morbidity, mortality, quality of life (QOL), and physiologic outcome, including spirometry, gas exchange, and exercise performance in 15 patients with severe emphysema and a resting PaCO2 of > 45 mm Hg (group 1), and compared the results with those from 31 patients with a PaCO2 of < 45 mm Hg (group 2). RESULTS: All preoperative physiologic and QOL indices were more impaired in the hypercapnic patients than in the eucapnic patients. The hypercapnic patients exhibited a lower preoperative FEV1, a lower diffusing capacity of the lung for carbon monoxide, a lower ratio of PaO2 to the fraction of inspired oxygen, a lower 6-min walk distance, and higher oxygen requirements. However, after surgery both groups exhibited improvements in FVC (group 1, p < 0.01; group 2, p < 0.001), FEV1 (group 1, p=0.04; group 2, p < 0.001), total lung capacity (TLC; group 1, p=0.02; group 2, p < 0.001), residual volume (RV; group 1, p=0.002; group 2, p < 0.001), RV/TLC ratio (group 1, p=0.03; group 2, p < 0.001), PaCO2 (group 1, p=0.002; group 2, p=0.02), 6-min walk distance (group 1, p=0.005; group 2, p < 0.001), oxygen consumption at peak exercise (group 1, p=0.02; group 2, p=0.02), total exercise time (group 1, p=0.02; group 2, p=0.02), and the perceived overall QOL scores (group 1, p=0.001; group 2, p < 0.001). However, because the magnitude of improvement was similar in both groups, and the hypercapnic group was more impaired, the spirometry, lung volumes, and 6-min walk distance remained significantly lower post-LVRS in the hypercapnic patients. There was no difference in mortality between the groups (p=0.9). CONCLUSIONS: Patients with moderate to severe resting hypercapnia exhibit significant improvements in spirometry, gas exchange, perceived QOL, and exercise performance after bilateral LVRS. The maximal achievable improvements in postoperative lung function are related to preoperative level of function; however, the magnitude of improvement can be expected to be similar to patients with lower resting PaCO2 levels. Patients should not be excluded from LVRS based solely on the presence of resting hypercapnia. The long-term benefit of LVRS in hypercapnic patient remains to be determined.     

Respiratory function and surgical reduction of lung volume

Emphysema is characterised by an enlargement of the terminal air spaces. Destructions of alveolar walls lead to a loss of the lung elastic recoil. The driving pressure for expiration is decreased and the outward forces acting on the bronchioles are lost, leading to bronchiolar collapse and airflow limitation. Hyperinflation of the lungs and overdistension of the chest wall cause the respiratory muscles to operate in unfavourable conditions. Patients with advanced emphysema have decreased quality of live: they are dyspneic at rest and are unable to perform exercise. Surgical excision of parts of diffusely emphysematous lungs (Lung Volume Reduction Surgery, LVRS) has been proposed since many years. Expansion of the remaining lung should increase lung elastic recoil and restore the outward forces on the bronchioles. It has been demonstrated that LVRS reduces dyspnea symptoms, improves exercise tolerance and enhances the quality of live. LVRS increases lung elastic recoil, airway conductance and maximal expiratory flow, reduces dynamic hyperinflation and improves the efficiency of the respiratory muscles. These improvements are maintained for at least 12 to 18 months. Preoperative evaluation, surgical-induced modifications of pulmonary functions and postoperative exercise training are exposed.     

Role of lung perfusion scintigraphy in relation to chest computed tomography and pulmonary function in the evaluation of candidates for lung volume reduction surgery

Lung perfusion scintigraphy is employed to evaluate patients with severe emphysema who are candidates for lung volume reduction surgery (LVRS). Our purpose was to investigate the role of scintigraphy in relation to chest computed tomography (CT) and lung function in this setting. Six observers blinded to clinical data retrospectively scored preoperative scintigrams of 70 patients undergoing bilateral video-assisted LVRS according to the distribution of lung perfusion as homogeneous, intermediately heterogeneous, or markedly heterogeneous. Heterogeneity of emphysema distribution was also assessed by chest CT. Dyspnea and pulmonary function were measured preoperatively and 3 mo postoperatively. In 42 patients with markedly heterogeneous, in 18 with intermediately heterogeneous, and in 10 with homogeneous perfusion, mean (+/- SE) FEV1 increased by 57 +/- 8% (p < 0.0001), 38 +/- 9% (p < 0.001), and 23 +/- 9% (p = NS) (p = NS for intergroup comparisons). In a multiple regression analysis, functional improvement after LVRS was more closely correlated with preoperative hyperinflation and the degree of emphysema heterogeneity estimated by chest CT than with the degree of perfusion heterogeneity assessed by scintigraphy. In 16 of 22 patients with homogeneous emphysema distribution in the chest CT scintigraphy revealed intermediately or markedly heterogeneous perfusion. We conclude that lung perfusion scintigraphy has a limited role in prediction of outcome, but it may help to identify target areas for resection in LVRS candidates with homogeneous CT morphology.     

