Management and outcomes of esophageal perforation.

BACKGROUND: Esophageal perforation is a morbid condition and remains a therapeutic challenge. We report the outcomes of a large institutional experience with esophageal perforation and identify risk factors for morbidity and mortality. METHODS: A retrospective analysis was conducted on 142 patients who presented with a thoracic or gastroesophageal junction esophageal perforation from 1995 to 2020. Baseline characteristics, operative or interventional strategies, and outcomes were analyzed by etiology of the perforation and management approach. Multivariable cox and logistic regression models were constructed to identify predictors of mortality and morbidity. RESULTS: Overall, 109 (77%) patients underwent operative intervention, including 80 primary reinforced repairs and 21 esophagectomies and 33 (23%) underwent esophageal stenting. Stenting was more common in iatrogenic (27%) and malignant (64%) perforations. Patients who presented with a postemetic or iatrogenic perforation had similar 90-day mortality (16% and 16%) and composite morbidity (51% and 45%), whereas patients who presented with a malignant perforation had a 45% 90-day mortality and 45% composite morbidity. Risk factors for mortality included age >65 years (hazard ratio [HR] 1.89 [1.02-3.26], P = 0.044) and a malignant perforation (HR 4.80 [1.31-17.48], P = 0.017). Risk factors for composite morbidity included pleural contamination (odds ratio [OR] 2.06 [1.39-4.43], P = 0.046) and sepsis (OR 3.26 [1.44-7.36], P = 0.005). Of the 33 patients who underwent stent placement, 67% were successfully managed with stenting alone and 30% required stent repositioning. CONCLUSIONS: Risk factors for morbidity and mortality after esophageal perforation include advanced age, pleural contamination, septic physiology, and malignant perforation. Primary reinforced repair remains a reasonable strategy for patients with an esophageal perforation from a benign etiology.

Use of Proteolytic Enzymes in the Treatment of Proteinaceous Esophageal Food Impaction.

BACKGROUND: Proteinaceous esophageal food impaction typically requires endoscopic intervention. An alternative approach is the use of proteolytic enzymes. Concerns regarding the use of proteolytic enzymes include the risk of perforation and aspiration pneumonitis. OBJECTIVE: We retrospectively reviewed our series of 69 patients treated with papain to determine the safety and efficacy of proteolytic enzymes. METHODS: Patients were retrospectively reviewed if treated for an esophageal food impaction from 1999 through 2008. RESULTS: Median age was 56 years (range 19-91 years), with 46 male and 23 female patients. In 27 patients (39%) this was their first presentation, in 14 (20%) it was the second, and 28 (41%) had multiple previous episodes. Meat was the cause in 49 (71%), chicken in 6 (9%), fish in 3 (4%), and unspecified in 11 (16%). All patients presented with dysphagia for solids, 56 (81%) could not tolerate liquids. Papain solution, 1 tsp in 8 oz of water, was given to patients in an unlimited quantity. Papain was successful in relieving the obstruction in 60 patients (87%). The remaining 9 patients (13%) underwent endoscopy with successful retrieval. No patient suffered a perforation, either with papain ingestion or endoscopy. There were no episodes of pneumonitis or pneumonia. CONCLUSIONS: We have used proteolytic enzymes with a high success rate and with minimal complication. Further, if proteolytic enzymes fail, endoscopy can be performed safely and effectively. We recommend the use of proteolytic enzymes as the initial management in all patients with proteinaceous food impaction of the esophagus.

Novel approaches for long-term lung transplant survival.

Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.

Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection.

BACKGROUND: Galactosyl transferase gene knock-out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection. METHODS: We perfused GalTKO miniature swine lungs with human blood. Results were compared with those from previous studies using wild-type and human decay-accelerating factor-transgenic (hDAF(+/+) ) pig lungs. RESULTS: GalTKO lungs survived 132 ± 52 min compared to 10 ± 9 min for wild-type lungs (P = 0.001) and 45 ± 60 min for hDAF(+/+) lungs (P = 0.18). GalTKO lungs displayed stable physiologic flow and pulmonary vascular resistance (PVR) until shortly before graft demise, similar to autologous perfusion, and unlike wild-type or hDAF(+/+) lungs. Early (15 and 60 min) complement (C3a) and platelet activation and intrapulmonary platelet deposition were significantly diminished in GalTKO lungs relative to wild-type or hDAF(+/+) lungs. However, GalTKO lungs adsorbed cytotoxic anti-non-Gal antibody and elaborated high levels of thrombin; their demise was associated with increased PVR, capillary congestion, intravascular thrombi and strong CD41 deposition not seen at earlier time points. CONCLUSIONS: In summary, GalTKO lungs are substantially protected from injury but, in addition to anti-non-Gal antibody and complement, platelet adhesion and non-physiologic intravascular coagulation contribute to Gal-independent lung injury mechanisms.

A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation.

BACKGROUND: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts. METHODS: Five cynomolgus macaques underwent left orthotopic lung transplantation. Initial immunosuppression included equine ATG and anti-IL6RmAb induction, followed by triple-drug immunosuppression for 4 mo. Post-transplant, a nonmyeloablative conditioning regimen was applied, including total body and thymic irradiation. Rabbit ATG, belatacept, anti-IL6RmAb, and donor bone marrow transplantation (DBMT) were given, in addition to a 28-d course of cyclosporine. All immunosuppressant drugs were stopped on day 29 after DBMT. RESULTS: One monkey rejected its lung before DBMT due to AMR, after developing donor-specific antibodies. Two monkeys developed fatal post-transplant lymphoproliferative disorder, and both monkeys had signs of cellular rejection in their allografts upon autopsy. The remaining 2 monkeys showed severe cellular rejection on days 42 and 70 post-DBMT. Cytokine analysis suggested higher levels of pro-inflammatory markers in the lung transplant cohort, as compared to kidney recipients. CONCLUSION: Although the clinically applicable protocol showed success in kidney transplantation, the study did not show long-term survival in a lung transplant model, highlighting the organ-specific differences in tolerance induction.

High-frequency chest-wall compression during the 48 hours following thoracic surgery.

BACKGROUND: Postoperative pneumonia continues to be a leading cause of mortality and morbidity after thoracic surgery. High-frequency chest-wall compression (HFCWC) is an established therapeutic adjunct for patients with chronic pulmonary disorders that impair bronchopulmonary secretion clearance. We studied the feasibility of applying HFCWC following thoracic surgery. METHODS: Twenty-five consecutive adult patients who underwent a variety of thoracic operations received at least one HFCWC treatment in the first 2 postoperative days, along with routine postoperative care. HFCWC was applied at 12 Hz, for 10 min. Routine hemodynamic and pulse oximetry data were collected before, during, and after HFCWC. We also collected qualitative data on patient tolerance and preference for HFCWC versus percussive chest physiotherapy. RESULTS: No major adverse events were encountered. Hemodynamic and pulse oximetry values remained stable before, during, and after HFCWC. Eighty-four percent of the subjects reported little or no discomfort during therapy, and the subjects who expressed a preference preferred HFCWC to conventional chest physiotherapy by more than two to one. CONCLUSIONS: HFCWC is a safe, well-tolerated adjunct after thoracic surgery. The observation of hemodynamic stability is especially important, considering that the patients were studied in the early postoperative period, during epidural analgesia.

Pulmonary Artery Resection During Lung Resection for Malignancy.

BACKGROUND: Complete resection of central tumors invading the main pulmonary artery (PA) requires arterial reconstruction to avoid pneumonectomy. Oncologic equivalence with pneumonectomy has been suggested. We review clinical selection and outcome for these uncommon procedures in the context of candidacy for pneumonectomy. METHODS: From 2000 to 2018, 9 different surgeons performed 34 pulmonary arterial resections for primary or metastatic pulmonary malignancy, with independent determination of pneumonectomy candidacy and arterioplasty technique. Patients undergoing limited lateral stapled PA resection (n = 3) or resection for metastasis (n = 3) were excluded from survival analysis. RESULTS: The PA was resected as a sleeve with primary anastomosis (14.7%) or noncircumferentially with primary (61.8%), stapled (8.8%), or patch (14.7%) closure. Arterial resections represented between 2.5% and 43% of each surgeon's pneumonectomy volume. Sixteen (47%) patients were candidates for pneumonectomy. There was no operative mortality and 1 death at 47 days. Postoperative complications occurred in 21 (61.8%) patients. No patient required completion pneumonectomy. Overall 5-year survival was 33% (95% confidence interval [CI], 12-53). Compared with pulmonary arterioplasty alone, patients undergoing bronchial sleeve resection and pulmonary arterioplasty had better disease-free 5-year survival (50% [95% CI, 18-82] vs 19% [95% CI, 5-43]; P = .04), higher complete resection rate (100% [95% CI, 83-100] vs 80% [95% CI, 56-94]; P = .23) and lower disease recurrence (8% [n = 1 of 13] vs 47% [n = 7 of 15]; P = .04); 80% of disease recurrence was distant. CONCLUSIONS: Resection and reconstruction of the PA for malignant lung disease may be safely performed. In candidates for pneumonectomy, arterial resection offers low operative risk. Long-term survival is impaired by distant, not local, recurrence emphasizing the importance of systemic therapy.

