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Biomedical subjects

H Reichenspurner

Publications and source records attributed to H Reichenspurner.

At least 55 records · Page 3Linked to original sources
PubMed2000

Reduced expression of systemic proinflammatory cytokines after off-pump versus conventional coronary artery bypass grafting.

BACKGROUND: Both cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of proinflammatory cytokines. We assessed the relative contribution of CPB on activation of various proinflammatory cytokines in patients undergoing coronary revascularization by comparing them with patients receiving coronary artery bypass grafts using off-pump (OPCAB) techniques. METHODS: Twenty-six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13) or were treated conventionally using extracorporeal circulation, blood cardioplegia and hypothermic arrest (29-31 degrees C; n = 13). C-reactive protein and systemic levels of TNF-alpha, TNF specific receptors Rp1 and Rp2, Interleukin-6 (IL-6) and soluble IL-2 receptors (sIL-2r) were assayed by ELISA or EIA. To account for systemic nitric oxide production, total nitrate/nitrite (NOx) was measured using the Griess reaction. RESULTS: Coronary revascularization with CPB was associated with a significant expression increase in the TNF-system and sIL-2r when compared to the OPCAB patients. Although IL-6 expression did not differ between both groups, C-reactive protein levels were significantly lower in the OPCAB group. Moreover, systemic NOx levels as the stable end-product of nitric oxide were lower in the OPCAB group. CONCLUSIONS: The data of the present study indicate that, despite comparable surgical trauma, the OPCAB revascularization procedure without the use of CPB and cardioplegic arrest significantly reduces the systemic inflammatory response syndrome and early catecholamine requirement. This may contribute to improved organ function, subsequently resulting in improved postoperative recovery from surgical revascularization procedures, particularly in critically ill patients.

Aged↗
PubMed1999

Lung procurement by low-potassium dextran and the effect on preservation injury. Munich Lung Transplant Group.

BACKGROUND: This clinical study was performed to evaluate the effect of low-potassium dextran (LPD) solution on organ function in human lung transplantation. METHODS: A total of 80 patients were included in this study. Donor lungs were flushed with Euro-Collins (EC) solution in 48 cases or LPD (Perfadex) in 32 cases. Subsequently, single- (EC: n = 31; LPD: n = 15) or double-lung transplantations (EC: n = 17; LPD: n = 17) were performed. The evaluation parameters of transplant function were the reperfusion injury score (grade I to V); the alveolar/arterial oxygen ratio; the duration of respirator therapy; and the length of intensive care treatment and survival. RESULTS: Incidence and severity of reperfusion injury score were more severe in the EC group (31 of 48: grade I: n = 13; II: n = 8; III: n = 5; IV: n = 2; V: n = 3; LPD group: 17 of 32 patients; grade I: n = 12; II: n = 1; III: n = 3; IV: n = 0 grade V: n = 0), leading to death in three patients. In the LPD group, despite of the use of cardiopulmonary bypass, alveolar/arterial oxygen ratio values were significantly (P = 0.009) better during the early postoperative phase. Thirty-day mortality was 12% in the EC group and 6% in the LPD group. The one-year survival rate was 79% after the use of LPD (vs. EC: 62%). CONCLUSIONS: Graft preservation using LPD leads to better immediate and intermediate graft function after pulmonary transplantation and also results in better long-term survival.

Adult↗
PubMed1999

Optimization of the immunosuppressive protocol after lung transplantation.

BACKGROUND: The successful use of tacrolimus (Tac)-based immunosuppressive therapy in organ transplantation and our own positive experience in heart transplantation led us to investigate regimens including this agent at our center for lung transplantation. METHODS: From 1991 to 1998, 86 patients underwent lung transplants at our center and 78 of them were included in this analysis. The first 34 patients were treated with cyclosporin (CsA), azathioprine (Aza), and rabbit antilymphocyte globulin; the subsequent 30 patients received Tac with Aza, and the most recent 12 patients Tac with mycophenolate mofetil (MMF). In addition, all patients received prednisone. RESULTS: The number of acute rejection episodes per 100 patient days was 1.5, 0.6, and 0.3 for three treatment groups, respectively. Similarly, the incidence of refractory acute rejection per 100 patient days was lower in both Tac groups (0.20, 0.03, and 0, respectively). Freedom from acute rejection was highest in the Tac-MMF group (P=0.0037 vs. Tac/Aza, P=0.0007 vs. CsA/Aza). Freedom from recurrent acute rejection was significantly higher in both Tac groups (P=0.027 Tac/ Aza vs. CsA/Aza and P=0.025 Tac/MMF vs. CsA/Aza). The incidence of infections per 100 patient days was similar (0.8, 0.5, and 0.8) in all three treatment groups, with a similar distribution of fungal, bacterial, and viral infections. Freedom from infection also showed no difference. The survival rate was significantly higher for the Tac population, with actuarial 1- and 3-year survival rates of 93% and 71%, compared with the CsA group (71% and 51%, respectively, P=0.04). Prevalence of renal dysfunction (creatinine >2.0 mg/ dL) was 18%, 13%, and 0% in the 3 treatment groups, respectively. The development of glucose metabolism disorders was lower in the CsA group than in the Tac-Aza group (15% vs. 27%, P<0.05). CONCLUSIONS: Tac-based immunosuppressive therapy results in a lower rate of acute rejection after pulmonary transplantation, with similar infection rates and a slightly higher incidence of new onset diabetes mellitus compared with CsA-based therapy.

