Immunopathology of hyperacute xenograft rejection in a swine-to-primate model.

Hyperacute rejection is the inevitable consequence of the transplantation of vascularized organs between phylogenetically distant species. The nature of the incompatibility and the pathogenetic mechanisms that lead to hyperacute xenograft rejection are incompletely understood. We investigated these issues by the immunopathological analysis of tissues from swine renal and cardiac xenografts placed in rhesus monkeys. Hyperacute rejection was associated with deposition of recipient IgM and classic but not alternative complement pathway components along endothelial surfaces, the formation of platelet and fibrin thrombi, and the infiltration of neutrophils. In animals from which natural antibody was temporarily depleted by organ perfusion, rejection was observed at 3 days to 5 days posttransplant. The immunopathology of rejection in these tissues revealed focal vascular changes similar to those observed in hyperacute rejection. A xenograft functioning for a prolonged period in a recipient temporarily depleted of circulating natural antibody contained recipient IgM along endothelial surfaces but no evidence for significant deposition of complement, formation of platelet and fibrin thrombi, or infiltration of neutrophils. These results suggest that rhesus IgM contributes significantly to the development of hyperacute rejection in the swine to Rhesus model and that the fixation of complement is a critical factor in the recruitment of the coagulation cascade and platelet aggregation--and possibly in the adherence and infiltration of PMN.

Long-term outlook for renal transplant recipients with one-year function. "Doctor, what are my chances"?

Patients with renal transplants that survive the first year often ask about the chance of long-term function. We studied 1850 patients with primary transplants from June 7, 1963 to September 1, 1988 who had graft survival of greater than 1 year. Patients were grouped by donor type, diabetic status, and whether or not they received cyclosporine (CsA). Half-life (T1/2) was used to compare long-term survival rates. We determined the long-term graft survival inclusive and exclusive of death with function (DwF) in order to study all patients and to direct attention to immunologic losses. Pre-CsA, DwF was the major cause of graft loss in each cohort. Cause of DwF was cardiovascular (49%), infection (26%), and cancer (14%). The percentage of patients experiencing DwF was much higher in the pre-CsA group vs. the CsA group: HLA-identical living related donor, 16% vs. 3%; non-HLA-identical LRD, 22% vs. 5%; and cadaver donors, 26% vs. 11%. T1/2 for 711 transplants to diabetics (DM) was 9.01 +/- .54 years, while for transplants to 1139 nondiabetics (NDM) T1/2 was 13.57 +/- .68 (P less than .05). When DwF is excluded (DwFex) DM T1/2 = 23.5 +/- 2.69 and NDM T1/2 = 22.2 +/- 1.55 (NS). Overall, for HLA-identical transplants (n = 297) T1/2 = 26.13 +/- 3.35 and DwFex T1/2 = 104.3 +/- 28.93. Nonidentical LRD (n = 845) T1/2 = 11.25 +/- .61 and DwFex T1/2 = 19.37 +/- 1.55. For CAD (n = 701) T1/2 = 9.10 +/- .54 and DwFex T1/2 = 17.49 +/- 1.65. Comparing pre- and post-CsA cohorts, CsA has not resulted in significant improvement in long-term graft survival by T1/2 analysis with DwFex. It appears that overall long-term graft survival has improved with the introduction of CsA. Much of the improvement may be attributed to better first year graft survival and a reduction in cases of DwF. DM patients have an equal opportunity for long-term graft survival if they do not die from other causes. Excluding DwF, especially as an older population is transplanted, is important in determining chances of immunologic loss. Use of this type of analysis suggests that long-term outlook for 1-year graft survivors is excellent.

Should lung volume reduction for emphysema be unilateral or bilateral?

