Serum but not myocardial TNF-alpha concentration is increased in pacing-induced heart failure in rabbits.
In animals and patients with severe heart failure (HF), the serum tumor necrosis factor-alpha (TNF-alpha) concentration is increased. It is, however, still controversial whether or not such increased serum TNF-alpha originates from the heart itself or is of peripheral origin secondary to gastrointestinal congestion and increased endotoxin concentration. We therefore now examined TNF-alpha 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-alpha 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-alpha was located mainly in the vascular endothelium (immunohistochemistry), and TNF-alpha protein (920 +/- 160 vs. 900 +/- 95 U/g) did not differ between groups. In the liver of HF rabbits, hepatocytes expressed TNF-alpha, and TNF-alpha 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-alpha (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-alpha is increased. The increased serum TNF-alpha originates from peripheral sources.
Institute of Pathophysiology, University of Essen Medical School, 45122 Essen, Germany.
Stephanie
S
Aker
Sergej
S
Belosjorow
Ina
I
Konietzka
Alexej
A
Duschin
Claus
C
Martin
Gerd
G
Heusch
Rainer
R
Schulz
D000818:Animals; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004731:Endotoxins / Q000378:metabolism; D006333:Heart Failure / Q000097:blood* / Q000378:metabolism*; D006439:Hemodynamics; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha