van Goor H, de Graaf J S, Kooi K, Sluiter W J, Bom V J, van der Meer J, Bleichrodt R P
Department of Surgery, University Hospital, Groningen, The Netherlands.
J Am Coll Surg. 1994 Oct;179(4):407-11.
During generalized peritonitis, intraabdominal fibrin deposition is stimulated whereas fibrinolytic activity is reduced, which predisposes intra-abdominal abscess formation. We investigated the effects of increasing the intra-abdominal fibrinolytic activity on abscess formation by intra-abdominal administration of recombinant tissue plasminogen activator (rt-PA). Potential side effects, such as bacteremia and bleeding, were also assessed.
A rat model of generalized peritonitis, induced by intraperitoneal injection of sterile feces contaminated with 10(4) cfu per mL Escherichia coli (E. coli) and 10(4) cfu per mL Bacteroides fragilis, was used.
Rats treated with rt-PA dissolved in methyl hydroxy propyl cellulose (MHPC) gel (0.5 mg per mL), had significantly less intra-abdominal abscesses than rats in the control group, treated with either Ringer's lactate solution or MHPC gel alone (p < 0.01). Other than E. coli, cultures of abscesses revealed species originating from the intestine, demonstrating bacterial translocation. The mortality rate was significantly higher in the rats treated with rt-PA as compared with rats in the control group (p < 0.01), which was surprising considering the absence of bacteremia. By challenging the rats with a higher dose of E. coli, early bacteremia was observed in the rats treated with rt-PA, not related to increased mortality rates. Intraabdominal use of rt-PA was not associated with an increased incidence of bleeding events.
Recombinant tissue plasminogen activator prevents abscess formation in rats with generalized peritonitis. However, early bacteremia and increased mortality rates are serious drawbacks of the intra-abdominal use of rt-PA in this rat model.
在弥漫性腹膜炎期间，腹腔内纤维蛋白沉积增加而纤溶活性降低，这易导致腹腔内脓肿形成。我们通过腹腔内给予重组组织型纤溶酶原激活剂（rt-PA）来研究提高腹腔内纤溶活性对脓肿形成的影响。还评估了潜在的副作用，如菌血症和出血。
采用大鼠弥漫性腹膜炎模型，通过腹腔注射每毫升含10⁴ 菌落形成单位（cfu）大肠杆菌（E. coli）和每毫升含10⁴ cfu脆弱拟杆菌的无菌粪便诱导。
用溶解于甲基羟丙基纤维素（MHPC）凝胶（每毫升0.5毫克）中的rt-PA治疗的大鼠，其腹腔内脓肿明显少于单独用乳酸林格液或MHPC凝胶治疗的对照组大鼠（p < 0.01）。除大肠杆菌外，脓肿培养物显示有来自肠道的菌种，表明存在细菌移位。与对照组大鼠相比，用rt-PA治疗的大鼠死亡率显著更高（p < 0.01），考虑到无菌血症，这一结果令人惊讶。通过用更高剂量的大肠杆菌攻击大鼠，在用rt-PA治疗的大鼠中观察到早期菌血症，这与死亡率增加无关。腹腔内使用rt-PA与出血事件发生率增加无关。
重组组织型纤溶酶原激活剂可预防大鼠弥漫性腹膜炎中的脓肿形成。然而，在该大鼠模型中，早期菌血症和死亡率增加是腹腔内使用rt-PA的严重缺点。
