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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.

Inadequate blood flow causing tissue hypoxia can result in failure of anastomotic healing. Tissue oxygen tension (ptO2) measurement has been used to predict anastomotic leakage in animals, but its use in humans has not been described previously. A Clark-type oxygen electrode was used to measure ptO2 on the colon of 50 patients undergoing colonic resection and anastomosis. Baseline ptO2 levels were lowest on the descending colon (31.8 +/- 7.4 mmHg, mean +/- SD) and tended to increase at all sites with increasing arterial paO2 (r greater than .76, P less than .001). Perianastomotic ptO2 levels were predictive of subsequent anastomotic leakage when they were less than either 20 mmHg; 50 percent of the preresection ptO2; 15 percent of the arterial paO2; or 40 percent of the ptO2 at a control site (ileum). It is concluded that perioperative ptO2 measurements are of value in the prediction of anastomotic leakage.

Using a Clark oxygen electrode and a 133Xe clearance technique, tissue oxygen tension (T02) and blood flow have been determined in the small and large bowel of a rabbit experimental model. The predictive value of perianastomotic T02 in colonic anastomoses was determined, healing being assessed by leakage rate, tensile strength and hydroxyproline content. The effect of suture technique on colonic perianastomotic T02 has also been studied. Colonic and small intestinal T02 correlated with blood flow (r = 0.93). Basal colonic blood flow and oxygen tension were significantly lower than in the small intestine (P less than 0.01). Interrupted and continuous suture techniques decreased colonic perianastomotic T02, although mean T02 in the continuous group was significantly lower than in the interrupted group (P less than 0.01). The leakage rate was 10 per cent (1/10) for anastomoses constructed with a perianastomotic T02 above 55 mmHg compared with 100 per cent (10/10) if less than 25 mmHg (P less than 0.001). Perianastomotic T02 correlated with breaking energy (P less than 0.001), breaking strength (P less than 0.01) and hydroxyproline content (P less than 0.05).

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.

Using a model of 'reperfusion injury' as a mechanism of oxygen radical (OR) production in vivo, we have demonstrated that superoxide (O2-) is the major source of damage. Inhibition of its production from polymorphonuclear leucocytes (PMNs) by aprotinin, a protease inhibitor, or by scavenging with superoxide dismutase (SOD), resulted in reduced oxidation of of tissue glutathione (P less than 0.002). Colonic healing after anastomosis was also improved by aprotinin as measured by histology (P less than 0.05), breaking energy (P less than 0.001), breaking strength (P = 0.02), and by hydroxyproline content (P = 0.01). Allopurinol, although inhibiting glutathione oxidation, had no effect on PMN leucocyte OR production and did not protect against histological damage. These data demonstrate that PMNs endogenous to the tissue or attracted there as a result of trauma are the source of OR production in 'reperfusion'. Their inhibition improves colonic healing.