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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombus removal using percutaneous rotational thrombectomy (PRT), followed by tissue plasminogen activator (t-PA), was studied by contrast angiography and fiberoptic angioscopy in a canine femoral artery model of thrombosis. After thrombus induction and following each treatment, comparisons were made between angioscopy and angiography for the detection of thrombus and subintimal dissection. Angioscopic images were scored in a blinded fashion for lining, protruding, or occlusive thrombus (class 1,2, or 3) as well as estimated wall coverage by thrombus. Angiograms were studied for percent diameter stenosis and the presence of flaps. Following external forceps crush injury of 18 arteries, two hour occlusion, and injection of thrombin, mean angiographic stenosis was 66%, thrombus coverage by angioscopy was 81%, and mean angioscopy class was 2.5. Following PRT, stenosis decreased to 27% (p less than 0.008), thrombus coverage was reduced to 49% (p less than 0.02), and angioscopy class dropped to 2.0 (p less than 0.07). After t-PA treatment, these values were further reduced to 25% (p = NS), 26% (p less than 0.02), and 1.3 (p less than 0.008), respectively. In comparison to angiography, subintimal dissection (seen as flaps) and thrombus (lining, protruding, or occlusive) were present significantly more often by angioscopy (p less than 0.001). It is concluded that PRT results in significant thrombolysis, apparent by angiography and angioscopy. Follow-up t-PA can produce additional, incremental thrombolysis, apparent only by angioscopy. A beneficial role for t-PA following mechanical thrombolysis is suggested by this model. The superior sensitivity of angioscopy for detection of flaps and thrombus is underscored by this study.
Cathet Cardiovasc Diagn 1991 Nov
PMID:Thrombolysis by rotational thrombectomy followed by tissue plasminogen activator: evaluation by angioscopy. 176 46

Intracoronary tissue-type plasminogen activator (t-PA) was employed successfully before, after, or in place of coronary artery angioplasty in four patients referred for emergency cardiac catheterization during evolving myocardial infarction. The potential roles of intracoronary thrombolysis, dose considerations for intracoronary t-PA, factors influencing the choice of plasminogen activator, and safety issues are discussed.
Cathet Cardiovasc Diagn 1990 Feb
PMID:Tissue-type plasminogen activator: intracoronary applications. 210 93

Many studies are currently evaluating the potential role of thrombolytic therapy in patients with ischemic syndromes who have undergone previous coronary artery bypass grafting. Limited experience has been published regarding the use of local urokinase and streptokinase infusions and the use of systemic recombinant tissue-type plasminogen activator as thrombolytic agents in patients with previous coronary artery bypass surgery. To date, however, there has been no published experience regarding the use of recombinant tissue-type plasminogen activator (rt-PA) either systemically or locally in the post-bypass patient where angiographic demonstration of aortocoronary saphenous vein graft obstruction was available pre- and post-therapy. Similarly there has been no previous report of the use of rt-PA infused locally to recanalize an occluded aortocoronary saphenous vein graft. This report describes successful thrombolysis and subsequent balloon angioplasty of saphenous vein grafts with angiographically documented thrombus using systemic and local rt-PA infusion.
Cathet Cardiovasc Diagn 1990 Mar
PMID:Systemic and local saphenous vein graft thrombolysis using a tissue plasminogen activator. 210 79

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.
Cathet Cardiovasc Diagn 1990 Jun
PMID:Prediction of coronary artery reperfusion after tissue plasminogen activator infusion. 211 85

The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Trial was a multicenter, randomized trial designed with the purpose of determining the clinical impact of immediate or deferred angioplasty on left ventricular function following successful myocardial reperfusion with tissue plasminogen activator (t-PA). Results from this trial indicate that immediate coronary angioplasty following successful thrombolysis, when coronary artery anatomy is suitable, offers no advantage over delayed elective angioplasty. The purpose of this article is to discuss and critically review the TAMI trial. Details of the trial will be discussed followed by a critique and implications for nursing.
Prog Cardiovasc Nurs
PMID:The thrombolysis and angioplasty in myocardial infarction (TAMI) trial: review and nursing implications. 211 22

