Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction--a report from the multicenter thrombolysis trial

The efficacy and safety of intravenous infusion of human tissue-type plasminogen activator (rt-PA), developed in Japan (TD-2061), were investigated in 205 patients (154 men and 51 women) with evolving myocardial infarction (EMI). TD-2061 was given at a rate of 3.2 to 50 mg over 1 h after angiographic documentation of complete or subtotal (99%) occlusion. Nineteen patients were excluded as they did not meet the inclusion criteria. A total of 186 patients were divided into 6 groups according to the total dose given: Group I, 3.2 mg, 10 patients (pts); Group II, 6.4 mg, 15 pts; Group III, 12.8 mg, 15 pts; Group IV, 25.6 mg, 38 pts; Group V, 33.3 mg, 70 pts; Group VI, 50.0 mg, 38 pts. Ages ranged from 30 to 70 years (mean 60 +/- 1). Coronary angiography was done at 30 min and 1 h. In patients with TIMI grades 0 and 1, reperfusion was accomplished after 1 h in 22% of Group I, 50% of Group II, 64% of Group III, 70% of Group IV, 67% of Group V, and 74% of Group VI patients. Complications were hypotension, nausea and vomiting, bradycardia and bleeding at the puncture site. These findings suggest that clot-selective coronary thrombolysis can be induced in patients with EMI by means of human tissue-type plasminogen activator without concomitant induction of a severe systemic lytic state. The optimal dose for Japanese patients is considered to be 33.3-50.0 mg from the standpoint of reperfusion.     

Intravenous recombinant tissue-type plasminogen activator in acute myocardial infarction]

The efficacy and safety of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA, made by Boehringer Ingelheim Corp.) was investigated in 10 patients with acute myocardial infarction (AMI). The rt-PA was given as a bolus dose of 10 mg followed by an infusion of 50 mg, 20 mg and 20 mg in successive hours. Heparin and aspirin were given to all the patients. The time interval from the onset of chest pain to thrombolysis was from 2.3 to 6.1 h with mean of 3.9 h. Coronary angiography, performed before administration of rt-PA and every 30 minutes thereafter, demonstrated total coronary occlusion (grade O) in 9 patients and grade 1 in 1 at baseline study. The infarct-related coronary artery were LAD in 5, RCA in 3 and LCX in 2. At 90 minutes after infusion of rt-PA reperfusion of the infarct-related artery was observed in 7 patients, the success rate was 70%. In one case the infarct-related LCX was not opened at 90 minutes, but it was reperfused at 170 minutes, after intracoronary administration of 10 mg of rt-PA. The total dose in this case was 130 mg. During 30 days of hospitalization death occurred in only one case with cardiogenic shock, in whom the infarct-related RCA was not reperfused by rt-PA but was successfully recanalized by PTCA. The patient died from rupture of the left ventricle on the 4th day. No patient had clinical evidence of reinfarction. Follow-up angiography in 2 patients showed that the arteries reperfused initially were patent.(ABSTRACT TRUNCATED AT 250 WORDS)     