Both unilateral and bilateral lung volume reduction procedures are being advocated for treatment of severe, generalized emphysema. We analyzed the results of 166 consecutive patients who underwent unilateral (n = 87) or bilateral (n = 79) thoracoscopic stapled lung volume reductions to help define the role for these procedures. There was no statistically significant difference in the operative mortality (3.5% vs 2.5%), mean length of stay (11.4 +/- 1 vs 10.9 +/- 1 days), or morbidity for the unilateral and bilateral groups, respectively (p not significant for all variables). Oxygen dependence was eliminated in 18 (36%) of 50 patients who had unilateral procedures and 30 (68%) of 44 of those who had bilateral procedures (p < 0.01). Prednisone was eliminated for 38 (54%) of 51 unilateral-procedure patients, compared with 30 (85%) of 35 bilateral-procedure patients (p = 0.02). Overall, bilateral procedures produced a mean improvement in the forced expiratory volume in 1 second (FEV1) of 57%, compared with 31% for unilateral reduction procedures (p < 0.01). Our bilateral staple procedure produced a 72.8% mean increase in the FEV1 for patients who had upper lobe emphysema. Especially compromised patients (age > or = 75, with preoperative room air Po2 < or = 50 mm Hg or FEV1 < or = 500 ml) had the same morbidity and operative mortality with unilateral or bilateral procedures, but they had a higher 1-year mortality (17% vs 5%), primarily because of respiratory failure after the unilateral operation (p < .001). Although unilateral staple lung volume reduction may produce an excellent result in a given patient, the bilateral procedure appears to be the procedure of choice, because it provides better overall results at no increased morbidity or mortality compared with the unilateral procedure. The results of bilateral staple lung volume reduction by thoracoscopy appear to be comparable to those of median sternotomy.

Combined operations for lung volume reduction surgery and lung cancer.

Fifty-three lung masses were found in 51 (16%) of 325 patients who underwent lung volume reduction surgery. This included 11 non-small cell lung cancers and 42 benign lung masses. Eleven patients (mean age, 69.4 years) underwent a combined lung volume reduction surgery and resection of clinical stage I lung cancers (lymph node dissection with either lobectomy [3] or wedge resection [8]). There were no deaths or major complications. The average length of stay was 8.7 days. The mean FEV1 was 654 mL (21.7% predicted) preoperatively and 1,079 mL (49% predicted) postoperatively. Patients who are screened for lung volume reduction surgery should be carefully evaluated for possible lung masses. Lung volume reduction surgery allows lung cancer surgery in patients who otherwise would be considered to have physiologically inoperable disease.

Rate of FEV1 change following lung volume reduction surgery.

INTRODUCTION: Lung volume reduction surgery (LVRS) improves pulmonary function and dyspnea symptoms acutely in selected patients with heterogeneous emphysema. Limited data are available regarding long-term function following LVRS. We analyzed short-term (<6 months) and long-term rate of change of pulmonary function in 376 patients who underwent unilateral or bilateral LVRS using thoracoscopic or median sternotomy, staple, laser, or combined techniques. We hypothesized that the long-term rate of deterioration in lung function would be dependent on the surgical procedure used and would be greatest in those with the largest short-term postoperative improvement. METHODS: Pulmonary function was assessed preoperatively and at repeated intervals following LVRS. The change in pulmonary function over time was assessed for each patient by determining the individual change in FEV1 using linear regression analysis short and long term. Overall rate of change in pulmonary function was calculated for the composite group of patients and subgrouped by operative procedure. RESULTS: Lung function appears to improve in the first few months following LVRS in most patients, maximizing at approximately 3 to 6 months and declining thereafter. The short-term incremental improvement following staple procedures is superior to improvements following laser procedures or unilateral surgery: FEV1 increase (mean+/-SD) of 0.39+/-0.03 L for bilateral staple, 0.25+/-0.03 L for unilateral staple, 0.10+/-0.03 L for unilateral laser, and 0.22+/-0.1 L for mixed unilateral staple/laser procedures. However, the long-term rate of decline in FEV1 was greatest for bilateral staple LVRS procedures as well: 0.255+/-0.057 L/yr for bilateral staple, 0.107+/-0.068 L/yr for unilateral staple, 0.074+/-0.034 L/yr for unilateral laser, and 0.209+/-0.12 L/yr for mixed staple laser procedures. There was a general correlation between the magnitude of short-term incremental improvement and the rate of deterioration in FEV1 (r=0.292, p=0.003). CONCLUSIONS: While bilateral staple LVRS procedures lead to greater short-term improvement in FEV1, the more rapid rate of FEV1 decline in these patients and the general association between greater short-term incremental improvement and higher rates of deterioration raise questions regarding optimal long-term procedures. Further studies will be needed to answer these important questions.

Serial lung function and elastic recoil 2 years after lung volume reduction surgery for emphysema.

STUDY OBJECTIVE: To evaluate serial lung function studies, including elastic recoil, in patients with severe emphysema who undergo lung volume reduction surgery (LVRS). To determine mechanism(s) responsible for changes in airflow limitation. METHODS: We studied 12 (10 male) patients aged 68+/-9 years (mean+/-SD) 6 to 12 months prior to and at 6-month intervals for 2 years after thoracoscopic bilateral LVRS for emphysema. RESULTS: At 2 years post-LVRS, relief of dyspnea remained improved in 10 of 12 patients, and partial or full-time oxygen dependency was eliminated in 2 of 7 patients. There was significant reduction in total lung capacity (TLC) compared with pre-LVRS baseline, 7.8+/-0.6 L (mean+/-SEM) (133+/-5% predicted) vs 8.6+/-0.6 L (144+/-5% predicted) (p=0.003); functional residual capacity, 5.6+/-0.5 L (157+/-9% predicted) vs 6.7+/-0.5 L (185+/-10% predicted) (p=0.001); and residual volume, 4.9+/-0.5 L (210+/-16% predicted) vs 6.0+/-0.5 L (260+/-13% predicted) (p=0.000). Increases were noted in FEV1, 0.88+/-0.08 L (37+/-6% predicted) vs 0.72+/-0.05 L (29+/-3% predicted) (p=0.02); diffusing capacity, 8.5+/-1.0 mL/min/mm Hg (43+/-3% predicted) vs 4.2+/-0.7 mL/min/mm Hg (18+/-3% predicted) (p=0.001); static lung elastic recoil pressure at TLC (Pstat), 13.7+/-0.5 cm H2O vs 11.3+/-0.6 cm H2O (p=0.008); and maximum oxygen consumption, 8.7+/-0.8 mL/min/kg vs 6.9+/-1.5 mL/min/kg (p=0.03). Increase in FEV1 correlated with the increase in TLC Pstat/TLC (r=0.75, p=0.03), but not with any baseline parameter. CONCLUSION: Two years post-LVRS, there is variable clinical and physiologic improvement that does not correlate with any baseline parameter. Increased lung elastic recoil appears to be the primary mechanism for improved airflow limitation.

Lung function 12 months following emphysema resection.

OBJECTIVE: To investigate the mechanism of airflow limitation before and 6 and 12 months after targeted emphysematous resection in 10 male patients aged 67 +/- 8 years (mean +/- SD) with very severe COPD undergoing bilateral thoracoscopic stapling techniques. DESIGN: Lung function, including static lung elastic recoil, was measured 2 weeks before and 6 and 12 months after surgery. RESULTS: Twelve months after surgery, there was a significant (p < 0.001) reduction in total lung capacity (TLC), 9.5 +/- 0.3 L (mean +/- SEM) to 8.5 +/- 0.3 L, functional residual capacity, and residual volume. Airway conductance and FEV1, 0.71 +/- 0.1 L (mean +/- SEM) to 0.95 +/- 0.1 L, improved significantly (p < 0.01). Lung elastic recoil increased markedly at TLC from 11.7 +/- 0.7 cm H2O (mean +/- SEM) to 15.0 +/- 1.0 cm H2O (p < 0.01) as did maximum expiratory airflow in every patient. However, when compared with data obtained in each patient at 6 months, lung volumes are significantly increased, and expiratory airflow and lung elastic recoil pressures are significantly reduced (p < or = 0.05). Analysis of maximum expiratory flow-static elastic recoil pressure curve indicates conductance of the S airway segment (Gs) increased from 0.20 +/- 0.03 L/s/cm H2O (mean +/- SEM) to 0.28 +/- 0.04 L/s/cm H2O (p < 0.02), and critical transmural pressure in the collapsible segment (Ptm') decreased from 3.2 +/- 0.2 cm H2O (mean +/- SEM) to 2.5 +/- 0.2 cm H2O (p < 0.01). CONCLUSION: The improvement in maximal expiratory airflow can be attributed primarily to increased lung elastic recoil and its secondary effect on enlarging airway diameter causing increased airway conductance, increased Gs, and decreased Ptm'. The improvement in lung function and elastic recoil peaks at 6 months.

