Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial infarction (MI) is the result of acute coronary occlusion and the prognosis depends on the infarct size. In experimental studies, infarct size is reduced by early coronary reperfusion which may be obtained by intravenous thrombolytic therapy. This simple, rapid and widely used technique is the clinical treatment of choice. The diagnosis of MI must be confirmed by clinical and electrocardiographic findings. The clinical history is important because the value of reperfusion when started after the 6th hour after the onset of chest pain is questionable. However, it is often difficult to determine the beginning of MI when preceded by unstable angina. Contraindications to thrombolytic therapy must be carefully excluded irrespective of the thrombolytic agent because of the risk of haemorrhage. This must be weighed up against the risk of the MI itself. Therefore, age is not a systematic exclusion criterion. The choice of thrombolytic is based on the efficacy, mode of administration and cost. Heparin therapy at effective doses is associated in all cases to prevent reocclusion. Aspirin is given orally. The association of a calcium inhibitor or a betablocker may also be considered. Reperfusion and ischaemia may give rise to arrhythmias and haemodynamic changes which have to be rapidly corrected. Haemorrhagic complications during thrombolysis are treated according to the severity and time of onset by blood transfusion sometimes associated with a plasmin inhibitor. Reocclusion is an indication for emergency coronary angioplasty but in some cases repeat thrombolytic therapy may be beneficial. When the MI is extensive, rapid transfer to a cardiological centre with catheter facilities is advisable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Thrombolytic therapy of myocardial infarction: practical management]. 153 Apr 12

To investigate whether addition of Ca2+ antagonists adds to the beneficial effects of thrombolysis we studied recovery of regional myocardial performance in pigs, in which occlusive thrombi were induced by electrical stimulation, with and without addition of nifedipine to the thrombolytic agent. To this end, four different groups of animals with thrombotic coronary occlusion were studied. Groups 1 and 2 received either saline or intracoronary nifedipine (0.1 micrograms.kg-1.min-1) 15 min after coronary artery occlusion. Groups 3 and 4 were treated with the thrombolytic agent plasmin which was infused directly into the left anterior descending coronary artery (LADCA) at a rate of 2 U.min-1. The animals in group 4 also received intracoronary nifedipine. 4 h after thrombus formation the animals were sacrificed. No important differences in systemic hemodynamics were observed between the four groups of animals. Reperfusion occurred only in the animals which received plasmin, with or without nifedipine. After intracoronary plasmin regional blood flow increased from 7 +/- 2 to 40 +/- 7 ml.min-1.100 g-1 in the LADCA-perfused subepicardial and from 9 +/- 2 to 30 +/- 6 ml.min-1.100 g-1 in the LADCA-perfused subendocardial layers. The combination of plasmin and nifedipine increased flow to the LADCA-perfused subepicardial layers from 8 +/- 2 to 74 +/- 21 ml.min-1.100 g-1 and that to the subendocardial layers from 8 +/- 2 to 57 +/- 16 ml.min-1.100 g-1 (in both cases: p less than 0.05 vs. plasmin alone). However, addition of nifedipine did not enhance recovery of regional myocardial function or high-energy phosphate metabolism. Because reperfusion was accompanied by a high ventricular ectopic activity, the question may be raised of whether reperfusion of ischemic myocardium which does not result in functional recovery could be deleterious.
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PMID:Coronary thrombolysis with and without nifedipine in pigs. 297 Aug 39

Recent trials have shown that recombinant tissue plasminogen activator (rt-PA) is an effective thrombolytic agent in patients with acute myocardial infarction. Because rt-PA converts plasminogen to plasmin, which is known to activate complement in vitro, we tested the hypothesis that rt-PA can induce in vivo activation of complement. Studies were performed in 12 patients with acute myocardial infarction. Six control patients had patent coronary arteries and did not receive rt-PA; these patients had normal values of the components of the complement system C4a (409 +/- 111 ng/ml) and C5a (8.8 +/- 1.8 ng/ml) with a slight elevation of C3a (204 +/- 6.6 ng/ml) in samples collected before coronary arteriography (253 +/- 25 minutes after onset of pain). After coronary arteriography, there was a slight decrease in the values of C4a (224 +/- 37 ng/ml), C5a (7.3 +/- 1.3 ng/ml) and C3a (164 +/- 35 ng/ml). The remaining six patients had complete coronary occlusion and received rt-PA (80 to 150 mg intravenously). In this treated group, before coronary arteriography the values of C4a (406 +/- 51.6 ng/ml) and C5a (8.1 +/- 1.9 ng/ml) were normal, and those of C3a were slightly elevated (250 +/- 76 ng/ml). All complement values obtained before rt-PA were similar to those in the untreated group. However, after administration of rt-PA (but before any angiographically detectable reperfusion), there was a striking increase in C4a (2,265 +/- 480 ng/ml; p less than 0.01), C3a (600 +/- 89 ng/ml; p less than 0.05) and C5a (30.0 +/- 4.5 ng/ml; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of the complement system by recombinant tissue plasminogen activator. 311 50

