The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
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J. Heart Lung Transplant. · Nov 1995
Comparative StudyLeflunomide prolongs pulmonary allograft and xenograft survival.
Leflunomide, an isoxazole derivative, has been shown to effectively prolong rodent allograft and cardiac xenograft survival. In vitro studies suggest that leflunomide inhibits the production of donor-specific antibodies and is capable of blocking both T- and B-cell proliferation. In light of the significant role that humoral immunity is believed to play in chronic pulmonary allograft rejection as well as hyperacute and accelerated acute xenograft rejection, we examined the efficacy of leflunomide in prolonging pulmonary allografts and xenografts and its effect on donor-specific antibody production. ⋯ Allograft and xenograft control animals receiving vehicle yielded graft survival times of 6.0 +/- 0.0 and 5.4 +/- 0.6 days, respectively. Although xenograft recipients treated with cyclosporine (7.5 mg/kg/day orally) showed no significant graft prolongation, pulmonary allograft survival in recipients receiving cyclosporine alone was significantly prolonged to 28.2 +/- 0.7 days. Leflunomide-treated allograft (15 mg/kg/day orally) and xenograft (20 mg/kg/day orally) recipients displayed significant graft prolongation to 28.2 +/- 0.7 days and 15.8 +/- 3.3 days, respectively. Cyclosporine (7.5 mg/kg/day orally) enhanced the effect of leflunomide (20 mg/kg/day orally) in xenograft recipients with a mean graft survival time of 36.0 +/- 3.0 days achieved when both drugs were administered concomitantly. Cyclosporine significantly suppressed donor-specific immunoglobulin G antibody titers in both pulmonary allograft and xenograft recipients while not affecting immunoglobulin M levels. Leflunomide markedly suppressed both immunoglobulin G and immunoglobulin M donor-specific antibody titers in allograft and xenograft recipients. Except for mild leukopenia and anemia, both cyclosporine- and leflunomide-treated allograft recipients showed no evidence of toxic side effects after 14 days of therapy. However, leflunomide-treated xenograft recipients displayed significant weight loss, anemia, and leukopenia after 14 days of treatment with one death in each treatment group.
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J. Heart Lung Transplant. · Nov 1995
Occult restrictive hemodynamics after pediatric heart transplantation.
Although resting hemodynamics after pediatric heart transplantation are generally within normal limits, we hypothesized that occult restrictive hemodynamics suggesting diastolic dysfunction may be unmasked by acute volume loading (fluid challenge) during cardiac catheterization. We wished to determine the incidence of diastolic dysfunction and to assess whether it progressed over time. ⋯ Diastolic dysfunction after heart transplantation is common; however, the abnormalities do not progress in severity, suggesting stable long-term graft function.
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J. Heart Lung Transplant. · Nov 1995
Comparative StudyEffects of calcium concentration, lactobionate content, and sodium/ potassium ratio of preservation solutions on resting left ventricular pressure and postreperfusion function of rabbit heterotopic heart transplants.
We tested the hypothesis that the University of Wisconsin solution has a ionic composition (i.e., intracellular, calcium-free, lactobionate-enriched) that may be beneficial for cold heart graft preservation independently from any additives. ⋯ After a 6-hour storage, University of Wisconsin and C solutions provided better preservation than B and St. Thomas' Hospital solutions: diastolic pressures were lower; developed pressure and rate of pressure rise were higher. C solution was superior to University of Wisconsin solution only for rate of pressure rise. A solution was intermediary. A significant alteration of resting pressure and hemodynamic parameters was generally observed during the 6-hour storage. Nonsignificant changes of developed pressure and rate of pressure rise were only observed in C and B solutions: This is explained by systolic alteration after immediate reimplantation for the B group and good preservation for the C group. Resting pressure was unchanged over a 6-hour storage only for the C group, but this measure was not determined for University of Wisconsin. A correlation exists for various left ventricular volumes between resting pressure and postreperfusion hemodynamic data. Replacement of chloride by lactobionate (A versus St. Thomas' Hospital) may have improved resting and diastolic pressures by other mechanisms than limitation of net water gain during storage.
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J. Heart Lung Transplant. · Jul 1995
Methotrexate therapy for complex graft rejection in pediatric heart transplant recipients. The Pediatric Heart Transplant Team--Loma Linda.
We retrospectively reviewed all pediatric heart transplant recipients at Loma Linda University Medical Center between January 1990 and September 1993 to evaluate the efficacy and safety of methotrexate when it is used for the treatment of graft rejection. ⋯ Methotrexate is an effective and safe adjunct in the management of chronic pediatric cardiac graft rejection.
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J. Heart Lung Transplant. · Jul 1995
Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique.
Donor management remains one of the most neglected areas of transplantation. A comprehensive donor management regimen has been developed. The results of the application of this strategy form the basis of this report. ⋯ The data indicate that, of the organs which initially fall outside our transplant acceptance criteria, 92% are capable of functional resuscitation. Conversely, superficial assessment may not show compromised function. Optimizing cardiovascular performance also has important implications for the viability of all transplantable organs. This aggressive approach to donor management has resulted in the transplantation of 44 donor hearts that may otherwise have been turned down or inappropriately managed.