Contribution of lung and chest wall mechanics following emphysema resection.

OBJECTIVE: To determine the contributions of (1) chest wall (Pcw) and (2) lung elastic recoil pressure (PL) to (3) total elastic recoil pressure exerted by the respiratory system (Prs) in 18 patients (12 men) aged 66 +/- 6 years (mean +/- 1 SD) with severe emphysema who underwent video-assisted thoracoscopic bilateral lung volume reduction surgery under paralyzed (vecuronium) general anesthesia (isoflurane). DESIGN: We measured preoperative and 6-week postoperative lung function studies, and intraoperative inspiratory lung conductance (GL), PL, Pcw, and Prs (cm H2O) at end-expiratory lung volume (EELV), EELV plus 0.60 +/- 0.0 L, and EELV plus 1.15 +/- 0.0 L. All values are mean +/- SEM. RESULTS: Preoperative vs postoperative FVC was 1.9 +/- 0.1 L vs 2.3 +/- 0.1 L (p = 0.03); FEV1 was 0.6 +/- 0.1 L vs 0.9 +/- 0.1 L (p < 0.02); total lung capacity was 7.4 +/- 0.4 L vs 5.9 +/- 0.3 L (p < 0.001); functional residual capacity was 5.7 +/- 0.4 L vs 4.4 +/- 0.2 L (p = 0.001). At EELV preoperative vs postoperative, PL was 0.0 +/- 0.3 vs 1.1 +/- 0.05 (p = 0.04), Pcw was 5.0 +/- 0.7 vs 2.4 +/- 0.9 (p = 0.02), and Prs was 5.0 +/- 0.8 vs 3.5 +/- 0.7 (p = 0.08). AT EELV plus 0.60 L, PL was 3.2 +/- 0.6 vs 6.1 +/- 0.9 (p < 0.001), Pcw was 8.8 +/- 0.8 vs 7.0 +/- 0.9 (p = 0.12), and Prs was 12.0 +/- 0.8 vs 13.1 +/- 0.7 (p = 0.80). At EELV plus 1.15 L, PL was 6.8 +/- 0.9 vs 10.3 +/- 1.1 (p < 0.001), Pcw was 13.5 +/- 1.0 vs 11.2 +/- 1.2 (p = 0.12), and Prs was 20 +/- 1.2 vs 21.5 +/- 1.0 p = 0.93). AT EELV plus 0.06 L, GL was 0.09 +/- 0.00 L/S/cm H2O vs 0.16 +/- 0.01 (p < 0.01). At EELV plus 1.15 L, GL was 0.12 +/- 0.01 vs 0.21 +/- 0.03 (p < 0.05) with similar preoperative vs postoperative GL/PL slopes. CONCLUSION: The increase in PL and decrease in Pcw following LVRS for emphysema may be responsible for the increase in spirometry and airway conductance.

Lung function 4 years after lung volume reduction surgery for emphysema.

