Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty patients in whom all aorta-coronary artery vein grafts became occluded within one year of operation, as demonstrated by cardiac catheterization, were evaluated for hypercoagulability. A total of 59 grafts were constructed in these patients. At operation, blood flows of 35 to 90 c.c. per minute were measured through the grafts. In 23 of the 30 patients, the blood was to be hypercoagulable, as evidenced by a low level of antithrombin III activity, high thrombin generation index, high factor VII values, or high platelet adhesivity. Another group of 11 patients (total number of grafts, 23) had all grafts patent at cardiac catheterization. These patients had flows through the grafts ranging from 20 to 125 c.c. per minute. None of the patients with patent grafts had hypercoagulable blood. The status of runoff was comparable between the patients with open grafts and those with occluded grafts.
J Thorac Cardiovasc Surg 1977 Feb
PMID:Coagulation factors influencing thrombosis of aorta-coronary bypass grafts. 29 8

One hundred patients were screened for hypercoagulability preoperatively and on the third, seventh, tenth, fourteenth, and twenty-first days postoperatively. Patients found to have hypercoagulability were treated with heparin, aspirin, and Coumadin. When the abnormality was present preoperatively, treatment was continued for the duration of the patient's life. Those patients in whom abnormalities developed postoperatively were given anticoagulants until cardiac catheterization 6 months following their operation. Twenty-four of the 100 patients had no coagulation abnormalities preoperatively or postoperatively. Fifteen patients were found to have abnormality prior to operation. Their predominant abnormality was low antithrombin III activity. Sixty-one patients became hypercoagulable postoperatively. Predominant abnormality in this group of patients was increased thrombin generation and increased platelet adhesiveness. Evaluation of patients in this study group revealed a decrease in the incidence of pulmonary embolism, an increase in the patency of vein grafts, and the elimination of anticoagulant therapy in 24 percent of the patients.
J Thorac Cardiovasc Surg 1978 Feb
PMID:Coagulation abnormalities in patients undergoing myocardial revascularization. 30 43

A method of heparinless, oxygenatorless, left heart bypass perfusion rewarming following surface hypothermia, with the use of a closed circuit with 130 ml. prime volume including heat exchanger, has been devised. The use of polyurethane-polyvinyl-graphite (PPG)-coated tubing has previously been reported. In this text, the use of an athrombogenic coating with cetyl-pyridinium chloride (CPC) as a regional heparin carrier was studied in dogs, comparing groups with PPG tubing and total systemic heparinization or plain polyvinyl tubing without systemic heparinization. Heparin compounded in the CPC coating eluted into the blood and caused mild transient whole-body heparinization during rewarming from 20 degrees to 25 degrees C., as evidenced by prolongation of the thrombin time. Alterations of hematologic parameters in all three groups were similar to those during surface rewarming except for those affected by heparinization. The left heart bypass method was found useful for hypothermic open-heart surgery when utilized with an athrombogenic surface coating or total body heparinization. It was concluded that the CPC coating is superior to the PPG coating since no cracking surface develops, it is translucent, and it provides a more effective athrombogenic surface.
J Thorac Cardiovasc Surg 1979 Feb
PMID:Use of athrombogenic tubing for perfusion rewarming following surface-induced deep hypothermia. 76 68

In order to investigate the safety of prolonged heparinless venoarterial bypass (HL-VAB), we subjected 18 sheep to prolonged HL-VAB for up to 6 days. Three animals died of granulomatous lung abscess and one died from intra-abdominal abscess. One animal died of generalized thromboembolism secondary to mechanical damage of the nonthrombogenic coating occurring at the time of cannulation. HL-VAB was successfully carried out in 13 sheep. Although clots were found at all tubing connections where blood turbulence occurred, only the previously mentioned animal showed evidence of thromboembolism. Damage to the nonthrombogenic tubing exposed to the roller pump head was seen in all animals, and its severity appeared to be related to the duration of bypass. Scanning electron microscopic examination revealed scattered platelet aggregates on the nonthrombogenic coated surfaces without clinical evidence of embolization. Hematocrit values, leukocyte counts, platelet counts, prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT), plasma fibrinogen levels, and factor V and VIII levels remained unchanged, whereas free plasma hemoglobin levels rose slightly during 6 days of HL-VAB. HL-VAB for up to 6 days appears to have little adverse effect on blood cells and blood coagulation factors. For current clinical use, the nonthrombogenic coated tubing circuit should be changed every 48 hours because of time-related trauma to the coated tubing from the roller pump.
J Thorac Cardiovasc Surg 1976 May
PMID:Successful prolonged heparinless venoarterial bypass in sheep. 126 48

