TIME-COURSE OF SYSTEMIC AND RENAL PLASMA PROSTANOID CONCENTRATIONS AND RENAL-FUNCTION IN OVINE HYPERDYNAMIC SEPSIS

1. We continuously recorded systemic and renal haemodynamic changes, a nd arterial, renal venous and urinary concentrations of thromboxane B- 2, 6-keto-prostaglandin F-1 alpha and prostaglandin E(2), and determin ed their relationship to renal function in an ovine model of progressi ve hyperdynamic sepsis. 2. Nine chronically instrumented unanaesthetiz ed sheep were given a continuous intravenous infusion of Escherichia c oli endotoxin (20 ng min(-1) kg(-1)) for 3 days. 3. Within the first 1 2 h of infusion, endotoxin induced a major hypotensive septic syndrome , including a persistent 30% reduction in mean arterial pressure, a 50 % decrease in systemic vascular resistance and a 50% increase in mean pulmonary artery pressure, associated with severe lactacidaemia. 4. Pe nal blood flow decreased by 40%, and creatinine clearance, urine flow, and fractional sodium excretion decreased by more than 75%, of baseli ne values. After 12 h of endotoxin infusion, cardiac output increased two-fold and renal blood flow recovered to baseline values, whereas cr eatinine clearance remained depressed. Four sheep died between 13 and 22 h of endotoxaemia; these animals (allocated to group 1) presented a significantly and persistently more reduced renal blood flow (- 23%) and creatinine clearance (- 77%) after 4 h than the remaining five she ep (allocated to group 2), which survived more than 36 h (- 16% and - 21%, respectively), whereas systemic and pulmonary haemodynamic and ga s exchange data remained similar in both groups. 5. The more pronounce d decreases in renal blood flow, creatinine clearance and urine flow i n group 1 were associated with higher plasma renin activity and plasma 6-keto-prostaglandin F-1 alpha concentrations and a lower fractional urinary excretion of 6-keto-prostaglandin F-1 alpha than in group 2, w hereas plasma thromboxane B-2 concentrations were similarly increased in both groups. Plasma prostaglandin E(2) concentrations and urinary e xcretion were not notably affected by endotoxin infusion in either gro up. 6. Our results are not in favour of a significant renal production of any of these three prostanoids during endotoxaemia. In both groups , values of creatinine clearance were linearly correlated with simulta neous mean arterial pressure values after starting endotoxin infusion (group 1: creatinine clearance = 1.99 x mean arterial pressure-105, r = 0.95; group 2: creatinine clearance = 2.06 x mean arterial pressure - 104, r = 0.80). 7. These findings indicate that during continuous en dotoxin administration in sheep (1) the renal haemodynamic and functio nal responses are biphasic, (2) severe impairment of renal function is associated with elevated plasma renin activity and 6-keto-prostagland in F-1 alpha plasma concentrations and with early fatality, and (3) re nal filtration capacity directly depends on renal perfusion pressure, suggesting a loss of renal filtration autoregulation during endotoxaem ia.