REPERFUSION The effect of streptokinase on intramyocardial hemorrhage , infarct size , and the no - reflow phenomenon during coronary reperfusion

The purpose of this study was to determine whether streptokinase (1) exacerbates intramyocardial hemorrhage during coronary reperfusion, (2) has any intrinsic effect on myocardial infarct size other than its ability to lyse proximal thrombi in coronary arteries, and (3) can abolish the no-reflow phenomenon. Anesthetized open-chest dogs underwent coronary occlusion for 3 hr followed by 3 hr of reperfusion. Area of infarct was assessed by tetrazolium staining, anatomic zone of no-reflow by injection of the fluorescent dye thioflavin S at the end of the reperfusion period, regional blood flow during occlusion and reperfusion by the radioactive microsphere technique, and extent of gross hemorrhage by assessment of photographic enlargements of the heart slices. Area of infarction of the left ventricle was similar in control ( 13.4 + 3.6%) and streptokinase-treated dogs ( 13.0 ± 2.9%; p = NS). Seven of eight dogs in the untreated group had anatomic perfusion defects as assessed by thioflavin S at the end of the reperfusion phase; seven of eight dogs in the streptokinase group had anatomic perfusion defects. There was no difference in the extent of gross hemorrhage between the two groups (6.5 ± 2. 1% of left ventricle in controls and 5.7 ± 2.3% in streptokinase-treated dogs). Severe depression of regional blood flow during reperfusion was present within the infarcted tissue and was associated with an anatomic perfusion defect as defined by thioflavin S; there was moderate depression of flow within the noninfarcted, salvaged subepicardium. In a separate series of experiments, infarcts were assessed for hemoglobin content. Intramyocardial hemoglobin levels were not higher after fibrinolytic therapy plus reperfusion compared with reperfusion alone. In conclusion, streptokinase did not exacerbate myocardial hemorrhage after coronary reperfusion, had no effect on infarct size, and did not abolish the no-reflow phenomenon. The no-reflow phenomenon is unlikely to be caused by fibrin thrombi. Circulation 70, No. 3, 513-521, 1984. OVER THE LAST 4 to 5 years there has been intense interest in the concept of treating patients with acute myocardial infarction with fibrinolytic therapy.'1 Several studies have shown that patients with acute myocardial infarction can safely undergo coronary angiography followed by intracoronary administration of streptokinase to lyse the intracoronary thrombus. Recent investigations show that intravenous streptokinase may also be effective.8 Approximately 80% to 85% of patients have successful thrombolysis with intracoronary streptokinase, which has been associated with amelioration of chest pain, improved electrocardiograFrom the Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston. Supported by grants HL 23140, HL 28048, and SCOR 26215 from the National Heart, Lung and Blood Institute. Address for correspondence: Robert A. Kloner, M.D., Harvard Medical School, 180 Longwood Ave., Room 235, Boston, MA 02115. Received Nov. 2, 1983; revision accepted May 10, 1984. This work was done during the tenure of Dr. Kloner as an Established Investigator of the American Heart Association, with funds contributed in part by the Massachusetts Heart Association. Vol. 70, No. 3, September 1984 phic findings, and improved thallium perfusion, suggesting salvage of ischemic tissue. Some studies have shown improvement of left ventricular function after coronary reperfusion, while others have not.9' 0 There are still several unknown factors concerning streptokinase. Since coronary reperfusion has been associated with hemorrhagic infarction"I 12 and since streptokinase is fibrinolytic, it is conceivable that reperfusion with this agent could exacerbate hemorrhagic infarction and perhaps result in hemorrhage dissecting beyond the necrotic area. There is a lack of data concerning the effect of streptokinase on the morphology of the reperfused infarct. Several pharmacologic agents have been shown to reduce the extent of myocardial infarction;'3' 1' there is even some suggestion that heparin may be capable of reducing myocardial infarction. '5 Although studies have suggested that coronary reperfusion with streptokinase has reduced infarct size,"' 2 it has been assumed that this was caused by the lysis of thrombi in the 513 by gest on M ay 8, 2017 http://ciajournals.org/ D ow nladed from