Search PubMed⌕ Search

Biomedical subjects

M Verstraete

Publications and source records attributed to M Verstraete.

At least 127 records · Page 7Linked to original sources
PubMed1986

Pharmacology of the interaction between platelets and vessel wall.

The evaluation of agents inhibiting platelet function is difficult because, in addition to primary aggregation by thrombin, there are three amplification loops involving respectively arachidonate, ADP and PAF-acether (platelet activating factor). Each amplification loop seems eventually to act via a common pathway: the mobilization of calcium ions from the dense tubular system into the cytoplasm. Inhibition of this mobilization would prevent platelet aggregation by any agonist. This could be an ideal step with which to intervene pharmacologically. An intracellular increase in cAMP reduces cytoplasm calcium levels and therefore counteracts the effect of whatever agonist is used (Vermylen et al, 1982, 1983; Verstraete et al, 1985). Depending on the pro-aggregatory stimulus, the relative importance of a given pathway of platelet activation may shift. There is also uncertainty about which pathway of platelet activation predominates in a given clinical condition. The second problem relates to the pharmacology of the ideal drug for the inhibition of platelet function. It is very difficult to delineate the desired profile of such a drug considering the properties of the various compounds presently being studied (see Table 1). Prolongation of a shortened platelet survival in man was considered to be one of the key markers of an anti-aggregatory agent; this characteristic was found to be present after administration of sulphinpyrazone, clofibrate, ticlopidine, suloctidil, dipyridamole (in patients with artificial heart valves) and dipyridamole (in patients with venous thrombosis). The protective antithrombotic effect is most clearly demonstrated for aspirin; it is rather surprising that this drug does not prolong the shortened platelet survival in man, not even in those clinical conditions in which it effectively prevents thromboembolism.

Animals↗
PubMed1986

[Prevention of deep venous thrombosis and pulmonary embolism in general surgery].

Among the various methods to diagnose deep venous thrombosis in the lower limbs, the radiofibrinogen uptake test has been mainly used in clinical studies. Physical means to accelerate venous return are of limited use and only in patients at a low thrombotic risk. Antivitamins K are efficient, but surgeons hesitate to use them because of the postoperative hemorrhagic risk. Dextran infusions are quite effective and without real risk of bleeding. The same holds for low dose heparin administered subcutaneously, particularly when combined with dihydroergotamine. Among the various anti-aggregating agents only aspirin may be effective in the prevention of venous thrombosis.

Blood Circulation↗
PubMed1985

Double-blind randomised trial of intravenous tissue-type plasminogen activator versus placebo in acute myocardial infarction.

In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.

Adult↗
PubMed1985

Questions and answers on prothrombin time standardisation in oral anticoagulant control.

One of the reasons why oral anticoagulants fell into disrepute is the absence of internationally accepted standardised procedures for controlling the level of anticoagulation. This deplorable situation resulted in over- and under-coagulation and uncertainty in the therapeutic range. International conformity can now be obtained by using an International Normalised Ratio (INR) which is derived from the individual result obtained in a given plasma sample and the International Sensitivity Index (ISI) of the tissue thromboplastin reagent used. Any thromboplastin reagent can be calibrated against an international primary or secondary W. H. O. reference preparation, so as to obtain its International Sensitivity Index. The new system of reporting the level of anticoagulation was designed and can only safely be applied in patients taking oral anticoagulants.

Administration, Oral↗
PubMed1985

Randomised trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Report from the European Cooperative Study Group for Recombinant Tissue-type Plasminogen Activator.

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1 500 000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the differences ranges from +/- 30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Adult↗
PubMed1985

Prevention of thrombosis in arteries: novel approaches.

A number of drugs such as unfractionated heparin, oral anticoagulants, and agents inhibiting platelet function, are being used in the prevention of arterial thrombosis; novel antithrombotic substances are in the making. Among the latter are low-mol-wt heparin and semisynthetic heparin analogs, unfractionated and low-mol-wt heparin covalently complexed or not with anti-thrombin III, pyridoxal phosphate, scavengers of free radicals, synthetic inhibitors of serine proteases, and stimulators of endogenous fibrinolysis.

Anticoagulants↗
PubMed1985

Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates.

Occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery (LAD) of 16 open-chest baboons. In six control animals, occlusive thrombosis persisting over a period of 4 h as evidenced by coronary arteriography resulted in large transmural infarction (63.1 +/- 3.5% of the perfusion area). In 10 animals, tissue-type plasminogen activator obtained by recombinant DNA technology (rt-PA) was infused systemically at a rate of 1,000 IU (10 micrograms)/kg per min for 30 min after 30-80 min of coronary thrombosis. Reperfusion occurred within 30 min in nine animals. In one animal, intravenous infusion was followed by an intracoronary infusion at the same rate, which resulted in thrombolysis within 8 min. In the rt-PA group, mean duration of occlusion before reperfusion was 77 +/- 24 min. Reocclusion occurred in one animal. Recanalization resulted in an overall reduction of infarct size (37.8 +/- 5.9%, P less than 0.05 versus controls). Residual infarction was related to the duration of occlusion (r = 0.80, P less than 0.01). Reperfusion was associated with reduced reflow. Myocardial blood flow in the perfusion area of the LAD was only 70% of normal after 4 h despite perfect angiographic refilling. The infusion of rt-PA was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown, or clinically evident bleeding. It is concluded that intravenous infusion of rt-PA may recanalize thrombosed coronary vessels without inducing systemic lysis. The extent of residual infarction is closely related to the duration of coronary artery occlusion before thrombolysis.

Angiography↗
PubMed1985

Clinical application of inhibitors of fibrinolysis.

The basic proteinase inhibitor from bovine organs, aprotinin, was first identified in 1930 and its effect on enzyme and other biological systems has since been extensively studied. Aprotinin can only be administered intravenously and has a half-life of about 2 hours. Its administration at the start of cardiopulmonary bypass surgery appears to reduce blood loss and to protect against global myocardial ischaemia. Similarly, a smaller infarct size seems to result from early administration of aprotinin within the first hour after myocardial infarction, though further studies are needed to confirm this effect. A combination of aprotinin with tranexamic acid may be effective in preventing or delaying rebleeding after rupture of an intracerebral aneurysm; the addition of aprotinin seems to decrease the incidence of delayed cerebral vasospasm and ischaemic complications which are sometimes noted when tranexamic acid alone is used. Aprotinin is also effective as adjuvant treatment in traumatic haemorrhagic shock. The recommended loading dose is 15,000 to 20,000 KIU/kg bodyweight administered as a short intravenous infusion, followed by 50,000 KIU/hour by continuous infusion. Side effects of aprotinin are very rare. Epsilon-Aminocaproic acid (EACA), p-aminomethylbenzoic acid (PAMBA) and tranexamic acid are synthetic antifibrinolytic amino acids. Saturation of the lysine binding sites of plasminogen with these inhibitors displaces plasminogen from the fibrin surface. On a molar basis tranexamic acid is at least 7 times more potent that epsilon-aminocaproic acid and twice as potent as p-aminomethylbenzoic acid. All 3 compounds are readily absorbed from the gastrointestinal tract and excreted in active form in the urine. The plasma half-life of tranexamic acid is about 80 minutes. The main indications for tranexamic acid are the prevention of excessive bleeding after tonsillectomy, prostatic surgery, and cervical conisation, and primary and IUD-induced menorrhagia. It is possible that gastric and intestinal bleeding can also be reduced as well as recurrent epistaxis. Tranexamic acid could also be useful after ocular trauma. The value of fibrinolysis inhibitors in the prevention of bleeding after tooth extraction in patients with haemophilia is well documented, as is the treatment of hereditary angioneurotic oedema. The usual dose of tranexamic acid is 0.5 to 1g (10 to 15 mg/kg bodyweight) given intravenously 2 to 3 times daily, or 1 to 1.5 g orally 3 to 4 times daily. This dose needs to be reduced in patients with renal insufficiency. The main side effects of tranexamic acid are nausea or diarrhoea.

4-Aminobenzoic Acid↗
PubMed1985

Pharmacokinetics and systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator (rt-PA) in humans.

The pharmacokinetics of recombinant human tissue-type plasminogen activator (rt-PA) were studied in 20 subjects during and after its i.v. infusion at three different rates (5.6, 8.3, and 10 micrograms/kg/min). Steady-state plasma concentrations of 0.9 to 1.6 micrograms/ml were reached. The plasma disappearance curves of rt-PA (both antigen and activity) after cessation of infusion were approximated by a sum of two exponential terms and the turnover of rt-PA was represented by a two-compartment mammillary model with peripheral (liver) elimination. The fractional efflux rate constant from the central compartment was 0.10 per min and the fractional catabolic rate constant about 0.02 per min. After cessation of infusion the initial half-life of the drug in plasma was 6 min. Fibrinogen levels were measured by a clotting rate assay and by sodium sulfite precipitation. Infusion of rt-PA at 10 micrograms/kg/min for 30 min did not cause systemic fibrinogen breakdown. Infusion of 5.6 micrograms/kg/min for 90 min was associated with a decrease of fibrinogen to 62% of the preinfusion value (4.5 g/l) as measured with the clotting rate assay, but only 2% was recovered as incoagulable fibrinogen-fibrin degradation products. Infusion of 8.3 micrograms/kg/min for 90 min resulted in a decrease of fibrinogen to 45% of the preinfusion level (2.5 g/l) and generation of 8.5% fibrinogen-fibrin degradation products. Fibrinogen assays with the sodium sulfite method showed a much less extensive decrease of fibrinogen. This extent of systemic fibrinolytic activation and fibrinogen breakdown at high infusion rates and prolonged durations is compatible with that anticipated from the kinetic parameters of the activation of plasminogen by rt-PA.

Fibrin Fibrinogen Degradation Products↗
PubMed1984

Platelet survival in patients with angiographically diseased and normal coronary arteries.

Platelets may contribute to the pathogenesis of atherosclerosis and to the complications of coronary artery disease. Therefore, platelet kinetics were studied in 69 patients with angiographically documented coronary artery disease and in 16 patients with a normal coronary angiogram. Platelet survival time was calculated from the decay of radioactivity after injection of 51Cr-labeled autologous platelets. None of the mathematical models used was able to discriminate between the two patients groups. No correlation existed between survival time and extent of the arterial disease. Patients with a high serum cholesterol did not exhibit an enhanced platelet consumption. Thus, these studies do not support the idea that turnover is enhanced in patients with coronary artery disease as compared to those with normal coronary arteries.

Angiography↗