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107: Preliminary Outcomes after Lung Transplantation from Donors with Cardiac Death
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
Methods and Materials: During gene infusion, the optimized low strength (10V/cm) electric field network was applied on the donor heart. Human recombinant IL-4 and IL-10 cDNAs driven by two identical CMV promoters in one vector was delivered ex vivo intracoronary into rabbit allografts. Results: LSEN is able to induce a localized and balanced dual gene transfer in the targeted organ. The LSEN gene transfer efficiency (75%) was 5 times higher than liposome-mediated IL-10 gene transfer. Both transfected genes were only expressed in the cardiac allografts, and did not cause any ectopic transgene expression. The IL-4 and IL-10 protein expression in LSEN-mediated combinatorial gene therapy was the same as that in IL-4 or 10 only gene transfer. Two third of allografts achieved indefinite survive. However, 1/3 of allografts failed around 2-3 weeks after operation. Half of them are due to excessive effusion around the allograft and seroma formation. Overexpressed IL-4 and IL-10 not only induced significant immunosuppression and T cell apoptosis, and also modulated the cytokine profile, and protected myocytes from apoptosis. The reduction of total amount of infiltrates and CD3⫹ T cells was significantly greater in LSEN-IL4&IL10 gene therapy group compared with that in LSEN-IL10 treated allografts (n⫽18, p⬍0.001). LSEN-mediated IL4 and IL10 gene transfer significantly improved the cardiac function. No arrhythmogenic effect and any other cardiac adverse effects were found. Conclusions: These results demonstrate that early initiated and balanced excessive exogenous IL-4 and IL-10 expression induced by LSEN-mediated localized gene transfer in cardiac allografts has better immunosuppressive effect than LSEN-mediated IL-10 gene therapy alone or liposome-mediated IL-4 and IL-10 combined gene therapy and is able to induce tolerance in allografts.
107 Preliminary Outcomes after Lung Transplantation from Donors with Cardiac Death I.M. Ahmed1, M. Yap2, A. Hamilton2, M. Harkess2, P.M. Spratt2, P. Jansz2, A. Farnsworth2, G. Emily2, P. Macdonald2, A.R. Glanville2 1Freeman Hospital, Newcastle upon Tyne, Northumbria, United Kingdom; 2St Vincents Hospital, Sydney, NSW, Australia Purpose: Donation after cardiac death (DCD) has potential to expand the current limited donor pool in Australia. We illustrate the challenges of starting such a programme and show our early results. Methods and Materials: Institutional guidelines were created to encompass potential ethical and legal issues with DCD lung transplantion, and an education programme initiated for hospital staff and donor coordinators. Initially all donors had elective withdrawal of ventilation (Maastricht III) in ITU or the operating room. No donor treatment of any kind was permitted. Our technique involved inflation of the lungs with FiO2 0.4 after re-intubation. Chest was opened simultaneously with the abdomen, and lungs were assessed prior to flushing antegrade and retrograde with cold Celsior/GTN mix. Implantation and postoperative management was as per our standard protocol for all lung transplants. Results: Since November 2007 lungs were transplanted from 5 DCD donors with a mean age of 46 (range 33-56). Cause of death was traumatic head injury (n⫽3) and subarachnoid haemorrhage (n⫽2). The 5 recipients had a mean age of 42 (range 22-61). Indications for lung transplant were emphysema, primary pulmonary hypertension and late graft failure after lung transplant. Mean time to asystole after withdrawal of treatment was 14 minutes (range 10-19). Mean warm ischaemic time was 22 minutes (range 12-31). Mean total ischaemic time was 231 minutes (range 184-275). Early function was excellent with mean PO2 on the 1st postoperative day of 100 (range 64 to 136)
Abstracts
