Etanercept reduces late endotoxin-induced pulmonary hypertension in the pig.
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.
Mutschler
D
D
Department of Anesthesiology & Intensive Care, University Hospital, S-751 85, Uppsala, Sweden.
Wikström
G
G
Lind
L
L
Larsson
A
A
Lagrange
A
A
Eriksson
M
M
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015150:Echocardiography, Doppler; D004731:Endotoxins / Q000494:pharmacology*; D000068800:Etanercept; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D010919:Placebos; D011446:Prospective Studies; D011897:Random Allocation; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014655:Vascular Resistance / Q000502:physiology
D004731:Endotoxins; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010919:Placebos; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept