EARLY HEMODYNAMIC AND RENAL EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA - ROLE OF THROMBOXANE

TNF alpha is an early mediator of endotoxemic shock. Its acute effect on renal hemodynamics is not known. In this study, the early hemodynam ic and renal effects of TNF alpha were investigated in a rabbit model of shock, in which the measurement of the aortic blood flow before the bifurcation of the renal arteries allows one to differentiate between prerenal factors and hemodynamic renal response. Six groups of rabbit s were studied, receiving either: (1) endotoxin, (2) endotoxin + throm boxane inhibitor Dazmegrel(R) (3) TNF alpha, (4) TNF alpha + Dazmegrel (R), (5) TNF alpha + indomethacin, or (6) placebo. Between 60 min and 3 hr after the injection, endotoxin induced a mean fall in arterial pr essure of 32% (P<0.01) and TNF(alpha of 16% (P<0.01). After endotoxin, the aortic blood flow decreased by 27% (P<0.01) and after TNF alpha b y 18% (P<0.001). Both specific thromboxane inhibition and indomethacin abolished the TNF alpha central hemodynamic effect. The renal blood f low (-53%), the renal fraction of the aortic blood flow (-38%), and th e glomerular filtration rate (-47%, P<0.05) decreased 1 hr after endot oxin injection. In contrast, TNF alpha induced only a slight fall of t he renal fraction of the aortic blood flow (-19%) after 2.5 hr. Glomer ular filtration was not modified after TNF alpha injection most likely because of a 17% mean increase of filtration fraction in this group ( P<0.001). These data indicate that TNF alpha is implicated in the earl y hemodynamic changes of endotoxemic shock. In contrast, the renal mod ifications of the parameters observed after TNF alpha injection were m ainly secondary to the hemodynamic changes, and the autoregulation of the kidney was preserved. The integrity of the arachidonate cascade sy stem is required for the early TNF alpha hemodynamic effect. (C) 1994 Wiley-Liss, Inc.