For decades management of acute myocardial infarction (AMI) consisted of bed rest, oxygen, prevention for thromboembolic complications, and treatment of arrhythmias and heart failure. In the last years a more aggressive treatment of AMI has been developed, based on the following three basic principles: (1) Mortality of patients with AMI is determined by the infarct size and the degree of left ventricular dysfunction. (2) The time interval between the onset of coronary occlusion and any intervention to limit infarct size is brief and takes usually not more than three to four hours. (3) After the acute phase of infarction a lot of patients remain at high risk of fatal coronary events, i.e. reinfarctions. The angiographic findings during the first hours of AMI showed in about 80% of patients an obstructive coronary thrombus and led to efforts to dissolve the offending thrombi. The demonstration that coronary thrombi can be lysed in about 80% of cases within 60 minutes after the intracoronary injection of thrombolytic agents (streptokinase or urokinase) has boosted the reperfusion therapy in AMI in the hope that ischemic myocardium might be salvaged. Intracoronary infusion of thrombolytic agents however, can be applied only in a minority of patients with AMI because coronary angiography and a skilled team of investigators are required, therefore a short-time intravenous high dose streptokinase infusion was developed. In the meantime two large double blind randomized trials (ISAM and GISSI) could demonstrate a reduction in hospital mortality in AMI especially by early treatment with intravenous streptokinase. Conventional thrombolytic agents produce a systemic lytic state with the possibility of hemorrhage, therefore recombinant tissuetype plasminogen activator (rt-PA) and two other drugs, acylated streptokinase and pro-urokinase, were developed with the aim of inducing coronary thrombolysis without severe systemic lytic state, but the efficacy of these new drugs remains to be demonstrated in randomized trials versus conventional thrombolytic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Thorac Cardiovasc Surg 1987 Dec
PMID:The therapy of acute myocardial infarction: current state of the art. 244 99

The pharmacokinetics and thrombolytic properties of a variant of human tissue-type plasminogen activator (t-PA), obtained by deletion mutagenesis of the NH2-terminal fibronectin-like finger (F) and epidermal growth factor (E) domains, and substitution of the three known glycosylated Asn residues by Gln (t-PA-delta FE3X), were studied in dogs with a copper coil-induced thrombosis of the left anterior descending coronary artery. Bolus injections were given during 2 min to groups of three dogs. Injection of 0.15 mg/kg resulted in peak antigen levels in plasma of 1.58 +/- 0.72 micrograms/ml (mean +/- SEM) and caused reperfusion within 14 +/- 6 min. With 0.075 mg/kg, corresponding values of 0.81 +/- 0.20 micrograms/ml and 31 +/- 15 min were obtained. A bolus of 0.038 mg/kg yielded plasma peak levels of 0.43 +/- 0.20 micrograms/ml but did not cause coronary recanalization within 3 h. A bolus injection of natural t-PA (Mel-t-PA) at a dose of 0.1 mg/kg in four dogs resulted in plasma peak levels of 0.46 +/- 0.09 micrograms/ml and caused partial coronary artery reperfusion within 3 h in one of four dogs (after 31 min). None of these injections caused a significant decrease of the fibrinogen level. Pharmacokinetic parameters for t-PA-delta FE3X were alpha half-life (t1/2) 14-18 min, beta t1/2 72-125 min, and plasma clearance 21-36 ml/min. For Mel-t-PA, the corresponding values were 3 min, 8 min, and 520 ml/min. We conclude that the variant t-PA-delta FE3X has a markedly longer plasma t1/2 than does Mel-t-PA and, when administered as a bolus injection, a higher thrombolytic efficacy.
J Cardiovasc Pharmacol 1988 Apr
PMID:Pharmacokinetics and thrombolytic properties of a nonglycosylated mutant of human tissue-type plasminogen activator, lacking the finger and growth factor domains, in dogs with copper coil-induced coronary artery thrombosis. 245 51