We wished to determine whether the metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, is involved in production of endothelium-derived relaxing factor(s) (EDRFs) in canine femoral veins. Veins were removed from anesthetized dogs and cut into rings. Endothelium was deliberately removed from some rings. In separate sets of experiments, rings were incubated with either AA861 (10(-5) M) or TMK777 (10(-6) M), inhibitors of 5-lipoxygenase, nordihydroguaiaretic acid (NDGA 3 x 10(-6) M), an inhibitor of lipoxygenase or proadifen (SKF 525A, 10(-6) M), an inhibitor of cytochrome P-450. In addition, some rings were incubated with a combination of indomethacin (10(-5) M) and NG-monomethyl-L-arginine (L-NMMA 10(-4) M) or, where appropriate, a solvent control. Concentration-response curves were obtained for acetylcholine, adenosine diphosphate, thrombin, A23187, and nitric oxide in rings contracted with a submaximal concentration of prostaglandin F2 alpha. AA861 and TMK777 did not alter endothelium-dependent relaxations to the agonists, whether with or without indomethacin and L-NMMA. However, indomethacin plus L-NMMA reduced endothelium-dependent relaxations to thrombin. These results suggest that metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, does not produce an EDRF in veins. However, thrombin receptor-activated relaxations are mediated in part by products of the cyclooxygenase pathway and nitric oxide.
J Cardiovasc Pharmacol 1992 Sep
PMID:Role of lipoxygenase and cytochrome P-450 in production of endothelium-derived relaxing factors in canine femoral veins. 127 84

The present study investigated whether or not thrombin may affect the induction of nitric oxide (NO) synthase caused by interleukin-1 beta in cultured smooth muscle cells (SMCs) from the rat aorta. The release of nitrite, an oxidation product of NO, from interleukin-1 beta-activated SMCs was inhibited by thrombin. The inhibitory effect of thrombin was prevented by hirudin, a thrombin inhibitor, and required the presence of thrombin during the induction period. Under bioassay conditions, the perfusate from interleukin-1 beta-activated SMCs relaxed endothelium-denuded rat aortic rings precontracted with phenylephrine. The perfusate from untreated SMCs or cells exposed to thrombin alone or to interleukin-1 beta in combination with thrombin relaxed only minimally the detector blood vessel. These observations demonstrate that thrombin inhibits the production of NO by the inducible NO synthase in cultured vascular SMCs.
J Cardiovasc Pharmacol 1992
PMID:The inducible nitric oxide synthase is impaired by thrombin in vascular smooth muscle cells. 128 51

Use of the proteinase inhibitor aprotinin significantly improves hemostasis and reduces bleeding after operations in which extracorporeal circulation is used. The mechanism of action, however, has been only partially clarified. In this work we investigated whether aprotinin influenced the production and release of the eicosanoids prostacyclin, measured as the stable metabolite 6-keto-prostaglandin F1 alpha, and thromboxane A2, measured as the stable metabolite thromboxane B2, from endothelial cells. Human umbilical vein endothelial cells were incubated with different concentrations of aprotinin (5.5, 20, 55, and 100 mumol/L). The levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 were measured at baseline and after thrombin stimulation. A concentration-dependent effect of aprotinin on 6-keto-prostaglandin F1 alpha synthesis was demonstrated. After incubation with 100 mumol/L of aprotinin, a 90% reduction in 6-keto-prostaglandin F1 alpha production was seen (31.69 versus 307.44 picograms per million cells; p less than 0.001). Conversely, thromboxane B2 production showed a 345% increase after incubation with aprotinin (287.80 versus 83.82 picograms per million cells; p less than 0.0001). Since 6-keto-prostaglandin F1 alpha inhibits and thromboxane B2 strongly enhances platelet aggregation, it appears that one mechanism of the clinically observed effectiveness of aprotinin lies in the altered ratio of 6-keto-prostaglandin F1 alpha: thromboxane B2 in endothelial cells, which leads to enhanced platelet aggregation and improved vessel sealing.
J Thorac Cardiovasc Surg 1992 Sep
PMID:Aprotinin decreases release of 6-keto-prostaglandin F1 alpha and increases release of thromboxane B2 in cultured human umbilical vein endothelial cells. 138 Oct 28

Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. The prolonged intravenous maintenance infusions have been replaced by a bolus injection, accelerated infusions, or the combined intravenous administration of thrombolytic agents. Numerous truncated alteplase or saruplase molecules have been constructed by deletion and domain substitution or hybrids made of the two molecules without gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen activator from bat saliva have some interesting properties and are being investigated. Thrombus-targeted thrombolytic drugs were constructed using monoclonal antibodies against fibrin fragments or against epitopes of activated platelets. Fibrin-specific thrombolytic drugs require the concomitant use of a potent antithrombotic drug to prevent reocclusion. Whether hirudin or synthetic thrombin inhibitors are superior to heparin and whether novel antiplatelet agents, including monoclonal antibodies to platelet receptors and disintegrins, are more effective than aspirin is under clinical investigation. The place of stable analogues of prostacyclin during thrombolytic treatment is still unsettled.
Cardiovasc Drugs Ther 1992 Apr
PMID:Advances in thrombolytic therapy. 139 Mar 21

The effects of combined thromboxane synthetase inhibition and thromboxane receptor antagonism (TSI/TRA) were studied in conscious and in anesthetized canine models of sudden cardiac death. Administration of the TSI/TRA, R68070 10 mg/kg intravenously (i.v.), decreased thrombin-stimulated thromboxane synthesis and significantly antagonized platelet aggregation in response to the thromboxane-mimetic U46,619. In the conscious canine model, R68070 did not change ventricular refractoriness, did not prevent induction of ventricular arrhythmias by programmed electrical stimulation, and failed to prevent development of spontaneous ventricular fibrillation (VF) in response to ischemia produced at a site remote from the area of previous myocardial infarction (R68070 mortality = 70%, vehicle = 100%, p = NS). In the anesthetized canine model, R68070 prevented development of ischemia in 7 of 11 animals and reduced mortality significantly (R68070 27% and vehicle 73%; p = 0.038). R68070 inhibited thrombus formation in both models (R68070 conscious 7.0 +/- 2.6 mg and vehicle conscious 15 +/- 7.6 mg, p = NS; R68070 anesthetized 5.9 +/- 1.9 mg and vehicle anesthetized 17.7 +/- 4.3 mg; p less than 0.05). The results suggest that inhibition of thromboxane-dependent activity during acute recovery from infarction was able to protect the myocardium from developing ischemia in response to current-mediated intimal damage in a noninfarct-related artery. In the subacute phase of recovery from infarction, when the underlying myocardial substrate is susceptible to electrical derangement induced by transient ischemia, thromboxane inhibition in itself was unable to prevent ischemia-induced sudden cardiac death. Although R68070 may delay onset of ischemia due to thrombotic occlusion of the coronary artery, there does not appear to be an antiarrhythmic/antifibrillatory action to be derived from interfering with the synthesis or receptor-mediated action of thromboxane. Furthermore, R68070 does not alter the electrophysiologic properties of the heart which would result in an antiarrhythmic or antifibrillatory action.
J Cardiovasc Pharmacol 1990 Jul
PMID:Effects of combined thromboxane synthetase inhibition/thromboxane receptor antagonism in two models of sudden cardiac death in the canine: limited role for thromboxane. 169 68

To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.
J Thorac Cardiovasc Surg 1991 Jun
PMID:Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation. 768 96


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