Acute effect of tumor necrosis factor-α is minimal on mechanics but significant on energetics in blood-perfused canine left ventricles

Objectives: We 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. Design: Prospective, experimental study. Setting: Research laboratory. Subjects: Nine isolated, blood-perfosed canine hearts. Interventions: Recombinant human TNF-alpha (90 mu g/min) was infused into the coronary circulation of the isolated hearts for 20 mins. Measurements and Main Results: In 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 (MVo(2)) relation. TNF-alpha concentration in coronary venous blood was >1000 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 mt oxygen.mL/mm Hg/beat, p<.05), indicating that MVo(2) for the excitation-contraction coupling increased. Conclusions: TNF-alpha minimally alters left ventricular mechanics, but significantly changes energetics. The latter effect may result from changes in intracellular calcium handling.