Protection of ischemic myocardium by exogenous phosphocreatine (neoton): pharmacokinetics of phosphocreatine, reduction of infarct size, stabilization of sarcolemma of ischemic cardiomyocytes, and antithrombotic action.
The effect of exogenous phosphocreatine on ischemic myocardium was studied in experimental infarction in rabbits and in total ischemia of pig heart tissue (in vitro). It is shown that single dose administration of phosphocreatine is followed by its rapid clearance from blood plasma (with a half lifetime of 4-6 min), but constantly high plasma concentration of phosphocreatine can be maintained by its intravenous infusion. When administered by this method into rabbits during experimental myocardial infarction, phosphocreatine reduces by 40% the size of the necrotic zone. Morphological electron microscopic studies using a lanthanum tracer method showed significant protection of the sarcolemma of cardiomyocytes in the perinecrotic zone by phosphocreatine. In vitro studies on the model of total ischemia also showed significant protection of cardiac sarcolemma from irreversible ischemic injury and reduction in the rate of high-energy phosphate depletion in the presence of phosphocreatine in the extracellular space. Additionally, it is demonstrated that creatine kinase released during myocardial infarction into the blood flow and exogenous phosphocreatine administered intravenously may significantly inhibit platelet aggregation by rapid removal of ADP, and thus potentially improve microcirculation during myocardial infarction.
D000328:Adult; D000818:Animals; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010725:Phosphocreatine / Q000097:blood / Q000627:therapeutic use*; D010974:Platelet Aggregation; D011817:Rabbits; D012508:Sarcolemma / Q000473:pathology*
D010725:Phosphocreatine; D003402:Creatine Kinase