Intracoronary thrombolysis in acute myocardial infarction

An analysis of the results of the 63 coronary care units in Boston, Massachussets, USA, disclosed no perceptible fall in the hospital mortality from acute myocardial infarction between the years 1973-4 and 19789.1 This disappointing, if not unexpected, reality coupled with the fundamental influence of left ventricular function in determining the prognosis of patients with coronary heart disease23 gives great impetus to the search for measures to limit the extent of myocardial necrosis in patients with acute infarction. Many types of intervention can restrict the size of experimental infarctions,4 but of these the most rational and, therefore, the most attractive is the early restoration of antegrade blood flow. After acute coronary artery occlusion in the dog necrosis begins in the subendocardial region and spreads outwards towards the subepicardial layer; this "wavefront of necrosis" can be arrested by reperfusion.5 In 1960, Boucek and Murphy6 infused fibrinolysin into the aortic sinuses of patients with acute myocardial infarction and reported circumstantial evidence that the manoeuvre resulted in the re-establishment of blood flow. During the past five years the technique has been refined and applied to a large number of patients. In this issue of the journal, Cribier and his colleagues from Rouen7 add their experience to the already numerous published reports on the subject, and so it is opportune to examine the evidence for and against its acceptance as a new therapeutic option in the management of patients with acute myocardial infarction. The reported studies have been remarkably consistent, both in their approach to the problem and in their results. They have confirmed the pathological observation that thrombotic occlusion of a coronary artery, usually but not invariably superimposed on a severe arteriosclerotic stenosis, is present in 80-95% of patients during the early hours after the onset of myocardial infarction.80 Infusion of a fibrinolytic agent (streptokinase or streptokinase plus plasminogen) into the ostium of the coronary artery has been followed by restoration of patency in 64%0I to 95%12 of patients. The sooner treatment is commenced the greater its chance of process and the more rapidly thrombolysis is likely to occur,'0 " 13 and the rate of recanalisation may possibly be increased by a preliminary attempt to perforate the thrombus with a guide wire'4 and by superselective infusion close to the site of occlusion.'215 Recanalisation does occur spontaneously. DeWood et al. 16 observed coronary occlusion in 87% of patients undergoing angiography within four hours but in only 67% of those studied between 12 and 24 hours after the onset of infarction. When angiography was delayed for seven to 21 days, less than half of the patients were found to have occluded coronary arteries.'7 It is clear from these figures, however, and confirmed by a small radomised controlled trial in which intracoronary streptokinase treatment was compared with a placebo infusion,'8 that in most patients recanalisation during the procedure is effected by the fibrinolytic agent. Restoration of blood flow has usually been accompanied by resolution of chest pain, by a return of the electrocardiographic ST segments towards the isoelectric line, by an early peak of the serum creatine phosphokinase activity, and in many cases by the occurence of a variety of ventricular tachyarrhythmias or by bradycardia or atrioventricular block. Patients in whom recanalisation has been accomplished within about four hours of the onset of their symptoms have shown evidence of improved regional, and usually global, left ventricular function compared with patients in whom recanalisation did not occur or with those in whom a longer period of time had lapsed between the onset of chest pain and the restoration of blood flow. Two recent randomised controlled trials appear to confirm the results of these uncontrolled observations. In the first,'8 the average time between the onset of chest pain and the start of the streptokinase infusion was over five hours and no difference in left ventricular function was observed between patients receiving