A Rat Model of Early Sepsis: Relationships between Gentamicin Pharmacokinetics and Systemic and Renal Effects of Bacterial Lipopolysaccharide Combined with Interleukin-2
Abstract
The study describes a model of early sepsis induced in Wistar rats by a bolus injection of bacterial lipopolysaccharide (LPS) combined with interleukin-2 (IL-2). Both the separate and combined effects of LPS+IL-2 and gentamicin (GE) on glomerular filtration rate (GFR), tubular function and plasma biochemical parameters were evaluated.
The major characteristics of the model are as follows: systemic microvascular leakage, a drop in GFR with only partially preserved tubular compensatory mechanisms, unchanged renal morphology, histologically proven pulmonary injuries and splenic alterations - signs of activation. In the range of therapeutic steady-state concentrations maintained over 3 hours, GE does not reduce GFR either in nonseptic or LPS+IL-2-treated rats.
This is in contrast to its marked decrease due to the effect of LPS+IL-2 alone. An enlarged distribution volume and half-life along with a drop in renal clearance of GE proportional to that of GFR are the remarkable changes of GE disposition in this model.
Nonrenal routes which, for the most part, compensate the reduced renal CL of GE in septic animals deserve further study.