The chief aim of this study was to maximize flap survival by counterac
ting the pathophysiological changes occurring during ischemia-reperfus
ion. Rabbit epigastric skin flaps given 21 hours of ischemia were infu
sed intra-arterially with selected drugs at the start of reperfusion.
Compared with control infused ischemic flaps, which had a 33% survival
rate on day 7 post-ischemia, significant improvement was found with v
asodilators nitrendipine (61%) and prostacyclin (65%) and the thrombol
ytic agent urokinase (65%); marginal improvement with the free radical
scavenger desferrioxamine (53%); but no change with streptokinase (44
%), heparin (21%), and ATP-MgCl2 (35%). A drug mixture comprising all
of these agents except streptokinase and urokinase produced 87% surviv
al, suggesting an additive effect. Biochemical assays on skin homogena
tes and blood implicated oxygen free radicals, neutrophil infiltration
, and thromboxane in flap failure. These results imply that multiple f
actors are responsible for ischemic flap failure and that a mixture of
drugs needs to be infused to counteract all of the detrimental change
s. (C) 1994 Wiley-Liss, Inc..