重组葡激酶与重组组织型纤溶酶原激活剂治疗急性心肌梗死的随机多中心临床试验

目的研究新型溶栓剂——重组葡激酶（r-Sak）治疗急性心肌梗死（AMI）的冠状动脉通畅率、临床疗效及安全性。方法本研究为多中心、随机、平行对照临床试验,入选发病12h内、年龄≤70岁、ST段抬高的AMI患者,随机分为r-Sak组104例,给予r-Sak 3mg静注,12mg于30min内静脉输注,总量15mg;重组组织型纤溶酶原激活剂（rt-PA）组106例,8mg静注,42mg在90min内输注,总量50mg。全部患者给予阿司匹林和静脉输注肝素,于用药90min行冠状动脉造影,对TIMI血流0～2级者行补救性PCI。结果主要终点：用药90min冠状动脉通畅率（TIMI血流2级或3级）,r-Sak组明显高于rt-PA组（77.8％比63.6％,P=0．0277）,TIMI 3级者两组间差异无统计学意义（57．6％比48．5％,P=0．1929）;1个月内死亡（8,7％比5,7％,P=0．3997）、非致死性再梗死（2,9％比3．8％,P=1．0000）、心肌缺血复发（8,7％比16．0％,P=0.1043）和复合临床终点（18．3％比21．7％,P=0。5345）两组间差异均无统计学意义。次要终点：r-Sak组出血发生率（28．8％）与rt-PA组（27．4％）比较,差异无统计学意义（P=0,8105）,其中严重或威胁生命的出血,两组间差异亦无统计学意义（1．9％比3．8％）,r-Sak组脑出血1例（0．96％）,rt-PA组脑出血4例（3．85％）。无其他药物相关的严重不良反应及过敏反应发生。结论r-Sak是一种安全、有效的治疗AMI的溶栓药物,其疗效及安全性至少与rt-PA 50mg相似。     

Coronary arterial thrombolysis with combined infusion of recombinant tissue-type plasminogen activator and urokinase in patients with acute myocardial infarction

To determine whether tissue-type plasminogen activator (t-PA) and urokinase (UK) act synergistically to achieve coronary thrombolysis, incremental doses of both drugs were infused intravenously over 60 min. In 146 consecutive patients treated 3.0 +/- 1.0 hr from symptom onset, coronary angiography was performed 90 min after the start of the infusion and at 7 days. The groups of patients treated by different dose regimen were as follows: group I, 14 patients treated with t-PA 25 mg and UK 0.5 million U; group II, 20 patients given t-PA 25 mg and UK 1.0 million U; group III, 24 patients given t-PA 1.0 mg/kg and UK 0.5 million U; group IV, 33 patients treated with t-PA 1.0 mg/kg and UK 1.0 million U; and group V, 55 patients given t-PA 1.0 mg/kg and UK 2.0 million U. In groups I and II, patency of the infarct-related vessel at 90 min was only 36% and 42%, respectively. With 1 mg/kg t-PA and increasing doses of UK (groups III to V), patency ranged from 72% to 75% (overall 73%). Repeat catheterization at 7 days demonstrated reocclusion in groups III to V in 10 of 110 (9%). The patency and reocclusion rates in groups III to V were not significantly different from those in our previous study of 386 patients treated with t-PA alone (150 mg over 6 to 8 hr). In that study the patency rate of the infarct-related vessel at 90 min was 75% (p = .66) and reocclusion occurred in 15% (p = .11).(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Single-bolus injection of recombinant tissue-type plasminogen activator in acute myocardial infarction

Recombinant tissue-type plasminogen activator (rt-PA) has hitherto been administered in acute myocardial infarction as an intravenous infusion with an initial bolus of about 10% of the total dose, both due to its short half-life and to avoid possible early reocclusions. A single-bolus dose would simplify the therapeutic regimen. Therefore, 20 patients with symptom duration of 125 +/- 58 minutes were given a single bolus of 50 mg of rt-PA over 2 minutes. Coronary angiography 60 minutes after the rt-PA bolus revealed a patent infarct-related artery in 15 of 20 patients (patency rate 75%, 95% confidence limits 51 to 91%). In the remaining patients, reperfusion was achieved by coronary angioplasty and intracoronary fibrinolysis; in 2 patients coronary artery bypass grafting was necessary. Control angiograms at 24 hours showed reocclusions in 4 of 18 patients. One woman died due to an intracranial hemorrhage 48 hours after the rt-PA bolus injection. Circulating fibrinogen decreased from 2.7 +/- 0.5 to 1.5 +/- 0.9 g/liter after 2 to 4 hours and reached the initial value within 24 hours. Pharmacokinetic parameters were obtained in 7 patients by measuring rt-PA antigen levels in multiple plasma samples. Mean peak rt-PA concentration was 9.8 +/- 3.6 micrograms/ml, total plasma clearance 476 +/- 148 ml/min and dominant half-life 4.8 +/- 1.0 minutes. Thus, rt-PA administered as a 50-mg single bolus appears to provide similar patency rates and shows similar kinetics in comparison with the conventional infusion regimen. Assessment of the incidence of bleeding complications requires further studies.     

