title: Pathobiology of acute myocardial ischemia: metabolic, functional and ultrastructural studies.
abstract: Acute myocardial ischemia induced by coronary occlusion in dogs is most severe in the subendocardial region, whereas more collateral blood flow is often present in the subepicardial region. Initially, all ischemic myocytes are reversibly injured, but beginning at 15 to 20 minutes after the onset, and continuing for 3 to 6 hours, there is a wave front of cell death from the subendocardial region to the less ischemic subepicardial region, such that by 6 hours, the final transmural extent of the infarct is established. Thus, ischemic myocardium cannot be salvaged by reperfusion after greater than or equal to 6 hours of coronary occlusion in open-chest anesthetized dogs. In the severely ischemic subendocardial region, most of the creatine phosphate is lost within the first 3 minutes of ischemia in vivo, and adenosine triphosphate (ATP) is depleted to 35% of control by 15 minutes (when cellular injury is still reversible), and to less than 10% of control at 40 minutes (when injury is irreversible). Tissue ATP content and other indexes of subcellular damage have also been compared after different periods of ischemia using a model of total myocardial ischemia in vitro. As long as the ATP of the tissue was not depleted below 5 mumols/g dry weight, incubated slices of injured myocardium resynthesized high-energy phosphates and excluded inulin. However, lower tissue ATP was associated with depressed high-energy phosphate resynthesis and failure of cell volume regulation. Overt membrane damage, as measured by an increased inulin-diffusible space, was detected only after the tissue ATP decreased to less than 2.0 mumols/g of dry weight. Thus, marked ATP depletion is associated with the onset of structural and functional indexes of irreversible injury. However, whether irreversibility is caused by the marked ATP depletion or by other concomitant metabolic consequences of ischemia is not known. Myocardial ischemic cellular injury is reversible despite depletion of 70% of the control ATP. Nevertheless, when myocyte injury is reversible, there is slow repletion of adenine nucleotides. This slow metabolic recovery may explain the delayed recovery of contractile function observed after reperfusion of ischemic myocardium.
mesh_terms: D000227:Adenine Nucleotides / Q000096:biosynthesis; D000255:Adenosine Triphosphate / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D006321:Heart / Q000503:physiopathology; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009336:Necrosis; D012508:Sarcolemma / Q000648:ultrastructure
chemical_list: D000227:Adenine Nucleotides; D000255:Adenosine Triphosphate; D003402:Creatine Kinase