Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs.
Whether systolic contractility or diastolic compliance changes soon after tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Accordingly, we measured hemodynamics, left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diastolic pressure-volume relationships in six control dogs and in six dogs receiving 60 micrograms.kg-1.h-1 i.v. of TNF-alpha. Mean aortic pressure decreased by 22% 1 h after TNF-alpha infusion and remained decreased (P < 0.05). Cardiac output increased by 19% 1 h after TNF-alpha infusion and remained significantly greater than control values (P < 0.05). Left ventricular contractility decreased by 23% (P < 0.05) 1 h after TNF-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha infusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not change after TNF-alpha infusion despite the decrease in contractility because afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new finding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator released very soon after TNF-alpha, is an important myocardial depressant factor.
Walley
K R
KR
Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Hebert
P C
PC
Wakai
Y
Y
Wilcox
P G
PG
Road
J D
JD
Cooper
D J
DJ
D000818:Animals; D001784:Blood Gas Analysis; D003864:Depression, Chemical; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D009200:Myocardial Contraction / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D014409:Tumor Necrosis Factor-alpha