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INFLAMMATION, CYTOKINES, AND TEMPERATURE REGULATION
concentration is increased in pacing-induced heart failure in rabbits
Institute of Pathophysiology, University of Essen Medical School, 45122 Essen, Germany
Submitted 26 March 2003 ; accepted in final form 8 May 2003
In animals and patients with severe heart failure (HF), the serum tumor
necrosis factor-
(TNF-
) concentration is increased. It is,
however, still controversial whether or not such increased serum TNF-
originates from the heart itself or is of peripheral origin secondary to
gastrointestinal congestion and increased endotoxin concentration. We
therefore now examined TNF-
in serum, myocardium, and liver of
sham-operated and HF rabbits. In nine rabbits in which HF was induced by left
ventricular (LV) pacing at 400 beats/min for 3 wk, LV end-diastolic diameter
was increased and systolic shortening fraction (9.4 ± 1.0 vs. 28.5
± 1.3%, echocardiography, P < 0.05) was reduced. Serum
TNF-
was higher in HF than in sham-operated rabbits (240 ± 24
vs. 150 ± 22 U/ml, WEHI-cell assay, P < 0.05). In the
heart, TNF-
was located mainly in the vascular endothelium
(immunohistochemistry), and TNF-
protein (920 ± 160 vs. 900
± 95 U/g) did not differ between groups. In the liver of HF rabbits,
hepatocytes expressed TNF-
, and TNF-
protein was increased
compared with sham-operated rabbits (2,390 ± 310 vs. 1,220 ± 135
U/g, P < 0.05) and correlated to the number of hepatic leukocytes
(r = 0.85) and serum TNF-
(r = 0.69). The intestinal
endotoxin concentration was 24.5 ± 1.2 vs. 17.0 ± 3.1 endotoxin
units/g wet wt (P < 0.05) in HF compared with sham-operated
rabbits. In this HF model, serum but not myocardial TNF-
is increased.
The increased serum TNF-
originates from peripheral sources.
liver; inflammation
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