Mechanisms of chronic rejection in cardiothoracic transplantation.

Despite significant improvements in early post-transplantation survival rates, long-term patient and graft survival have remained poor, due in large part to the vexing problem of chronic allograft rejection. Attempts to combat this problem with intensification of immunosuppression have led to concomitant increases in the rates of fatal malignancies and infections. In cardiac transplantation, chronic rejection is manifested primarily by a disease entity known as cardiac allograft vasculopathy, an occlusive narrowing of the coronary vessels. In lung transplantation, chronic rejection is typified by obliterative bronchiolitis, an airflow limiting narrowing of the bronchioles. From an immunologic standpoint, chronic rejection is believed to be the end result of repeated immune and non-immune insults to the graft. This review examines the pathophysiology of heart and lung chronic, with emphasis on both immune and non-immune causes.

The effects of tolerance on allograft damage caused by the innate immune system.

BACKGROUND: It is not known whether tolerance can be induced in a strong proinflammatory milieu or whether the induction of tolerance can prevent interferon (IFN)-gamma-associated graft injury. To address these questions, we studied the effects of rIFN-gamma infusion on porcine cardiac allograft survival. METHODS: Recombinant interferon (rIFN)-gamma was continuously infused into the left anterior descending artery of hearts transplanted into major histocompatibility complex-inbred miniature swine treated with a 12-day course of cyclosporine A. Group 1 recipients received a nearly syngeneic heart, group 2 recipients received a class I disparate heart, and group 3 recipients were cotransplanted with a class I-disparate heart and kidney, a procedure demonstrated to induce tolerance to both grafts. A fourth group of animals were not transplanted but received intracoronary rIFN-gamma infusion into the native heart. RESULTS: rIFN-gamma perfusion not only accelerated the acute rejection of class I-disparate hearts (mean survival time, 19+/-7.21 vs. 38+/-8.19; P=0.025) but caused near-syngeneic heart transplants, which otherwise survived indefinitely, to reject within 35 days. In contrast, rIFN-gamma perfusion had no demonstrable effects on hearts grafts in tolerant recipients or on autologous hearts. CONCLUSIONS: These results suggest that tolerance induction can occur in the presence of IFN-gamma-mediated inflammation, and that tolerance induction can prevent the tissue injury caused by the overproduction of IFN-gamma. This suggests that the beneficial effects of tolerance may include protection from nonspecific inflammatory responses, such as those produced by ischemia-reperfusion injury and brain death.

Operational tolerance to class I disparate lungs can be induced despite pretransplant immunization with class I allopeptides.

BACKGROUND: Using a class I-disparate swine lung transplant model, we examined whether an intensive course of tacrolimus could induce operational tolerance and whether preoperative allopeptide immunization would prevent the development of tolerance. METHODS: Left lung grafts were performed using class I-disparate (class II-matched) donors. Recipients were treated with 12 days of postoperative tacrolimus. Three recipients were immunized prior to transplantation with class I allopeptides. Three other recipients were not immunized. RESULTS: The nonimmunized recipients maintained their grafts long term (>497, >451, and >432 days), without developing chronic rejection. The immunized swine also maintained their grafts long term (>417, >402, >401 days), despite developing a variety of in vitro and in vivo responses to the immunizing peptides, as well as having strong mixed lymphocyte reactions to donor cells prior to transplantation. CONCLUSIONS: Using only a brief course of tacrolimus, we have been able to induce a state of operational tolerance in a class I-disparate preclinical lung transplant model. Moreover, preoperative alloimmunization did not block tolerance induction or induce chronic rejection. These data show that it is possible to create a state of operational tolerance to lung allografts even in the presence of donor-sensitized cells.

