Wang P, Ba Z F, Zhou M, Tait S M, Chaudry I H
Department of Surgery, Michigan State University, East Lansing 48824-1315.
Surgery. 1993 Aug;114(2):352-8; discussion 358-9.
Although pentoxifylline produces various beneficial effects in a preheparinized model of hemorrhagic shock, it was unknown whether this agent restores the depressed cardiac output (CO) and tissue perfusion in a nonheparinized model of trauma-hemorrhage and resuscitation and, if so, whether it decreases the susceptibility to sepsis after hemorrhage.
After laparotomy (i.e., induction of trauma), rats 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 of Ringer's lactate. The animals were then resuscitated with Ringer's lactate, 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 after 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 hours thereafter.
CO and tissue perfusion in the liver, kidney, spleen, and small intestine decreased significantly after hemorrhage and resuscitation. Pentoxifylline treatment, however, restored the depressed CO and tissue perfusion. The elevated liver enzyme levels were also significantly reduced by pentoxifylline treatment. Moreover, pentoxifylline prevented the increased mortality of posthemorrhaged rats subjected to sepsis.
Because pentoxifylline restored the depressed CO and tissue perfusion and decreased the susceptibility to sepsis, this agent appears to be a useful adjunct to crystalloid resuscitation after trauma and hemorrhage, even in the absence of blood resuscitation.
尽管己酮可可碱在肝素化的失血性休克模型中产生多种有益作用，但在非肝素化的创伤-出血和复苏模型中，该药物是否能恢复降低的心输出量（CO）和组织灌注，以及如果能恢复，它是否能降低出血后败血症的易感性尚不清楚。
剖腹术后（即创伤诱导），将大鼠放血并维持平均动脉压在40 mmHg，直到以乳酸林格液的形式回输40%的最大失血量。然后用四倍失血量的乳酸林格液对动物进行复苏。在复苏期间及复苏后超过95分钟静脉输注己酮可可碱（50 mg/kg体重）或生理盐水。在复苏后1.5小时和4小时，测定心输出量、组织灌注和血浆肝酶水平。在出血后20小时通过盲肠结扎和穿刺诱导败血症，此后10小时切除坏死的盲肠。
出血和复苏后，肝脏、肾脏、脾脏和小肠的心输出量和组织灌注显著降低。然而，己酮可可碱治疗可恢复降低的心输出量和组织灌注。己酮可可碱治疗还可显著降低升高的肝酶水平。此外，己酮可可碱可预防出血后遭受败血症的大鼠死亡率增加。
由于己酮可可碱可恢复降低的心输出量和组织灌注，并降低败血症的易感性，即使在没有血液复苏的情况下，该药物似乎也是创伤和出血后晶体液复苏的有用辅助药物。
