The effect of chemokines on T regulatory cells following heart transplantation

Heart transplantation (HTx) is now an established therapy for end-stage cardiac failure not responding to medical treatment. Recent decades have seen improved outcome following HTx due to more effective and targeted immunosuppressive therapy. However, acute and chronic rejection remains a major cause of morbidity and mortality. At the same time, immunosuppressive strategies are associated with significant side effects, including development of tumours. Hence, the induction of immunologic tolerance to alloantigen is considered the “holy grail” of transplant research. T regulatory cells (Tregs) are a subset of T cells that appear to suppresscytotoxic cell and initiate tolerance to foreign tissues. The Tregs suppresscytotoxic cells through specific cytokine pathways and cell-cell contact. In-vivo T reg migration has been a matter of debate in recent years. Treg trafficking is governed by chemokines, which are small secreted proteins, acting via their distinct trans-membrane serpentine receptors. Experimental work has demonstrated an involvement of distinct chemokine pathways in Tregs migration and localization following cardiac transplantation; however, there is paucity of data in humans. I investigated the effects of chemokines on Tregs in heart transplant recipients through a series of observational studies. My study demonstrated that acute rejection following heart transplantation is associated with a significant elevation of peripheral blood Th1 chemokine levels. I hereby further show that peripheral blood Treg counts in stable heart transplant recipients are not affected by immunosuppression but are significantly lower in patients taking statins. I have demonstrated via in-vitro chemotaxis assays a specific pattern of chemotactic response for Tregs and the effector T cells. Using double immunofluorescence staining and immunostaining, I show for the first time that Tregs may migrate to the allograft under the influence of CCL17.EThOS - Electronic Theses Online ServiceUniversity Hospital of South ManchesterGBUnited Kingdo

Zonal allocation for thoracic organs in the united kingdom: Has it been successful? A single-center view

AbstractObjectives: The purpose of this study was to analyze the impact of the zonal allocation system for thoracic organs on the outcome of our transplant activity. Methods: We analyzed the results of thoracic transplants performed between 1987 and 1998. The transplants were divided into 3 groups: local donors retrieved by our team (171 hearts and 61 lungs; DL group); distant donors retrieved by our team (58 hearts and 35 lungs; DD group); and distant donors retrieved by other teams (51 hearts and 41 lungs; DX group). Results: No significant differences were observed among the groups in early postoperative events for either heart or lung transplantation. Heart transplants: Cardiac index was 2.6 ± 0.4 L/m2 for the DL group, 2.7 ± 0.6 L/m2 for the DD group, and 2.5 ± 0.7 L/m2 for the DX group (P = .4). The 30-day mortalities were 9.1%, 9.1%, and 8.3% ( P = .5) and the 1-year survivals 83%, 80%, and 82% ( P = .4) for the DL, DD, and DX groups, respectively. Lung transplants: Alveolar-arterial oxygen gradient was 358 ± 19 mm Hg for the DL group, 345 ± 17 mm Hg for the DD group, and 329 ± 21 mm Hg for the DX group (P = .07). The 30-day mortalities were 9.9%, 10.5%, and 12.8% (P = .2) and the 1-year survivals 79%, 75%, and 77% (P = .3) for the DL, DD, and DX groups, respectively. Conclusion: Zonal allocation for thoracic organs has been successfully applied to our program. Using donor organs retrieved by other teams, we have achieved equivalent outcomes for both heart and lung transplantation. (J Thorac Cardiovasc Surg 1999;118: 733-9

Donor heart selection: the outcome of "unacceptable" donors

BACKGROUND: The decline in the number of suitable donor hearts has led to an increasing interest in the use of previously unacceptable donors. In the United Kingdom, if one centre declines a donor heart on medical grounds it may be offered to other centres. This multi-centre study aimed to evaluate the outcome of recipients of donor hearts considered medically unsuitable for transplantation by one centre that were used in other centres. METHODS: Between April 1998 and March 2003, ninety-three donor hearts (group A) were transplanted, after being considered medically unsuitable for transplantation by another centre. During the same period, 723 hearts (group B) were transplanted in the UK using donors not previously rejected. Data on the donors and recipients was obtained from the UK transplant database. Comparative analysis on the two groups was performed using SPSS 11.5 for Windows. RESULTS: The characteristics of recipients were similar in both groups. The main reasons for refusal of hearts are listed below. In most cases there was more than one reason for refusing the donor heart. We did not find significant differences in the post-operative mortality (up to 30 days), ICU and hospital stay and cardiac cause of death between the two groups. Kaplan-Meier survival curves showed no significant difference in the long-term survival, with Log Rank test = 0.30. CONCLUSION: This study demonstrates that some hearts declined on medical grounds by one centre can safely be transplanted and should be offered out nationally. The use of these hearts was useful to expand the scarce donor pool and there does not seem to be a justification for denying recipients this extra source of organs

Extracorporeal membrane oxygenator as a bridge to successful surgical repair of bronchopleural fistula following bilateral sequential lung transplantation: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Lung transplantation (LTx) is widely accepted as a therapeutic option for end-stage respiratory failure in cystic fibrosis. However, airway complications remain a major cause of morbidity and mortality in these patients, serious airway complications like bronchopleural fistula (BPF) are rare, and their management is very difficult.</p> <p>Case presentation</p> <p>A 47-year-old man with end-stage respiratory failure due to cystic fibrosis underwent bilateral sequential lung transplantation. Severe post-operative bleeding occurred due to dense intrapleural adhesions of the native lungs. He was re-explored and packed leading to satisfactory haemostasis. He developed a bronchopleural fistula on the 14^thpost-operative day. The fistula was successfully repaired using pericardial and intercostal vascular flaps with veno-venous extracorporeal membrane oxygenator (VV-ECMO) support. Subsequently his recovery was uneventful.</p> <p>Conclusion</p> <p>The combination of pedicled intercostal and pericardial flaps provide adequate vascular tissue for sealing a large BPF following LTx. Veno-venous ECMO allows a feasible bridge to recovery.</p