Intravascular ultrasound (IVUS) assists in the early diagnosis of cardiac allograft vasculopathy (CAV). Early on, we found that CAV was less prevalent in infant recipients. This study extends the follow-up period to determine if that difference persists.

The procurement of donor organs with prolonged ischemic time for pediatric heart transplant recipient has raised some concern over the potential increased risk of using organs with long ischemic time. We hypothesized that there would be no difference in outcome based on prolonged donor ischemic time.

Purpose: The ultrasound cardiac output monitor (USCOM) is an FDA approved non-invasive device that can quickly determine cardiac output based on outflow tract velocity measured by continuous doppler and outflow valvular surface area deduced by patients' height and weight. This investigation examines USCOM measurements in pediatric cardiac transplant patients.

Background: With improvement in medical outcomes, the current research has shifted toward understanding and enhancing the quality of life after pediatric heart transplantation. Previous research has indicated that infant heart transplant recipients are generally at risk for neurodevelopmental delays; however, no longitudinal studies exploring the patterns of development within this medical population have been performed.Methods: Using the Bayley Scales of Infant Development-II, 39 children (2 to 38 months of age) who underwent heart transplantation in infancy (<1 year) at Loma Linda University Children's Hospital were assessed consecutively over time.Results: Mean Mental Development Index (MDI) scores for all age groups were within normal limits, except for the age ranges of 18 to 23 and 24 to 35 months, which were mildly delayed. Average Psychomoter Development Index (PDI) scores for all age groups reflected mildly delayed performance, except for the 36- to 38-month age group, which was within normal limits. Repeated measures analyses of variance on a sub-set of participants with at least 4 consecutive assessments revealed within-subject effects on MDI scores (F = 5.7, P < 0.01), but not on PDI scores (F = 1.6, p = 0.22). Significant decreases,in MDI scores at 18 and 28 to 36 months were noted.Conclusions: Motor development in this population was consistently mildly delayed. Age-dependent variability in cognitive skills was apparent. The delays appeared due to speech/language acquisition (18 months), and abstract reasoning/goal-directed behaviors (28 to 36 months). Possible etiologies for cognitive delays include test artifacts, auditory functioning and effects of immunosuppressive agents. Understanding risk factors in this patient population will allow for early and effective intervention.

Purpose: Cardiac Transplantation (Tx) is offered as a therapy for a variety of congenital or acquired incurable heart conditions. Currently, an increasing number of children are referred for Tx, having had prior surgical palliation. This study evaluates the effect of pretransplant diagnosis and palliation on the early morbidity and the long-term results of Tx.

A retrospective analysis of 381 pediatric heart-transplant recipients was performed to determine the frequency, characteristics, and risk factors for post-transplant diabetes. The rate of post-transplant diabetes was 1.8% with antithymocyte globulin, cyclosporine and azathioprine as primary immunosuppressive therapy. Time from transplant to diabetes was 0.25-13 years. Diabetes was characterized by reversibility, and lack of insulinopenia and autoimmunity. The post-transplant diabetes rate in tacrolimus-converted children (n = 45) was 8.8%. In tacrolimus-converted children, age at transplant, mean and maximum tacrolimus blood levels, and first-year rejection episodes were higher in the post-transplant diabetes group, which also consistently had DR-mismatched transplants and HLA DR3/DR4 haplotypes. Body mass index was not different between diabetic and control tacrolimus-converted children. In conclusion, pediatric post-transplant diabetes may be related to reversible insulin resistance. Tacrolimus levels, HLA DR mismatch, and older age at transplant may predispose to post-transplant diabetes.

