Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig

• Published in: Journal of interferon & cytokine research Vol. 26; no. 9; pp. 661 - 667
• Main Authors: Mutschler, D, Wikström, G, Lind, L, Larsson, A, Lagrange, A, Eriksson, M
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.09.2006
• Subjects: Animals; Blood Pressure - physiology; Echocardiography, Doppler; Endotoxins - pharmacology; Etanercept; Humans; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - drug therapy; Immunoglobulin G - therapeutic use; Immunosuppressive Agents - therapeutic use; MEDICIN; MEDICINE; Placebos; Prospective Studies; Random Allocation; Receptors, Tumor Necrosis Factor - therapeutic use; Swine; Tumor Necrosis Factor-alpha - metabolism; Vascular Resistance - physiology
• ISSN: 1079-9907; 1557-7465; 1557-7465
• DOI: 10.1089/jir.2006.26.661

To evaluate whether etanercept, a tumor necrosis factor (TNF)-blocking agent, may counteract hemodynamic deterioration in endotoxemic shock, we designed a prospective, randomized placebo-controlled trial with parallel groups, consisting of 13 pigs aged 10-14 weeks receiving general anesthesia. Five pigs were given 25 mg of etanercept, 1 h before the start of a 4-h continuous infusion of endotoxin. Another 5 pigs were given the corresponding volume of saline, 1 h before the start of a 4-h continuous infusion of endotoxin. Three pigs were given 25 mg of etanercept, 1 hr before the start of a 4-h continuous infusion of saline. At 1 h of endotoxemia, mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) increased identically in both groups of pigs receiving endotoxin. Thereafter, two distinct different patterns in hemodynamics were observed. TNF-blocked pigs showed significantly lower MPAP and PVRI compared to controls. In the etanercept-treated endotoxemic pigs, Doppler analysis of the diastolic mitral inflow demonstrated a significantly increased E/A-ratio (early mitral wave inflow was divided by the atrial wave) at 2 h. The TNFblocking agent etanercept normalized two hemodynamic features of endotoxin-induced septic shock in pigs: (1) the sustained pulmonary hypertension and (2) diastolic dysfunction.