The thrombolytic dose-response effectiveness and pharmacokinetics of tissue-type plasminogen activator (rt-PA) was evaluated in anesthetized, open-chest dogs instrumented for the measurement of systemic hemodynamics. Intracoronary thrombi were formed by injecting thrombin (100 U) and CaCl2 (50 microM) into a cannulated, isolated segment of the left anterior descending coronary artery (LAD). Coronary blood flow was measured by placing an electromagnetic flow probe proximal to the LAD thrombus. Thirty minutes after formation of a stable LAD thrombus, intravenous infusion of rt-PA was given at rates of 0.5, 1, 2, 4, or 8 micrograms/kg/min (n = 8/dose) for 60-90 min, and the animals were followed for an additional 30 min. In vehicle-treated animals, residual thrombus wet weight, determined at the end of the experiment, was 30 +/- 4 mg (mean +/- SEM, n = 8) and spontaneous reperfusion did not occur. The rt-PA produced a dose-related increase in the number of animals reperfusing, a decrease in the time to reperfusion, and a decrease in residual thrombus weight, but had no effect on systemic hemodynamics. The increase in infusion rate from 0.5 to 4 micrograms/kg/min resulted in a linear increase in both the steady-state rt-PA plasma concentration and the area under the rt-PA plasma concentration versus time curve (n = 3-5 animals/dose); between the infusion rates of 4 and 8 microgram/kg/min there was a disproportionate increase in both these parameters that was due to a decrease in the total systemic clearance of rt-PA. The postdosing elimination half-life (t1/2 alpha) did not differ significantly at any dose of rt-PA, and the pooled half-life (t1/2 alpha) for all doses of rt-PA was 2.36 +/- 0.12 min (n = 19).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1988 Sep
PMID:Evaluation of the acute hemodynamic effects and pharmacokinetics of coronary thrombolysis produced by intravenous tissue-type plasminogen activator in the anesthetized dog. 246 3

The current revolution in the treatment of acute myocardial infarction by means of thrombolytic therapy has as its underlying strategy three aims: early restoration of the blood flow in order to salvage jeopardized but still viable tissues; limitation of acute consequences of ischemic heart disease, such as infarct size, ventricular fibrillation, and pericardial effusion; and preservation, as far as possible, of ventricular function. It is also hoped that these three achievements will result in reduced short- as well as long-term mortality rates. The techniques employed in this overall strategy are still under investigation, and several leading pharmacological compounds vie for supremacy: streptokinase (SK) and its anisoylated form (APSAC), recombinant technique tissue type plasminogen activator (rt-PA), and urokinase (UK) with or without prourokinase (PUK). Other pharmacological agents, such as angiotensin converting enzyme (ACE) inhibitors, beta-blockers, Ca2+ antagonists, and O2 radical scavengers, might find here their "finest hour" yet. In addition, the underlying anatomy may require early or, where needed, delayed PTCA, backed up by coronary artery bypass grafting. Thus, the tactics of the intervention may vary from case to case and indeed from center to center depending on experience and facilities, but the strategic conclusion is clearly the same: early reperfusion is a must if one wishes to save ischemic but still viable tissue.
J Cardiovasc Pharmacol 1989
PMID:Acute consequences of ischemic myocardial damage. 248 24

Intracoronary thrombi resulting in acute myocardial ischemia can often be lysed by thrombolytic agents. We examined the potential of a fibrin(ogen)-degradation product pentapeptide 6A (Ala-Arg-Pro-Ala-Lys), which increases coronary blood flow partly by stimulation of prostacyclin release, in reestablishing coronary blood flow in dogs with experimentally induced thrombus. An occlusive thrombus in the circumflex coronary artery was created by electrical stimulation of the endothelial surface. After the occlusive thrombus was stable without electrical current for at least 15 min, peptide 6A (5 mumol/min for 20 min intracoronary) or tissue-plasminogen activator (t-PA) [10 micrograms/kg/min for 20 min intravenously (i.v.)] was randomly administered. Peptide 6A administration reestablished coronary blood flow (peak 16 +/- 2 ml/min, mean +/- SE) in 6 of 12 animals with occlusive coronary thrombus. Mean time to blood flow reestablishment was 5.3 +/- 2.2 min, but the reflow was short lived (mean duration of reflow: 15.7 +/- 1.6 min). t-PA reestablished coronary blood flow (peak 19 +/- 3 ml/min) in 4 of 10 animals. The time of flow reestablishment was 12.0 +/- 3.9 min and the reflow persisted for 22.0 +/- 3.1 min. Peptide 6A administration was associated with an increase in coronary venous plasma 6-keto-PGF1 alpha, indicating stimulation of prostacyclin release. This study demonstrates the potential of peptide 6A in reestablishing coronary blood flow in a canine model of coronary thrombosis. This transient effect is associated with release of prostacyclin, which may be beneficial because of its vasodilator and platelet inhibitory effects.
J Cardiovasc Pharmacol 1989 Jun
PMID:Effects of peptide 6A on coronary blood flow dynamics in canine coronary thrombosis. 248 73


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