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on FiO2 0.4. Mean length of ITU stay was 6 days (range 3-10) and time to discharge 30 days (range 25-36). There was no mortality. Conclusions: Our initial experience in this new venture to expand our donor pool taught us some key principles in setting up such a programme and our preliminary results demonstrate the safety of this technique. 108 NHBD Meet the Standard of HBD Regarding Early Outcome after LTx S. De Vleeschauwer, D. Van Raemdonck, B. Vanaudenaerde, R. Vos, G. Verleden Katholieke Universiteit Leuven, Leuven, Belgium Purpose: The use of non-heart beating donors (NHBD) to overcome donor organ shortage is moving into the clinic. In 2007, we performed 5 lung transplantations (LTx) with lungs from NHBD (10%). Previously it has been shown that brain death can upregulate IL8-inducing cytokines like IL6 in the peripheral organs. Elevated levels of IL8, associated with brain death, were demonstrated to correlate inversely with the oxygenation capacity of the graft. The aim of this study was to investigate if NHBD meet up with standard heart-beating donors (HBD) at the early (neutrophilic) inflammatory levels. Methods and Materials: Each NHBD LTx recipient was compared with 2 age, gender, underlying disease and time of surgery matched HBD controls. Primary graft dysfunction (PGD) was assessed at 0, 6, 12, 24 and 48 hours after LTX. Broncho-alveolar lavage (BAL) was performed on post-operative day (POD) 1, 21, 90 and 180 and total and differential cell counts were performed. IL8, IL6 and TGF in BAL were assessed by ELISA. Results: No significant differences between the NHBD and the control HBD group in PGD grades (Figure 1), neutrophil % nor IL8, IL6 and TGF levels (table 1) were seen. Conclusions: The early outcome after NHBD and HBD is comparable and therefore NHBD are a valid tool to increase the donor pool.
109 Heart-Lung Transplantation: A Single Center Experience with 152 Cases E. Fadel, O. Mercier, S. Mussot, D. Fabre, J. Cerrina, F. LeRoy Ladurie, P. Dartevelle Hopital Marie Lannelongue, Le Plessis Robinson, France Purpose: To determine factors affecting early and long-term outcome after heart-lung transplantation (HLT) in a single center experience. Methods and Materials: From 1986 to 2007, 152 HLT were performed in 151 patients using the same surgical technique. Indicationswere primary pulmonary hypertension (PH) (n⫽75), secondary
Methods and Materials: During gene infusion, the optimized low strength (10V/cm) electric field network was applied on the donor heart. Human recombinant IL-4 and IL-10 cDNAs driven by two identical CMV promoters in one vector was delivered ex vivo intracoronary into rabbit allografts. Results: LSEN is able to induce a localized and balanced dual gene transfer in the targeted organ. The LSEN gene transfer efficiency (75%) was 5 times higher than liposome-mediated IL-10 gene transfer. Both transfected genes were only expressed in the cardiac allografts, and did not cause any ectopic transgene expression. The IL-4 and IL-10 protein expression in LSEN-mediated combinatorial gene therapy was the same as that in IL-4 or 10 only gene transfer. Two third of allografts achieved indefinite survive. However, 1/3 of allografts failed around 2-3 weeks after operation. Half of them are due to excessive effusion around the allograft and seroma formation. Overexpressed IL-4 and IL-10 not only induced significant immunosuppression and T cell apoptosis, and also modulated the cytokine profile, and protected myocytes from apoptosis. The reduction of total amount of infiltrates and CD3⫹ T cells was significantly greater in LSEN-IL4&IL10 gene therapy group compared with that in LSEN-IL10 treated allografts (n⫽18, p⬍0.001). LSEN-mediated IL4 and IL10 gene transfer significantly improved the cardiac function. No arrhythmogenic effect and any other cardiac adverse effects were found. Conclusions: These results demonstrate that early initiated and balanced excessive exogenous IL-4 and IL-10 expression induced by LSEN-mediated localized gene transfer in cardiac allografts has better immunosuppressive effect than LSEN-mediated IL-10 gene therapy alone or liposome-mediated IL-4 and IL-10 combined gene therapy and is able to induce tolerance in allografts.
