Open versus endoscopic saphenous vein harvesting: wound complications and vein quality.

BACKGROUND: The saphenous vein is an important conduit for coronary artery bypass grafting. Wound complications from traditional open vein harvesting occur often. Minimally invasive endoscopic saphenous vein harvesting may decrease wound complications. Vein quality may be an issue with endoscopic harvesting. METHODS: We reviewed 568 patients who had bypass grafting and saphenous vein harvesting either endoscopic (group A, n = 180) versus open (group B, n = 388). Both groups were demographically similar and management identical. Wound complication was defined by the need for intervention and included lymphocele, hematoma, cellulitis, edema, eschar, and infection. Multiple vein segments were obtained from 8 patients, 4 from each group, and examined histologically. RESULTS: Wound complications were significantly less in group A (9/180, 5%) versus group B (55/388, 14.2%), p value equal to or less than 0.001. Open harvesting (p< or =0.001), diabetes (p< or =0.001), and obesity (p< or =0.02) were risk factors for wound complication by univariate analysis. By multiple logistic analysis, open harvesting (p< or = 0.0007) and diabetes (p< or =0.0001) were independent risk factors for wound infection. Histologic evaluation of vein samples showed that there was no difference between the groups and vascular structural integrity was maintained. CONCLUSIONS: Endoscopic saphenous vein harvesting was associated with fewer wound complications and infections. Vein quality was not adversely effected because of endoscopic harvesting.

Salvage by volume reduction of chronic allograft rejection in emphysema.

BACKGROUND: We hypothesized that native lung volume reduction surgery (LVRS) would improve respiratory function in patients who had previously undergone single lung transplantation for emphysema and who were disabled by obliterative bronchiolitis. METHODS: Seven single lung transplant recipients who had advanced bronchiolitis obliterans syndrome (BOS grade 3b), absence of active infection, and suitable anatomy underwent native LVRS. Mean time from lung transplantation to LVRS was 39 +/- 17 months. RESULTS: Mean FEV1 rose from 684 +/- 164 ml before LVRS to 949 +/- 219 ml at 3 months after LVRS, an increment of 40% (p = .002). Mean 6-minute walk rose from 781 +/- 526 ft before LVRS to 887 +/- 539 ft at 3 months after LVRS (p = .031), and mean dyspnea index declined from 3.1 +/- 1.1 before LVRS to 1.6 +/- 0.5 at 3 months after LVRS (p = .010). Mean native lung volume declined from 2956 +/- 648 ml before LVRS to 2541 +/- 621 ml at 3 months after LVRS, but the change was not statistically significant (p = .12). Mean transplant lung volume was little changed before and after LVRS (2099 +/- 411 ml and 1931 +/- 607 ml, respectively, p = NS). There was also a trend toward increased ventilation and perfusion of the native lung and reduction in ventilation and perfusion of the transplant lung, but these changes did not achieve statistical significance. By six months after LVRS, three patients died (two as a consequence respiratory failure), and survivors began to show evidence of deteriorating spirometry. CONCLUSIONS: LVRS is capable of salvaging respiratory function in chronic allograft rejection in emphysema by reducing native lung hyperinflation. These benefits, however, appear to be limited in magnitude and duration by the severity of the underlying allograft dysfunction.

Preliminary experience with mycophenolate mofetil used after lung transplantation.

This study reports our preliminary experience with mycophenolate mofetil (MMF)-based immune suppression after lung transplantation. Thirteen patients (group 1) received MMF as primary therapy immediately after transplantation. Use of MMF was associated with a linearized rate of 0.85 episodes of acute rejection per 100 patient days during the first 3 months after transplantation, as compared with rates of 1.49 and 1.38, observed in two groups of historical control subjects (p = .094 and p = .053, respectively). Rejection rates after the first 3 months were not lower than in historical control subjects. Nine additional patients were switched from azathioprine to MMF because of recurrent episodes of high-grade acute rejection (group 2). In this group, the linearized rate of acute rejection episodes declined significantly (p = .004) after initiation of MMF therapy. These data suggest a potential role for MMF in reducing the rate of acute rejection episodes after lung transplantation.

The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates.

