Search

Background Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation. Methods A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups. Results No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm ( p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC. Conclusions RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.

Background Xenotransplantation could provide a solution to the donor shortage that is currently the major barrier to solid-organ transplantation. The ability to breed pigs with multiple genetic modifications provides a unique opportunity to explore the immunologic challenges of pulmonary xenotransplantation. Methods Explanted lungs from wild-type and 3 groups of genetically modified pigs were studied: (i) α1,3-galactosyltransferase gene knockout (GTKO); (ii) GTKO pigs expressing the human complementary regulatory proteins CD55 and CD59 (GTKO/CD55-59); and (iii) GTKO pigs expressing both CD55-59 and CD39 (GTKO/CD55-59/CD39). The physiologic, immunologic and histologic properties of porcine lungs were evaluated on an ex vivo rig after perfusion with human blood. Results Lungs from genetically modified pigs demonstrated stable pulmonary vascular resistance and better oxygenation of the perfusate, and survived longer than wild-type lungs. Physiologic function was inversely correlated with the degree of platelet sequestration into the xenograft. Despite superior physiologic profiles, lungs from genetically modified pigs still showed evidence of intravascular thrombosis and coagulopathy after perfusion with human blood. CONCLUSIONS The ability to breed pigs with multiple genetic modifications, and to evaluate lung physiology and histology in real-time on an ex vivo rig, represent significant advances toward better understanding the challenges inherent to pulmonary xenotransplantation.

s S237 Therapy (BTT) may include either medical or social criteria. We sought to find the rate at which patients who were originally implanted as DT candidates changed their classification to BTT. Methods: We reviewed charts of patients who received LVADS at our center as Destination Therapy between February, 2012 and September, 2014. There was a cohort of 56 patients during this timeframe. Patients who were implanted at other centers were not included in this review. Results: Of the fifty-six DT LVAD patients, six of twenty-two with elevated Body Mass Index eventually were listed for heart transplant (conversion rate 27%); five of thirteen patients who had active/recent smoking or other tobacco use were eventually listed (38%); two out of four patients with uncontrolled diabetes mellitus (50%) eventually met transplant criteria and were listed; two of three patients initially not candidates due to active or recent malignancy were cleared for listing; one of four patients with active or recent drug use (25%) later were listed; one of two patients within insufficient support established support after LVAD and were listed for transplant (50%); one patient who did not originally have sufficient insurance coverage did acquire it and was listed for transplant. Those DT patients who were implanted due to age, pulmonary hypertension or other end-organ dysfunction have not been listed for transplant. One patient transferred care after LVAD placement and was lost to followup. The average time from LVAD implant to listing was 150 days. Two of the patients who were listed after LVAD implant are currently inactive due to elevated BMI. Conclusion: For those with controllable factors such as elevated BMI, smoking, or diabetes control, there is an assumption that the patients can quickly modify these factors to enable transplant listing. This review showed that a large percentage of these patients do not. It also showed that some patients temporarily modify behaviors in order to be listed for transplant, but then later again become ineligible.

Prolonged Ex-Vivo Pulmonary Xenograft Function Using GeneticallyModified Porcine Donor Lungs G.P. Westall, B. Levvey, J. Gooi, M. Silvana, R. McEgan, M. Mennen, F. Rosenfeldt, G. Snell, P. Cowan. Lung Transplant Unit, Alfred Hospital, Melbourne, VIC, Australia; Department of Immunology, St Vincent’s Hospital, Melbourne, VIC, Australia; Department of Immunology, The University of Adelaide, Adelaide, SA, Australia.