重组组织型纤溶酶原激活剂与直接冠状动脉内支架术治疗心肌梗死的疗效比较

目的　比较小剂量重组组织型纤溶酶原激活剂 (rt PA)与直接冠状动脉 (冠脉 )支架术治疗急性心肌梗死 (AMI)的临床疗效。方法　 131例患者接受小剂量rt PA 5 0mg静脉溶栓治疗 (溶栓组 ) ,130例患者接受梗死相关动脉 (IRA)直接冠脉支架术 (支架组 ) ,比较两组之间患者的临床治疗效果。结果　小剂量rt PA溶栓治疗组IRA再通率为 81 7%,直接冠脉支架组再通率为 98 5 %,两组差异有显著性 (P <0 0 0 0 0 1)。溶栓组再发心肌梗死、需要择期冠脉支架术明显高于支架组 (分别为7 6 %比 1 5 %,P <0 0 5 ;2 0 6 %比 0 ,P <0 0 0 0 1)。溶栓组住院期间左心室射血分数明显低于支架组[(5 5 6± 13 4 ) %比 (6 5 8± 9 2 ) %,P <0 0 0 0 1]。溶栓组平均住院天数也明显多于支架组 (16± 7比11± 4,P <0 0 0 0 1)。溶栓组住院病死率高于支架组 ,但差异无显著性 (6 1%比 3 1%,P >0 0 5 )。结论　与小剂量rt PA静脉溶栓比较 ,直接冠脉支架术可明显增加IRA的再通率 ,更好地保护心功能 ,并缩短患者的住院时间。     

Pericardial effusion after intravenous recombinant tissue-type plasminogen activator for acute myocardial infarction

The effect of thrombolytic therapy on the frequency, time course and sequelae of pericardial effusion after myocardial infarction are unknown. A prospective, serial, 2-dimensional echocardiographic study of patients with myocardial infarction who received recombinant tissue-type plasminogen activator (rt-PA) was undertaken to address this issue. The study population comprised 52 of the 112 patients enrolled in the first Thrombolysis and Angioplasty in Myocardial Infarction trial at Duke University Medical Center. Enrollment in the serial echocardiography protocol was determined by equipment and support staff availability. Complete echocardiographic studies were performed within 90 minutes after initiation of thrombolytic therapy (day 0), and on days 1, 3 and 6. Patients undergoing serial echocardiography did not differ in demographic or clinical characteristics from those who did not. Pericardial effusion was present in 3 of 38 patients (8%) at day 0, in 2 of 44 (5%) at day 1, in 8 of 43 (19%) at day 3, and in 10 of 42 (24%) at day 6. By day 6, 3 of 10 pericardial effusions were moderate in size, 1 of 10 was large and the remainder were small. No patients developed echocardiographic or hemodynamic signs of cardiac tamponade. The prevalence and time course of pericardial effusion among patients with acute myocardial infarction who received rt-PA in this study are similar to observations reported in earlier studies in which patients did not receive thrombolytic therapy. Adverse sequelae of pericardial effusion after thrombolytic therapy are rare.     

