ObjectivesWe hypothesized that tumor necrosis factor-alpha (TNF-alpha) acutely alters left ventricular mechanoenergetics in blood-perfused hearts. To test this hypothesis, we examined the relation between left ventricular mechanics and energetics, both before and after infusion of TNF-alpha.DesignProspective, experimental study.SettingResearch laboratory.SubjectsNine isolated, blood-perfused canine hearts.InterventionsRecombinant human TNF-alpha (90 [micro sign]g/min) was infused into the coronary circulation of the isolated hearts for 20 mins.Measurements and Main ResultsIn the isolated, cross-circulated, blood-perfused canine left ventricles, left ventricular contractility was assessed through measurement of end-systolic elastance (Ees). Energetics were examined in terms of the end-systolic pressure-volume area-myocardial oxygen consumption (MVO21000 ng/mL throughout the experiments. Nevertheless, infusion of TNF-alpha barely affected contractility acutely, i.e., there was a minimal decrease during the infusion (8.1 +/- 2.8% at 10 mins, p < .01) and a minimal increase after the infusion (11.2 +/- 2.5% at 10 mins, p < .01). Neither did the TNF-alpha infusion affect the slope of the end-systolic pressure-volume area-MVO (2) relation. This finding indicated that the chemomechanical conversion efficiency remained unchanged. However, TNF-alpha infusion significantly increased the oxygen cost of contractility by 40% (1.25 +/- 0.13 vs. 1.75 +/- 0.24 mL oxygen[center dot]mL/mm Hg/beat, p < .05), indicating that MVO2for the excitation-contraction coupling increased.ConclusionsTNF-alpha minimally alters left ventricular mechanics, but significantly changes energetics. The latter effect may result from changes in intracellular calcium handling. (Crit Care Med 1999;27:168-176)