STUDY OBJECTIVES: Current data for patients > 2 years after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline data and provides long-term results in 26 patients. INTERVENTION: Bilateral targeted upper lobe stapled LVRS using video thoracoscopy was performed in 26 symptomatic patients (18 men) aged 67 +/- 6 years (mean +/- SD) with severe and heterogenous distribution of emphysema on lung CT. Lung function studies were measured before and up to 4 years after LVRS unless death intervened. RESULTS: No patients were lost to follow-up. Baseline FEV(1) was 0.7 +/- 0.2 L, 29 +/- 10% predicted; FVC, 2.1 +/- 0.6 L, 58 +/- 14% predicted (mean +/- SD); maximum oxygen consumption, 5.7 +/- 3.8 mL/min/kg (normal, > 18 mL/min/kg); dyspneic class > or = 3 (able to walk < or = 100 yards) and oxygen dependence part- or full-time in 18 patients. Following LVRS, mortality due to respiratory failure at 1, 2, 3, and 4 years was 4%, 19%, 31%, and 46%, respectively. At 1, 2, 3, and 4 years after LVRS, an increase above baseline for FEV(1) > 200 mL and/or FVC > 400 mL was noted in 73%, 46%, 35%, and 27% of patients, respectively; a decrease in dyspnea grade > or = 1 in 88%, 69%, 46%, and 27% of patients, respectively; and elimination of oxygen dependence in 78%, 50%, 33%, and 22% of patients, respectively. The mechanism for expiratory airflow improvement was accounted for by the increase in both lung elastic recoil and small airway intraluminal caliber and reduction in hyperinflation. Only FVC and vital capacity (VC) of all preoperative lung function studies could identify the 9 patients with significant physiologic improvement at > 3 years after LVRS, respectively, from 10 patients who responded < or = 2 years and died within 4 years (p < 0.01). CONCLUSIONS: Bilateral LVRS provides clinical and physiologic improvement for > 3 years in 9 of 26 patients with emphysema primarily due to both increased lung elastic recoil and small airway caliber and decreased hyperinflation. The 9 patients had VC and FVC greater at baseline (p < 0.01) when compared to 10 short-term responders who died < 4 years after LVRS.

Survival following bilateral staple lung volume reduction surgery for emphysema.

STUDY OBJECTIVES: Despite numerous reports of short-term response to lung volume reduction surgery (LVRS) for treatment of emphysema, to our knowledge, longer-term survival has not been reported. We describe survival following LVRS in a large cohort of 256 patients treated with bilateral staple LVRS (n = 236 video-assisted thoracic surgery [VATS] approaches, n = 20 median sternotomy) by a single group of physicians over a 3 1/2-year period from April 1994 to November 1997. DESIGN: Prospective survival study. Overall survival, survival stratified by preoperative presentation, and acute postoperative response were investigated using Kaplan-Meier methods. The simultaneous effects of preoperative predictors and postoperative response variables on survival were examined using a Cox proportional hazards model. SETTING: Community hospital and university medical center. PATIENTS: We studied 256 consecutive patients with severe emphysema treated with LVRS. INTERVENTIONS: Bilateral staple LVRS by VATS. MEASUREMENTS AND RESULTS: Overall survival information was known with certainty for 246 of 256 patients as of February 1, 1998. Median follow-up time was 623 days (range, 0 to 1,545 days). Mean FEV1 was 0.635L+/-0.015 L preoperatively and rose to 1.068L+/-0.029 L postoperatively. By standard analysis methods (missing patients censored at the time of last contact), 1-year survival was 85+/-2.3% compared with 83+/-2.4% 1-year survival with "worst case" analytic methods (assuming all missing patients died). Two-year survival averaged 81+/-2.7% by standard analysis vs 76+/-2.9% by worst case evaluation. Survival was significantly better for patients who were younger (< or = 70 years old, p = 0.02) and with higher baseline FEV1 (> 0.5, p < 0.03) and PO2 (> 54, p < 0.001). Patients who had greatest short-term improvement in FEV1 following surgery (> 0.56 L increase) also had significantly better longer-term survival following LVRS. CONCLUSIONS: To our knowledge, this is the first longer-term survival analysis of a large series of patients who underwent bilateral staple LVRS for emphysema. Substantial long-term mortality is seen, particularly within identifiable high-risk subgroups. Careful comparison to comparably matched control patients will be needed to definitively assess the benefits and risks of LVRS. This study suggests that prospective, controlled trials may need to stratify patient randomization based on preoperative risk factors to obtain meaningful results.

Patient selection criteria for lung volume reduction surgery.

OBJECTIVE: Our intent was to refine the patient selection criteria for lung volume reduction surgery because various centers have different criteria and not all patients benefit from the procedure. METHODS: Patient information, x-ray results, arterial blood gases, and plethysmographic pulmonary function tests in 154 consecutive patients who underwent bilateral thoracoscopic staple lung volume reduction surgery were compared with clinical outcome (change in forced expiratory volume in 1 second and dyspnea scale) with t tests and analysis of variance. RESULTS: Three hundred thirty-three of 487 (69%) patients evaluated for lung volume reduction surgery were rejected for lack of heterogeneous emphysema (n = 212), medical contraindications (n = 88), hypercapnia (n = 20), uncontrolled anxiety or depression (n = 10), or pulmonary hypertension (n = 1). Two patients died during the evaluation process. When tested by analysis of variance, there was no difference in clinical outcome associated with preoperative forced expiratory volume in 1 second, residual volume, total lung capacity, single-breath diffusing, and arterial oxygen or carbon dioxide tension. All patients selected for the operation had a heterogeneous pattern of emphysema. The upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan was strongly associated with improved outcome with a mean (95% confidence interval) improvement in forced expiratory volume in 1 second of 73.2% (63.3 to 83.1) for the upper lobe compared with a mean (95% confidence interval) improvement of 37.9% (22.9 to 53.0) for the lower lobe or diffuse pattern of emphysema. CONCLUSION: The most important selection criteria for lung volume reduction surgery is the presence of a bilateral upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan. After patients have been selected on the basis of a heterogeneous pattern of emphysema, clinical factors and physiology are not associated with clinical outcome well enough to further refine patient selection criteria. These results do not support the arbitrary patient selection criteria for lung volume reduction surgery reported in the literature.

Lung volume reduction surgery for emphysema.

There has been dramatic resurgence of interest in surgical treatment of emphysema, particularly "lung volume reduction" procedures. Recent studies have demonstrated improvements in pulmonary function, lung mechanics, exercise tolerance, and quality of life in selected patients following volume reduction procedures. However, considerable uncertainty remains regarding overall benefit, optimal patient selection, operative techniques, and duration of response. This summarizes current approaches to lung volume reduction surgery, available clinical outcome information, selection criteria, and physiologic mechanisms of response, and discusses the potential role for surgical volume reduction in treatment of emphysema. Recent data appear to support the efficacy of bilateral staple lung volume reduction surgery in patients with severe symptomatic heterogeneously distributed emphysema. Further studies will be needed to determine relative value of different operative techniques and benefit in patients with other clinical presentations.

Successful human double-lung transplantation after five and one-half hours of preservation.

Successful clinical double-lung transplantation after 5 1/2 hours of pulmonary ischemia is reported. Static hypothermic preservation with a high-volume, high flow rate-modified Collin's solution pulmonary artery flush was used. Excellent early and late pulmonary function demonstrates the efficacy of the technique that is described in detail. Lung transplantation remains limited by the lack of reliable methods of long-term storage of donor organs, but refinement of current techniques may soon allow its wider application.

Dyspnea response following bilateral thoracoscopic staple lung volume reduction surgery.

