ANTITUMOR NECROSIS FACTOR-ALPHA PREVENTS DECREASED VENTRICULAR CONTRACTILITY IN ENDOTOXEMIC PIGS

It is not known how the decrease in left ventricular contractility fol lowing endotoxin exposure is mediated, or whether this decrease is pre ventable by antibodies to tumor necrosis factor-alpha (TNF alpha). Fou r groups of six anesthetized and instrumented pigs were pretreated wit h ovine polyclonal antibody to human TNF alpha (anti-TNF alpha), nonsp ecific IgG, or saline, and then treated with either endotoxin or salin e. We measured hemodynamics and left ventricular pressures (Millar cat heter) and volumes (conductance catheter). Left ventricular contractil ity was assessed using the slope (E(max)) of the end-systolic pressure -volume relationship. Four hours after the start of endotoxin infusion In the nonspecific IgG pretreated group, E(max) had decreased by 44 /- 6% (p < 0.05), mean arterial pressure had decreased from 115 +/- 7 mm Hg to 70 +/- 10 mm Hg (p < 0.05), and cardiac output was rapidly de creasing after an initial increase (p < 0.05). Anti-TNF alpha signific antly reduced the decrease in E(max) (11 +/- 9%, p < 0.05), and the sy stemic hypotension (108 +/- 15 mm Hg to 99 +/- 6 mm Hg, p < 0.05), at 4 h, and prevented the late decrease in cardiac output. This suggests that TNF alpha is an important early mediator in sepsis leading to dec reased left ventricular contractility.