Acute lung injury after hepatic cryoablation:: Correlation with NF-κB activation and cytokine production

被引:54
作者
Blackwell, TS [1 ]
Debelak, JP [1 ]
Venkatakrishnan, A [1 ]
Schot, DJ [1 ]
Harley, DH [1 ]
Pinson, CW [1 ]
Williams, P [1 ]
Washington, K [1 ]
Christman, JW [1 ]
Chapman, WC [1 ]
机构
[1] Vanderbilt Univ, Med Ctr, Div Hepatobiliary Surg & Liver Transplantat Patho, Nashville, TN 37232 USA
关键词
D O I
10.1016/S0039-6060(99)70093-0
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Previous clinical reports have documented multisystem organ injury after hepatic cryoablation. We hypothesized that hepatic cryosurgery, but not partial hepatectomy, induces a systemic inflammatory response characterized by distant organ injury and overproduction of nuclear factor kappa B (NF-kappa B)-dependent, proinflammatory cytokines. Methods. In this study, rats underwent either cryoablation of 35% of liver parenchyma or a similar resection of left hepatic tissue. Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels and NF-kappa B activation were assessed by electrophoretic mobility shift assay at 30 minutes 1, 2, 6, and 24 hours after either procedure. Results, Cryoablation of 35% of liver (n = 22 rats) resulted in lung injury and a 45% mortality rate within 24 hours of surgery, whereas 7% treated with 35% hepatectomy (n = 15 rats) died during the 24 hours after surgery (P <.05, cryoablation vs hepatectomy). Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels were markedly increased in rats (n = 10 rats) 1 hour after hepatic cryoablation compared with rats that underwent partial hepatectomy (P <.005). We evaluated NF-kappa B activation by electrophoretic mobility shift assay in nuclear extracts of liver and lung after cryosurgery and found that NF-kappa B activation was strikingly increased in the liver but not the lung at 30 minutes and in both organs 1 hour after cryosurgery, and returned to baseline in both organs by 2 hours. In rats undergoing 35% hepatectomy, no increase in NF-kappa B activation was detected in nuclear extracts of either liver or lung at any time point. Conclusions. These data show that hepatic cryosurgery results in systemic inflammation with activation of NF-kappa B and increased production of NF-kappa B-dependent cytokinetics. Our data suggest that lung injury and death in this animal model is mediated by an exaggerated inflammatory response to cryosurgery.
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页码:518 / 526
页数:9
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