Surgical treatment of severe emphysema: lung transplantation or volume reduction?

In recent years, lung transplantation (LT) and volume reduction surgery (LVRS) have been proposed for selected patients with end-stage pulmonary emphysema. Retrospectively, we analyzed the perioperative time course of 30 patients with emphysema who underwent either LVRS (n = 17) or LT (n = 13). In the LVRS group, patients were significantly older, presented less severe functional disability and all but one could be extubated at the end of surgery. In contrast, patients undergoing LT required postoperative mechanical ventilation (19 +/- 11 hrs) and had a prolonged hospital stay (37 [25-60] days vs 19 [11-42] days in LVRS patients) due to reperfusion lung edema, infection, hemorrhage and acute rejection. Six months postoperatively, forced expiratory volume in 1 second was improved and was significantly larger after LT compared with LVRS (+200% vs +63%). Our preliminary results suggest that, although LT produces greater functional improvement, LVRS is associated with lower surgical risk and is an alternative therapy in selected patients with severe emphysema.     

Two-year results after lung volume reduction surgery in alpha1-antitrypsin deficiency versus smoker's emphysema

Lung volume reduction surgery (LVRS) improves exercise capacity and relieves dyspnoea in patients with smoker's emphysema (SE). It is unclear, however, whether LVRS similarly improves lung function in alpha1-antitrypsin-deficiency emphysema (alpha1 E). To address this question, this study prospectively compared the intermediate-term functional outcome in 12 consecutive patients with advanced alpha1E and 18 patients with SE who underwent bilateral LVRS. Before surgery there were no statistically significant differences between the two groups in the six-minute walking distance, dyspnoea score, respiratory mechanics or lung function data, except for the forced expiratory volume in one second, which was lower in the deficient group (24 versus 31% of the predicted value; p<0.05). In both groups, bilateral LRVS produced significant improvements in dyspnoea, the six-minute walking distance, lung function and respiratory mechanics. In the alpha1E group, the functional data, with the exception of the six-minute walking distance, returned to baseline at 6-12 months postoperation and showed further deterioration at 24 months. The functional status of the SE group remained significantly improved over this period. In conclusion, the functional improvements resulting from bilateral lung volume reduction surgery are sustained for at least 2 yrs in most patients with smoker's emphysema, but this type of surgery offers only short-term benefits for most patients with alpha1E.     

Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.     

Effects of heat and moisture exchangers on minute ventilation, ventilatory drive, and work of breathing during pressure-support ventilation in acute respiratory failure

