Hepatic cryoablation-induced acute lung injury: Histopathologic findings

We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ i njury and overproduction of NF-kappaB-dependent cytokines. Serum tumor necr osis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with part ial hepatectomy where no elevation occurs. NF-kappaB activation (by electro phoretic mobility shift assay) is strikingly increased in the noncryo fiver (but not in the lung) at 30 min and in both the liver and lung tissue Ih a fter cryo, returning to the baseline by 2 h and beyond. The current study i nvestigated the histopathologic changes associated with cryoablation-induce d acute lung injury. Animals underwent 35% hepatic resection or a similar v olume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary hist ologic features were assessed using hematoxylin and eosin and immunoperoxid ase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilu tion, Dako, Carpinteria, CA). The following features were graded semiquanti tatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary f indings after hepatic cryo (n = 22) included prominent perivascular lymphoi d cuffs 1 and 2 h following hepatic injury that were not present at any oth er time point (P 0.01). Marginating PMNs and foamy macrophages were more co mmon after cryo at all time points (P < 0.05, cryo vs resection). Severe lu ng injury, as evidenced by airspace edema and parenchymal hemorrhage, was p resent in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo-treated liver prior to thawing pre vented the pulmonary changes. The findings of pulmonary perivascular inters titial macrophages 2 h following hepatic cryo suggests that hepatic cytokin e production may induce downstream recruitment of pulmonary macrophages, wh ich may contribute to subsequent severe lung injury. This study suggests th at a soluble mediator from direct liver injury leads to neutrophilic lung i nflammation and this is associated with the thawing phase of cryoablation. (C) 2000 Academic Press.