Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. Physiopathology and prevention.

Revascularization of a limb after a severe and prolonged period of ischemia may be associated with high rates of mortality and amputation, because of the development of a postrevascularization syndrome, regardless the cause of occlusion (ischemia, trauma, iatrogenic) or the methods used to achieve reperfusion (fibrinolysis, surgery, resuscitative therapy). This "revascularization" syndrome includes several complications, both local (explosive swelling of the limb, compartment syndrome and skeletal muscle infarction (rhabdomyolysis) and general (acidosis, hypercalcemia, hypovolaemic shock, renal, hepatointestinal and pulmonary failures, arrhythmias and cardiac arrest (multiple organ dysfunction). Current therapies are directed against complications after they occurred, once revascularization is completed: fasciotomy, mannitol and diuretics administration for forced diuresis, fluid administration to correct hypovolaemia, use of resins, insulin and glucose or haemodialysis to deal with hypercalcemia, administration of buffers (THAM, bicarbonate) to correct acidosis, control of hypercalcaemia with orthophosphates and calcitonin.... Nevertheless, a substantial percentage of the injury is generated upon reperfusion and the muscle may remain viable after prolonged period of ischemia. Intra and extraacellular swelling, tissue acidosis, free radical mediated damage, loss of adenine nucleotide precursors, and intracellular calcium overload have been suggested to be the mechanisms responsible for reperfusion injury. Careful control of both the composition and the physical conditions of the initial reperfusion (controlled reperfusion) may result, in selected cases, in improvements in the metabolism, structure and function of the limb after reperfusion.