The role of plasminogen activator in adhesion prevention.
The reduction in peritoneal plasminogen activator activity (believed to be the pathogenic mechanism of adhesion formation) and its replacement with recombinant tissue plasminogen activator (rt-PA) have been investigated in the prevention of initial (primary) and recurrent adhesion production. Other, potentially harmful, effects of intra-abdominal rt-PA application have also been examined. This included effects on wound and colonic healing and hemostasis. The prevention of adhesion formation was studied in primary and recurrent adhesion formation using a rabbit model. Primary adhesions formed in one of 14 occasions (7 per cent) with rt-PA compared with 12 of 15 occasions (80 per cent) with placebo (chi-square equals 15.542, p less than 0.001). Recurrent adhesions formed on two of 27 occasions (7 per cent) with rt-PA compared with 22 of 28 occasions with placebo (79 per cent) and 12 of 12 occasions with control rabbits (100 per cent, chi-square equals 40.588, p less than 0.0001). The application of rt-PA to abdominal wounds in the rabbit failed to show any reduction in wound strength at four, seven and ten days. Colonic anastomotic healing was unaltered by rt-PA at three, five and seven days. There was no difference seen in hemorrhagic events between control, placebo or rt-PA rabbits at any stage. The use of rt-PA is an exciting development in the field of adhesion prevention; it is an effective inhibitor of adhesion formation and intra-abdominal administration appears safe in a rabbit model.
Menzies
D
D
Westminster Hospital, London, United Kingdom.
Ellis
H
H
D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D003106:Colon / Q000601:surgery; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006488:Hemostasis, Surgical; D006801:Humans; D010532:Peritoneal Diseases / Q000209:etiology / Q000517:prevention & control*; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D000267:Tissue Adhesions / Q000209:etiology / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator