The effects of inhaled nitric oxide, gabexate mesilate, and retrograde flush in the lung graft from non-heart beating minipig donors

Background The use of lung grafts from non-heart-beating donors (NHBD) is o ne way of solving the donor organ shortage problem. In this experiment, we studied the effect of retrograde flush (RF) from the left atrium before har vest, inhaled nitric oxide (NO), and gabexate mesilate (FOY), a protease in hibitor, in the lung grafts from NHBD, Methods. Forty-eight Lee-Sung, small-ear, miniature pigs (15-20 kg) were di vided into 24 pairs (donor and recipient) and four groups. The donor lungs were flushed and harvested 90 min after cardiac arrest. No i.v. heparin was administered until the time before flush and harvest. Left single lung tra nsplantation was undertaken, and the recipients were observed for 18 hr. Th e grafts warm and cold ischemia times were 90 (controlled) and 183+/-23.4 m in. Group 1 (untreated control, UC, n=6) had core perfusion through a Swan- Ganz catheter followed by a single, antegrade flush with modified Euro-Coll in's solution containing heparin, urokinase, and PGE1. Group 2 (RF group, n =6) had the same as group 1, except that one additive retrograde flush thro ugh the left atrium was administered. Group 3 (NO group, n=6) had the same as group 1, except that 20 parts per million (ppm) inhaled NO was administe red for the cadaver donors before the graft harvest, and for the recipients after the grafts reperfusion. Group 4 (FOY group, n=6) had the same as gro up 1, except that the recipients received FOY i.v. infusion from the beginn ing of the recipient's operation and continuously throughout the experiment s. Results. Compared with the group 1 (control), group 2 (RF) had significantl y (P<0.05) lower mean pulmonary artery pressure, pulmonary vascular resista nce (PVR), lung wet/dry ratio, histological lung injury score, and higher P aO2/FiO2 and pulmonary dynamic compliance. Group 3 (NO) had significantly l ower mean pulmonary arterial pressure, PVR, lung injury score, degree of ti ssue neutrophils infiltration (histological and myeloperoxidase assay), bro nchoalveolar lavage fluid protein content and neutrophils (PMNs) percentage , and higher PaO2/FiO2 and pulmonary dynamic compliance. Group 4 (FOY) had significantly lower PMNs infiltration, lung injury score, wet/dry ratio, br onchoalveolar lavage fluid protein and PMNs percentage, and higher PaO2/FiO 2, Group 2 (RF) revealed better gas exchange (PaO2/FiO2) than the control ( group 1) at earlier reperfusion periods (Ist and 5th hr), On the contrary, group 4 (FOY) had higher PaO2/FiO2 than group 1 only at later period (18th hr). Pathologically, retrograde flush (group 2, RF) inhibited the intravasc ular thrombi formation more effectively than the NO or FOY treatment. Howev er, the NO or FOY treatment inhibited the neutrophil infiltration more effe ctively than did the retrograde flush. Conclusion. The retrograde flush, inhaled NO and FOY infusion are beneficia l to the protection of the NHBD lung grafts at an early reperfusion period, through different mechanisms. The use of these treatments in combination m ight help us to find a better way to protect the NHBD grafts against the pr eservation and reperfusion injury.