The Additive Beneficial Effect of Uw Solution and Urokinase on Experimental Microvascular Free-Flap Survival

ABSTRACT

Pharmacologic manipulation of free flaps to enhance tolerance to ischemia has become a subject of great interest in the research literature. In an effort to improve survival, perfusion washout of experimental free flaps was performed following an episode of primary ischemia. The perfusates utilized were lactated Ringer's solution (LR), University of Wisconsin solution (UW), a high-molecular-weight medium used in organ preservation, and urokinase, a thrombolytic agent.

Seventy-five rats were used in this study and divided into groups of 5 each. A 3 × 6-cm abdominal free flap based on the superficial inferior epigastric vessels was raised in each rat. The free flaps were subjected to either 12 or 18 hr of primary ischemia. Following the period of ischemia, perfusion washout was performed with either LR, UW solution, or urokinase at increasing concentrations alone or in combination with UW solution.

Urokinase was first evaluated as a perfusate alone at increasing concentrations. In the 12-hr ischemia group, free-flap survival was shown to increase from 0 percent in the LR-perfused flaps to 20 percent, 60 percent, and 80 percent in flaps perfused with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). A similar increase in survival was demonstrated in the 18-hr ischemia group, where 0 percent, 20 percent, and 40 percent of flaps survived following perfusion with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05).

Urokinase was then perfused along with UW solution to evaluate the combined effect on flap survival. In the 12-hr ischemia group, free-flap survival was shown to increase from 40 percent in the UW-solution-perfused group to 80 percent, 100 percent, and 100 percent in the groups perfused with UW solution in combination with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). A similar increase in survival was demonstrated in the 18-hr ischemia group where 0 percent of flaps perfused only with UW solution survived, compared with 0 percent, 20 percent, and 60 percent survival following perfusion with UW solution in combination with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05).

When urokinase was perfused in combination with UW solution, an additive effect on free-flap survival was demonstrated, compared to urokinase alone in the 12-hr group (p < 0.05). This additive effect was not present in the 18-hr group.

Based on these data, perfusion washout with increasing concentrations of urokinase results in significantly increased survival of experimental free flaps following a period of primary ischemia. Furthermore, when urokinase is perfused in combination with UW solution after 12 hr of primary ischemia, there is an additive beneficial effect on flap survival.