Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the thrombolytic dose-response relationship of a recombinant plasminogen activator (rPA) (BM 06.022) compared with alteplase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle 2 and protease domains of human tissue PA (tPA) and lacks oligosaccharide side chains because of its expression in Escherichia coli. Thrombus formation in anesthetized, open-chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery in the presence of a critical stenosis. Intravenous bolus injection of BM 06.022 (50, 100, 140, and 200 kU/kg) or of alteplase (200, 800, 1,130, and 1,600 kU/kg) 30 min after coronary occlusion to six heparinized dogs per group achieved a dose-dependent increase in reperfusion rate and decrease in residual thrombus wet weight. Vehicle-treated dogs did not reperfuse. Semilogarithmic regression analysis showed that the effective dose that produced 50% reperfusion of BM 06.022 (83 kU/kg) was 11.6-fold lower than that of alteplase (951 kU/kg). Comparison with infusion experiments showed that intravenous bolus injection of 140 kU/kg of BM 06.022 was equieffective to a 90-min infusion of 800 kU/kg (= 1 mg/kg) of alteplase as a standard treatment regarding reperfusion rate (66%) and time to reperfusion (15 +/- 6 vs. 18 +/- 8 min). Pharmacokinetic analysis for functionally active BM 06.022 or alteplase in plasma revealed a total plasma clearance of 4.1-6.6 ml/min/kg for BM 06.022 and of 12.6-42.3 ml/min/kg for alteplase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary thrombolytic properties of a novel recombinant plasminogen activator (BM 06.022) in a canine model. 171 79

The purpose of this study was to determine if idazoxan, an alpha 2-adrenergic antagonist, could enhance the antithrombotic activity of pelrinone, a PDE III inhibitor, in a canine model of coronary thrombosis that uses electrical current to injure the coronary endothelium. Thrombus mass in vehicle-treated animals was 37.9 +/- 8 mg. Pelrinone, 0.625 and 2.5 mg/kg decreased thrombus size by 46 and 21%, respectively, while idazoxan, 0.75 mg/kg decreased thrombus mass by 43%. When this dose of idazoxan was combined with pelrinone, 0.625 and 2.5 mg/kg, thrombus mass was decreased by 71 and 91%, respectively. Antithrombotic efficacy correlated with the ability of these treatments to inhibit epinephrine-sensitized, collagen-induced platelet aggregation. Sixty minutes following drug administration, idazoxan, 0.50 mg/kg inhibited aggregation by 50%, while pelrinone, 0.625 and 2.5 mg/kg inhibited aggregation by 55 and 68%, respectively. Combined administration of idazoxan with pelrinone, 0.625 and 2.5 mg/kg resulted in 80 and 95% inhibition of aggregation, respectively. Similar trends in inhibiting platelet aggregation to epinephrine-sensitized ADP and arachidonic acid were also observed. Experimental treatments did not affect hematocrit or circulating platelet count, although pelrinone was observed to prolong prothrombin time slightly. To examine the effect of drug-induced increases in coronary blood flow on thrombus formation, the potassium channel activator drug cromakalim was studied at a dose (0.1 mg/kg) that increased coronary blood flow by 25-35 ml/min above baseline in sham control animals. Animals treated with cromakalim showed a shorter time to coronary occlusion (103 +/- 11 min) vs. vehicle (173 +/- 24 min) and developed larger thrombi (53.7 +/- 19 mg). These results demonstrate that coronary vasodilation does not contribute to antithrombotic activity in this model. Results from the study also show that alpha-adrenergic inhibition of platelet function can potentiate phosphodiesterase inhibitor antiaggregatory and antithrombotic activity.
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PMID:Antithrombotic activity of the phosphodiesterase III inhibitor pelrinone in a canine model of coronary artery thrombosis: enhancement of efficacy with concurrent alpha 2-adrenergic antagonism. 172 88

To assess the contribution of Factor IX/IXa, to intravascular thrombosis, a canine coronary thrombosis model was studied. Thrombus formation was initiated by applying current to a needle in the circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycyl-arginyl-Factor IXa (IXai), a competitive inhibitor of Factor IXa assembly into the intrinsic Factor X activation complex, bovine Factor IX, or heparin. Animals receiving saline or Factor IX developed coronary occlusion due to a fibrin/platelet thrombus in 70 +/- 11 min. In contrast, infusion of IXai prevented thrombus formation completely (greater than 180 min) at doses of 460 and 300 micrograms/kg, and partially blocked thrombus formation at 150 micrograms/kg. IXai attenuated the accumulation of 125I-fibrinogen/fibrin at the site of the thrombus by approximately 67% (P less than 0.001) and resulted in approximately 26% decrease in serotonin release from platelets in coronary sinus (P less than 0.05). Hemostatic variables in animals receiving IXai, remained within normal limits. Animals given heparin in a concentration sufficient to prevent occlusive thrombosis had markedly increased bleeding, whereas heparin levels that maintained extravascular hemostasis did not prevent intracoronary thrombosis. This suggests that Factor IX/IXa can contribute to thrombus formation, and that inhibition of IXa participation in the clotting mechanism blocks intravascular thrombosis without impairing extravascular hemostasis.
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PMID:Active site-blocked factor IXa prevents intravascular thrombus formation in the coronary vasculature without inhibiting extravascular coagulation in a canine thrombosis model. 193 60

