title: Disruption of myofibrillar energy use: dual mechanisms that may contribute to postischemic dysfunction in stunned myocardium.
abstract: The abnormalities in regional function produced by myocardial ischemia persist after the ischemic episode resolves. Since a close functional coupling exists between myofibrillar creatine kinase and myosin ATPase, a disruption of this coupling could adversely influence myocardial function and might provide a mechanism for the myocardial dysfunction observed. The purpose of the present study was to determine if an alteration in the activity of creatine kinase associated with the myofibril occurs in the postischemic period. Anesthetized open-chest dogs (n = 6) underwent coronary occlusion for 15 minutes, followed by reperfusion for 15 minutes. In reperfused myocardium, adenine nucleotide content was decreased (72 +/- 10% of nonischemic myocardium, p less than 0.05), documenting the presence of previous ischemia. The creatine phosphate content of reperfused myocardium returned to normal, indicating resumption of myocardial energy production. The creatine kinase activity of purified myofibrils isolated from reperfused myocardium was decreased by 17 +/- 7% compared to that of nonischemic myofibrils (p less than 0.03). In addition, the free adenosine diphosphate concentration in reperfused myocardium was calculated to be 96 microM and was less than the Km of adenosine diphosphate determined for myofibrillar creatine kinase (105 microM). The results suggest two putative mechanisms for disruption of energy use in postischemic myocardium: decreased creatine kinase activity associated with the myofibril, and limitation of substrate necessary for maximal creatine kinase activity.
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000201:enzymology* / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D004734:Energy Metabolism; D006321:Heart / Q000503:physiopathology*; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology*
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases