Skeletal muscle is unique in its ability to tolerate relatively long periods of
ischemia without demonstrable damage following reperfusion. Prolonged
ischemia, however, has been associated with muscle
necrosis and poor recovery of function. Using a rabbit model of hind limb
ischemia, periods of
ischemia of 1, 2, 3, and 5 hours were studied. Whereas almost complete recovery was seen after 1 or 2 hours of
ischemia, a progressive loss of function is seen with increasing ischemic interval. In addition, within the 5 hour group, up to 40% of preparations did not recover function during reperfusion, with no Doppler signals audible over the pedicle. In these, microscopic thrombi was demonstrated histologically. Thus it appears that the "
no reflow" phenomenon plays a major role after prolonged (greater than 4 hrs)
ischemia. In order to evaluate the effect of
fibrinolytic drugs on the "
no reflow" phenomenon,
urokinase was infused prior to reperfusion, and after 5 hours of
ischemia, in a separate group of animals. All of these reperfused without any evidence of "no reflow". We conclude that
reperfusion injury may have two major components: the "
no reflow" phenomenon secondary to poor reperfusion, and cellular injury resulting from reperfusion itself. Infusion of
fibrinolytic agents during the initial phases of reperfusion may have a salutory effect in preventing the "
no reflow" phenomenon. It is likely, however, that attempts at effective and safe retrieval of ischemic tissue will necessarily have to address both mechanisms.