MODULATION OF SKELETAL-MUSCLE LACTATE METABOLISM FOLLOWING BACTEREMIABY INSULIN OR INSULIN-LIKE GROWTH-FACTOR-I - EFFECTS OF PENTOXIFYLLINE

Hyperlactatemia is a frequent complication of sepsis. We investigated the effect of pentoxifylline on plasma lactate concentrations and lact ate release by epitrochlearis incubated in vitro following intravenous injection of Escherichia coil. Plasma lactate concentrations were ele vated on day 2 postinfection and remained elevated for at least anothe r 4 days. Lactate production by incubated epitrochlearis was not incre ased in septic rats on day 2 postinfection, and lactate production fro m muscles incubated with insulin (2 nM) or insulin-like growth factor- I, (10 nM) was similar in control and septic rats. On day 6 postinfect ion, lactate production was augmented 1.8-fold in muscles from septic rats and both insulin and IGF-I caused an exaggerated stimulation of l actate production compared with control. Pentoxifylline decreased plas ma TNF concentrations 100-fold following injection of bacteria, and pr evented the sepsis-induced hyperlactatemia and increase in lactate pro duction by incubated muscles in presence or absence of insulin or IGF- I. Thus, pentoxifylline prevented the sepsis-induced abnormalities in skeletal muscle lactate production and plasma lactate concentrations.