Pentoxifylline improves bacterial clearance during hemorrhage and endotoxemia

Objective: The aim of this study was to investigate whether the methylxanthine-derivative pentoxifylline (PTX) affects bacterial clearance of the organism in states of hemorrhage and endotoxemia. Design: Prospective, randomized, controlled trial. Setting: Experimental laboratory in a university hospital. Subjects: Fifty-four female chinchilla rabbits. Interventions: To quantify the clearance process, defined numbers (10(7) CFO) of Escherichia coli bacteria were injected intravenously into anesthetized rabbits, 60 mins after induction of hemorrhage (n = 9 + 3) or infusion of endotoxin (lipopolysaccharide [LPS]; 40 mu g/kg/hr; n = 9 + 3) and after saline infusion (control; n = 9), respectively. Hemorrhage was induced by bleeding, standardized by defined reduction of mean arterial pressure (30% of baseline value). To evaluate the potential effects of PTX on bacterial elimination and killing, in states of hemorrhage and endotoxemia, blood clearance of E. coli and colonization of different organs were investigated after pretreatment with PTX (30 mg/kg) as a bolus injection followed by continuous infusion of PTX (50 mg/kg/hr) in hemorrhagic (n = 9) and endotoxemic rabbits (n = 9). Three additional experiments were performed to evaluate the effects attributable to PTX itself. Measurements and Main Results: Parameters monitored were rates of bacterial and LPS elimination from the blood, arterial blood pressure, blood gases, and serum lactate concentrations. Additionally, flow cytometric analysis of respiratory burst activity was performed. Three hours after bacterial injection, the animals were killed, and tissue samples of liver, kidney, spleen, and lung were collected for bacteriologic examinations. Compared with the controls, hemorrhage and endotoxemia resulted in a significantly prolonged elimination of injected E. coli from the blood. The delayed blood clearance was associated with a significantly (p <.01) higher bacterial colonization of all organs, which was most pronounced in the lung. Pretreatment with PTX slightly enhanced blood clearance of E; coli as well as of LPS, and significantly reduced (p <.05) the colonization of lung and kidney after hemorrhage and endotoxemia. Furthermore, PTX suppressed polymorphonuclear neutrophil respiratory burst activity. Conclusions: Hemorrhage and endotoxemia induce impaired bacterial clearance from blood and tissue. Treatment with PTX may reduce the risk of bacterial infections by attenuating bacterial colonization of organs in states of hemorrhage and endotoxemia.