Evans D M, McAree K, Guyton D P, Hawkins N, Stakleff K
Department of Surgery, Akron General Medical Center, Ohio 44307.
Am J Surg. 1993 Feb;165(2):229-32. doi: 10.1016/s0002-9610(05)80516-1.
Intra-abdominal adhesions have been shown to result from the impairment of peritoneal fibrinolysis by inhibitors present in ischemic tissue. A reproducible model for the formation of intra-abdominal adhesions was utilized for the evaluation of the effectiveness of intraperitoneal applications of recombinant tissue plasminogen activator (rtPA) in adhesion prevention. Concentrations of rtPA required to overcome the inhibition of fibrinolysis in this model were estimated by titration of that amount of rtPA required to lyse blood clot in the presence of a measured amount of ischemic tissue. Adhesions were graded, and the hydroxyproline content of the abdominal wounds was analyzed. The effect of intraperitoneal administration of rtPA on adhesion formation was strongly dose related. Levels of rtPA of 0.01 mg/mL showed no effect (p < 0.75) on adhesion formation, whereas levels of 0.1 mg/mL either prevented or significantly modified the formation of intra-abdominal adhesions (p < 0.05). Concomitantly, wound hydroxyproline content was significantly reduced (p = 0.004). Prior investigations have shown a strong correlation between wound bursting strength and hydroxyproline content. The results of this study indicated that the levels of rtPA required to alter or prevent intra-abdominal adhesion formation also produce a significant impairment of the early phase of wound healing as measured by the wound content of hydroxyproline.
腹腔内粘连已被证明是由缺血组织中存在的抑制剂损害腹膜纤维蛋白溶解所致。一种可重复的腹腔内粘连形成模型被用于评估腹腔内应用重组组织型纤溶酶原激活剂(rtPA)预防粘连的有效性。通过在存在一定量缺血组织的情况下滴定溶解血凝块所需的rtPA量,来估计该模型中克服纤维蛋白溶解抑制所需的rtPA浓度。对粘连进行分级,并分析腹部伤口的羟脯氨酸含量。腹腔内给予rtPA对粘连形成的影响与剂量密切相关。0.01mg/mL的rtPA水平对粘连形成无影响(p<0.75),而0.1mg/mL的水平可预防或显著改变腹腔内粘连的形成(p<0.05)。同时,伤口羟脯氨酸含量显著降低(p=0.004)。先前的研究表明伤口抗破裂强度与羟脯氨酸含量之间存在很强的相关性。本研究结果表明,改变或预防腹腔内粘连形成所需的rtPA水平,也会导致伤口愈合早期出现显著损害,这可通过伤口羟脯氨酸含量来衡量。