ABSTRACT
The basis for tissue injury during ischemia depends on depletion of tissue oxygen and energy substrates with predominance of anaerobic metabolism. Decreasing cellular energy stores and accumulation of toxic metabolic byproducts[1,2] alter cellular membrane integrity leading to fluid and electrolyte movement, release of intracellular components, cell injury, and ultimately cell death.[3] Cell injury appears to begin after only 30 minutes of ischemia, as is evidenced by progressive cellular edema[4] and lysosomal degranulation.[5]
Irreversible changes in skeletal muscle occur after 4-6 hours of warm ischemia.[4]
The injury associated with acute arterial occlusion is not limited to the period of ischemia alone. Revascularization and restoration of blood flow initiates a series of complex events that lead to the reperfusion syndrome. Light microscopic studies have documented that cell injury following an ischemic period occurs after blood flow has been reestablished.[4] This injury also has been found to be maximal in areas with the greatest degree of blood flow during reperfusion.[5]
The reintroduction of molecular oxygen appears to be an important and critical event in the genesis of reperfusion injury in postischemic muscle. Damage occurs in part as the result of the formation of oxygen-derived free radicals leading to lipid peroxidation.[6,7] Reperfusion with hypoxic blood decreases the incidence of injury while reperfusion with normoxic blood leads to postischemic damage.[8] Similar results are obtained by limiting the rate of blood flow during the first hour of reperfusion.[9] The reintroduction of
molecular oxygen occurs after ischemia has depleted or reduced cellular energy stores. Under these conditions it appears that cellular oxygen sensors adjust themselves to an apparently lower pO2, so that reintroduction of normoxic blood constitutes a hyperoxic and toxic insult to the ischemic tissues.
