Ischemia-reperfusion injury of the appendicular musculoskeletal systemIschemia-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.
NeovascularizationNeovascularization is the natural formation of new blood vessels (neo- + vascular + -ization), usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circulation in response to local poor perfusion or ischemia. Growth factors that inhibit neovascularization include those that affect endothelial cell division and differentiation.
CytotoxicityCytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (Bitis arietans) or brown recluse spider (Loxosceles reclusa) or spike proteins. Treating cells with the cytotoxic compound can result in a variety of cell fates. The cells may undergo necrosis, in which they lose membrane integrity and die rapidly as a result of cell lysis. The cells can stop actively growing and dividing (a decrease in cell viability), or the cells can activate a genetic program of controlled cell death (apoptosis).
Mitochondrial permeability transition poreThe mitochondrial permeability transition pore (mPTP or MPTP; also referred to as PTP, mTP or MTP) is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke. Opening allows increase in the permeability of the mitochondrial membranes to molecules of less than 1500 Daltons in molecular weight. Induction of the permeability transition pore, mitochondrial membrane permeability transition (mPT or MPT), can lead to mitochondrial swelling and cell death through apoptosis or necrosis depending on the particular biological setting.