Acute Disease↗
PubMed1999

Mitral commissurotomy, a technique outdated? Long-term follow-up over a period of 35 years.

BACKGROUND: The objective of this study was to evaluate long-term survival, valve-related complications as well as prognostic factors for early and late outcome after open and closed mitral commissurotomy covering a follow-up period of 35 years. METHODS: From 1955 to 1977, 183 patients with mitral stenosis underwent mitral commissurotomy at our institution. Closed valvotomy was performed on 143 patients (group A) and open valvotomy on 40 patients (group B). RESULTS: Survival rates after 10, 20, and 30 years were 89%, 67.8%, and 49.1% in group A and 91.7%, 66.7%, and 45.9% in group B (p = not significant). The risk of late death increased significantly with an advanced preoperative New York Heart Association functional class, atrial fibrillation, higher age at operation, pre- or postoperative mitral regurgitation, and leaflet calcification. Forty-four patients in group A and 5 patients in group B required reoperation (p < 0.05). Independent predictors for reoperation in a multivariate analysis were a remaining postoperative mitral stenosis or regurgitation. A total of 68 patients showed valve-related complications. The linearized rate of valve-related morbidity and mortality was 2.1% per patient-years in group A versus 1.1% per patient-years in B (p < 0.01). CONCLUSIONS: Long-term survival for open and closed commissurotomy are excellent, showing no difference between the groups. However, both the incidence of reoperation as well as valve-related morbidity and mortality were significantly lower after open commissurotomy. In well-selected patients with pure mitral stenosis and no leaflet calcification, open commissurotomy still remains a valid surgical option.

Adult↗
PubMed1999

Early experience with robotic technology for coronary artery surgery.

BACKGROUND: To achieve an endoscopic coronary bypass anastomoses we performed a study with endoscopic robotic instrumentation and camera guidance using three-dimensional (3-D) visualization. METHODS: The surgical robotic system ZEUS (Computer Motion Inc, Goleta, CA) consists of three interactive robotic arms and a control unit allowing the surgeon to move the instrument arms in a scaled down mode. The third arm (AESOP, Computer Motion Inc, Goleta, CA) positions the endoscope via voice control. The study had three phases. Phase I: In a phantom model, end-to-side anastomoses between vein grafts and the left anterior descending coronary artery (LAD) of 109 pig hearts were performed. Phase II: In 6 dogs (FBI, 20-25 kg) the left internal mammary artery (LIMA) was harvested endoscopically. During Port-Access (Heartport Inc, Redwood City, CA) cardiopulmonary bypass (CPB), LIMA and LAD were then anastomosed endoscopically with the help of telemetric ZEUS instruments (Computer Motion Inc). Phase III: A total of seven patients were operated on with help of the ZEUS system (Computer Motion Inc). After endoscopic LIMA harvesting and CPB using the Port-Access (Heartport Inc) system, the bypass graft (LIMA to LAD) was anastomosed endoscopically through three thoracic ports in 2 patients. Another 3 patients were operated on off-pump with regional stabilization and 2 patients with sternotomy and routine CPB. RESULTS: The practice with the phantom model and the subsequent animal experiments allowed the surgeons to gain sufficient experience for the clinical setting. In the clinical cases, times for anastomoses ranged from 20 to 42 minutes. Median internal mammary artery flow rate was 74 mL per minute (range 36-110 mL per minute). One patient in the off-pump group was converted to CPB and routine anastomosis. All patients had an uneventful angiographic control and postoperative course. CONCLUSIONS: Using telemetic technology, a completely endoscopic anastomosis of LIMA to LAD is possible on the arrested heart, as well as on the beating heart.