重组葡激酶在急性心肌梗死中的溶栓疗效

目的 :观察重组葡激酶 (r SAK)在急性心肌梗死 (AMI)患者中的溶栓疗效。方法 :入选AMI患者 5例 ,年龄 <6 0岁 ,胸痛持续 <6h。冠状动脉造影 (CAG)明确梗死相关血管后 ,予r SAK 15mg静脉溶栓结合静脉肝素抗凝治疗 ,在溶栓后 15、30、45、6 0、90min ,1～ 2周重复CAG ,观察溶栓后梗死相关血管TIMI血流和残余狭窄 ,记录胸痛缓解情况、再灌注心律失常、ST段的演变、心肌酶峰值时间、相关并发症及心脏事件。结果 :CAG显示右冠状动脉近端病变和第一对角支近端病变各 1例 ;前降支近端病变 3例 ,溶栓前均完全闭塞。r SAK溶栓后血管再通率 10 0 % ,90min血流达TIMIⅢ级者 2例 ,TIMIⅡ～Ⅲ级者 2例 ,TIMIⅡ级者 1例 ,平均再通时间为(34 .0± 14.7)min。 5例均符合临床冠状动脉再通标准。随访中未见严重出血和心脏事件发生。结论 :r SAK 15mg静脉溶栓有较佳的效果 ,患者有良好的耐受性。     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗死23例临床分析

目的观察重组组织型纤溶酶原激活剂(recombinant tissue—type plasminogen activator,rt—PA)静脉溶栓治疗急性心肌梗死的疗效,探讨溶栓时间窗。方法23例心肌梗死患应用rt—PA静脉溶栓治疗,通过观察临床症状、心电图、心肌酶谱的变化,判断冠状动脉再通率,并观察出血的发生率及严重程度。结果23例患溶栓后冠状动脉再通17例,其中,发病6小时内13例溶栓冠状动脉再通11例,发病6～12小时内10例溶栓冠状动脉再通6例;1例再通24小时发生再梗死;2例出现牙龈出血;1例出现皮下出血。结论rt—PA静脉溶栓治疗心肌梗死在发病6小时内应用疗效显,发病6～12小时应用仍然有效。     

Renal artery embolism: thrombolysis with recombinant tissue-type plasminogen activator

The case of a patient with acute occlusion of the right renal artery due to an embolus is described. Using transoesophageal echocardiography, the left atrial appendage could be identified as the source of embolism. Twenty hours after the onset of symptoms, the embolus could be successfully dissolved with an intra-arterial low-dose infusion of recombinant tissue-type plasminogen activator (10 mg loading dose, 20 mg continuous infusion within 12 h).     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗死20例分析

目的 :探讨重组组织型纤溶酶原激活剂 (rt PA)静脉溶栓治疗急性心肌梗死 (AMI)的疗效及安全性。方法 :选择 2 0例AMI患者应用rt PA静脉溶栓治疗 ,观察临床症状、心电图、心肌酶谱的变化 ,判断冠状动脉再通率。结果 :① 2 0例AMI患者 ,冠状动脉再通 12例 ,再通率 6 0 %,其中发病 6h以内溶栓再通率 87.5 %(7/ 8) ,发病 6～ 2 4h溶栓再通率 4 1.7%(5 / 12 ) ,两者相比差异有显著性意义 (P <0 .0 5 )。②≤ 6 5岁患者的血管再通率与不良反应发生率与 >6 5岁组相比差异无显著性意义 (P >0 .0 5 )。结论 :rt PA静脉溶栓治疗AMI是一种安全、有效的方法 ,宜提倡急诊室溶栓。 >6 5岁患者行静脉溶栓治疗是安全可行的 ,但要根据患者的具体情况而定。     

A randomized, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator and emergency coronary angioplasty in patients with acute myocardial infarction

