Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine. Requirement for graft vascular homeostasis beyond harvest vasodilation.

Nitric oxide (NO) produced within the lungs maintains pulmonary vascular homeostatic properties, modulating leukocyte traffic, platelet aggregation, and vasomotor tone. Because reactive oxygen intermediates generated during reperfusion react rapidly with available NO, we hypothesized that the NO donor nitroglycerin (NTG) would enhance lung preservation for transplantation by improving graft blood flow and reducing graft neutrophil and platelet sequestration. By use of an orthotopic rat left lung transplant model, with ligation of the native right pulmonary artery to ensure that recipient survival and physiological measurements depend entirely on the transplanted lung, transplants were performed in 70 male Lewis rats after 6-hour 4 degrees C preservation in Euro-Collins solution (EC) alone or EC with supplemental NTG.

Newborn baboon serum lacks natural anti-pig xenoantibody.

Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the shortage of donor organs currently available for cardiac allotransplantation. Unfortunately, discordant xenotransplantation is still limited by hyper-acute rejection, a process thought to be mediated by natural anti-xenodonor antibody. Based on data that cytotoxic natural xenoantibodies are IgM in nature, we postulated that natural xenoantibodies may be absent from newborn serum.

Posttransplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus.

Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are seen in immunocompromised hosts and in many lymphoid neoplasms associated with immunocompromise.

Experience with heart transplantation for cardiac tumors.

Background: Primary cardiac tumors are rare clinical entities. Benign tumors are often amenable to surgical excision, whereas malignant tumors are seldom resectable. Five patients have been reported to undergo orthotopic heart transplantation for inoperable primary cardiac tumors.

Management strategies for pulmonary vein thrombosis following single lung transplantation.

Pulmonary vein thrombosis following lung transplantation is an infrequently reported and often fatal vascular complication. Two cases of early pulmonary vein thrombosis following single lung transplantation are described. Both patients underwent surgical thrombectomy and anastomotic reconstruction following institution of cardiopulmonary bypass, but died of multiorgan failure within 5 days of diagnosis.

Immunohistochemical demonstration of 15-lipoxygenase in transplant coronary artery disease.

15-Lipoxygenase (15-LO) catalyzes the oxygenation of arachidonic and linoleic acids and has been implicated in the oxidative modification of low-density lipoproteins (LDL). 15-LO mRNA and protein have previously been demonstrated in macrophages of rabbit and human atherosclerotic lesions. The purpose of this study was to investigate whether 15-LO is also present in the accelerated form of coronary artery disease that can complicate cardiac transplantation (TCAD).

Absence of hyperacute rejection in pig-to-primate orthotopic pulmonary xenografts.

The shortage of organ donors for transplantation is more pronounced for the lung than for any other solid organ. To address this problem, we evaluated the feasibility of pulmonary xenotransplantation. Preliminary investigations demonstrated that orthotopically placed pig lungs in cynomologous monkey recipients could be engrafted up to 9 hr after reperfusion without evidence of hyperacute rejection.

Nitroglycerin maintains graft vascular homeostasis and enhances preservation in an orthotopic rat lung transplant model.

Transplanted lungs often fail during the peritransplantation period for poorly understood reasons. Because the nitric oxide pathway regulates pulmonary vascular tone, helps to maintain the integrity of the endothelial barrier, and modulates neutrophil adhesivity and activation, we hypothesized that perturbation of this pathway during the preservation and reperfusion of transplanted lungs might play a critical role in mediating early graft failure. To evaluate whether supplementing the preservation solution with the nitric oxide donor nitroglycerin enhances lung preservation for transplantation, we obtained hemodynamic measurements in a model of orthotopic left lung transplantation in the rat after ligation of the native right pulmonary artery.

Absence of hyperacute rejection in newborn pig-to-baboon cardiac xenografts.

The shortage of organs for transplantation is especially severe for the critically ill newborn infant, for whom donors of the appropriate size are particularly scarce. One way to overcome this problem is to use animals in lieu of humans as organ donors. The major limitation to using animals for this purpose is the susceptibility of animal organs to hyperacute rejection, a violent rejection reaction thought to be mediated by antidonor antibody and complement.

Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders.

The posttransplantation lymphoproliferative disorders (PT-LPDs) are a morphologically heterogeneous group of Epstein-Barr virus (EBV)-driven lymphoid proliferations of varying clonal composition. Some PT-LPDs regress after a reduction in immunosuppression, while others progress in spite of aggressive therapy. Previously defined morphologic categories do not correlate with clonality, and neither morphology nor clonality has reliably predicted the clinical behavior of PT-LPDs.

Abrogation of baboon natural xenoantibody to pig splenocytes by DL-penicillamine.

Natural xenoantibodies are believed to be IgM in nature and are known to play a critical role in the hyperacute rejection of distantly related xenografts. The purpose of this study was to determine whether the reducing agent DL-penicillamine could inactivate baboon natural xenoantibodies to pig splenocytes. Pooled baboon serum was treated with varying concentrations of DL-penicillamine over different lengths of time and a complement-mediated cytotoxicity assay was used to determine the reactivity of baboon natural xenoantibodies to pig splenocytes.

The nitric oxide/cyclic GMP pathway in organ transplantation: critical role in successful lung preservation.

Reestablishment of vascular homeostasis following ex vivo preservation is a critical determinant of successful organ transplantation. Because the nitric oxide (NO) pathway modulates pulmonary vascular tone and leukocyte/endothelial interactions, we hypothesized that reactive oxygen intermediates would lead to decreased NO (and hence cGMP) levels following pulmonary reperfusion, leading to increased pulmonary vascular resistance and leukostasis. Using an orthotopic rat model of lung transplantation, a porphyrinic microsensor was used to make direct in vivo measurements of pulmonary NO.

Cerebral blood flow during low-flow hypothermic cardiopulmonary bypass in baboons.

Background: Neurologic injury after cardiopulmonary bypass (CPB) is a frequent and devastating complication of cardiothoracic surgery. Disordered cerebral hemodynamics during CPB has been implicated as an important factor in the etiology of these injuries. Evidence of disordered cerebral hemodynamics includes reports of a progressive time-dependent decrease in cerebral blood flow (CBF) during stable full-flow CPB.

Incidence of pulmonary vein complications after lung transplantation: a prospective transesophageal echocardiographic study.

Objectives: This study attempted to document the incidence of pulmonary vein complications and their potential relation to clinical outcome in patients after lung transplantation.

Background: Several case reports have documented the presence of pulmonary venous thrombosis causing graft failure in patients after lung transplantation. Because the presentation of these complications mimics that of other postoperative problems, the true incidence of pulmonary vein abnormalities remains unclear.

Induction of myocardial nitric oxide synthase by cardiac allograft rejection.

Cardiac transplantation, effective therapy for end-stage heart failure, is frequently complicated by allograft rejection, the mechanisms of which remain incompletely understood. Nitric oxide (NO), a vasodilator which is cytotoxic and negatively inotropic, can be produced in large amounts by an inducible NO synthase (iNOS) in response to cytokines. To investigate whether iNOS is induced during cardiac allograft rejection, hearts from Lewis or Wistar-Furth rats were transplanted into Lewis recipients.

Novel technique for extending the use of allografts in cardiac operations.

Small cryopreserved allografts for use in neonates and infants are increasingly difficult to find. We describe a technique for surgically reducing the size of the more readily available large-diameter allografts to make them conform to size requirements appropriate for neonates and infants. This technique involves a longitudinal incision of the allograft from its muscular annulus to its distal orifice with the excision of a single valve leaflet.

Posttransplantation lymphoproliferative disorders treated with cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy.

Background: Posttransplantation lymphoproliferative disorders after solid organ transplantation are a serious complication occurring in 1-10% of patients. Different therapies have been used, but the optimal treatment is unknown. There is relatively little information in the literature on the experience with cytotoxic chemotherapy.

Pediatric retransplantation.

Previous studies have attempted to outline the efficacy of heart retransplantation in adults. A limited number of these retransplantation procedures have been performed in children; however, no study to date has evaluated the risk of heart retransplantation in this specific patient population. We conducted a retrospective review of 17 pediatric (non-neonatal) heart transplant recipients who subsequently underwent heart retransplantation.