5 years ago

Glycine intravenous donor preconditioning is superior to glycine supplementation to low-potassium dextran flush preservation and improves graft function in a large animal lung transplantation model after 24 hours of cold ischemia

The potential role of glycine in combination with standard lung preservation with low-potassium dextran solution in lung ischemia-reperfusion injury has not been investigated in a preclinical porcine transplant model. Methods In a control group (n = 6), donor lungs were flushed with 1 liter of low-potassium dextran solution. In a second group (LPD-glyc, n = 6), low-potassium dextran solution was supplemented with 3.75 g of glycine. In a third group (IV-glyc, n = 6), donor preconditioning was performed by intravenous administration of 3.75 g glycine 1 hour before low-potassium dextran preservation. Grafts were stored in low-potassium dextran at 4°C for 24 hours. Posttransplant graft function was assessed throughout a 7-hour observation period. Results In the control group, 2 recipients died of right-sided heart failure caused by severe ischemia-reperfusion injury. All animals of the glycine groups survived the entire observation period. Pulmonary vascular resistance remained significantly (P < .01) lower in both glycine groups when compared with controls. At the end of the observation period pulmonary vascular resistance in the control group was higher (P < .01) compared with the glycine groups (1310 ± 319 dyn × sec × cm−5 vs 879 ± 127 dyn × sec × cm−5 [LPD-glyc] vs 663 ± 191 dyn × sec × cm−5 [IV-glyc]). Changes of lung tissue water content were lower in the IV-glyc group compared with the LPD-control (P < .01) and LPD-glyc lungs (P < .05). Oxygenation (Po 2/Fio 2) was higher in the IV-glyc group compared with the LPD-glyc and control lungs (445 ± 110 mm Hg vs 388 ± 124 mm Hg [P < .01] vs 341 ± 224 mm Hg [P < .001], respectively). Discussion Modification of low-potassium dextran solution with glycine or donor preconditioning ameliorates ischemia-reperfusion injury in lung transplantation. This intriguing approach merits further evaluation with respect to the mechanisms involved and may improve results in clinical lung preservation.

Publisher URL: www.sciencedirect.com/science

DOI: S0022522305017988

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