Pentoxifylline improves bacterial clearance during hemorrhage and endotoxemia

Objective: The aim of this study was to investigate whether the methylxanth ine-derivative pentoxifylline (PTX) affects bacterial clearance of the orga nism 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) CF O) of Escherichia coil bacteria were injected intravenously into anesthetiz ed rabbits, 60 mins after induction of hemorrhage (n = 9 + 3) or infusion o f endotoxin (lipopolysaccharide [LPS]; 40 mu g/kg/hr; n = 9 + 3) and after saline infusion (control; n = 9), respectively. Hemorrhage was induced by b leeding, standardized by defined reduction of mean arterial pressure (30% o f baseline value). To evaluate the potential effects of PTX on bacterial el imination and killing, in states of hemorrhage and endotoxemia, blood clear ance of E. coli and colonization of different organs were investigated afte r pretreatment with PTX (30 mg/kg) as a bolus injection followed by continu ous infusion of PTX (50 mg/kg/hr) in hemorrhagic (n = 9) and endotoxemic ra bbits (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 inje ction, 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 clearanc e was associated with a significantly (p <.01) higher bacterial colonizatio n of all organs, which was most pronounced in the lung. Pretreatment with P TX slightly enhanced blood clearance of E; coli as well as of LPS, and sign ificantly reduced (p <.05) the colonization of lung and kidney after hemorr hage and endotoxemia. Furthermore, PTX suppressed polymorphonuclear neutrop hil 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 he morrhage and endotoxemia.