PENTOXIFYLLINE RESTORES CARDIAC-OUTPUT AND TISSUE PERFUSION AFTER TRAUMA-HEMORRHAGE AND DECREASES SUSCEPTIBILITY TO SEPSIS

Background. Although pentoxifylline produces various beneficial effect s in a preheparinized model of hemorrhagic shock, it was unknown wheth er this agent restores the depressed cardiac output (CO) and tissue pe rfusion in a nonheparinized model of trauma-hemorrhage and resuscitati on and, if so, whether it decreases the susceptibility to sepsis after hemorrhage. Methods. After laparotomy (i.e., induction of trauma), ra ts were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form o f Ringer's lactate. The animals were then resuscitated with Ringer's l actate, four times the volume of shed blood. Pentoxifylline (50 mg/kg body weight) or normal saline solution was infused intravenously more than 95 minutes during and after resuscitation. At 1.5 and 4 hours aft er resuscitation, CO, tissue perfusion, and plasma liver enzyme levels were determined. Sepsis was induced by cecal ligation and puncture at 20 hours after hemorrhage, and the necrotic cecum was excised 10 hour s thereafter. Results. CO and tissue perfusion in the liver, kidney, s pleen, and small intestine decreased significantly after hemorrhage an d resuscitation. Pentoxifylline treatment, however, restored the depre ssed CO and tissue perfusion. The elevated liver enzyme levels were al so significantly reduced by pentoxifylline treatment. Moreover, pentox ifylline prevented the increased mortality of posthemorrhaged rats sub jected to sepsis. Conclusions. Because pentoxifylline restored the dep ressed CO and tissue perfusion and decreased the susceptibility to sep sis, this agent appears to be a useful adjunct to crystalloid resuscit ation after trauma and hemorrhage, even in the absence of blood resusc itation.