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A randomized controlled trial was performed to assess the effect of intravenous aprotinin (Trasylol) on the healing of experimental colonic anastomoses in the rabbit following a standard left colonic resection anastomosis. Assessment of tensile strength was by means of both bursting pressure and breaking strength. Those animals subjected to bursting pressure assessment received intravenous aprotinin 80 000 KIU (kallikrein inhibitory units) at the time of anaesthesia, and postoperatively 160 000 KIU per day given in divided doses for three days. Control animals received saline placebo. A further group of animals received a lower loading and maintenance aprotinin dose (40 000 KIU and 60 000 KIU per day respectively) with control animals receiving saline. Breaking strength was employed as the means of assessment. The mean bursting pressures were 47.7 +/- 2.9 mmHg and 37.5 +/- 3.4 mmHg for aprotinin and controls respectively (P less than 0.05). The mean difference in collagen content of the anastomosis compared to the resected specimen was +1.25 +/- 0.50 microgram/mg and -1.02 +/- 0.47 microgram/mg for aprotinin and placebo groups (P less than 0.005). The mean breaking strength in the aprotinin group was 169.6 +/- 74.5 g and 110.0 +/- 65.9 g for the saline group (P less than 0.02). The mean difference in collagen content of the anastomosis compared to the resected specimen was +0.95 +/- 0.69 microgram/mg and -1.5 +/- 0.78 microgram/mg for the aprotinin and saline groups respectively (P less than 0.05). The significant elevation of both bursting pressure and breaking strength assessments, with a significant improvement in the collagen content of the anastomoses, may be the result of collagenase inhibition following the use of intravenous aprotinin in the experimental model.

A randomized controlled trial to assess the effect of intravenous Trasylol on postoperative intraperitoneal adhesion formation has been performed in rats. Before undergoing a standard left colonic resection, animals received i.v. Trasylol 10 000 KIU. This dose was repeated 8-hourly for 3 days postoperatively. Control animals received saline placebo. The mean percentage circumference of the anastomosis covered with adhesions in the Trasylol group animals was 20.86 +/- 6.08 compared with 45.24 +/- 5.97 in the control group (P less than 0.01). Significantly more animals treated with Trasylol were completely free of adhesions than those receiving saline. Bursting pressures did not differ between the two groups. Intravenous Trasylol clearly inhibits intraperitoneal adhesion formation in this model.

We have proposed that reperfusion injury results from the overproduction of reactive oxygen metabolites by PMN as a result of increased sensitivity to oxygen during the low oxygen phase. Aprotinin was demonstrated to inhibit this overproduction and also radical production evoked by chemotactic peptide, 50% inhibitions occurring in the range 5-20 microM. Over this range, no effect on cell viability was observed. This inhibitory effect may provide a scientific basis for the protective effect of aprotinin in reperfusion induced injury.

A randomized controlled trial to assess the effect of intravenously administered Trasylol on the healing of experimental colonic anastomoses in the rabbit has been performed. Before undergoing a standard left colonic resection and anastomosis, the animals received intravenous Trasylol (80,000 KIU). Postoperatively 160,000 KIU were given in divided doses per day for 3 days. Control animals received saline placebo. The mean bursting pressure of the anastomoses in the Trasylol-treated group was 47.7 +/- 3.0 mm Hg compared with 37.5 +/- 3.3 mm Hg for the control group (p less than 0.05). The mean difference in collagen content of the anastomosis compared to the resected specimen was +1.25 +/- 0.50 micrograms/mg and -1.02 +/- 0.47 microgram/mg for Trasylol and placebo, respectively (p less than 0.005). In this model intravenous Trasylol produces a significant elevation of the bursting pressure and a significant improvement in the collagen content of the anastomosis. This may be the result of collagenase inhibition.

Animal studies have demonstrated the value of the proteolytic enzyme inhibitor, aprotinin, in reducing collagen breakdown and improving the healing of experimental colonic anastomoses. A double-blind, multicenter, prospective trial has evaluated the use of aprotinin in the prevention of anastomotic leakage in patients. Two hundred sixteen patients undergoing colonic resection and anastomosis were studied. Patients were randomized to receive either aprotinin or placebo intravenously, peroperatively, and for the first three postoperative days. Anastomotic integrity was assessed clinically and by Hypaque enema on the tenth postoperative day. Although the use of aprotinin was not associated with a significant overall decrease in anastomotic leakage rates, in 95 patients undergoing anterior resection, leakage rates in those receiving aprotinin (clinical 10.8 percent; radiologic 32.4 percent) were lower than in those receiving placebo (17.2 percent and 43.1 percent, respectively). An apparent adverse association was noted, however, in patients undergoing left hemicolectomy or sigmoid colectomy who received aprotinin.