Combined Therapy with Antithrombotic Agents and Radical Scavengers for Reperfusion Injury of Flaps

ABSTRACT

The usefulness of combining antithrombotic agents and radical scavengers in the treatment of reperfusion injury (an almost ideal approach) was substantiated using an ischemic flap model. The cause(s) of reperfusion injury was hypothesized on the basis of differences in effects between antithrombotic agents and radical scavengers in the experimental groups. Flap specimens were also obtained regularly for histologic examination.

The experiment was conducted in nine rabbit groups. For continuous treatment with intraarterial antithrombotic agents, both heparin and urokinase were continuously injected at respective administration rates of 20 U/kg/hr and 200 IU/kg/hr for seven consecutive days immediately before reperfusion. For intraarterial radical scavenger treatment, a solution of both 30,000 U/kg SOD and 30,000 U/kgcatalase in 5 ml of a lactated Ringer's solution was injected over a period of about 30 min immediately before reperfusion.

The ischemic time of the flaps was 10 hr for Group 1 and 12 hr for Group II. Each group was comprised of subgroups a, b, c, and d: a = control; b = continuous intraarterial antithrombotic agent injection; c = intraarterial lactated Ringer's solution alone; and d = intraarterial radical scavenger injection. For Group II, an additional subgroup e was established, which received continuous injection of both intraarterial antithrombotic agents and injected intraarterial radical scavenger.

In the 10-hr ischemic treatment group, an effect was obtained by continuous intraarterial antithrombotic agents alone. In the 12-hr ischemic treatment group, a significant improvement in flap-take ratio was obtained using intraarterial radical scavenger, in combination with antithrombotic agents. Observation of the flaps that survived in subgroups Ib and lie revealed skin thinning, vascular wall thickening, and muscular tissue degeneration, although the skin architecture was well preserved.