To determine the role of tissue-type plasminogen activator (t-PA) and immediate percutaneous transluminal coronary angioplasty (PTCA) in treating patients with evolving transmural myocardial infarction, 50 patients received t-PA (1.25 mg/kg iv over 3 hrs) or placebo according to 3:1 double-blind randomization 3.8 +/- 1.1 hr after onset of symptoms. At emergency coronary arteriography, patency of the infarct-related vessel was demonstrated in 32 of 38 (84%) patients receiving t-PA vs two of 12 (17%) receiving placebo (p less than .001). Of the 32 patients with recanalization after t-PA, 28 had a residual stenosis of at least 50% and underwent randomization a second time to immediate (n = 15) or no PTCA (n = 13). Immediate PTCA of the infarct-related vessel was successful in all 15 patients, with reduction of the residual diameter stenosis from 80.8 +/- 8.2% to 32.5 +/- 15.6% (p less than .001). The incidence of postinfarction angina (greater than or equal to 20 min of chest discomfort and reversible electrocardiographic changes) and reinfarction (documented by recurrent creatine kinase isoenzyme elevation) was reduced in the patients receiving t-PA and PTCA (2/15) compared with that in patients receiving t-PA alone (7/13; p = .006). At 1 week there was no difference in patency of the infarct-related vessel (12/15 t-PA and PTCA vs 9/13 t-PA only) or in global ventricular functional change between the two groups (0.5 +/- 10.4 SD/chord for t-PA and PTCA vs -2.1 +/- 8.2 SD/chord for t-PA only).(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary patency after intravenous infusion of recombinant tissue-type plasminogen activator in acute myocardial infarction

The relation between coronary patency after infusion of recombinant tissue-type plasminogen activator (rt-PA) and clinical and laboratory findings was assessed in patients with acute myocardial infarction. This study focused primarily on information available early in the hospitalization phase. Data were available for 243 patients who received the full dose of rt-PA and who had assessable coronary angiograms 90 min after the start of the intravenous infusion. The infarct-related vessel was scored by an independent assessment committee as being patent in 65% of patients. The left anterior descending coronary artery was involved in 53% of patients, and proximal localization of the infarct-related vessel occurred in 65%. In the majority of patients (85%), the infusion was started within 4 h of the acute event. Neither the angiographic location of the infarct-related vessel nor electrocardiographic evidence of infarct severity or location appeared to have a bearing on thrombolysis with rt-PA. Multivariate logistic regression analysis identified three independent predictors of coronary patency: hematocrit 43 to 47%, blood plasminogen level greater than or equal to 90% of normal and serum alkaline phosphatase greater than or equal to 82% of the local upper normal limit. In addition, the use of intravenous nitrates suggests a positive association with patency.     

Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial

Forty-five patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were prospectively randomized, two for one, to treatment of acute coronary thrombosis with intravenous recombinant human tissue-type plasminogen activator (rt-PA) or placebo. Each of five additional consecutive patients was treated with a high dose of rt-PA for 2 hr. Twenty-five of 33 patients (75%) receiving 0.5 to 0.75 mg/kg of rt-PA over 30 to 120 min had angiographically proven recanalization within 90 min of initiation of therapy. Only one of 14 patients given placebo had spontaneous recanalization within 45 min (p less than .001). Thirteen placebo-treated patients were crossed over to the intracoronary rt-PA group. Nine (69%) exhibited subsequent recanalization within 45 min. Levels of circulating fibrinogen decreased after treatment with rt-PA by an average of only 8% of baseline values. None of the patients manifested a depletion of fibrinogen level to below 100 mg/dl. Six patients who were completely unresponsive to rt-PA were subsequently treated with intracoronary streptokinase and none responded. Thus, either intravenous or intracoronary rt-PA induced coronary thrombolysis without eliciting clinically significant fibrinogenolysis in patients with evolving myocardial infarction due to thrombotic coronary occlusion.     

Coronary arterial thrombolysis with low-dose synergistic combinations of recombinant tissue-type plasminogen activator (rt-PA) and recombinant single-chain urokinase-type plasminogen activator (rscu-PA) for acute myocardial infarction

The effect of combined intravenous infusion of 10 mg of recombinant tissue-type plasminogen activator (rt-PA) and 10 mg of recombinant single-chain urokinase-type plasminogen activator over 1 hour on coronary artery recanalization and on the blood fibrinolytic system was studied in 9 patients with acute myocardial infarction and angiographically confirmed coronary artery occlusion. In 3 of these patients, prior infusion of 10 mg of rt-PA over 1 hour before the first angiogram had not produced coronary artery reperfusion. Complete recanalization was achieved in 7 patients and transient recanalization with reocclusion in 1 patient, whereas coronary artery occlusion persisted in 1 patient. At the end of the infusion, the fibrinogen level remained unchanged and no increase in fibrinogen degradation products was observed, whereas the alpha 2 antiplasmin level had decreased to 61 +/- 16% (mean +/- standard deviation) of the preinfusion level. Thus, combined intravenous infusion of rt-PA and recombinant single-chain urokinase-type plasminogen activator induces fibrin-specific coronary thrombolysis at approximately one-fourth of the dose currently used for each agent alone, which further documents the pharmacologic synergism of these agents.     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗死后的QT离散度变化