Anastomosis, Surgical↗
PubMed1999

Less invasive, continuous hemodynamic monitoring during minimally invasive coronary surgery.

BACKGROUND: Minimally invasive coronary surgery has gained more and more clinical acceptance. A clear contrast to the minimally invasive idea is the highly invasive pulmonary artery catheter used for hemodynamic monitoring during the operation. We evaluated a less invasive device which calculates cardiac output (CO) and hemodynamics based on arterial pulse-contour analysis. METHODS: In 20 patients revascularized by the off-pump technique with the octopus system, agreement of CO by pulse-contour was compared to pulmonary arterial and femoral arterial thermodilution and hemodynamic alterations during the operation were recorded. Pulse-contour CO is computed by measuring the area under the arterial pressure waveform and dividing it by aortic impedance. Aortic impedance is determined by an arterial thermodilution at the onset of the system. RESULTS: Correlation of pulmonary arterial and arterial thermodilution CO to pulse-contour CO was 0.91 and 0.90 respectively (both p<0.01). Coefficients of variations were 6.2% and 6.7%. The bias was 0.1 L per minute and standard deviations were 0.42 L per minute and 0.55 L per minute. Hemodynamic changes during the operations were seen mainly during the distal anastomosis of the first diagonal branch; only slight changes occurred during the anastomosis of the left anterior descending coronary artery. CONCLUSIONS: Arterial pulse-contour analysis is easy to use and minimally invasive, thus qualifies as a reliable routine monitoring tool during minimally invasive coronary surgery with tissue stabilizers.

Aged↗
PubMed1999

Use of the voice-controlled and computer-assisted surgical system ZEUS for endoscopic coronary artery bypass grafting.

OBJECTIVE: With the aim of performing a completely endoscopic coronary bypass anastomosis, we have undertaken an experimental and clinical study using robotic instrumentation and voice-controlled camera guidance. METHODS: The ZEUS Robotic Surgical System (Computer Motion Inc, Goleta, Calif) consists of three interactive robotic arms and a control unit, allowing the surgeon to move the instrument arms in a scaled down mode. The third arm (AESOP, Computer Motion) positions the endoscope via voice control. PHASE I: In a phantom model, vascular grafts were anastomosed to the left anterior descending coronary artery (LAD) of 50 pig hearts with either 2- or 3-dimensional visualization. PHASE II: In 6 dogs (FBI 20-25 kg) the left internal thoracic artery (LITA) was harvested endoscopically. Then the animals were placed on an endovascular cardiopulmonary bypass system (Port-Access, Heartport, Inc, Redwood City, Calif). Anastomosis of the LITA to the LAD was performed endoscopically with the telemetric ZEUS instruments. Flow rates through the LITA were measured by Doppler analysis. PHASE III: Two patients were operated on with the ZEUS system. After endoscopic harvesting of the LITA and cardiopulmonary bypass with the Port-Access system, the bypass graft (LITA-LAD) was anastomosed endoscopically with the ZEUS system through three thoracic ports. RESULTS: In the dry laboratory, the time range required for the robotically assisted coronary anastomosis was 35 to 60 minutes with 2-dimensional visualization and 16 to 32 minutes with 3-dimensional visualization. In the animal experiments, the median time for endoscopic harvesting of the LITA was 86 minutes (range 56-120 minutes) and for the anastomosis, 42 minutes (range 35-105 minutes); flow rates through the LITA ranged between 22 and 45 mL/min. In the clinical cases, preparation times for the LITA were 83 and 110 minutes, respectively, and anastomosis times, 42 and 40 minutes, respectively. Doppler flow rates measured 125 and 85 mL/min, respectively. Both patients had an uneventful follow-up angiogram and postoperative course. CONCLUSIONS: With sophisticated robotic technology, a completely endoscopic anastomosis of the LITA to the LAD is possible, allowing technically precise operations within acceptable time limits.

Anastomosis, Surgical↗
PubMed1999

The influence of antibody and complement removal with a Ig-Therasorb column in a xenogeneic working heart model.

