The role of fibrinolysis during reperfusion of ischemic skeletal muscle.
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.
Quiñones-Baldrich
W J
WJ
Section of Vascular Surgery, UCLA School of Medicine 90024-6904.
D000818:Animals; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology; D009132:Muscles / Q000098:blood supply* / Q000473:pathology; D009336:Necrosis; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology*
D005343:Fibrinolytic Agents