SERUM TUMOR-NECROSIS-FACTOR-ALPHA DOES NOT MEDIATE ENDOTOXIN-INDUCED MYOCARDIAL DEPRESSION IN RABBITS

Tumor necrosis factor-alpha (TNF-alpha) is an endogenous mediator for several effects of endotoxin. To evaluate whether TNF-alpha mediates e ndotoxin-induced left ventricular (LV) dysfunction, we measured LV fun ction (sonomicrometers) and serum TNF-alpha (cytolytic assay) in anest hetized rabbits given endotoxin (100 mu g/kg iv). In the control group (n = 8), systolic depression (defined by a >10% increase in end-systo lic volume at a matched end-systolic pressure) developed in four rabbi ts and diastolic dilation (>10% increase in end-diastolic volume at a matched end-diastolic pressure) developed in three rabbits. Neither th e increase in end-systolic volume nor the increase in end-diastolic vo lume correlated with the increase in TNF-alpha, which reached a peak o f 2,875 +/- 762 U/ml. In a second group of rabbits (n = 7), a goat pol yclonal anti-rabbit antibody to TNF-alpha was given 30-60 min before e ndotoxin. Anti-TNF-alpha antibody alone did not alter LV function. Alt hough the TNF-alpha response to endotoxin was effectively blunted (pea k TNF-alpha remained <100 U/ml), all seven rabbits developed systolic depression (P = 0.08 compared with control group) and diastolic dilati on (P = 0.03). We conclude that serum TNF-alpha does not mediate endot oxin-induced LV systolic depression or diastolic dilation in this mode l.