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 hemodynamic 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 rabbits were studied, receiving either: (1) endotoxin, (2) endotoxin + thromboxane inhibitor Dazmegrel, (3) TNF alpha, (4) TNF alpha + Dazmegrel, (5) TNF alpha+indomethacin, or (6) placebo. Between 60 min and 3 hr after the injection, endotoxin induced a mean fall in arterial pressure 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 by 18% (P < 0.001). Both specific thromboxane inhibition and indomethacin abolished the TNF alpha central hemodynamic effect. The renal blood flow (-53%), the renal fraction of the aortic blood flow (-38%), and the glomerular filtration rate (-47%, P < 0.05) decreased 1 hr after endotoxin injection. In contrast, TNF alpha induced only a slight fall of the renal fraction of the aortic blood flow (-19%) after 2.5 hr. Glomerular 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 early hemodynamic changes of endotoxemic shock.(ABSTRACT TRUNCATED AT 250 WORDS)
Girardin
E
E
Department of Pediatrics, Hôpital des Enfants, Geneva, Switzerland.
Grau
G E
GE
Paunier
L
L
Le Coultre
C
C
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D011464:Epoprostenol / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology*
D004731:Endotoxins; D007093:Imidazoles; D013931:Thromboxanes; D014409:Tumor Necrosis Factor-alpha; C039242:dazmegrel; D011464:Epoprostenol; D007213:Indomethacin