American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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Lung transplantation is the treatment of choice for end-stage pulmonary diseases. A limited donor supply has resulted in 4,000 patients on the waiting list. Currently, 10-20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15-25% fail due to primary graft dysfunction (PGD). ⋯ From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress-activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD.
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Renal dysfunction is frequently seen after orthotopic liver transplantation (OLT). Aprotinin is an antifibrinolytic drug which reduces blood loss during OLT. Recent studies in cardiac surgery suggested a higher risk of postoperative renal complications when aprotinin is used. ⋯ No differences in renal function were noted at 30 and 365 days postoperatively. Moreover, no significant differences were found in the need for renal replacement therapy (OR = 1.52, 95% CI = 0.94-2.46; p = 0.11) or in 1-year patient survival rate (OR = 1.14, 95% CI = 0.73-1.77; p = 0.64) in patients who received aprotinin or not. In conclusion, aprotinin is associated with a higher risk of transient renal dysfunction in the first week after OLT, but not with a higher need for postoperative renal replacement therapy or an increased risk of mortality.
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Carbon monoxide (CO) provides protection against oxidative stress via anti-inflammatory and cytoprotective actions. In this study, we tested the hypothesis that a low concentration of exogenous (inhaled) CO would protect transplanted lung grafts from cold ischemia-reperfusion injury via a mechanism involving the mitogen-activated protein kinase (MAPK) signaling pathway. Lewis rats underwent orthotopic syngeneic or allogeneic left lung transplantation with 6 h of cold static preservation. ⋯ The beneficial effects of CO were associated with p38 MAPK phosphorylation and were significantly prevented by treatment with a p38 MAPK inhibitor, suggesting that CO's efficacy is at least partially mediated by activation of p38 MAPK. Furthermore, CO markedly suppressed inflammatory events in the contralateral naïve lung. This study demonstrates that perioperative exposure of donors and recipients to CO at a low concentration can impart potent anti-inflammatory and cytoprotective effects in a clinically relevant model of lung transplantation and support further evaluation for potential clinical use.