title: Ischemia-reperfusion injury: influencing the microcirculatory and cellular environment.
abstract: Ischemia-reperfusion injury forms the basis of tissue damage and cellular apoptosis in many pathologic and traumatic processes. The tissue damage follows a natural progression of cellular and metabolic events initiated by an ischemic episode. Ischemia causes intracellular/extracellular changes principally resulting in increased intracellular calcium, pH changes, and adenosine triphosphate depletion that end in cell death if the process is not interrupted. This interruption takes the form of reperfusion, characterized by a "flushing" of tissues with toxic metabolites, principally reactive oxygen species. The immediate effect is mitochondrial pore permeability, complement activation, cytochrome release, cytokine activation, inflammation, edema, neutrophil platelet adhesion, capillary plugging, and thrombosis. This sets the stage for the long recognized "no-reflow" phenomenon and progressive tissue death. Current recognition of cellular "cross-talk" and molecular events have introduced new logical strategies to sequentially combat the events occurring in relation to ischemia-reperfusion injury. These include mechanical preconditioning and pharmacological preconditioning and postconditioning strategies. It is likely that success in reversing or limiting tissue damage will be found in a sequential multitargeted approach using a combination of these strategies-clinical trials in this regard are sorely needed.
authors.affiliation: From the Laboratory for Tissue Engineering & Regenerative Medicine Aesthetic & Plastic Surgery Institute, University of California, Irvine, CA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Widgerow
mesh_terms: D002317:Cardiovascular Agents / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors; D045462:Endothelium-Dependent Relaxing Factors / Q000627:therapeutic use; D016166:Free Radical Scavengers; D006801:Humans; D006862:Hydrogen Sulfide / Q000627:therapeutic use; D007036:Hypothermia, Induced; D007511:Ischemia / Q000503:physiopathology; D057775:Ischemic Postconditioning; D019194:Ischemic Preconditioning; D008833:Microcirculation / Q000502:physiology; D009569:Nitric Oxide / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*
chemical_list: D002317:Cardiovascular Agents; D015815:Cell Adhesion Molecules; D045462:Endothelium-Dependent Relaxing Factors; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D006862:Hydrogen Sulfide