OBJECTIVE: Organ transplantation is limited by the number of brain-dead human donors. Xenotransplantation could be an alternative to guarantee a constant supply of organs. A major problem of xenotransplantation are xenogeneic natural antibodies (XNAb) directed against species-specific antigens of a discordant donor species (e.g. pig). They trigger the hyperacute xenograft rejection (HXR). Re-usable immunoapheresis (LA)-columns Ig-Therasorb (Therasorb, Baxter) were used to adsorb these XNAb. The effect of immunoapheresis of the perfusing human blood was investigated in ex vivo working pig hearts. METHODS: Hearts of 12 landrace pigs (body weight 14-31 kg) were explanted after inducing cardiac arrest with 4 degrees C Celsior solution. Human blood (500 ml, heparinized) was obtained from healthy volunteers. In group 1 (G1, n = 6), blood as perfusate remained untreated. In group 2 (G2, n = 6), native blood was separated by plasmapheresis into cellular components and plasma. The latter passed through the Ig-Therasorb column for removal of immunoglobulins (so-called immunoadsorption or immunoapheresis). After back-table preparation the hearts were mounted to the working heart model. After 20 min of reperfusion in Langendorff mode, the working heart mode was established. Blood samples were taken isochronously for measurement of: CK(-MB), LDH, ASAT, troponin, immunoglobulins, complement activity, anti-pig antibodies and others. After cessation of the heart, atrial and ventricular tissue samples were taken for histological examinations (light/electron microscopy and immunohistochemistry). RESULTS: Two cycles of immunoapheresis reduced the levels of IgG by 84%, IgM by 83.3% and IgA by 76%. In G2, the antibody immunoadsorption of blood prolonged the duration of the working heart mode significantly to 335+/-37.5 min. In contrast, hearts of group 1 (control) failed after 125+/-31.3 min. Heart rate was significantly different between both groups (G1, 77.3+/-6.1 beats/min; G2, 86.5+/-5.5 beats/min). In G2 cardiac output was 118% and mean coronary flow was 154.6% higher than in G1. CK, LDH and ASAT showed no differences in the two groups. Heart weight increased significantly more in group 1 than in G2. Histological examination indicated specific signs of HXR in G1 after 1.5 h, whereas in G2 only slight unspecific damages were found after 6 h. CONCLUSION: Antibody removal by means of immunoapheresis results in a significantly improved xenogeneic cardiac function. Immunoapheresis may, therefore, become an important adjunct in future pig-to-man clinical xenotransplantation.

Animals↗
PubMed1999

Minimally invasive mitral valve surgery using three-dimensional video and robotic assistance.

Different techniques have been developed for the common goal to minimize surgical trauma for mitral valve surgery. This article focuses on Port-Access (Heartport, Inc, Redwood City, CA) mitral valve replacement or repair (PAMVR) with emphasis on three-dimensional video and robotic assistance. PAMVR was undertaken using a small right anterior minithoracotomy using an endovascular cardiopulmonary bypass (CPB) system. A three-dimensional minicamera allowed visualization of the mitral valve apparatus during this limited access surgery. The three-dimensional (3D) image was displayed inside a helmet just above the real surgical image (VISTA system [Vista, Inc, Westborough, MA]). In addition, the camera was attached to a robotic arm (AESOP [Computer Motion, Inc, Goleta, CA]) that allows stabilization and voice-activated movement of the camera. Fifty patients (16 men, 34 women), aged 36 to 77 years (median, 61.5 years) underwent PAMVR. The underlying diseases were mitral valve insufficiency (n = 36) and combined mitral valve disease (n = 14). With optimal visualization, mitral valve repair was performed in 26 patients with quadrangular resection of the posterior leaflet (n = 26) and repair of the anterior leaflet (n = 3) together with insertion of a posterior or complete anuloplasty ring. The valve was replaced in 24 patients with a mechanical valve prosthesis. Intraoperative and postoperative mortality was 0%. One patient (2%) needed reoperation after a failed repair of an anterior leaflet prolaps. Three-month follow-up was complete in 40 patients, with 34 patients (85%) in New York Heart Association (NYHA) class I and 6 patients in class II. In conclusion, using 3D video and robotic assistance, it was possible to minimize the length of skin incision but at the same time to optimally visualize the whole mitral valve apparatus to perform true Port-Access mitral valve surgery, including complex repair techniques.

Adult↗
PubMed1999

Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: importance of mycophenolic acid therapeutic drug monitoring.