The incidence of major complications associated with nonionic contrast media has not been defined in a large study. Accordingly, cardiovascular complications, especially thrombotic events, were prospectively evaluated in 8,517 consecutive patients undergoing diagnostic cardiac catheterization with either iopamidol (n = 6,293) or iohexol (n = 2,224). Thrombotic events were defined as coronary embolus, coronary occlusion, transient ischemic attack or stroke occurring at the time of catheterization. Thrombotic events occurred in 15 patients (0.18%). Coronary thrombus or embolus occurred in 7 patients, a thromboembolus from the ventricular catheter occurred in 1 patients and transient ischemic attack or stroke occurred in 7 patients. Six of 15 patients with thrombotic events were premedicated with heparin. Thrombotic events were unusual in that they tended to occur in clusters within short time intervals. On 1 occasion, a thrombus was observed in the catheter tip before embolization. Other cardiovascular complications were similarly low with an incidence of ventricular tachycardia/fibrillation of 0.1%, profound bradycardia of 0.2% and prolonged angina of 0.3%. There were 2 deaths unrelated to thrombotic events. Although the clinical thrombotic events associated with nonionic contrast have an unusual temporal clustering and may result in major complications, the overall incidence (0.18%) of these thrombotic complications with nonionic contrast agents is quite similar to that reported with ionic contrast media.
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PMID:Thrombotic and cardiovascular complications related to nonionic contrast media during cardiac catheterization: analysis of 8,517 patients. 235 55

Thrombotic coronary artery occlusion is now recognized as the usual cause of acute myocardial infarction. The thrombus usually forms at the site of intimal disruption over an atherosclerotic plaque. Following coronary occlusion, myocardial necrosis begins within 40 minutes in the subendocardium and progresses outward toward the epicardium over the next several hours. The intracoronary infusion of streptokinase will produce lysis of the occluding thrombus in up to 80% of patients. It appears that reperfusion with streptokinase in the first few hours following the onset of the myocardial infarction produces a small increase in late left ventricular function, though ECG and enzyme evidence of acute myocardial infarction are not prevented. The improvement in left ventricular function is variable from patient to patient and has not been demonstrated in all the randomized studies to date. The time limit for myocardial salvage may not be the same in all patients. The greatest benefit is probably achieved with reperfusion in the first 4-6 hours, although some benefit may occur as late as 18 hours after the onset of infarction. Many patients who receive intracoronary infusion of streptokinase develop a systemic lytic state, though serious bleeding complications in carefully selected patients are infrequent. High-dose IV streptokinase is easier, cheaper, and quicker to initiate than intracoronary streptokinase but is probably less effective than the intracoronary route in producing rapid lysis of the occluding coronary thrombus. The optimal dose and rate of administration of IV streptokinase have not been determined. The final role and ultimate benefit of thrombolytic therapy of myocardial infarction have not yet been determined, but some of the issues may be clarified by the larger randomized trials now under way. It appears, at present, that the use of intracoronary streptokinase may have a role in the treatment of selected patients with acute myocardial infarctions in institutions with the facilities and the personnel necessary to perform this procedure safely. In the future, thrombolytic therapy may also have a place in the treatment of selected patients with unstable angina and post-myocardial infarction angina. The future availability of more selective thrombolytic agents may make the early IV therapy of myocardial infarction a safer, more effective option and expand the indications for thrombolytic therapy.
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PMID:Thrombolytic therapy of acute myocardial infarction. 666 25

The angiographic features of non-Q-wave acute myocardial infarction (AMI) soon after symptom onset have not been previously reported. Accordingly, this study reviewed the coronary angiographic findings of 86 patients with AMI studied within 6 hours of symptom onset: 58 had Q-wave and 28 had non-Q-wave AMI. Patients with Q-wave and non-Q-wave AMI were comparable in terms of clinical characteristics, frequency of 1-vessel disease, and infarct-related artery location. Thrombus was observed in 49 patients (84%) with Q-wave AMI versus 12 (43%) with non-Q-wave AMI (p = 0.0002). Whereas complete occlusion of the infarct-related artery was present in 53 patients (91%) with Q-wave AMI, total coronary occlusion was present in only 11 (39%) with non-Q-wave AMI (p = 0.0001). Collaterals to occluded infarct arteries were seen in 10 patients (19%) with Q-wave AMI versus 5 (45%) with non-Q-wave AMI (p = 0.06). Residual perfusion of the infarct artery by either anterograde or collateral flow was typical of patients with non-Q-wave AMI (22 of 28, 79%) but was uncommon in those with Q-wave AMI (15 of 58, 26%) (p = 0.0001). Thus, coronary angiography performed within 6 hours of symptom onset demonstrates important differences between Q-wave and non-Q-wave AMI. Non-Q-wave AMI is characterized by partial perfusion of the infarct-related artery by either anterograde or collateral flow, and a lower incidence of thrombus than Q-wave AMI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of coronary angiographic findings during the first six hours of non-Q-wave and Q-wave myocardial infarction. 763 81