３６例急性心肌梗死患者接受重组组织型纤溶酶原激活剂（ｒｔ－ＰＡ）静脉溶栓治疗。其中有效２１例，无效１３例。有效组在溶栓后２小时、８小时、２４小时的ＱＴｃ离散度（ＱＴｃｄ）与溶栓前相比较，有下降趋势，但未达到统计显著性。无效组在溶栓后２小时、８小时、２４小时的ＱＴｃｄ与溶栓前相比较，有显著性延长（Ｐ＜０００１）。有效组与无效组相比，溶栓后２小时、８小时、２４小时之ＱＴｃｄ，差异有显著性（Ｐ＜０００１）。     

Comparative properties of two clinical preparations of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction

The biologic properties of two clinical preparations of recombinant human tissue-type plasminogen activator were studied in 52 patients with acute myocardial infarction. The first preparation (G11021) has been used in all clinical trials reported to date, whereas the second preparation (G11035) is now produced for future clinical use. When both preparations were infused intravenously for 90 minutes at rates of 4 to 11 micrograms/kg per min, plateau levels of the drug in plasma ranged from 0.52 +/- 0.15 to 1.8 +/- 0.4 micrograms/ml and were linearly correlated with the infusion rate. However, G11035 yielded plasma levels that were approximately 35% lower than those obtained with G11021 (p less than 0.025). The postinfusion disappearance rate of the drug from plasma could be described by a two compartment disposition model with the following pharmacokinetic variables. For G11021, an alpha half-life of 4.1 to 6.3 minutes, a beta half-life of 41 to 50 minutes, a central compartment volume of 3.5 to 5.4 liters, a total distribution volume of 28 to 44 liters and a plasma clearance of 450 to 640 ml/min. For G11035 these variables were 3.6 to 4.6 minutes, 39 to 53 minutes, 3.8 to 6.6 liters, 27 to 40 liters and 520 to 1,000 ml/min, respectively, indicating that G11035 is cleared more rapidly from the circulation. G11021 at 4 micrograms/kg per min and G11035 at 7 micrograms/kg per min did not effectively produce thrombolysis. A coronary reperfusion rate of 81% (13 of 16 patients) was obtained with 5.3 micrograms/kg per min of G11021 and a rate of 86% (6 of 7 patients) was obtained with 9.4 micrograms/kg per min of G11035.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anaphylactoid reaction during an infusion of recombinant tissue-type plasminogen activator for acute myocardial infarction

Potentially life-threatening immediate hypersensitivity reactions are extremely rare among patients treated with thrombolytic agents for suspected acute myocardial infarction. A patient who developed a severe reaction during an infusion of recombinant tissue-type plasminogen activator is described. Potential causal mechanisms for the reaction could be related either to nonmedicinal additives or complement activation. Implications for treatment in the setting of acute myocardial infarction are discussed.     

Coronary thrombolysis with tissue-type plasminogen activator

Although the value of reperfusion has not yet been convincingly established in humans, initial data with precise end points appear to indicate salutary effects. t-PA will have a clear role in the initial phase of treatment of myocardial infarction, but it must be administered promptly, and residual stenosis must be evaluated and treated if reocclusion is to be prevented. Optimum therapy may involve concomitant pharmacologic agents as well as mechanical or surgical intervention. Long-term goals must address the underlying pathophysiology of coronary atheromata formation and thrombogenesis and primary prevention.