Post-esophagectomy gastric outlet obstruction: role of pyloromyotomy and management with endoscopic pyloric dilatation.

OBJECTIVE: Gastric outlet obstruction is common after esophagectomy. Our goal was to determine the incidence of gastric outlet obstruction after esophagectomy with or without pyloromyotomy and analyze its management by endoscopic pyloric dilatation. METHODS: Two hundred forty-two patients underwent esophagectomy with gastric conduit from January 2002 to June 2006. Subjects were divided into two groups: Group A had no pyloromyotomy (n=83) and Group B had a pyloromyotomy (n=159). Gastric outlet obstruction was strictly defined to include patients with clinical delayed gastric emptying supported by symptoms, barium swallow studies, persistent air-fluid level and dilated conduit on radiography, or endoscopic or surgical intervention to improve gastric drainage. RESULTS: The groups were similar except for a higher percentage of cervical anastomosis and older age (64- vs 61-year-old) in Group A. The overall incidence of gastric outlet obstruction was 15.3% (37/242). Pyloromyotomy did not reduce the incidence of gastric outlet obstruction (Group A 9.6% vs Group B 18.2%, p=0.078). One patient required a late pyloroplasty. Successful management of gastric outlet obstruction with pyloric dilatation (96.7%, 28/29) was unaffected by pyloromyotomy. There was no difference in length of stay, pneumonia (Group A 27.7% vs Group B 19.5%, p=0.15), respiratory failure or anastomotic stricture. There was no difference in anastomotic leaks when controlling for the anatomic location of the anastomosis (p=0.36). Mortality was equivalent between groups (2.4 vs 2.5%, p=0.96). CONCLUSION: Pyloromyotomy does not reduce the incidence of symptomatic delayed gastric emptying after esophagectomy. Post-operative gastric outlet obstruction can be effectively managed with endoscopic pyloric dilatation. Routine pyloromyotomy for the prevention of post-esophagectomy gastric outlet obstruction may be unwarranted.

Surgical Management of Esophageal Epiphrenic Diverticula: A Transthoracic Approach Over Four Decades.

BACKGROUND: Epiphrenic esophageal diverticula are infrequent. Although surgical treatment is generally recommended, technique varies widely and optimal management remains controversial. This study evaluated a single-institution experience for surgical treatment of epiphrenic diverticula. METHODS: A retrospective review was made of medical records of 31 patients undergoing surgical treatment for epiphrenic diverticula from 1974 to 2016. RESULTS: There were 17 men (55%); median age was 65 years. Dysphagia (87%) and regurgitation (71%) were the most common symptoms. Three patients (10%) presented acutely: 2 with ruptured diverticula and 1 with hematemesis. All patients underwent an open transthoracic approach. Diverticulectomy was performed in 28 patients (90%), myotomy in 28 (90%), and a concomitant antireflux procedure in 6 (19%). A total of 22 patients (71%) underwent diverticulectomy and myotomy, 4 (13%) underwent diverticulectomy with myotomy and antireflux procedure, 2 (6%) had myotomy and antireflux, 2 had diverticulectomy alone, and 1 patient had imbrication of the diverticulum after myotomy. Overall, morbidity occurred in 11 patients (35.5%), with major morbidity in 6 (19.4%). There was one postoperative esophageal leak (3%). Ninety-day mortality was zero. Mean follow-up was 30 ± 43 months in 28 patients. Additional procedures (ie, reoperation, balloon dilation) were needed in 7 patients (25%). An excellent outcome (ie, absence of symptoms) was accomplished in 21 patients (75%). Acute presentation was associated with need for further procedures (p = 0.011) and symptoms at follow-up (p = 0.011). CONCLUSIONS: A tailored transthoracic approach to the surgical management of epiphrenic diverticula can provide excellent results. The need for a concomitant antireflux procedure remains controversial and may not be routinely necessary. Acute presentation is associated with poor functional outcome.

Myeloid sarcoma: an unusual presentation for acute tracheal stenosis.

