Ischemia-reperfusion injury of the appendicular musculoskeletal system

Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis. "Ischemia": an inadequate blood supply to an organ or part of the body. "Reperfusion": the restoration of blood flow to an organ or tissue after having been blocked. Serum lactate level is a proxy measure of tissue oxygenation. When tissues do not have adequate oxygen delivery (i.e., are ischemic), they revert to less efficient metabolic processes, producing lactic acid. Myoglobin is released from damaged muscle, as in the case of ischemia. Serum creatinine and BUN may be elevated in the setting of acute kidney injury. Epigenetics Stem cells While some investigations suggest a possible beneficial effect of mesenchymal stem cells on heart and kidney reperfusion injury, to date, none have explored the role of stem cells in muscle tissue exposed to ischemia-reperfusion injury. Stem cells have been implicated in the regeneration of skeletal muscle after traumatic and blast injuries, and have been shown to hone to muscle damaged after exercise. Systemic effects of IR injury During periods of ischemia, cellular break down products accumulate in the local tissue. Once reperfusion occurs, these cellular products are returned to the systemic circulation, and are exposed to other organs.