OBJECTIVES: To evaluate the effect of two commonly used heat and moisture exchangers on respiratory function and gas exchange in patients with acute respiratory failure during pressure-support ventilation. DESIGN: Prospective, randomized trial. SETTING: Intensive care unit of a university hospital. PATIENTS: Fourteen patients with moderate acute respiratory failure, receiving pressure-support ventilation. INTERVENTIONS: Patients were assigned randomly to two treatment groups, in which two different heat and moisture exchangers were used: Hygroster (DAR S.p.A., Mirandola, Italy) with higher deadspace and lower resistance (group 1, n = 7), and Hygrobac-S (DAR S.p.A.) with lower deadspace and higher resistance (group 2, n = 7). Patients were assessed at three pressure-support levels: a) baseline (10.3 +/- 2.4 cm H2O for group 1, 9.3 +/- 1.3 cm H2O for group 2); b) 5 cm H2O above baseline; and c) 5 cm H2O below baseline. Measurements obtained with the heat and moisture exchangers were compared with those values obtained using the standard heated hot water humidifier. MEASUREMENTS AND MAIN RESULTS: At baseline pressure-support ventilation, the insertion of both heat and moisture exchangers induced in all patients a significant increase in the following parameters: minute ventilation (12.4 +/- 3.2 to 15.0 +/- 2.6 L/min for group 1, and 11.8 +/- 3.6 to 14.2 +/- 3.5 L/min for group 2); static intrinsic positive end-expiratory pressure (2.9 +/- 2.0 to 5.1 +/- 3.2 cm H2O for group 1, and 2.9 +/- 1.7 to 5.5 +/- 3.0 cm H2O for group 2); ventilatory drive, expressed as P41 (2.7 +/- 2.0 to 5.2 +/- 4.0 cm H2O for group 1, and 3.3 +/- 2.0 to 5.3 +/- 3.0 cm H2O for group 2); and work of breathing, expressed as either power (8.8 +/- 9.4 to 14.5 +/- 10.3 joule/ min for group 1, and 10.5 +/- 7.4 to 16.6 +/- 11.0 joule/min for group 2) or work per liter of ventilation (0.6 +/- 0.6 to 1.0 +/- 0.7 joule/L for group 1, and 0.8 +/- 0.4 to 1.1 +/- 0.5 joule/L. for group 2). These increases also occurred when pressure-support ventilation was both above and below the baseline level, although at high pressure support the increase in work of breathing with heat and moisture exchangers was less evident. Gas exchange was unaffected by heat and moisture exchangers, as minute ventilation increased to compensate for the higher deadspace produced in the circuit by the insertion of heat and moisture exchangers. CONCLUSIONS: The tested heat and moisture exchangers should be used carefully in patients with acute respiratory failure during pressure-support ventilation, since these devices substantially increase minute ventilation, ventilatory drive, and work of breathing. However, an increase in pressure-support ventilation (5 to 10 cm H2O) may compensate for the increased work of breathing.     

Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation

OBJECTIVES: Despite improvements in organ preservation, reperfusion injury remains a major source of morbidity and mortality after lung transplantation. This pilot study was designed to investigate the effects of controlled reperfusion after lung ischemia. METHODS: Twenty adult pigs underwent 2 hours of warm lung ischemia by crossclamping the left bronchus and pulmonary artery. In five (group 1), the clamp was simply removed at the end of ischemia (uncontrolled reperfusion). The 15 other pigs underwent modified reperfusion using blood from the femoral artery to perfuse the lung through the pulmonary artery (pressure 40 to 50 mm Hg) for 10 minutes before removing the pulmonary artery clamp. In five (group 2), the blood was mixed with crystalloid, resulting in a substrate-enriched, hypocalcemic, hyperosmolar, alkaline solution. In five (group 3), the blood was circulated through a leukocyte-depleting filter, and the last five (group 4) underwent reperfusion with both a modified solution and white blood cell filter. Lung function was assessed 60 minutes after reperfusion, and biopsy specimens were taken. RESULTS: Controlled reperfusion with both a white blood cell filter and modified solution (group 4) completely eliminated the reperfusion injury that occurred with uncontrolled reperfusion (group 1), resulting in complete preservation of compliance (98% +/- 1% vs 77% +/- 1%; p < 0.001, and arterial/alveolar ratio (97% +/- 2% vs 27% +/- 2%; p < 0.001); no increase in pulmonary vascular resistance (106% +/- 1% vs 198% +/- 1%; p < 0.001); lowered tissue edema (82.1% +/- 0.4% vs 84.3% +/- 0.2%; p < 0.001), and myeloperoxidase activity (0.18 +/- 0.02 vs 0.35 +/- 0.02 deltaOD/min/mg protein; p < 0.001). In contrast, using either a white blood cell filter or modified solution separately improved but did not avoid the reperfusion injury, resulting in pulmonary function and tissue edema levels that were intermediate between group 1 (uncontrolled reperfusion) and group 4 (white blood cell filter and modified solution). CONCLUSION: After 2 hours of warm pulmonary ischemia, (1) a severe lung injury occurs after uncontrolled reperfusion, (2) controlled reperfusion with either a modified reperfusion solution or white blood cell filter limits, but does not avoid, a lung reperfusion injury, (3) reperfusion using both a modified reperfusate and white blood cell filter results in complete preservation of pulmonary function. We therefore believe surgeons should control the reperfusate after lung transplantation to improve postoperative pulmonary function.     

Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph

Diaspirin crosslinked hemoglobin (DCHb) is a new blood substitute manufactured from human blood. To evaluate its microvascular filtration properties, we infused DCLHb into unanesthetized sheep (10%, 20 ml/kg) and measured the flow and composition of lung and soft tissue lymph. For comparison, we also infused human serum albumin (HSA; 10%, 20 ml/kg). DCLHb raised systemic and pulmonary arterial pressures from baseline values of 83 +/- 7 and 13 +/- 2 mm Hg, respectively, to peak values of 113 +/- 9 and 26 +/- 3 mm Hg (p < 0.05 versus baseline). These increases were significantly greater than those associated with HSA, which raised systemic and pulmonary arterial pressures from baseline values of 86 +/- 4 and 13 +/- 2 mm Hg, respectively, to peak values of 97 +/- 3 and 21 +/- 7 mm Hg (p <= 0.05 versus baseline and versus DCLHb). These differences reflect the known pressor properties of DCLHb. Accordingly, DCLHb raised lung and soft tissue lymph flows to peak values of 12.2 +/- 3.8 and 1.6 +/- 0.7 ml/30 min, respectively, while HSA raised lung and soft tissue lymph flows to peak values of 7.5 +/- 4.8 and 4.6 +/- 1.9 ml/30 min, respectively (p <= 0.05 versus DCLHb). The half-times of DCLHb equilibration from plasma into lung and soft tissue lymph of 1. 0 +/- 0.3 and 2.1 +/- 1.1 h, respectively, were significantly faster than HSA equilibration half-times of 3.1 +/- 0.2 and 3.8 +/- 0.9 h. Filtration differences between DCLHb and HSA appear to be due to the pressor properties DCLHb.     

Pulmonary function after one-lung ventilation in newborns: the basis for neonatal thoracoscopy

BACKGROUND: To maintain good exposure during major video-assisted thoracic surgery it is necessary to deflate completely the ipsilateral lung. However, little is known about the effects of one-lung ventilation (OLV) on pulmonary function in newborn patients. METHODS: Ten neonatal domestic pigs with a mean age of 6+/-0.6 days were intubated and ventilated in pressure-controlled mode (inspired oxygen fraction=1.0). One-lung ventilation was maintained for 120 minutes. Serial measurements of hemodynamics and gas exchange were done before, during, and until 90 minutes after OLV. Pulmonary function testing was performed before and after OLV for each lung separately. RESULTS: With the inspired oxygen fraction set at 1.0, arterial oxygen saturation remained stable at 100% during OLV. Venous admixture and alveolar-arterial oxygen tension gradient increased slightly from the baseline value of 2.6% +/-0.3% to 3.8%+/-0.3% during OLV (mean+/-standard error of the mean; p=0.02), and from 358+/-28 to 407+/-18 mm Hg (not significant), respectively. Both values returned to baseline during the subsequent ventilation of both lungs. Static compliance and resistance of the ventilated lung did not change. Compliance of the collapsed lung decreased after reexpansion from 0.42+/-0.07 to 0.29+/-0.06 mL x cm H2O(-1) x kg(-1), p=0.008). Resistance remained unchanged (0.22+/-0.02 versus 0.25+/-0.05 cm H2O x L(-1) x s(-1); not significant). CONCLUSIONS: There were only minor effects on pulmonary function during and after OLV in the neonatal piglet. Alterations in gas exchange during OLV were minimal. Prolonged collapse of the lung with subsequent reexpansion was associated with a slight decrease in compliance, indicating some mild lung injury.     

Isolated single-lung perfusion with TNF-alpha in a rat sarcoma lung metastases model

We conducted a trial of isolated lung perfusion using tumor necrosis factor (TNF) in an experimental sarcoma lung metastasis model. In an in vitro experiment, methylcholanthrene-induced sarcoma cells were incubated for 48 hours with 42 micrograms/mL of either human or murine TNF. Controls were incubated with Hank's balanced salt solution. In an in vivo experiment, 23 F344 rats were injected with 10(7) methylcholanthrene-induced sarcoma cells. On day 7, 4 animals were perfused with 210 micrograms of murine TNF, 5 animals were perfused with 420 micrograms of murine TNF, 10 animals underwent isolated lung perfusion with 420 micrograms of human TNF, and 4 animals were injected systemically with 420 micrograms of human TNF. Animals were sacrificed on day 14 and the lung nodules counted. The cells incubated with murine TNF exhibited a 21% decrease in growth (p = 0.07); cells incubated with human TNF showed a 37% decrease in growth (p < 0.05). Animals perfused with 210 micrograms/mL of murine TNF and animals treated by systemically administered human TNF showed no tumor response. Animals perfused with 420 micrograms/mL of murine TNF had 7.8 +/- 14.2 nodules on the left lung and 58.5 +/- 66.0 nodules on the right lung (p = 0.07). Animals perfused with 420 micrograms/mL of human TNF had 21.7 +/- 18.3 nodules on the left lung and 91.7 +/- 66.2 nodules on the right lung (p < 0.01). On the basis of these findings, we conclude that isolated lung perfusion with TNF can be done safely in the rat and is effective in decreasing the growth of sarcoma lung metastases.     

