Serum tumor necrosis factor [alpha] does not mediate endotoxin
-induced myocardial depression in rabbits.
Nishikawa, Yasuhiro, John Mathison, and Wilbur Y. W. Lew.
Cardiology Division, Department of Medicine, Department of Veterans
Affairs Medical Center and University of California, San Diego, San
Diego, California 92161, Department of Immunology, Scripps Research
Institute, 10666 N. Torrey Pines Road, La Jolla, California 92037
APStracts 2:0338H, 1995.
Tumor necrosis factor[alpha] (TNF[alpha]) is an endogenous mediator
for several effects of endotoxin. To evaluate if TNF[alpha] mediates
endotoxin-induced left ventricular (LV) dysfunction, we measured LV
function (sonomicrometers) and serum TNF[alpha] (cytolytic assay) in
anesthetized rabbits given 100 [mu]g/kg i.v. endotoxin. In the
control group (n=8), systolic depression (defined by a >10%
increase in end-systolic volume at a matched end-systolic pressure)
developed in four rabbits and diastolic dilation (>10% increase
in end-diastolic volume at a matched end-diastolic pressure)
developed in three rabbits. Neither the increase in end-systolic nor
end-diastolic volume correlated with the increase in TNF[alpha],
which reached a peak of 2875 +/- 762 (S.E.) U/ml. In a second group
of rabbits (n=7), a goat polyclonal anti-rabbit antibody to
TNF[alpha] was given 30-60 minutes before endotoxin. Anti-TNF[alpha]
antibody alone did not alter LV function. Although the TNF[alpha]
response to endotoxin was effectively blunted (peak TNF[alpha]
remained <100 U/ml), all seven rabbits developed systolic
depression (p=0.08 compared with control group) and diastolic
dilation (p=0.03). We conclude that serum TNF[alpha] does not mediate
endotoxin-induced LV systolic depression nor diastolic dilation in
this model.
Received 10 March 1995; accepted in final form 17 July 1995.
APS Manuscript Number H230-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.