107 Preliminary Outcomes after Lung Transplantation from Donors with Cardiac Death I.M. Ahmed1, M. Yap2, A. Hamilton2, M. Harkess2, P.M. Spratt2, P. Jansz2, A. Farnsworth2, G. Emily2, P. Macdonald2, A.R. Glanville2 1Freeman Hospital, Newcastle upon Tyne, Northumbria, United Kingdom; 2St Vincents Hospital, Sydney, NSW, Australia Purpose: Donation after cardiac death (DCD) has potential to expand the current limited donor pool in Australia. We illustrate the challenges of starting such a programme and show our early results. Methods and Materials: Institutional guidelines were created to encompass potential ethical and legal issues with DCD lung transplantion, and an education programme initiated for hospital staff and donor coordinators. Initially all donors had elective withdrawal of ventilation (Maastricht III) in ITU or the operating room. No donor treatment of any kind was permitted. Our technique involved inflation of the lungs with FiO2 0.4 after re-intubation. Chest was opened simultaneously with the abdomen, and lungs were assessed prior to flushing antegrade and retrograde with cold Celsior/GTN mix. Implantation and postoperative management was as per our standard protocol for all lung transplants. Results: Since November 2007 lungs were transplanted from 5 DCD donors with a mean age of 46 (range 33-56). Cause of death was traumatic head injury (n⫽3) and subarachnoid haemorrhage (n⫽2). The 5 recipients had a mean age of 42 (range 22-61). Indications for lung transplant were emphysema, primary pulmonary hypertension and late graft failure after lung transplant. Mean time to asystole after withdrawal of treatment was 14 minutes (range 10-19). Mean warm ischaemic time was 22 minutes (range 12-31). Mean total ischaemic time was 231 minutes (range 184-275). Early function was excellent with mean PO2 on the 1st postoperative day of 100 (range 64 to 136)
Abstracts
S103
on FiO2 0.4. Mean length of ITU stay was 6 days (range 3-10) and time to discharge 30 days (range 25-36). There was no mortality. Conclusions: Our initial experience in this new venture to expand our donor pool taught us some key principles in setting up such a programme and our preliminary results demonstrate the safety of this technique. 108 NHBD Meet the Standard of HBD Regarding Early Outcome after LTx S. De Vleeschauwer, D. Van Raemdonck, B. Vanaudenaerde, R. Vos, G. Verleden Katholieke Universiteit Leuven, Leuven, Belgium Purpose: The use of non-heart beating donors (NHBD) to overcome donor organ shortage is moving into the clinic. In 2007, we performed 5 lung transplantations (LTx) with lungs from NHBD (10%). Previously it has been shown that brain death can upregulate IL8-inducing cytokines like IL6 in the peripheral organs. Elevated levels of IL8, associated with brain death, were demonstrated to correlate inversely with the oxygenation capacity of the graft. The aim of this study was to investigate if NHBD meet up with standard heart-beating donors (HBD) at the early (neutrophilic) inflammatory levels. Methods and Materials: Each NHBD LTx recipient was compared with 2 age, gender, underlying disease and time of surgery matched HBD controls. Primary graft dysfunction (PGD) was assessed at 0, 6, 12, 24 and 48 hours after LTX. Broncho-alveolar lavage (BAL) was performed on post-operative day (POD) 1, 21, 90 and 180 and total and differential cell counts were performed. IL8, IL6 and TGF in BAL were assessed by ELISA. Results: No significant differences between the NHBD and the control HBD group in PGD grades (Figure 1), neutrophil % nor IL8, IL6 and TGF levels (table 1) were seen. Conclusions: The early outcome after NHBD and HBD is comparable and therefore NHBD are a valid tool to increase the donor pool.
109 Heart-Lung Transplantation: A Single Center Experience with 152 Cases E. Fadel, O. Mercier, S. Mussot, D. Fabre, J. Cerrina, F. LeRoy Ladurie, P. Dartevelle Hopital Marie Lannelongue, Le Plessis Robinson, France Purpose: To determine factors affecting early and long-term outcome after heart-lung transplantation (HLT) in a single center experience. Methods and Materials: From 1986 to 2007, 152 HLT were performed in 151 patients using the same surgical technique. Indicationswere primary pulmonary hypertension (PH) (n⫽75), secondary