BACKGROUND:We evaluated the role of total lymphoid irradiation (TLI) in the management of refractory rejection among pediatric heart transplant patients.METHODS:Eleven of 298 patients underwent TLI at 6 to 195 months of age and were divided into subgroups: those who survived (group A, n = 7) and those who did not survive beyond 1 year after TLI (group D, n = 4). Non-TLI recipient data were considered as the controls.RESULTS:Six out of 11 patients died eventually (54%). TLI was initiated 3 to 107 months after transplantation with a dosage of 600 to 840 cGy. The pre-TLI rejection rate (0.62 +/- 0.40 per month) was higher (p < 0.0001); however, the post-TLI rejection rate (0.24 +/- 0.65 per month) showed no significant difference from the control rejection rate. The Cox proportional hazard model found significance for TLI as a risk factor for development of posttransplant coronary artery disease (relative risk, 4.8; 95% CI, 1.1 to 21.3) and posttransplant lymphoproliferative disease (relative risk, 47.9; 95% CI, 1.6 to 1,475.3), respectively. Although the rejection rate decreased after TLI in both groups (group A pre/post, 0.51 +/- 0.31/0.06 +/- 0.08 per month; group D pre/post, 0.82 +/- 0.49/0.57 +/- 1.09 per month), significance was obtained only in group A (p = 0.018).CONCLUSIONS:TLI was an effective adjunct for reversal of refractory rejection in pediatric heart transplantation by reducing the rejection rate. Great care must be taken for the risk of development of coronary artery disease or lymphoproliferative disease.

Background. Cardiac retransplantation (re-CTx) in children is a controversial therapy, yet it remains the best treatment option to recipients with failing grafts. Our objective was to determine the incidence of re-CTx in a large pediatric population of recipients and evaluate the outcome of such therapy.Methods. Between November 1985 and November 1999, 347 children underwent cardiac transplantation at the Loma Linda University Medical Center. Of these, 32 children were listed for re-CTx. Ten patients died while waiting, and 22 recipients underwent re-CTx. Median age at re-CTx was 7.1 years (range, 52 days to 20.1 years).Results. Indications for re-CTx were allograft vasculopathy (n = 16), primary graft failure (n = 5), and acute rejection (n = 1). Two patients with primary graft failure underwent retransplantation within 24 hours of the first transplantation procedure while on extracorporeal membrane oxygenation support. Median time interval to re-CTx for the others was 7.2 years (range, 32 days to 9.4 years). Operative mortality for all cardiac re-CTx procedures was 13.6%. Causes of hospital mortality were pulmonary hypertension with graft failure (n = 2) and multiorgan failure (n = 1). Median hospital stay after re-CTx was 14.1 days (range, 6 to 45 days). There was one late death from severe rejection. Actuarial survival at 3 years for re-CTx was 81.9% +/- 8.9% compared with 77.3% +/- 2.6% for primary cardiac transplantation recipients (p = 0.70).Conclusions. Elective re-CTx can be performed with acceptable mortality. Although the number of patients undergoing retransplantation in this report is small and their long-term outcome is unknown, the intermediate-term survival after re-CTx is similar to that of children undergoing primary cardiac transplantation. (Ann Thorac Surg 2001;71:66-70) (C) 2001 by The Society of Thoracic Surgeons.

DISCORDANT cardiac xenografts are hyperacutely rejected owing to the binding of natural antibody (NAb) to xenograft endothelial cells and activation of the complement pathway. Depletion of NAb and complement from recipients can prevent hyperacute rejection. However, delayed xenograft rejection (DXR) has become a major barrier to long-term xenograft survival after overcoming hyperacute rejection. The pathogenesis of DXR has been demonstrated to be macrophage-mediated cellular rejection and newly developed NAb. Total lymphoid irradiation (TLI) has been used as a conditioning regimen for bone marrow transplantation, a treatment designed to remove or suppress peripheral T and B cells while leaving bone marrow stem cells intact. TLI has been shown, with some success, to induce specific transplant tolerance to allografts and xenografts. Our previous study has shown alteration of humoral immune response in a rhesus monkey-to-baboon cardiac xenograft model treated with methotrexate and cyclosporine A. In this study, we utilized TIL combined with immunosuppression of humoral immunity by methotrexate to establish donor bone marrow engraftment and immune tolerance, and to prevent DXR in a pig-to-baboon cardiac xenograft model.

Previous articleNext article No AccessShould Children with Severe Cognitive Impairment Receive Solid Organ Transplants?Robert D. Orr, Joyce K. Johnston, Stephen Ashwal, and Leonard L. BaileyRobert D. OrrLoma Linda University Medical Center; Loma Linda University Children's Hospital Search for more articles by this author , Joyce K. JohnstonLoma Linda University Children's Hospital Search for more articles by this author , Stephen AshwalLoma Linda University Children's Hospital Search for more articles by this author , and Leonard L. BaileyLoma Linda University Medical Center; Loma Linda University Children's Hospital Search for more articles by this author PDFPDF PLUS Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Volume 11, Number 3Fall 2000 Published on behalf of the MacLean Center for Clinical Medical Ethics Article DOIhttps://doi.org/10.1086/JCE200011304 © 2000 The University of Chicago. All rights reserved.PDF download Crossref reports no articles citing this article.

Background. Changes in healthcare delivery have affected the practice of congenital cardiac surgery. We recently developed a strategy of limited sternotomy, early extubation, and very early discharge, and reviewed the perioperative course of 198 pediatric patients undergoing elective cardiovascular surgical procedures, to assess the efficacy and safety of this approach.Methods. One hundred ninety-eight patients aged 0 to 18 years (median 3.2 years) underwent 201 elective car; diovascular surgical procedures over a 1-year period. All patients were admitted on the day of surgery. Patients were divided into six diagnostic groups: group 1, complex left-to-right shunts (n = 14, 7.0%); group 2, simple left-to-right shunts (n = 83, 41.3%); group 3, right-to-left shunts with pulmonary obstruction (n = 33, 16.4%); group 4, isolated, nonvalvular obstructive lesions (n = 30, 14.9%); group 5, isolated valvular anomalies (n = 20, 10.0%); and group 6, miscellaneous (n = 21, 10.4%).Results. After 201 procedures, 175 patients (87.1%) were extubated in the operating room and 188 (93.6%) within 4 hours from operation. Four patients (2.0%) were extubated more than 24 hours from completion of the procedure, and 2 (1.0%) died while on respiratory support (never weaned). Five patients (2.6%) failed early extuba- tion (<4 hours). Early discharge was achieved for the vast majority of patients. Overall median length of stay (LOS, including day of surgery as day 1) was 2.0 days, with a median LOS of 3.0 days for those patients requiring circulatory arrest duration exceeding 20 minutes. Of 195 patients, 4,3 (24.6%), 121 (74.0%), and 159 (81.5%) were discharged, respectively, at < 24, < 48, < 72 hours from admission. Longest and shortest mean postoperative LOS were in group 6 (9.9 +/- 14.5 days) and group 2 (1.6 = 0.7 days), respectively Six patients (2.9%) died, and 11 (5.5%) suffered in-hospital complications. Thirty patients (15.4%) were either treated as outpatients (n = 11, 5.7%) or readmitted (n = 19, 9.7%) within 30 days from the time of surgery. Only 8 of 195 patients (4.1%) were readmitted with true surgical complications requiring invasive therapeutic procedures.Conclusions. Selected patients with a broad spectrum of congenital heart disease may enjoy same-day admission, limited sternotomy, immediate extubation, and very early discharge with excellent outcomes and acceptable morbidity. (C) 2000 by The Society of Thoracic Surgeons.

332 The causes of post-transplant coronary artery disease (PTCAD) are multifactorial. Although we have previously shown no ill effect of prolonged donor ischemic times on subsequent late graft function, it has been suggested that prolonged ischemic times may promote the development of PTCAD due to endothelial injury. We studied the development of PTCAD in 212 infant and pediatric heart transplant (HTx) patients and compared grades 3&4 PTCAD to hourly donor heart ischemic times up to 9.5 hours. Determination of PTCAD was made with angiograms, intravascular ultrasound, autopsy or donor heart examination at the time of retransplantation. A total of 30/212 pts developed PTCAD (14%). Donor heart ischemic times were divided into hourly intervals starting at 2 hours. The number of hearts with PTCAD versus hourly ischemic times are shown below: (Table)TableThese results demonstrate no correlation between donor heart ischemic times and the subsequent development of PTCAD. Indeed, some of the longest ischemic times were associated with lesser rates of PTCAD. These data suggest that a single nationwide waiting list is feasible for pediatric heart transplantation.

Objective: Our objectives were to study delayed xenograft rejection and the effectiveness of pretransplantation total lymphoid irradiation combined with immunosuppression on rejection in a pig-to-baboon cardiac xenograft model. Methods: Baboons were treated with pretransplantation total lymphoid irradiation, cyclosporine A (INN: ciclosporin), and methotrexate. Orthotopic pig-to-baboon cardiac transplantations were performed after depletion of circulating xenoreactive natural antibody by pretransplantation donor organ hemoperfusion. Tissue samples were collected for immunologic and immunopathologic evaluation. Results: Pig cardiac xenografts survived more than 18 and 19 days without evidence of hyperacute rejection. Immunologic analysis of serum samples demonstrated that circulating xenoreactive natural antibody levels did not return to pretransplantation levels. The production of xenoreactive natural antibodies from the recipient's splenocytes was inhibited completely. Histologic examination of xenografts showed the feature of acute vascular rejection. Immunohistochemical studies demonstrated infiltration of cardiac xenografts by large numbers of macrophages, small numbers of natural killer cells, and a few T cells. The infiltrating macrophages also showed expression of interleukin-1 and tumor necrosis factor. Diffuse deposition of immunoglobulin G, C1Q, C3, and fibrin on xenograft vasculature was observed. Interleukin-2 expression was not found in rejected cardiac xenografts. Xenograft endothelial cells also showed evidence of activation (expression of cytokines interleukin-1 and tumor necrosis factor). Conclusions: This study demonstrates prolonged discordant cardiac xenograft survival and delayed xenograft rejection in a pig-to-baboon model. The delayed xenograft rejection is mediated by both humoral and cellular mechanisms. Pretransplantation total lymphoid irradiation combined with cyclosporine A and methotrexate can inhibit xenoreactive natural antibody production but not elicited antipig antibody production and the xenoreactivity of macrophages. (J Thorac Cardiovasc Surg 1998;115:1342-9)

Bovine leukemia virus (BLV) proviral load is controlled by T-cell responses, which require vitamin A (VA) derived from food. However, whether dietary VA restriction for marbling impairs the T-cell responses that control BLV proviral load in beef cattle is unknown. We assessed T-cell subsets, interferon (IFN)-γ gene expression, and BLV proviral load in naturally BLV-infected Japanese Black cattle that were fed a diet with decreased VA levels. We found that the percentage of CD4+ T cells increased over time during dietary VA restriction. In addition, BLV proviral load was negatively correlated with the percentage of CD4+ T cells and with the level of IFN-γ gene expression. These observations suggest that dietary VA restriction for marbling enhances T-cell responses that control BLV proviral load and thus does not promote leukemogenesis in fattening beef cattle.

BACKGROUND:The surgical technique of heart transplantation as therapy in infants with hypoplastic left heart syndrome was first reported over a decade ago. Since that time, incremental refinements have evolved that both facilitate the operation and potentially reduce the perceived neurologic hazards associated with the use of hypothermic circulatory arrest.METHODS:Minor technical adjustments have permitted infant heart transplantation to be accomplished with relative ease while markedly limiting the need for complete circulatory arrest. Low-flow hypothermic systemic perfusion is used for atrial implantation, reserving circulatory arrest for arch reconstruction only. This is accomplished by use of an active (pump) sucker for venous return.RESULT:Mean circulatory arrest time with the current technique has been 26 minutes.CONCLUSION:Minor technical refinements have resulted in a marked reduction in hypothermic circulatory arrest time during infant heart transplantation for hypoplastic left heart syndrome.