PURPOSE: Lung volume reduction surgery (LVRS) has shown promise for treating patients with severe emphysema in recent clinical trials. However, response following surgery is difficult to assess due to frequent discrepancies between subjective and objective outcomes. We evaluated the relationship between improvement in dyspnea and pulmonary function response in 145 consecutive patients with inhomogeneous emphysema enrolled in a bilateral thoracoscopic lung volume reduction protocol in order to assess predictors of improved dyspnea outcome and correlation of subjective and objective improvement measures. MATERIALS AND METHODS: Baseline complete pulmonary function testing, spirometry, gas exchange, plethysmography, gas dilution lung volumes, along with resting dyspnea index determinations were performed preoperatively, and repeated short term (mean, 33 days; n=129) and long term (>6 months; mean, 276 days; n=84) following surgery. RESULTS: Improvement in FEV1 percent predicted was significantly associated with improvement in dyspnea scores, though considerable variability exists (r=0.04, p<0.01, short term; r=0.4, p=0.1, long term). In this preselected patient group, those with the extreme degrees of hyperinflation may have less improvement in dyspnea following LVRS than those with milder preoperative hyperinflation. Greater improvement in dyspnea short term and long term was seen in patients with lower presenting residual volume/total lung capacity ratios (r=0.4, p=0.02, short term; r=0.4, p<0.05, long term). CONCLUSIONS: Bilateral thoracoscopic staple LVRS results in significant objective and subjective improvement in patients with severe emphysema and hyperinflation. There was considerable variability between improvement in dyspnea and improvement in spirometry, and preoperative predictors of response may differ between these outcome variables. Further studies are needed to define the long-term implications of these findings.

Diffusing capacity limitations of the extent of lung volume reduction surgery in an animal model of emphysema.

OBJECTIVE: The purpose of this study was to investigate in an elastase-induced emphysema rabbit model the effects of increasing resection volumes during lung volume reduction surgery on pulmonary compliance, forced expiratory air flow, and diffusing capacity to assess factors limiting optimal resection. METHODS: Emphysema was induced in 68 New Zealand White rabbits with 15,000 units of aerosolized elastase. Static respiratory system compliance, forced expiratory flow, and single-breath diffusing capacity were measured before the induction of emphysema, after the induction of emphysema, and 1 week after a bilateral upper and middle lobe lung volume reduction operation. RESULTS: Static respiratory system compliance with 60 mL insufflation above functional residual capacity increased with emphysema induction and then decreased progressively with resection of larger volumes of lung tissue (P =.001 by analysis of variance). Expiratory flow improved after lung resection in the rabbits with large resection volumes. In contrast, diffusing capacity tended to deteriorate with larger resection volumes (P =. 18). CONCLUSION: Improvements in respiratory system compliance and forced expiratory flow after lung volume reduction operations may account for the improvements seen clinically. Declines in diffusing capacity with extensive lung reduction may limit the clinical benefits associated with greater tissue resection volumes. Future investigations with animal models may reveal other physiologic parameters that may further guide optimal lung volume reduction procedures.

Changes in pulmonary physiology after lung volume reduction surgery in a rabbit model of emphysema.

OBJECTIVE: The purpose of this study is to investigate the effects of lung volume reduction surgery on pulmonary compliance, airway flow, and helium lung volumes in an elastase-induced emphysema animal model. METHODS: A 15,000-unit bolus of elastase was aerosolized through an endotracheal tube in 14 New Zealand White rabbits to induce emphysema. Stapled lung volume reduction of bilateral upper and middle lobes was performed through a midline sternotomy at 4 weeks after induction of emphysema. Lung functions were measured at baseline before induction of emphysema, preoperatively at 4 weeks, and 1 week postoperatively. RESULTS: Compliance increased after induction of emphysema and decreased in response to lung volume reduction surgery. Functional residual capacity decreased after lung volume reduction surgery in proportion to the amount of excised lung tissue. Expired flows suggested improvement in response to lung volume reduction surgery. Histologic examination confirmed presence of diffuse heterogeneous emphysema in each animal at necropsy. CONCLUSIONS: The decreased compliance and increased airway flow after volume reduction surgery in this model parallels findings in human studies and suggests that similar mechanisms of increased elastic recoil and airway support contribute to improvement.

Survival after unilateral versus bilateral lung volume reduction surgery for emphysema.

OBJECTIVE: Bilateral staple lung volume reduction surgery (LVRS) immediately improves pulmonary function and dyspnea symptoms in patients with advanced heterogeneous emphysema to a greater degree than do unilateral procedures. However, the long-term outcome after these surgical procedures needs to be critically evaluated. We compare 2-year survival of patients who underwent unilateral versus bilateral video-assisted LVRS in a large cohort treated by a single surgical group. METHODS: The cases of all 260 patients who underwent video-assisted thoracoscopic stapled LVRS from April 1994 to March 1996 were analyzed to compare results after unilateral versus bilateral procedures. Overall survival was calculated by Kaplan-Meier methods; Cox proportional hazard methods were used to adjust for patient heterogeneity and baseline differences between groups. RESULTS: Overall survival at 2 years was 86.4% (95% CI 80. 9%-91.8%) after bilateral LVRS versus 72.6% (95% CI 64.2%-81.2%) after unilateral LVRS (P =.001 for overall survival comparison). Improved survival after bilateral LVRS was seen among high- and low-risk subgroups as well. Average follow-up time was 28.5 months (range, 6 days to 46.6 months) for the bilateral LVRS group and 29.3 months (range, 6 days to 45.0 months) for the unilateral LVRS patients. CONCLUSIONS: Comparison of unilateral versus bilateral thoracoscopic LVRS procedures for the treatment of emphysema reveals that bilateral LVRS by video-assisted thoracoscopy resulted in better overall survival at 2-year follow-up than did unilateral LVRS. This survival study, together with other studies demonstrating improved lung function after bilateral LVRS, suggests that bilateral surgery appears to be the procedure of choice for patients undergoing LVRS for most eligible patients with severe heterogeneous emphysema.

Effects of prostaglandin E1 in twelve-hour lung preservation.

The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac xenografting in the pig-to-rhesus monkey model: manipulation of antiendothelial antibody prolongs survival.

Transplantation of immediately vascularized grafts across species barriers in which preformed cytotoxic antibodies exist, otherwise known as discordant combinations, has uniformly resulted in hyperacute rejection. We studied how well plasma exchange and perfusion through organs removes preformed immunoglobulin M cytotoxic antibodies and prolongs survival of a porcine heart heterotopically transplanted into a rhesus monkey. With the use of plasma exchange or absorption of antibodies by porcine kidney perfusion with or without immunosuppression, graft survival was prolonged, although antibody-mediated rejection ultimately occurred. In one case in which plasma exchange, kidney perfusion, and immunosuppression were combined, a functioning pig heart survived in a rhesus monkey for 8 days without evidence of rejection. The animal was killed on day 8 according to protocol because of a wound dehiscence. With this animal we were able to demonstrate that circulating antibodies against graft endothelium had bound to the graft endothelium without inducing rejection, a process referred to as accommodation. In this case, despite the presence of antiendothelial antibodies, complement did not appear to be activated, and fibrin thrombi did not form. Although we have achieved this rejection-free survival only in one animal, this case suggests that it may be possible to maintain xenotransplants in discordant species without rejection if preformed antibodies are appropriately lowered or altered during the initial period of graft implantation.

Bovine pericardium versus bovine collagen to buttress staples for lung reduction operations.

BACKGROUND: Air leaks after stapled lung volume reduction operations for emphysema remain the most common postoperative complication. Cooper developed the use of bovine pericardium buttress for the staple lines in an attempt to decrease the occurrence of prolonged postoperative air leaks. However, the materials cost for a bilateral procedure may add $3,000 to $4,000 to the cost of the operation. We undertook this study to evaluate the efficacy of a less expensive buttress. METHODS: Fifty-seven patients underwent a bilateral thoracoscopic stapled operation with bovine pericardium (Peri-Strips) on one side and bovine collagen (INSTAT) on the contralateral side to buttress the staples. RESULTS: The average time to chest tube removal was 8.6 +/- 7.2 days for Peri-Strips and 10.7 +/- 8.7 days for INSTAT (p = 0.16). No significant differences were seen when right-sided and left-sided application were considered separately (p = 0.12). CONCLUSIONS: Peri-Strips or INSTAT for buttressing staple lines in thoracoscopic stapled bilateral lung volume reduction operations were equally effective. Materials cost savings of up to 80% per case can be realized by using the less expensive but equally effective INSTAT for buttressing staple lines.