title: Cellular-phase fibrinolysis and coronary reperfusion during acute myocardial infarction: a study in patients receiving intravenous streptokinase-methylprednisolone therapy.
abstract: Activation of plasma plasminogen to plasmin is the objective of current strategies for thrombolytic therapy. Although thrombolytic activity in blood involves a large cellular component as well as that in plasma, the contribution of this cellular phase to clinical thrombolysis has not been examined. Using a 125I-fibrin test tube assay, we determined blood, plasma and calculated cellular phase fibrinolytic activities in 39 patients with acute myocardial infarction before, immediately after, and at 2 hours after therapy with an intravenous streptokinase-methylprednisolone regimen. By coronary angiography and time to peak creatine phosphokinase levels, 32 patients had coronary reperfusion and 7 did not. Before streptokinase therapy, cellular phase activity of patients who reperfused was more than 2-fold greater than that of patients who did not reperfuse (p less than 0.001), while plasma activities were identical, suggesting that intrinsic cellular phase activity may be a determinant of the success of subsequent thrombolytic therapy. In both groups, in addition to the expected (and similar) increases in plasma activity, cellular phase activity increased when compared with pre-treatment values (+96% to +248%; p less than 0.001), with accompanying increase in blood granulocyte count (+23% to +65%), indicating that blood cells, as well as plasma, are major contributors to streptokinase-mediated fibrinolysis. Cellular phase stimulation was reproduced in a patient receiving streptokinase without methylprednisolone, and by addition of streptokinase to normal blood in vitro, indicating that streptokinase alone could account for these effects. Increased cellular phase activity in patients who reperfused after streptokinase was similar to that in those who did not reperfuse, when pre-treatment values were considered. These findings indicate that initial cellular phase activity in blood may determine subsequent fibrinolytic response, and that there is a significant cellular phase component to the fibrinolytic response to streptokinase, probably mediated by increased numbers of blood neutrophils, with a possible contribution from increased activity of individual neutrophils.
authors.affiliation: Department of Medicine, Lady Davis Research Institute, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Langleben
authors.forename: L A
authors.initials: LA
authors.lastname: Moroz
authors.forename: R D
authors.initials: RD
authors.lastname: Schlesinger
mesh_terms: D001772:Blood Cell Count / Q000187:drug effects; D001773:Blood Cells / Q000502:physiology*; D003402:Creatine Kinase / Q000097:blood; D005342:Fibrinolysis / Q000187:drug effects*; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008775:Methylprednisolone / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy; D010976:Platelet Count / Q000187:drug effects; D013300:Streptokinase / Q000627:therapeutic use*; D015912:Thrombolytic Therapy
chemical_list: D003402:Creatine Kinase; D013300:Streptokinase; D008775:Methylprednisolone