(Circulation. 1999;100:1189-1193.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Decreased Expression of Tumor Necrosis Factor-
in Failing Human Myocardium After Mechanical Circulatory Support
A Potential Mechanism for Cardiac Recovery
From the Departments of Medicine, Section of Cardiology (G.T.-A., S.J.S., J.-B.D.) and Department of Surgery (G.P.N.), The DeBakey Heart Center (K.A.Y., M.L.E.), and The Winters Center for Heart Failure Research (G.T.-A.), Baylor College of Medicine and The Methodist Hospital; and The Texas Heart Institute (B.R., R.M.D., O.H.F.), Houston, Tex.
Background—An increasing number
of observations in patients with end-stage heart failure suggest that
chronic ventricular unloading by mechanical circulatory
support may lead to recovery of cardiac function. Tumor necrosis
factor-
(TNF-) is a proinflammatory cytokine capable of
producing pulmonary edema, dilated
cardiomyopathy, and death. TNF- is produced in
the myocardium in response to volume overload; however, the
effects of normalizing ventricular loading conditions on
myocardial TNF- expression are not known. We hypothesize that
chronic ventricular unloading by the placement of a left
ventricular assist device (LVAD) may eliminate the stress
responsible for persistent TNF- expression in human failing
myocardium.
Methods and Results—Myocardial tissue was obtained from normal
hearts and from paired samples of 8 patients with nonischemic
end-stage cardiomyopathy at the time of LVAD
implantation and removal. Tissue sections were stained for TNF-, and
quantitative analysis of the stained area was performed. We
found that TNF- content decreased significantly after LVAD support.
Furthermore, the magnitude of the changes did not correlate with the
length of LVAD support, although greater reductions in myocardial
TNF- content were found in patients who were successfully weaned off
the LVAD who did not require transplantation.
Conclusions—These data show for the first time that chronic
mechanical circulatory assistance decreases TNF- content in failing
myocardium; furthermore, we suggest that the magnitude of
the change may predict which patients will recover cardiac function.
Key Words: heart assist device • heart failure • tumor necrosis factor-
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