The humoral and cell-mediated immune responses to subsequent allografts were determined in primate recipients after concordant xenotransplantation as a bridge to allotransplantation. Heterotopic heart transplants (n = 4) were performed from cynomolgus monkeys into ABH type-matched olive baboons followed 2 weeks later by allotransplantation from ABH type-matched baboon donors. Allografts were explanted at 8 weeks. All recipients underwent splenectomy at the time of xenotransplantation and received immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Concordant xenotransplantation in these primates did not induce humoral or cell-mediated immune responses that jeopardized subsequent allografts. The degree of xenospecific immune reactivity, as determined by specific cytotoxicity of recipient T-cell lines derived from the xenograft and extent of histologic xenograft rejection, did not predict the severity of subsequent allograft rejection. In two of the four recipients, xenotransplantation induced an alloreactive humoral response against antigens expressed by the B cells of more than 50% of members from a panel of 12 unrelated baboons. In all recipients, priming with xenogeneic splenocytes in vitro induced an accelerated proliferative T-cell response to allogeneic lymphocytes from 16% of this panel. This study affirms the role of concordant xenografts as appropriate biologic bridges to human allotransplantation. However, our results suggest that xenoreactive baboon memory CD4 T cells may recognize major histocompatibility complex class II--like structures shared between the xenogeneic and allogeneic targets. The potential allorecognition induced by a xenograft may affect the process of subsequent allograft donor selection.

Newborn baboon immunity: lessons in cross-species transplantation.

BACKGROUND: The critical shortage of organ donors has greatly limited the number of heart transplantations performed each year. This is particularly true of the newborn patient, for whom xenotransplantation may provide an alternative therapeutic option to allotransplantation. The role of newborn immunity in xenotransplantation is not clearly understood. METHODS: We examined the humoral immune responses of 9 nonimmunosuppressed newborn baboons (900 to 1200 g) aged 28 to 44 days undergoing heterotopic pig heart transplantation. Grafts were explanted between 1 and 87 hours after transplantation. RESULTS: Despite the degree of species, disparity, hyperacute rejection was not observed in any of the nine transplanted grafts. Whole-cell enzyme-linked immunosorbent assay demonstrated newborn baboon serum to contain very low binding levels of anti-pig natural immunoglobulin M xenoantibody when compared with adult baboon serum. Newborn serum, like adult serum, contained anti-pig natural immunoglobulin G xenoantibody. However, newborn baboon serum was not cytotoxic to pig endothelial cells, suggesting that immunoglobulin M and not immunoglobulin G is the primary xenoreactive antibody. CONCLUSIONS: The low binding levels of anti-pig immunoglobulin M xenoantibody, the absence of cytotoxicity to pig endothelial cells, and the avoidance of hyperacute rejection after heart transplantation suggest that newborn primates may have an immunologic advantage as the recipients of hearts transplanted across species barriers. Whether this advantage can be extended to the human condition is currently being explored in our laboratory.

Inhibition of chronic vascular rejection in primate cardiac xenografts using mycophenolate mofetil.

Similar to human allografts, cardiac xenografts also appear susceptible to chronic vascular rejection. The study described here evaluated the influence of mycophenolate mofetil on the incidence and severity of vascular rejection in a primate model of heart xenotransplantation. Nine baboons received heterotopic cardiac xenografts from donor cynomolgus monkeys. All baboons were placed on a cyclosporine and methylprednisolone-based immunosuppressive regimen. In addition, group 1 baboons received azathioprine (4 mg.kg-1.day-1) and group 2 baboons received mycophenolate mofetil (70 mg.kg-1.day-1). Biopsy specimens were obtained at regular intervals and reviewed blindly by a pathologist. A total of 50 biopsy specimens, 29 from group 1 and 21 from group 2, were reviewed. Histologic evidence of vascular rejection was present in 16 of the 29 biopsy specimens from the group 1 animals and in only 2 of the 21 specimens from the group 2 animals (p < 0.005). The mean graft survival was 3 months in group 1 versus 10 months in group 2. At 1-year follow-up, profound intimal proliferation in the coronary vasculature was noted in the biopsy specimens from group 1, whereas the coronary vessels were found to be normal in the specimens from group 2. The use of mycophenolate mofetil, in combination with cyclosporine and steroids, resulted in reduced vascular rejection and prolonged xenograft survival.

