Heparin has been found to decrease ischemia/reperfusion injury in skel
etal muscle and other tissue/organ systems. The timing of heparin admi
nistration to the muscle vasculature has not been explored. We investi
gated the use of heparinized blood as a washout solution during ischem
ia to reduce ischemia/reperfusion injury. A rat cutaneous maximus musc
le free flap was subjected to a 10-hr period of room temperature ische
mia, then was heterotopically transplanted to the groin via microsurgi
cal revascularization to the femoral vessels, In three experimental gr
oups, flaps were subjected to brief ex vivo perfusion with autologous
heparinized blood, at 2, 5, or 8 hr into the 10-hr ischemic interval.
In the two other groups, the flaps were not perfused, and the animals
were systemically heparinized either before ischemia or before transpl
antation, respectively. A control group underwent no flap perfusion or
systemic heparinization. After transplantation, flaps were given a 48
-hr period of in vivo reperfusion, then were harvested for evaluation,
Flaps undergoing ex vivo perfusion or preischemic heparinization had
no significant differences in weight gain (edema) compared with flaps
receiving posttransplant heparinization or no heparinization (controls
). The dehydrogenase staining of muscle biopsies was significantly fas
ter (indicative of viable tissue) for perfused flaps and the flaps for
which the animals received preischemic heparinization, when compared
with flaps for which the animals received posttransplant heparinizatio
n or no heparinization. From these results, we conclude that heparin o
ffers protection from ischemia/reperfusion injury when it can be intro
duced into the vascular network either prior to or during the ischemia
period. These findings suggest the possibility of using heparinized w
ashout solutions to enhance survival in amputated extremities. (C) 199
5 Wiley-Liss, Inc.