BACKGROUND: Interest has recently been expressed in tacrolimus and mycophenolate mofetil (MMF), two potent immunosuppressants, for a variety of transplant indications. The efficacy of this combination was assessed as primary therapy following cardiac transplantation. METHODS: Forty-five patients were enrolled; 15 into Phase I and 30 to Phase II of the study. Intravenous tacrolimus was administered for 2-3 days to all patients prior to conversion to oral therapy; target blood concentrations were 10-15 ng/mL. Treatment also consisted of steroids and MMF. During Phase I, a fixed 2 g/day dose of MMF was given whilst doses were adjusted according to mycophenolic acid (MPA) plasma levels during Phase II (target range 2.5-4.5 microg/mL). Mean follow-up was 696 +/- 62 days and 436 +/- 88 days for Phases I and II, respectively. RESULTS: Phase I: Patient survival was 100%. Rejection was diagnosed in 66.7% of patients (mean number of episodes per patient 1.33 +/- 1.18). Retrospective analyses indicated that whereas mean MPA plasma levels >3.0 microg/mL were not associated with rejection, no correlation was found with tacrolimus blood concentrations. Phase II: A survival rate of 96.7% was evident, one patient having died from aspergillosis. Diagnoses of rejection were made in 10.0% of patients (0.10 +/- 0.31 episodes per patient) and confounding factors were present in all 3 cases. MPA trough levels were 1.0 +/- 0.3 microg/mL at this time. Resolution was apparent following pulse steroid therapy. Steroids were successfully withdrawn from all patients who completed 6 months' treatment. CONCLUSIONS: Combination therapy with tacrolimus and MMF is associated with suppression of acute myocardial rejection; however, this is dependent upon routine therapeutic drug monitoring.

Adolescent↗
PubMed1999

Effects of prolonged cold storage time in xenotransplantation.

BACKGROUND: Ischemia and reperfusion injury after prolonged ischemic time (IT) has a marked influence on hyperacute xenograft rejection (HXR). The aim of the study was to investigate the impact of different cold ischemic times on the HXR of ex vivo "working pig hearts" perfused with human blood. Xenoreactive natural antibodies (XNAb) as the trigger of HXR were reduced by immunoadsorption (IA) using an Ig-Therasorb column. METHODS: Hearts of 24 Landrace pigs (13-31 kg) were harvested after cardioplegia with Celsior-solution and split into 4 groups. In Group C1 (n = 6) the short ischemic time (IT) lasted 48.9+/-10 minutes on the average prior to start of xenoperfusion, in Group I1 IT lasted 4 hours instead. Groups C2 and 12 experienced the same IT as C1 and I1, respectively, but underwent 2 cycles of IA in addition. IA removed immunoglobulins IgG, IgM and IgA from the perfusate. In the working heart mode hemodynamic parameters were measured in defined intervals. Blood samples were collected at the same time to determine myocardial enzymes, immunoglobulins, complement and anti-pig-antibodies. At the end of the study (cardiac arrest) tissue was sampled for histologic examination (light/electron microscopy (LM/EM) and immunohistochemistry). RESULTS: Survival time of the control Group C1 was 125 minutes. IA resulted in an extension of perfusion time to 6.5 hours in C2. Four hours of IT (I1) prolonged the working time of hearts when compared with C1. IA had no additional impact (I2). Heart weight increased significantly in C1 without IA. Cardiac output and coronary flow in C1 were significantly lower when compared with the other 3 groups. IA improved cardiac output (CO) in C2 (vs C1, p < 0.001). Histologic signs of HXR (LM/EM) could be found in C1 in contrast to the other groups. Serologic parameters for myocardial damage were higher in groups with prolonged IT than in groups with short IT. CONCLUSION: Prolonged ischemia and reperfusion injury showed controversial effects in this specific xenogeneic heart transplant model. In contrast to observations in allogeneic transplantation 4 hours of IT showed a beneficial behaviour of the xenografts. Reasons could be either a protective effect of the Celsior solution or changes of the endothelial cell surface (in terms of glycosylation or loss of alpha1-3Gal-epitopes). Tolerance of prolonged IT would allow transportation of xenografts over long distances.

Animals↗
PubMed1999

Minimally invasive extirpation of a left-ventricular myxoma.

As myxomas usually are benign neoplasms a minimally invasive technique would be an interesting alternative for their extirpation because the surgical trauma is reduced. In one male patient with a diagnosed left-ventricular myxoma minimally invasive surgery was carried out using the Port-Access method. 2D echocardiography, EBT, and MRI were performed preoperatively to obtain exact information about topography, calcifications, and malignity. Minimally invasive extirpation was successful and the mitral valve could be preserved. Histopathological examination revealed a cardiac myxoma extirpated in toto. At one-year follow-up there was no recurrence of the tumor.

Adult↗
PubMed1999

Tacrolimus (FK506) as primary immunosuppressant after lung transplantation.

BACKGROUND: Our positive experience with tacrolimus (FK 506) in heart transplantation has led to our assessing the use of this medication as a primary immunosuppressant in lung transplantation. 62 of our patients after lung transplantation were included in this study. The first 34 patients were treated with cyclosporine A (CyA), the remaining 28 with tacrolimus. No meaningful differences were found in baseline characteristics. The actuarial one-year survival rate was 70.6% for the CyA group and 92.3% for the tacrolimus group. The number of acute rejection episodes per patient was 1.50 for the CyA group versus 1.18 for the tacrolimus group (p < 0.05). The incidence of infection and their spectrum were comparable in both groups. The most frequently reported adverse events were diabetes mellitus 57% (tacrolimus) vs 23% (CyA), and renal insufficiency (27% vs 15%). Tacrolimus seems to be a more potent immunosuppressant after lung transplantation than CyA; on the other hand, diabetes and nephrotoxicity were diagnosed more frequently using tacrolimus. Although our results are very promising, further follow-up on the incidence of obliterative bronchiolitis is warranted.

Actuarial Analysis↗
PubMed1999

Cardiopulmonary exercise testing before and after lung and heart-lung transplantation.

Heart-lung (HLT) and lung transplantation (LT) have been shown to be effective procedures for patients with end-stage cardiopulmonary disorders. As yet, few data exist on the exercise performance of patients before and after thoracic transplantation except with regard to 6-min walk tests. In this article we report cardiopulmonary exercise test results of lung and heart-lung transplant recipients in comparison with their pretransplant values. We studied 103 consecutive recipients of single-lung (n = 46), bilateral lung (n = 32), and heart-lung (n = 25) transplants. Cardiopulmonary exercise testing with a cycle ergometer was performed before and shortly after surgery. Before transplantation, all patients showed severe exercise intolerance and markedly impaired parameters reflecting cardiopulmonary function (e.g., work capacity: 20 +/- 11% predicted; oxygen uptake: 34 +/- 12% predicted; oxygen pulse: 50 +/- 18% predicted; functional dead space ventilation: 57 +/- 10% of minute ventilation; alveolar-arterial oxygen difference during exercise: 79 +/- 15 mm Hg). At 55 +/- 9 d after transplantation, transplant recipients reached maximum oxygen uptakes in the range of 22 to 71% of predicted values; the peak oxygen uptake was increased after transplantation (13.1 +/- 3.4 ml/min/kg versus 10.4 +/- 3.8 ml/min/kg; p < 0.001). Work capacity, oxygen pulse, tidal volume, and peak minute ventilation did not differ in patients following single- or double-lung tranplantation or HLT. Ventilatory factors did not appear to limit exercise capacity in any group. Despite the persistent limitations in aerobic capacity and work rate seen in many of the recipients, cardiopulmonary performance is reasonably well restored shortly after LT and HLT.

Adult↗
PubMed1999

Bronchiolitis obliterans syndrome after (heart-)lung transplantation. Impaired antiprotease defense and increased oxidant activity.

Increased numbers of neutrophils are a common finding in bronchoalveolar lavage fluid (BALF) samples obtained from patients after (heart-)lung transplantation [(H)LTX]. Since proteases and reactive oxygen species secreted by neutrophils are capable of causing substantial damage to the lung tissue if not counterbalanced by the antiprotease and antioxidant screen, we hypothesized that neutrophil products may play a role in the development of obliterative bronchiolitis (OB). A total of 72 BALF samples obtained from 33 patients after (H)LTX were evaluated. Sixteen of these patients were suffering from bronchiolitis obliterans syndrome (BOS) at the time of bronchoalveolar lavage (BAL). As a control, BALF samples from 17 healthy volunteers were analyzed. Anti-neutrophil elastase (NE) activity was quantified by a titration assay. Concentrations of alpha(1)-protease inhibitor (API), secretory leukocyte protease inhibitor (SLPI), NE-API complex, and myeloperoxidase (MPO) were measured by ELISA. Oxidized methionine [Met(O)] was quantified by high-performance liquid chromatography (HPLC). Epithelial lining fluid (ELF) from patients suffering from BOS showed significantly increased neutrophil counts, significantly elevated concentrations of NE-API complex and Met(O), and a significant decrease in the concentration of SLPI. Furthermore, a trend toward an increased NE activity and MPO concentration was observed. These findings suggest that neutrophils may be involved in the development of BOS.

Bronchiolitis Obliterans↗