BACKGROUND AND AIMS: Extramedullary involvement of acute myelogenous leukemia (AML) is rare and has been reported under the terms myeloid sarcoma (MS), granulocytic sarcoma, chloroma, extramedullary acute myeloid leukemia, myeloblastoma and myelosarcoma. The most common extramedullary involvement includes soft tissues and lymph nodes, but it may arise in different sites of the body. There are only very few reports about MS in the pulmonary system, and involvement of the trachea is extremely rare. METHODS: This is the first report of initial presentation of MS by severe acute tracheal stenosis. RESULTS: After failed tracheal dilatation, a tracheostomy was performed where tracheal tissue was submitted for pathology. Histology of the tracheal biopsy and bone marrow revealed AML. The patient was subsequently referred to our oncology service for further management. CONCLUSION: Myeloid sarcoma should be part of the differential for acute tracheal stenosis.

Induced regulatory T cells in allograft tolerance via transient mixed chimerism.

Successful induction of allograft tolerance has been achieved in nonhuman primates (NHPs) and humans via induction of transient hematopoietic chimerism. Since allograft tolerance was achieved in these recipients without durable chimerism, peripheral mechanisms are postulated to play a major role. Here, we report our studies of T cell immunity in NHP recipients that achieved long-term tolerance versus those that rejected the allograft (AR). All kidney, heart, and lung transplant recipients underwent simultaneous or delayed donor bone marrow transplantation (DBMT) following conditioning with a nonmyeloablative regimen. After DBMT, mixed lymphocyte culture with CFSE consistently revealed donor-specific loss of CD8+ T cell responses in tolerant (TOL) recipients, while marked CD4+ T cell proliferation in response to donor antigens was found to persist. Interestingly, a significant proportion of the proliferated CD4+ cells were FOXP3+ in TOL recipients, but not in AR or naive NHPs. In TOL recipients, CD4+FOXP3+ cell proliferation against donor antigens was greater than that observed against third-party antigens. Finally, the expanded Tregs appeared to be induced Tregs (iTregs) that were converted from non-Tregs. These data provide support for the hypothesis that specific induction of iTregs by donor antigens is key to long-term allograft tolerance induced by transient mixed chimerism.

Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model.

BACKGROUND: Acute coronary syndrome is the leading cause of mortality worldwide. However, treatment of acute coronary occlusion inevitably results in ischemia-reperfusion injury. Circulating natural IgM has been shown to play a significant role in mouse models of ischemia-reperfusion injury. A highly conserved self-antigen, nonmuscle myosin heavy chain II, has been identified as a target of pathogenic IgM. We hypothesized that a monoclonal antibody (m21G6) directed against nonmuscle myosin heavy chain II may inhibit IgM binding and reduce injury in a preclinical model of myocardial infarction. Thus, our objective was to evaluate the efficacy of intravenous m21G6 treatment in limiting infarct expansion, troponin release, and left ventricular dysfunction in a swine myocardial infarction model. METHODS AND RESULTS: Massachusetts General Hospital miniature swine underwent occlusion of the midleft anterior descending coronary artery for 60 minutes, followed by 1 hour, 5-day, or 21-day reperfusion. Specificity and localization of m21G6 to injured myocardium were confirmed using fluorescently labeled m21G6. Treatment with m21G6 before reperfusion resulted in a 49% reduction in infarct size (P<0.005) and a 61% reduction in troponin-T levels (P<0.05) in comparison with saline controls at 5-day reperfusion. Furthermore, m21G6-treated animals recovered 85.4% of their baseline left ventricular function as measured by 2-dimensional transthoracic echocardiography in contrast to 67.1% in controls at 21-day reperfusion (P<0.05). CONCLUSIONS: Treatment with m21G6 significantly reduced infarct size and troponin-T release, and led to marked preservation of cardiac function in our study. Overall, these findings suggest that pathogenic IgM blockade represents a valid therapeutic strategy in mitigating myocardial ischemia-reperfusion injury.

Combination treatment with donor-specific transfusions and cyclosporine a induces long-term survival of cardiac allografts in miniature Swine.

