Use of twenty-four hour infusions of intracoronary tissue plasminogen activator to increase the application of coronary angioplasty

Coronary arteries occluded by long lengths of thrombus are usually considered unattractive for angioplasty. Nine patients (8 male, mean age 50.1 years) undergoing angiography for unstable angina were found to have single vessel disease considered unsuitable for angioplasty as the vessel was occluded by a long length of thrombus. These patients were treated with 24 hr intracoronary infusions of 100 mg tPA in an attempt to make angioplasty feasible. Marked thrombolysis occurred in 7 patients who received uncomplicated infusions. One case was unsuccessful due to catheter displacement, while another had the infusion ceased due to an intracerebral bleed from a previously silent A-V malformation. This was the only major complication. Angioplasty was attempted in 6 of 7 cases where lysis had been achieved, with success in all lesions attempted. This reports shows that intracoronary tPA infused over prolonged periods produces excellent thrombolysis, making angioplasty feasible in some patients who were previously unsuitable. © 1992 Wiley-Liss, Inc.     

Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: importance of coronary angioplasty

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.     

Use of twenty-four hour infusions of intracoronary tissue plasminogen activator to increase the application of coronary angioplasty.

Coronary arteries occluded by long lengths of thrombus are usually considered unattractive for angioplasty. Nine patients (8 male, mean age 50.1 years) undergoing angiography for unstable angina were found to have single vessel disease considered unsuitable for angioplasty as the vessel was occluded by a long length of thrombus. These patients were treated with 24 hr intracoronary infusions of 100 mg tPA in an attempt to make angioplasty feasible. Marked thrombolysis occurred in 7 patients who received uncomplicated infusions. One case was unsuccessful due to catheter displacement, while another had the infusion ceased due to an intracerebral bleed from a previously silent A-V malformation. This was the only major complication. Angioplasty was attempted in 6 of 7 cases where lysis had been achieved, with success in all lesions attempted. This reports shows that intracoronary tPA infused over prolonged periods produces excellent thrombolysis, making angioplasty feasible in some patients who were previously unsuitable.     

Use of tissue plasminogen activator in the emergency department for acute myocardial infarction

Tissue plasminogen activator (t-PA) is a new intravenously administered thrombolytic agent currently being tested for emergency treatment of acute myocardial infarction (AMI). This report summarizes our clinical experience using t-PA to treat AMI in the emergency department and describes current protocols for its use in treating AMI. Between September 1985 and August 1986, t-PA was administered to 105 patients with AMI according to clinical research protocols. All were treated within six hours of the onset of pain. Thrombolysis was achieved in 80 patients (76%). Percutaneous transluminal coronary angioplasty was performed acutely for residual stenosis in 58 (55%). Thirty-three patients (31%) exhibited cardiac arrhythmias during treatment, 18 (17%) requiring emergency intervention. Periaccess hematoma developed in 50 patients (48%); transfusion of one or more units of blood was required in 22 of 97 (23%), excluding those undergoing urgent coronary artery bypass grafting. Overall 30-day survival was 94%. Recombinant t-PA appears to be an effective thrombolytic agent that may soon be standard emergency therapy for patients with AMI. Administration begun in the ED can achieve a high rate of reperfusion, but requires careful monitoring and the support of a coordinated acute cardiac care program, including emergency cardiac catheterization and cardiac surgery, to achieve the best results.     

Intracranial hemorrhage after use of tissue plasminogen activator for coronary thrombolysis

Tissue plasminogen activator (tPA), an approved coronary thrombolytic agent, can cause serious bleeding. We report the cases of six patients with intracranial hemorrhage after tPA treatment for acute myocardial infarction. None of the patients were hypertensive at admission, and only one was hypertensive during therapy. Intravenous tPA, 100 mg, was followed by continuous intravenous heparin infusion; intracranial hemorrhage occurred between 2 and 14 hours after tPA infusion ended and between 3 and 17 hours after heparin therapy was started. The partial thromboplastin time (PTT) was excessively prolonged (from 81 s to more than 150 s) in all patients at onset of intracranial hemorrhage. The intracerebral hematomas were predominantly of lobar location, and two patients had multiple simultaneous hemorrhages. Four patients died from massive intracranial hemorrhage; the mechanism for these hemorrhages was unclear. Factors possibly related to hemorrhage include a systemic fibrinolytic state or a platelet anti-aggregant effect produced by tPA and enhanced hemorrhagic tendency caused by the combined effects of tPA and heparin. Local vascular changes at the bleeding site remain as potential contributing factors for isolated intracranial hemorrhage.     

Heparin monitoring in the coronary care unit after percutaneous transluminal coronary angioplasty

The rate of acute restenosis in patients after percutaneous transluminal coronary angioplasty (PTCA) is related to thrombotic complications triggered by the PTCA. This risk is reduced by anticoagulating the patients with heparin after the procedure. The anticoagulation state of patients receiving heparin therapy is routinely monitored with the activated partial thromboplastin time (APTT) test. In an effort to provide more timely results regarding the status of patients who are receiving heparin after PTCA, a study was conducted to see whether low-range activated clotting time measurement (LR ACT) performed at the bedside could provide information comparable to that from APTT values determined in the laboratory. The study showed that the LR ACT values were comparable to laboratory-generated APTT values (R2 = 0.68). The LR ACT data generated were superior to the APTT data in terms of timeliness and the wider range of heparin levels covered. Having these values available allowed the CCU staff to react rapidly to changes in the patient's coagulation status.     

Prediction of coronary artery reperfusion after tissue plasminogen activator infusion

We investigated whether clinical and laboratory variables can predict perfusion status after t-PA administration, by using the data from 138 patients who received t-PA during the Thrombolysis in Myocardial Infarction (TIMI) I study. All clinical and laboratory variables that were collected at baseline or during perfusion for TIMI I were evaluated by the current study. Via stepwise discriminant analysis, 7 variables were closely associated with perfusion status at 90 minutes (listed in the order of their discriminant effect): baseline grade of stenosis in the infarct-related coronary artery, whether nausea was present during the infusion, baseline aspartate aminotransferase (SGOT) concentration, whether arrhythmias were present during the infusion, baseline fibrinogen concentration, baseline partial thromboplastin time, and baseline diastolic blood pressure. Baseline severity of stenosis and the likelihood of there being reperfusion were inversely related. Eighty-four percent of patients with adequate perfusion after 90 minutes of t-PA infusion were classified correctly, but only 50% of those without perfusion at 90 minutes were classified correctly. In addition, since 70% of the TIMI I patients, on average, did achieve perfusion, the use of these 7 variables added little predictive information. Our findings suggest that 1) there is as yet no practical way to predict reperfusion after t-PA therapy and 2) the severity of coronary stenoses, if known ahead of time, should be considered when selecting patients for thrombolytic therapy.     

Intracranial hemorrhage after coronary thrombolysis with tissue plasminogen activator.

PURPOSE AND METHODS: We analyzed the clinical, laboratory, and radiologic data in nine patients who sustained an intracranial hemorrhage (ICH) after receiving intravenous recombinant tissue plasminogen activator (rt-PA) and heparin for treatment of acute myocardial infarction (MI). Our purpose was to delineate the clinical and radiologic features of the ICHs, as well as to determine their potential risk factors and mechanisms. RESULTS: Among 1,700 patients with an acute MI treated with an investigational two-chain rt-PA, duteplase (Burroughs Wellcome Co., Research Triangle Park, NC), nine (0.53%) developed symptomatic ICH. Neurologic symptoms occurred between 7 and 96 hours after onset of rt-PA therapy. All patients received heparin concomitantly for prevention of coronary reocclusion. The activated partial thromboplastin times (aPTTs) in five of eight (63%) patients at onset of ICH were excessively prolonged (greater than two times control); hypofibrinogenemia occurred in only one of five (20%) patients tested; and thrombocytopenia was present in only one of the nine (11%) patients. Fibrin degradation products (FDPs) were elevated in all five patients tested. Minor hemorrhage (not requiring transfusion) outside the central nervous system occurred in five of the nine patients with ICH. The ICHs were often of lobar location and of moderate to large size. They occurred at multiple sites in three patients, and were fatal in four instances (44%). CONCLUSIONS: The incidence of ICH in this series was low, and consistent with figures reported from studies with alteplase in patients with acute MI. The mechanisms of these hemorrhages remain unclear; while hypofibrinogenemia was not a uniform finding, excessive prolongation of the aPTT and elevated FDPs may have contributed to the occurrence of ICH in some patients. Still unidentified local cerebrovascular factors may play an additional role in causing ICH. In order to further clarify the mechanisms of ICH in the setting of thrombolytic therapy, prospective data collection on probable risk factors for ICH in patients with acute MI treated with rt-PA will be required.     

Use of FemoStop system for arterial puncture site closure after coronary angioplasty

Different protocols exist concerning the method and timing of post-coronary angioplasty arterial puncture site closure. Easy handling and good effectiveness are well-documented for the Femostop femoral artery compression system; however, no hard data exist concerning the relationship between heparin anticoagulation level and femoral artery compression time (FSCT). Thus, we prospectively randomized 267 patients after elective percutaneous transluminal coronary angioplasty (PTCA) into two groups [group A (n=137) had early sheath removal 6 to 8 hours after PTCA; group B (n=130) had late sheath removal 14 to 16 hours after PTCA] and analyzed the dependence of the FSCT on the heparin anticoagulation level (aPTT) and the incidence of vagal reactions and puncture site complications. FSCT was significantly longer in group A (69+/-27 minutes versus 45+/-15 minutes; p<0.001) with high heparin anticoagulation level (aPTT, 88+/-46 seconds) in comparison to group B with low heparinization (aPTT, 59+/-34 seconds). Vagal reactions occurred more frequently in group A (15.3% versus 10.0%; p<0.01) and the incidence of minor hemorrhage at the arterial puncture site was also increased (9.5% versus 3.1%; p<0.05). In the clinical setting of intensive heparin anticoagulation and early sheath removal after PTCA (<8 hours), the FemoStop system cannot be recommended due to prolonged femoral artery compression times.     

急性脑梗死患者重组组织型纤溶酶原激活物静脉溶栓后脑出血

重组组织型纤溶酶原激活物(recombinant tissue plasminogen activator,rtPA)静脉溶栓是急性缺血性卒中最有效的治疗手段,其最严重的并发症为有症状脑出血,文献撒道其总体发生率为6%,与血管损伤和通透性增加有关.某些临床特征、影像学和实验室检查可预测脑出血并发症风险.溶栓治疗后发生脑出血并发症的患者病死率和致残率极高,预后很差.文章对溶栓后脑出血的分型、发生率、预测因素和预后进行了综述.     

Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction

Infarct artery patency rates at 90 minutes after coronary thrombolysis using recombinant tissue-type plasminogen activator (rt-PA) with and without concurrent heparin anticoagulation have been shown to be comparable. The contribution of heparin to efficacy and safety after thrombolysis with rt-PA is unknown. In this pilot study, 84 patients were treated within 6 hours of onset of acute myocardial infarction (mean of 2.7 hours) with the standard dose of 100 mg of rt-PA over 3 hours. Forty-two patients were randomized to receive additionally immediate intravenous heparin anticoagulation (5,000 U of intravenous bolus followed by 1,000 U/hour titrated to a partial thromboplastin time of 1.5 to 2.0 times control) while 42 patients received rt-PA alone. Coronary angiography performed on day 3 (48 to 72 hours, mean 57) after rt-PA therapy revealed infarct artery patency rates of 71 and 43% in anticoagulated and control patients, respectively (p = 0.015). Recurrent ischemia or infarction, or both, occurred in 3 (7.1%) anticoagulated patients and 5 (11.9%) control patients (difference not significant). Mild, moderate and severe bleeding occurred in 52, 10 and 2% of the group receiving anticoagulation, respectively, and 34, 2 and 0% of patients in the control group, respectively (p = 0.006). These data indicate that after rt-PA therapy of acute myocardial infarction, heparin therapy is associated with substantially higher coronary patency rates 3 days after thrombolysis but is accompanied by an increased incidence of minor bleeding complications.     

Applicability of percutaneous transluminal coronary angioplasty to patients with recombinant tissue plasminogen activator mediated thrombolysis

To test the utility and safety of percutaneous transluminal coronary angioplasty (PTCA) after recombinant tissue plasminogen activator (t-PA), we performed the procedure in all suitable candidates with acute myocardial infarction (MI) who had successful t-PA mediated coronary thrombolysis. Twenty consecutive patients with MI received t-PA after coronary angiographic conformation of total occlusion. Successful recanalization with t-PA was achieved in 13 patients, leaving a residual obstruction of 84 ± 6% in the nine patients for whom PTCA was attempted at a mean of 21.6 h. Success was achieved in seven patients, leading to a residual lesion of 29 ± 7%. In the two patients for whom PTCA was unsuccessful, total reocclusion occurred prior to the attempt despite therapy with heparin, aspirin, dipyridamole, and nifedipine. All PTCA procedures were uncomplicated. Serial two-dimensional echocardiography at 10 days, compared to admission, demonstrated infarct zone wall motion index improvement in the patients with successful PTCA (group A, 0.83 ± 0.36 to 1.46 ± 0.49) as compared to the 13 patients without thrombolysis or successful PTCA (group B, 0.61 ± 0.26 to 0.66 ± 0.39), (P < 0.05). One patient of group A sustained a massive stroke at 2 weeks after hospital discharge. In the remaining six patients, follow-up exercise testing and/or coronary arteriography demonstrated a negative treadmill test and/or patent infarct vessel, respectively. After successful PTCA, no patient had clinical signs of reocclusion, reinfarction, postinfarction angina, or congestive heart failure. At 9.4 ± 2 months, all six patients are asymptomatic and have returned to work. Thus, sequential PTCA after t-PA can be performed safely and successfully in patients with MI and this approach may be associated with improved regional function and a favorable post-MI course.     

Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty

To determine predictors of acute coronary closure after PTCA performed with steerable catheter systems, we compared 140 procedures complicated by acute closure and 311 representative successful attempts from 4,772 procedures performed between April 1982 and March 1986. Sixteen clinical, 35 angiographic, and seven procedural variables were analyzed. Multivariate analysis found seven independent preprocedural factors related to closure: stenosis length of 2 or more luminal diameters, female gender, stenosis at a bend point of 45 degrees or more, stenosis at a branch point, stenosis-associated thrombus (filling defect or staining), other stenoses in the same vessel, and multivessel disease. In addition, four procedural factors were found to be associated with closure by univariate analysis: post-PTCA percent stenosis (p less than .001), intimal tear or dissection (p less than .001), use of prolonged heparin infusion (p less than .001), and post-PTCA gradient of 20 mm Hg or more (p = .004). Multivariate analysis of both preprocedural and procedural variables found six factors independently related to closure: post-PTCA percent stenosis, dissection, prolonged post-PTCA use of heparin, branch point location, fixed bend point location, and other stenoses in the vessel dilated. The risk of coronary closure after PTCA has many determinants. While an estimation of risk can be made before performing PTCA, the most powerful predictors of closure can only be assessed during the procedure itself.     

Streptokinase and tissue plasminogen activator in acute myocardial infarction

The use of thrombolytic agents for the treatment of myocardial infarction is increasing. Many community hospitals are infusing SK intravenously and those with cardiac catheterization laboratories often use intracoronary SK and angioplasty. Tissue plasminogen activator is undergoing extensive clinical trials, and reports of this research should add to our knowledge of this new therapy. Recently, benefits from thrombolytic therapy such as increased ejection fraction, improved regional wall motion, and short-term decreases in mortality have been documented. Both the GISSI trial that recruited 11,712 patients in Italy and the Netherlands trial documented significant short-term decreases in mortality after therapy with SK compared with control groups. As this information reaches the medical community, we may see an increase in the use of thrombolytic therapy during acute myocardial infarction. Additionally, community education service organizations should reemphasize the importance of seeking help early after the signs and symptoms of acute myocardial infarction appear to promote early treatment and potential salvage of greater amounts of myocardium. The long-term prognosis of patients who have been successfully reperfused and the best management after thrombolytic therapy is not yet known. Future problems and benefits from this therapy are still to be determined.     

急性冠状动脉综合征患者内皮组织纤溶酶原激活剂储备功能的研究

目的 探讨急性冠状动脉综合征９ＡＣＳ）患者内皮组织纤溶酶原激活剂（ｔＰＡ）储备功能的变化规律。方法 ３５例ＡＣＳ患者,其中急性心肌梗死１５例和不稳定心绞痛２０例,于入院当日和入院后第１０天采集静脉血样以测定纤溶、凝血指标,以评价内皮ｔＰＡ储备功能;同时做静脉闭塞试验以确定最大内皮ｔＰＡ释放,并与稳定性心绞痛９ＳＡＰ）和正常人作对比。结果 ＡＣＳ患者ｔＰＡ含量、纤溶酶原激活剂抑制物－１（ＰＡＩ－１）     

Coronary stent implantation in acute vessel closure 48 hours after an unsatisfactory coronary angioplasty

We report the implantation of a balloon-expandable stent in a patient with acute vessel closure in the state of evolving myocardial infarction following 48 hr after unsatisfactory coronary angioplasty. The stent was implanted after successful recanalization of an occluded left anterior descending artery, with repeated unsatisfactory results of balloon angioplasty. Adjunct thrombolytic therapy was contraindicated. No residual stenosis was documented in immediate control angiograms, or after 24 hr, 3 weeks, and 4 months.     

Beyond tissue plasminogen activator: mechanical intervention in acute stroke

Mechanical interventions in acute ischemic stroke promise to provide emergency physicians with tools to treat patients in whom conventional thrombolysis might be ineffective or contraindicated, including most patients with stroke who arrive at the emergency department beyond the 3-hour time window for intravenous tissue plasminogen activator. A systematic MEDLINE literature review was performed. Endovascular interventions currently in early human clinical trials include the use of lasers, ultrasonography, angioplasty, microsnares, and a variety of clot-retrieval devices. Potential advantages of these approaches include more rapid recanalization of occluded vessels, reduced or no exposure to fibrinolytic agents, and a longer treatment window. Early safety trials are promising, with serial improvements in device design to minimize trauma to cerebrovascular endothelium and accelerate vessel recanalization. The purpose of this review is to provide the emergency medicine community with an understanding of these promising and emerging approaches to acute stroke therapy.     

介入封堵术对成人先天性心脏病患者血浆t-PA和PAI-1水平的影响

目的评价介入封堵术对成人先天性心脏病(CHD)患者血浆组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制物-1(PAI-1)水平的影响.方法采用酶联免疫吸附法检测70例CHD患者及30例健康人(正常对照组)血浆t-PA、PAI-1水平.所有CHD患者分别于介入封堵术前头天,术后24 h,1、3、6、12个月检测血浆t-PA、PAI-1水平.结果介入封堵术前,CHD患者血浆t-PA、PAI-1水平比正常对照组明显增高(P＜0.01).介入封堵术后1个月,CHD组血浆PAI-1水平开始逐渐下降,术后6个月恢复正常水平;血浆t-PA水平在术后1个月升高,术后3个月始下降,术后6个月恢复正常水平.结论介入封堵术可通过改变血浆t-PA、PAI-1水平而改善成人CHD患者的内源性纤溶功能.     

急性脑梗死超早期的r-tPA溶栓治疗

目的　探讨重组组织型纤溶酶原激活物 (r- t PA)溶栓治疗发病 6h内脑梗死的疗效及并发症。方法　共收集本院 2 0 0 1～ 2 0 0 3年 43例溶栓治疗的急性脑梗死病例 ,其中 32例经静脉溶栓 ,1 1例经动脉溶栓。分别对两组病例进行溶栓前后的 NIHSS,ESS及 ADL量表评分 ,根据 3个月时的随访记录判断溶栓疗效 (分为治愈、显效、有效、无效 )。结果　静脉溶栓组和动脉溶栓组的总有效率分别为 79.3%、90 .9% ;治愈率分别为2 7.6%、45.5% ,溶栓后脑出血率分别为 1 0 .3%、1 8.2 % ,但由于动脉组例数较少 ,两组疗效差异无统计学意义。结论　 6 h内溶栓治疗是安全有效的 ,低 NIHSS的患者有较好转归。