Early effect of hepatic artery TNF-[alpha] infusion on systemic hemodynamics and inflammation: a dose-response study in pigs

• Published in: International journal of colorectal disease 2010-04, Vol.25 (4), p.523
• Main Authors: Schäfer, Thilo, Sperling, Jens, Kollmar, Otto, Richter, Sven, Schilling, Ma, Menger, Michael D, Lindemann, Werner
• Format: Article
• Language: English
• Subjects: Analysis; Health aspects; Heart beat; Inflammation; Liver; Metastasis; Tumor necrosis factor
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-009-0827-7

Purpose Therapy of unresectable hepatic metastases may include tumor necrosis factor (TNF)-[alpha] treatment. Because of its serious systemic side effects, TNF-[alpha] is only used in isolated hepatic perfusion. This, however, is a technically demanding procedure with a substantial mortality rate. The infusion of TNF-[alpha] via the hepatic artery without hepatic isolation would be less invasive. Systemic side effects, however, have not been studied yet. Therefore, we evaluated in pigs the effects of TNF-[alpha] hepatic artery infusion (HAI) on systemic hemodynamics, inflammation, and organ injury. Methods Animals were randomized in three groups. In group 1, HAI was performed with 0.9% NaCl (n = 6). In group 2, 20 [micro]g/kg TNF-[alpha] (n = 6), and in group 3, 40 [micro]g/kg TNF-[alpha] (n = 6) were added. HAI was performed over 15 min, followed by 120 min of observation. Finally, 250 ml hydroxyethylstarch (HAES; 6%) was administered for resuscitation and hemodynamics were analyzed for another 30 min. Results Hepatic artery TNF-[alpha] infusion did not cause complications such as bleeding, cardiac depression, pulmonary dysfunction, or SIRS. TNF-[alpha] induced a 30% decrease of MAP and systemic vascular resistance, as well as a rise in heart rate and endexspiratory pCO.sub.2. TNF-[alpha] also moderately (10-20%) lowered the cardiac preload and induced a metabolic acidosis, which, however, could easily be controlled. TNF-[alpha] HAI did not induce liver toxicity, and all hemodynamic changes normalized either spontaneously within the 120-min observation period, or, at least, after HAES resuscitation. Conclusions TNF-[alpha]-based HAI, which may represent a minimally invasive alternative to isolated hepatic perfusion, can be performed without early systemic hemodynamic complications.