Occlusive coronary thrombi are responsible for the preponderance of acute Q-wave infarctions.

Occlusive coronary thrombi are responsible for the preponderance of acute Q-wave infarctions, and a large proportion of patients can potentially benefit from concretion lysis (Fig 1). in the same state [i]or[/i] condition reperfusion early in the course of acute infarction salvages infarcting tissue if it were not that also creates a new put of challenges for the long-term maintenance of bottom patency. It is now well recognized that late reocclusion of infarct-related coronary arteries during the week following initially prosperous thrombolytic therapy is associated with greater impairment of segmental systolic function within the infarct girth a more complicated hospital course, and an increased in-hospital mortality.[1] Thus, the goals of reperfusion therapy are (1) to reestablish patency of the infarct related artery at an early point in time to obstruct the evolution of irreversible myocardial necrosis, and (2) to maintain patency of the infarct-related artery to hinder recurrent ischemic jeopardy of the salvaged myocardium. Beyond the short-term limitation of myocardial necrosis and the amelioration of the mechanical, electrical, and hemodynamic effects of myocardial ischemia and infarction, reperfusion therapy and the maintenance of an make open infarct-related artery may have an long-term benefits as well. Evidence is accumulating that the air of a patent infarct-related coronary artery may (1) stabilize the arrhythmogenic substrate following acute infarction,[2,3] (2) debar recurrent ischemia at a distance from the infarct cincture by improving collateral flow,[4] and (3) favorably influence ventricular remodeling at reducing infarct zone expansion.[5]

THROMBOLYTIC APPROACHES TO REPERFUSION

Early studies employing intracoronary streptokinase (dosages ranging from 2000 to 4000 U/min) confirmed the efficacy of this means of reopening occlud coronary arteries and confirmed the importance of early achievement of utensil patency if ischemic myocardium is to be salvaged[6-10] (Fig 2) Using quantitative angiography to assess segmental wall motion 2 to 3 weeks following reperfusion, Mathey et al[10] demonstrated greater preservation of regional function with earlier administration of thrombolytic therapy. For instance, when therapy was instituted les than 2 h from symptom storm 85 percent of patients had normal infarct belt regional wall motion (within 2 SD of the norm) at late follow-up whereas merely 46 percent of patients had normal infarct climate regional wall motion if therapy was instituted 2 to 5 h after attack of symptoms.

To make thrombolytic therapy widely available in hospital settings where cardiac catheterization (and hence intracoronary thrombolytic therapy) is not available and to maximize the opportunity for early treatment, investigators diverted to the intravenous (IV) administration of thrombolytic agents. Five large randomized placebo-controlled studies, each studying in exces of 1000 patients, have evaluated the impact of IV thrombolytic therapy upon mortality following acute myocardial infarction.[11-15] Three of the studies (GISSI [Gruppo Italiano by lo Studio della Streptochinas, nell Infarto Miocardico)],[11] ISIS-2 [Second International thought of Infarct Survival],[12] ISAM [Intravenous Streptokinase in Acute Myocardial Infarction][13] compared IV streptokinase (15 x [10sup2] U/1 h) with placebo. The AIMS reflection group (APSAC Intervention Mortality Study)[14] compared IV APSAC (anisoylated plasminogen streptokinase activator compages anistreplase, 30 U/5 min) v placebo and the ASSET contemplation (Anglo Scandinavian Study of Early Thrombolysis)[15] compared intravenous rt-PA (recombinant tissue image plasminogen activator, alteplase 100 mg/3 h) with placebo. Selecting data from relatively comparable portions of each of these trials (intravenous thrombolytic administration at les than 4 to 6 h of attack of infarction, short-term follow-up of 21 to 35 days) mortality in the various thrombolytic treatment arms ranged from 63 to 102 percent while mortality in the placebo arms ranged from 71 to 128 percent The reduction in mortality befitting to IV thrombolytic therapy ranged from 11 to 47 percent and was statistically significant in all on the contrary one trial. These studies taken collectively provide convincing evidence that intravenous thrombolytic therapy administered early in the course of acute myocardial infarction to patients exempt of contraindications to thrombolysis significantly abridges short-term mortality compared with placebo controls

The couple largest controlled trials of IV thrombolytic therapy, the GISSI contemplation and the ISIS-2 study, provide a certain quantity of important comparisons with respect to the following: (1) the timing of thrombolytic therapy; (2) the incidence of complications (allergic reactions, hypotension, bleeding, cerebrovascular accidents); and (3) the risk of reinfarction. In the GISSI trial,[11] more than 11000 patients with chest pain and significant ST part changes were randomized to 15 x [10sup6] U of IV streptokinase administered through the whole extent of 1 h or conventional care without thrombolytic therapy. At 21 days there was a statistically significant 18 percent reduction in mortality for patients treated with streptokinase within 12 h of the assault of symptoms and this benefit has been sustained to 12 month follow-up by means of substantially all of the advantage in survival had been achieved at 21 days.[11] Whether analyzed for short- (21 day) or long-term (12 month) follow-up the survival advantage for streptokinase therapy was confined to patients treated within 6 h of attack of symptoms with the in the greatest degree marked reduction in mortality (47 percent) occurring in patients treated within 1 h of first brunt of symptoms. The ISIS-2 trial randomized 17000 patients within 24 h of assault of symptoms to four arms: (1) IV streptokinase (15 x [10sup6] U from one side of to the other 1 h); (2) enteric-coated aspirin (1625 mg/d for 1 month); (3) the two streptokinase and aspirin; and (4) masterys Comparing the streptokinase alone arm v the restrain arm at 35 days follow-up there was a statistically significant 23 percent reduction in vascular mortality (which was parallelled according to overall mortality) for streptokinase treatment within 24 h of the charge of symptoms, and this benefit was sustained to a median follow-up of 15 months[12] While patients treated within 0 to 4 hours of the first brunt of symptoms experienced the greatest reduction in vascular mortality (33 percent) with streptokinase therapy, there was also a statistically significant reduction in vascular mortality (21 percent) for patients treated with streptokinase 5 to 24 h following the attack of symptoms. In contrast to the GISSI meditation the ISIS-2 study enrolled patients with a broader range of clinical presentations, including patients without ST portion elevation. The possibility exists that patients presenting 5 to 24 h following the storming of their presumed infarction were actually experiencing unstable angina progressing to infarction, renewed infarction, or infarct extension, conditions that might still benefit from "late" thrombolytic therapy.

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