BACKGROUND: To evaluate whether pretransplant donor-specific transfusions (DST) can induce tolerance to cardiac allografts in large animals, heterotopic cardiac transplants were performed across a class I MHC barrier in inbred miniature swine. METHODS: Experimental animals received two DSTs, each containing 1.4x10 viable peripheral blood mononuclear cells, 14 and 7 days prior to transplantation together with a 12-day course of cyclosporine (CyA) (13 mg/kg IV) starting on postoperative day (POD) 0. RESULTS: Untreated (n=2) and DST-only (n=2) treated control animals rejected between POD 6 and 8. Animals treated with CyA alone (n=3) exhibited graft survival to 53, 52 and 59 days. In contrast, the combination of DST and CyA (n=3) led to stable graft function for >200 days. Long-term survivors maintained peripheral CML response against donor antigen. Following DSTs, the donor-specific proliferative response of CD8+ recipient T cells was significantly increased (P=0.011), and a significant number of CD8+ T cells underwent apoptosis (10.1% on POD 0; 5.2% on POD -14; P=0.04). None of the DST-treated animals developed donor-specific antibodies. CONCLUSIONS: These results are the first to demonstrate the ability of DST to induce operational tolerance to cardiac allografts in large animals, and they suggest that peripheral mechanisms of tolerance mediate this effect.

Cytokines in immunity and allograft rejection.

Cytokines are highly potent regulatory molecules that are secreted by a variety of cells into the local microenvironment. These chemical messengers participate in the activation and regulation of immune function by a variety of mechanisms, including the stimulation and inhibition of cellular proliferation and differentiation. Cytokines also may have chemotactic activity. Six cytokine receptor families have been described, on the basis of their conserved structural features. Many cytokines are classified as proinflammatory cytokines, which promote both innate and adaptive immune responses. Solid-organ transplantation presents several unique challenges to the immune system, and cytokines play an important role in both antigen-dependent and antigen-independent immune recognition. The selective blockade of cytokine-mediated immune responses is a cornerstone of modern immunosuppressive therapy.

Twelve-Hour Hypothermic Machine Perfusion for Donor Heart Preservation Leads to Improved Ultrastructural Characteristics Compared to Conventional Cold Storage.

BACKGROUND Hypothermic machine perfusion of donor hearts has the theoretical advantage of continuous aerobic metabolism and washes out toxic metabolic byproducts. Here, we studied the effect of hypothermic machine perfusion on cardiac myocyte integrity when hearts are preserved for longer ischemic times (12 hours). MATERIAL AND METHODS Pig hearts were harvested and stored in Celsior® solution for 12 hours using either conventional cold storage on ice (12 h CS, n=3) or pulsatile perfusion with the Paragonix Sherpa Perfusion™ Cardiac Transport System at different flow rates (12 h PP, n=3 or 12 h PP low flow, n=2). After cold preservation, hearts were reperfused using an LV isovolumic Langendorff system. Controls (n=3) were reperfused immediately after organ harvest. Biopsies were taken from the apex of the left ventricle before storage, after storage and after reperfusion to measure ATP and endothelin-1 content in the tissue. TUNEL staining for signs of apoptosis and electron microscopy of the donor hearts were performed. RESULTS 12 h PP hearts showed significantly more weight gain than 12 h CS and controls after preservation. Pulsatile perfused hearts showed less ATP depletion, lower endothelin-1 levels and less apoptosis after preservation compared to CS. Electron microscopy showed damaged muscle fibers, endothelial cell rupture, and injury of mitochondria in the 12 h CS group, while machine perfusion could preserve the cell structures. CONCLUSIONS Hypothermic machine perfusion of donor hearts can preserve the cell structures better than conventional cold storage in prolonged ischemic times. Hypothermic pulsatile perfusion may therefore enable longer preservation times of donor hearts. Whether this method is able to avoid primary graft failure after orthotopic heart transplantation remains to be evaluated in further studies.

Recipient-matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

BACKGROUND: Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by passenger leukocytes in the rejection or acceptance of an organ is unclear. We tested whether recipient-matching of donor graft passenger leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation. METHODS: In the experimental group (group 1), donor lungs were obtained from chimeric swine, in which the passenger leukocytes (but not the parenchyma) were major histocompatibility complex-matched to the recipients (n = 3). In the control group (group 2), both the donor parenchyma and the passenger leukocytes were major histocompatibility complex-mismatched to the recipients (n = 3). RESULTS: Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of passenger leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing passenger leukocytes matched to the lung recipient (group 1) survived on average 107 days (range, 80-156). Control lung allografts (group 2) survived on average 45 days (range, 29-64; P < 0.05). CONCLUSIONS: Our data indicate that recipient-matching of passenger leukocytes significantly prolongs lung allograft survival.