Immunosuppressant combinations in primate cardiac xenografts. A review.

ABO matched cynomolgus monkey to baboon heterotopic xenografts were performed using three different immunosuppressant regimens. Group 1 (n = 4) baboons, which did not receive immunosuppression, had a mean graft survival of 9 days. Group 2 (n = 6) received cyclosporine (CsA) and methylprednisolone acetate which prolonged graft survival to an average of 78 days. Group 3 (n = 5) received CsA, Pred, and azathioprine (Aza) as well as steroid pulses and antithymocyte globulin (ATG) for rejection episodes. Survival in this group averaged 94 days. In Group 4 (n = 3), the same regimen as group 3 was used; however, Mycophenolate Mofetil was substituted for Aza. This resulted in a mean survival of 296 days. Histologic examination of the coronary vasculature in baboons treated with Mofetil showed a reduction in vascular pathologic changes when compared to those treated with Aza. Long-term cardiac xenograft survival is possible using currently available immunosuppressive agents.

Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants.

Hyperacute rejection is a serious complication of xenogeneic organ transplantation. It is believed that platelets play a pivotal role in this phenomenon. In this study, we provide the first known evidence of the efficacy of the PAF receptor antagonist, tulopafant, in improvement in graft function and histology of discordant cardiac xenografts. Transplantation of guinea pig hearts into recipient rats resulted in hyperacute rejection. Pretreatment of recipient animals with tulopafant (but not indomethacin) extended rejection time by 4-5-fold. Histological examination revealed marked diminution of both interstitial hemorrhage and deposition of platelet and granulocytes in capillaries of cardiac xenografts when recipient animals were pretreated with tulopafant.

Patients who die awaiting heart transplantation.

In the United States, heart donor availability has increasingly failed to keep pace with rising demand. Transplant data were obtained from the United Network for Organ Sharing for 1988, 1989, and 1990 and by survey of 50 heart transplantation centers, which performed 1932 transplantations between 1983 and 1989. According to the United Network for Organ Sharing, 512 patients on the waiting list died in 1988; 527, in 1989; 650, in 1990, and if present trends continue more than 800 will have died in 1991. Similar numbers of patients were inactivated or removed from the list each year. Only 49% of patients (1647 of 3390) on the heart transplant waiting list at some time in 1988 underwent the procedure in that year. For 1989 the figure fell to 42% (1630 of 3915 patients). Survey data revealed a threefold increase in the ratio of the number of patients who died/number of patients who underwent transplantation from 0.07 in 1983 to 0.21 in 1989 and in the ratio (number of patients who died+number of patients who were removed from the list)/number of patients who underwent transplantation from 0.12 in 1983 to 0.38 in 1989. The major causes of death among waiting patients were congestive heart failure (46%) and arrhythmia (29%). From 1983 to 1989, 55% (134 of 243) of those patients with documented urgency status died in the intensive care unit; 45% (109 of 243) died elsewhere. Waiting time for patients dying in the intensive care unit rose from 10.7 days in 1985 to 50.3 days in 1989; patients dying out of the intensive care unit waited 103.7 days in 1985 and 85.6 days in 1989. In conclusion, the number and proportion of potential recipients who die awaiting heart transplantation is increasing every year. Congestive heart failure and arrhythmia are the major causes of death, and similar numbers of patients die in and out of the intensive care unit.

Pediatric heart transplantation for doxorubicin-induced cardiomyopathy.

The prognosis of patients with a history of successfully treated malignancy, who subsequently undergo organ transplantation and long-term immunosuppression, is uncertain. We report the case of a 14-year-old girl in whom doxorubicin-induced cardiomyopathy developed after aggressive therapy for a fibroblastic osteosarcoma. The patient underwent orthotopic heart transplantation and remains in remission 14 months after surgery.

Cyclosporine-associated central neurotoxicity after heart transplantation.

Cyclosporine central neurotoxicity has been described after bone marrow, kidney, and liver transplantation but has not been well documented after heart transplantation. This case illustrates severe reversible neurotoxicity after heart transplantation with characteristic radiographic changes in magnetic resonance imaging.