After experimental studies in dogs confirmed the feasibility and safety of rapid intracoronary thrombolysis by local infusion of Thrombolysin (streptokinase and plasmin), intracoronary thrombolysis was attempted in 20 patients with evolving myocardial infarction who were hospitalized within 3 hours from the onset of symptoms during the day and within 2 hours at night. Thrombolysin was infused in the immediate vicinity of the site of coronary occlusion using a 0.85 mm outer diameter catheter advanced through the lumen of the Judkins catheter. Reperfusion was achieved in four patients after an average of 43 minutes of Thrombolysin infusion at a rate of 2000 IU/min and in 15 patients after an average of 21 minutes of Thrombolysin infusion at a rate of 4000 IU/min. The failure to open the artery in one patient may have been caused by our inability to advance the infusion catheter close to the site of occlusion. Rethrombosis occurred in one patient 8 days after reperfusion and 2 days after discontinuation of anticoagulants because of a history of chronic alcoholism. Wall motion and perfusion studies showed improvement following reperfusion. Patency of the artery was achieved an average of 4 hours after the onset of symptoms. The need for earlier reperfusion is emphasized.
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PMID:Intracoronary thrombolysis in evolving myocardial infarction. 645 May 27

The plasma fibrinolytic/proteolytic balance was assessed in 60 stable angina patients who underwent control coronary catheterization and the results were correlated with angiographic findings and control samples (n = 20). The concentrations of t-PA, PAI-1, collagenase (MMP-1), tissue inhibitor of MMP (TIMP-1), plasmin-antiplasmin (PAP) complexes and alpha2-macroglobulin (alpha2-M) were measured in plasma samples. The results showed a significant increase of PAP (p <0.001) and a reduction of alpha2-M (p <0.001) in the group of patients when compared to controls, indicating a degree of fibrinolysis/proteolysis activation. There was no correlation between the different parameters analyzed and the extent of angiographically proven atherosclerosis (one or more stenotic vessels), while the t-PA levels were significantly elevated (p <0.03) in patients with coronary stenosis > or =75% or occlusion. We conclude that there is a disturbance of the plasma fibrinolysis/proteolysis in patients with stable angina not related to the extent of atherosclerosis. The t-PA levels may be a good marker for coronary occlusion in these patients.
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PMID:Fibrinolysis/proteolysis balance in stable angina pectoris in relation to angiographic findings. 1152 15

Myocardial ischemia-reperfusion (I/R) is associated with the activation of matrix metalloproteinases (MMPs) and serine proteases. We hypothesized that activation of MMPs and the serine protease plasmin contribute to early cardiac myocyte death following I/R and that broad-spectrum protease inhibition with doxycycline (DOX) preserves myocyte viability. Rats treated daily with or without DOX beginning 48 h prior to experimentation were subjected to 30 min of coronary occlusion and 2 days of reperfusion. DOX pre-treatment reduced infarct size by 37%. DOX attenuated increases in MMP-9 and plasmin levels as determined by gelatin zymography and immunoblot, respectively. Neutrophil extravasation was unaltered by DOX as assessed by myeloperoxidase (MPO) activity. To examine the contribution of MMP-9 and plasmin to myocyte injury, cultures of neonatal rat ventricular myocytes (NRVMs) were treated for 48 h with 83 kDa MMP-9 or plasminogen in the presence or absence of DOX. MMP-9 treatment did not affect myocyte viability. Plasminogen treatment led to increased plasmin activity, resulting in loss of beta1-integrin, NRVM detachment and apoptosis. DOX co-treatment inhibited plasmin activity and preserved NRVM attachment, whereas co-treatment with the broad-spectrum MMP inhibitor GM6001 had no effect. These results indicate that plasmin causes disruption of myocyte attachment and viability independently of MMP activation in vitro and that inhibition of plasmin by DOX may reduce I/R-induced myocyte death in vivo through the inhibition of plasmin.
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PMID:Reduction of myocardial infarct size by doxycycline: a role for plasmin inhibition. 1579 48