Bioelectrical impedance analysis of body composition in patients with pulmonary emphysema

In this study we utilized bioelectrical impedance analysis (BIA) to compare the body composition of 36 stable pulmonary emphysema (PE) patients with 19 healthy controls. We compared the PE patients and healthy controls in terms of fat-free mass (FFM) and body fat (BF) as percentages of ideal body weight (FFM/IBW, BF/IBW). FFM/IBW and BF/IBW were significantly lower in the PE patients than in the controls (75.0 +/- 9.8% vs. 85.2 +/- 7.3%, p < 0.001 and 11.8 +/- 6.4% vs. 16.7 +/- 7.7%, p < 0.05, respectively). We divided the PE patients into two subgroups according to FFM, then investigated the relationships between FFM and skeletal muscle strength, and between FFM and respiratory muscle strength. In patients with reduced FFM (FFM < 43.5 kg) grip strength as an index of skeletal muscle strength was significantly lower than in patients without reduced FFM (FFM > or = 43.5 kg) (25.7 +/- 7.8 kg vs. 36.2 +/- 7.2 kg, p < 0.005). As indexes of respiratory muscle strength, maximal expiratory pressure (PEmax) and maximal inspiratory pressure (PImax) were lower in the patients with reduced of FFM, but not to a statistically significant degree (49.6 +/- 20.8 cm H2O vs. 58.7 +/- 23.9 cm H2O and 40.5 +/- 19.2 cm H2O vs. 50.2 +/- 22.1 cm H2O, respectively). In the PE patients, FFM correlated closely with vital capacity (r = 0.528, p < 0.001), forced vital capacity (FVC) (r = 0.531, p < 0.001), FEV1.0 (r = 0.554, p < 0.001), FEV1.0/FVC (r = 0.467, p < 0.005), RV/TLC (r = -0.395, p < 0.05), DLco (r = 0.770, p < 0.001), and DLco/VA (r = 0.622, p < 0.001). However no correlation was observed between BF and any of the measures of lung function. The findings of our study suggest that FFM correlates with skeletal muscle strength, respiratory muscle strength and some measures of lung function in patients with PE, and that assessments of body composition are valuable to their clinical management.     

Comparison of helium dilution and plethysmographic lung volumes in pregnant women

The multibreath helium equilibration method is the technique recommended for routine measurement of static lung volumes in normal subjects. However, pregnancy could be an exception to this general rule, due to airway closure during the second half of gestation. The aim of this study was to compare the measurements of lung volumes by plethysmography and helium dilution during pregnancy. Twenty three healthy women were studied at 12, 24 and 36 weeks of pregnancy, and 4 months postpartum. Total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) were measured by multibreath helium equilibration (TLCHe, FRCHe and RVHe) and by plethysmography (TLCbox, FRCbox and RVbox). Only at 36 weeks were there differences between the two methods. RVbox was significantly larger than RVHe (1.01+/-0.18 vs 0.77+/-0.21 L; p<0.001). FRCbox was larger than FRCHe (1.95+/-0.32 vs 1.60+/-0.32 L; p<0.001) and TLCbox was larger than TLCHe (4.83+/-0.52 vs 4.45+/-0.51 L; p<0.05). The 95% limits of agreement for differences between lung volumes measured by the two techniques (helium dilution - plethysmography) at 36 weeks were: -0.42 to -0.06 L for RV; -0.54 to -0.17 L for FRC; and -0.66 to -0.11 L for TLC. We conclude that using the multibreath helium equilibration method to measure lung volumes in at-term pregnant women results in underestimation of functional residual capacity and total lung capacity.