EFFECTS OF TREATMENT WITH PENTOXIFYLLINE ON THE CARDIOVASCULAR MANIFESTATIONS OF GROUP-B STREPTOCOCCAL SEPSIS IN THE PIGLET

Pentoxifylline (PTXF) is a methylxanthine derivative which modifies le ukocyte function and inhibits tumor necrosis factor (TNF)-alpha releas e. As TNF-alpha is considered a proximal mediator in the cascade leadi ng to septic shock, we evaluated the ability of PTXF to attenuate the cardiovascular manifestations of sepsis secondary to an infusion of gr oup B beta-hemolytic streptococci (GBS). Fifteen anesthetized, mechani cally ventilated piglets (weight, 2815 +/- 552 g) were randomly assign ed to a treatment group which received a continuous infusion of PTXF ( 5 mg/kg/h) beginning 30 min after GBS (7.5 X 10(8) colony-forming unit s/kg/min) administration was started or to a control group which recei ved GBS plus saline as placebo. Comparison of the hemodynamic measurem ents and arterial blood gases over the first 120 min of bacterial infu sion for treatment and control groups revealed the following statistic ally significant differences (120-min values presented): cardiac outpu t was significantly higher in the PTXF group (0.159 +/- 0.035 versus 0 .09 +/- 0.026 L/kg/min; p < 0.05) as was stroke volume (0.54 +/- 0.11 versus 0.27 +/- 0.126 mL/kg/beat; p < 0.01). Pulmonary and systemic va scular resistances remained lower in the PTXF-treated animals (167 +/- 45 versus 233 +/- 69 mm Hg/L/kg/min; p < 0.03) and (427 +/- 162 versu s 828 +/- 426 mm Hg/L/kg/min; p < 0.03, respectively). Median survival time was significantly longer in the PTXF group (180 versus 120 min; p < 0.05). In an additional group of animals, PTXF administration befo re GBS infusion revealed no attenuation in the rise of TNF-alpha, acco mpanying sepsis. These data demonstrate that treatment with PTXF may a meliorate some of the deleterious hemodynamic manifestations of GBS se psis and result in improved survival in a young animal model without s ignificantly modifying plasma TNF-alpha levels.