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2006 - UZ Leuven

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Conclusions: This study demonstrates for the first time that BALmacrophages and lymphocytes increase significantly during warmischemia and correlate with IL-1beta levels.GEUDENS N., VANAUDENAERDE B., NEYRINCK A., REGA F., VAN DEWAUWER C., VERLEDEN G., VERBEKEN E., VAN RAEMDONCK D.: N-Acetyl cysteine reduces inflammatory triggers in bal from mice lungfollowing warm ischemia and reperfusion. J. Heart Lung Transplant.,<strong>2006</strong>; 25: S 163 (347).Purpose: The warm ischemic period prior to cold preservation of nonheart-beatingdonor (NHBD) pulmonary grafts may increase the risk ofischemia reperfusion injury (IRI). Leukocytes and IL-1β are importanttriggers in the development of IRI. N-Acetyl Cysteine (NAC) is knownto be a potent anti-oxidant. We investigated the impact of NAC oninflammatory events in Broncho-Alveolar Lavage (BAL) in a mousemodel of in situ warm ischemia and reperfusion.Methods: Female SWISS mice were divided in 5 groups (n=6/group).After thoracotomy, the hilum of the left lung was clamped to inducewarm ischemia (I) for 90 minutes in all groups, except in SHAM, andfurther unclamped in 2 study groups for 4 hours of reperfusion (I + R).NAC (10mg/kg, 50µl) or Saline (50µl) were instilled endotracheally 15minutes before the onset of ischemia. After sacrifice, cell count and IL-1β levels were analyzed in BAL from the left lung.Results: (mean ±SD) are listed in Table. There was a positivecorrelation between IL-1β levels and the number of macrophages(r=0,73; p < 0.0001) as well as lymphocytes (r=0.63; p < 0.0001).GroupTotal cells Macrophages Lymphocytes Neutrophils IL-1β(n=6/group) (*10 4 /ml) (*10 4 /ml) (*10 4 /ml)(*10 4 /ml)SHAMSaline+INAC+ISaline + I + RNAC + I + R40.0 ± 7.2195.3 ± 25.1*46.5 ± 7.6*166.0 ±27.764.0 ±22.6 SS 35.7 ± 6.7151.6 ± 20.3*39.3 ±7.1 #119.5 ± 19.953.4 ± 20.0 SS 4.2 ±0.842.6 ± 11.3*7.0 ±1.8 #23.3 ± 7.07.9 ± 1.8 SS 0.4 ± 0.50.9 ±1.40.2 ±0.323.2 ± 9.43.2 ± 3.2 SS 58.6 ± 26.6208.9 ± 37.9*64.4 ± 13.4 #203.2 ± 48.499.0 ±20.5 S* p< 0.001 versus SHAM; # p < 0.001 vs Saline +I; S < 0.01 and SS p < 0.01 vs Saline + I + RConclusion: Administration of NAC attenuated the lymphocyticincrease during ischemia and the rise in neutrophils after reperfusion.Whether there is a biochemical trigger between lymphocytes andneutrophils needs to be further investigated. Preharvest treatment withNAC could be a promising tool to reduce IRI in NHBD lungtransplantation.101

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