DECREASE IN LEFT-VENTRICULAR CONTRACTILITY AFTER TUMOR-NECROSIS-FACTOR-ALPHA INFUSION IN DOGS

Decrease in left ventricular contractility after tumor necrosis factor -alpha infusion in dogs. J. Appl. Physiol. 76(3): 1060-1067, 1994. - W hether systolic contractility or diastolic compliance changes soon aft er tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Acco rdingly, we measured hemodynamics left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diast olic pressure-volume relationships in six control dogs and in six dogs receiving 60 mu g.kg(-1).h(-1) iv 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 infusio n and remained significantly greater than control values (P < 0.05). L eft ventricular contractility decreased by 23% (P < 0.05) 1 h after TN F-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha i nfusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not ch ange after TNF-alpha infusion despite the decrease in contractility be cause afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new f inding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator releas ed very soon after TNF-alpha, is an important myocardial depressant fa ctor.