Thrombotic coronary artery occlusion dominates pathophysiology of coronary artery disease. Thrombolysis, therefore, is the decisive approach for the treatment of coronary artery obstruction. Development and size of myocardial infarction as a consequence of coronary occlusion, however, is also dependent on certain myocardial factors, among which the size of the myocardial area supplied by the occluded vessel duration of coronary occlusion myocardial oxygen consumption the extent of collateral blood flow ischemic tolerance and ischemic preconditioning are the most important. In unfavorable circumstances, the duration of ischemia is the dominating factor. Therefore, the highest priority must be given to initiate treatment as early as possible.
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PMID:[Vascular occlusion and myocardial infarct]. 832 86

We sought to evaluate the underlying coronary pathology of fatal postoperative myocardial infarction (MI). It has been hypothesized that most MIs following noncardiac surgery occur in the setting of increased oxygen demand that exceeds coronary blood supply. However, most MIs not associated with surgery are caused by plaque rupture and intracoronary thrombosis. In a retrospective cohort study, we reviewed 1841 consecutive autopsy records from 1981 to 1995 at two institutions and identified 26 cases of postoperative MI with coronary arteries available. Plaque rupture was present in 12 cases (46%, 95% confidence interval [CI] 27%-67%). Of the 9 (35%) patients with intracoronary thrombus, 5 (56%; 19% of entire group) had total occlusion. Thrombus occurred on a >50% stenosis (by cross-sectional area) in a total of 33% (95% CI 16%-55%) of patients. The only statistically significant difference in clinical variables between patients with and without plaque rupture was longer interval from surgery to death in patients with plaque rupture (7.8+/-4.4 days versus 4.4+/-4.8 days; p = 0.047). In this autopsy series, coronary plaque rupture was associated with almost half of fatal postoperative MI cases. Strategies aimed at reducing triggers of plaque rupture with coronary occlusion might reduce postoperative MI fatality.
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PMID:Histological analysis of coronary artery lesions in fatal postoperative myocardial infarction. 1072 35

The evaluation of adolescents with chest pain, elevated cardiac enzymes, and abnormal electrocardiograms (ECGs) continues to pose diagnostic and management dilemmas. Myocardial infarction is an uncommon finding in this population and alternative diagnoses must be considered. Our database was retrospectively reviewed for adolescents age 16-18 years without prior cardiac history who underwent cardiac catheterization. Patients who presented with chest pain, elevated cardiac enzymes, normal ejection fraction, and abnormal ECGs were included. Management, diagnostic testing, and final diagnosis were reviewed. Nine adolescents (eight males and one female) without prior cardiac history were identified. The ECG findings in all patients were consistent with myocardial ischemia in a coronary distribution. Thrombotic coronary occlusion was not found in any patient. In adolescents without prior cardiac history of risk factors for myocardial infarction such as Kawasaki disease, familial hypercholesterolemia, or drug use who present with chest pain, multiple diagnoses must be considered even in the presence of focal ischemic ECG changes and elevated cardiac enzymes. Thrombolytic therapy or anticoagulation should be withheld until a definitive diagnosis of myocardial infarction has been made. Magnetic resonance imaging is the most useful tool to differentiate focal myocarditis from myocardial infarction.
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PMID:"Myocardial infarction" in adolescents: do we have the correct diagnosis? 1554 13

Thrombus aspiration therapy allows for the examination of thrombus and atheroma fragments in acute coronary syndrome (ACS). Inflammatory cells and platelet activation play key roles in thrombus formation in ACS. However, histopathologic evaluation of thrombi in ACS has not been adequately addressed. We performed histologic analysis of tissue samples obtained by thrombus aspiration therapy. We studied 165 samples from patients with ACS. The area of each sample, percentage of red thrombus, and percentage of white thrombus were measured. Samples were stained immunohistochemically with antibodies against macrophages, activated platelets, and interleukin (IL)-5. Seventy-six samples included atheroma fragments. Macrophages, neutrophils, and activated platelets were observed in thrombi and in atheroma fragments. Eosinophil infiltration was also observed predominantly in the area between white thrombus and red thrombus in 106 samples. We categorized all samples into 3 groups according to the grade of eosinophil infiltration (eos-, eos+, eos++ group). Sample area in the eos++ group was greater than that in the eos- group (P < 0.0001). In addition, the percentage of the red thrombus areas in the eos++ group and the eos+ group was greater than that in the eos- group (P < 0.009, P < 0.02, respectively). However, there was no difference in the percentage of white thrombus area between the 3 groups. Staining for IL-5 was identified in inflammatory cells within thrombi. Eosinophils may play an important role in coronary occlusion by promoting thrombus growth.
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PMID:Eosinophils may be involved in thrombus growth in acute coronary syndrome. 1950 31


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