Pentoxifylline maintains hepatocellular function and improves cardiac performance during early sepsis

Although pentoxifylline (PTX) produces various beneficial effects after endotoxemia, it remains unknown whether this agent attenuates the depressed hepatocellular function and improves heart performance during early sepsis. The aim of this study, therefore, was to determine whether PTX maintains hepatocellular function and improves cardiac function during the early hyperdynamic stages of polymicrobial sepsis.

Rats were subjected to sepsis by cecal ligation and puncture (CLP). At 1 hour after CLP, PTX (50 mg/kg body weight), or an equal volume of saline, was infused intravenously over 30 minutes. At 2 or 5 hours after CLP (i.e., early hyperdynamic stages of sepsis), hepatocellular function was assessed by in vivo indocyanine green clearance. Cardiac output was determined by dye dilution. Left ventricular performance parameters such as maximal rates of left ventricular pressure rise and fall (+/-dP/dtmax), ventricular peak systemic pressure, etc., were determined using a heart performance analyzer.

The results indicate that hepatocellular function was significantly depressed at 2 and 5 hours after CLP. Administration of PTX, however, maintained hepatocellular function to sham levels. Although cardiac output increased after CLP with or without PTX treatment, this agent markedly improved cardiac performance as evidenced by significantly higher + dP/dtmax and ventricular peak systemic pressure as well as other heart performance parameters.

Pentoxifylline appears to be a useful adjunct for maintaining hepatocellular function and improving cardiac performance during the early hyperdynamic stages of polymicrobial sepsis.