PubMed Health⌕ Search

Biomedical subjects

F Doutremepuich

Publications and source records attributed to F Doutremepuich.

At least 19 recordsLinked to original sources
PubMed1998

Aspirin and fraxiparine in the prevention of laser induced thrombosis in the presence of iodinated contrast media.

The purpose of this study was to investigate the thromboembolic properties of ionic and nonionic contrast media in rats pretreated with aspirin and/or fraxiparine using an experimental model of laser induced thrombosis in the mesenteric microvessels of 17 groups of five male Wistar rats each. Two ionic (ioxaglate and diatrizoate) and two nonionic contrast media (iopamidol and iohexol), alone or associated with antithrombotic drugs (aspirin and/or fraxiparine) were studied. To evaluate the effects of these substances in this model, the number of laser beams needed to induce platelet thrombus formation, the number of emboli detached from the thrombus and the duration of embolization were quantified. Platelet aggregation induced by ADP, induced hemorrhagic time (IHT) and haemoglobin loss level were also determined. Both contrast media injected at 3 ml/kg caused a significant increase in the number of emboli and the duration of embolization (p<0.05). Pretreatment with aspirin and/or fraxiparine in the presence of ionic contrast media showed antithrombotic activities equal to those obtained when they were tested alone (p<0.05), while in the presence of nonionic contrast media, these drugs only neutralised the prothrombotic effects. There were no differences with the NaCl treated group (p>0.05). The ionic contrast media, and to a lesser extent the nonionic contrast medium: iohexol, inhibited platelet aggregation, while iopamidol behaved as an activator. The antithrombotic drugs tested in this study prevent the prothrombotic activities of contrast media therefore suggesting their use before radiographic procedures.

Animals↗
PubMed1998

Combination of two doses of acetyl salicylic acid: experimental study of arterial thrombosis.

The antithrombotic effect of high dose acetylsalicylic acid is well known, and recently, in vitro studies hinted the potent thrombotic effect of ultra-low dose of acetylsalicylic acid (<1mg/day) showing a significant decrease in bleeding time. In this study, we investigated the effect of a combination between a high and an ultra-low dosage (100 mg/kg+ 10(-30) mg/kg) on an arterial thrombosis induced by a laser beam. We used an intravital microscopic technique, allowing to evaluate (anti)-thromboembolic events at previously determined locations of microvasculature. Thrombus formation was induced by argon-laser shot. The instrumental test setup was completed with a video system, to select mesenteric arterioles with the same diameter (between 15 and 25 microm). The changes in platelet aggregability were determined by Cardinal and Flower method, and the concentration of acetylsalicylic acid in the plasma was measured by high pressure liquid chromatography. Antithrombotic effect of high dose (100 mg/kg) acetylsalicylic acid was confirmed in all results obtained. Asa injected at ultra-low dose (10(-30) mg/kg) had a potent thrombotic properties and decreased significantly the bleeding time. The subcutaneous administration of the combination of the two doses permitted to come back to the control values, and the bleeding time was shortened compared to control group.

Administration, Cutaneous↗
PubMed1998

Fibrinogen as a factor of thrombosis: experimental study.

Epidemiological, clinical, and experimental studies have clearly demonstrated the strong association between baseline fibrinogen level and risk of thromboembolic complications. The pathogenesis of postoperative or post-traumatic thrombosis in man is associated with fibrinogen level in plasma. The purpose of this study was to evaluate the effects of fibrinogen administration on thrombus formation at different dosages. To investigate these effects, we used an experimental model of induced thrombosis in rat microcirculation. This model allows single endothelial cell destruction by laser injuries, thus leading to thrombus formation. Fibrinogen was injected intravenously via penis vein and tested at various dosages (50, 100, and 200 mg/kg), 60 minutes after injection on arterial thrombosis induction and 120 minutes after injection on venous thrombosis induction. Results showed that the administration of fibrinogen increases the number of emboli, the duration of embolization, the amplitude, and the velocity of the ex-vivo platelet aggregation induced by ADP (p < 0.05). A positive correlation between the percent of fibrinogen increase in plasma and the enhancement of thromboembolic risk in the experimented animals was observed.

Adenosine Diphosphate↗
PubMed1998

Thromboembolic complications several days after a single-dose administration of aspirin.

The antithrombotic properties of acetyl salicylic acid (ASA) used at current doses are largely demonstrated. However, our previous study showed unexpected thrombotic potencies associated with the use of this drug. In this study we investigate the effect of aspirin on an experimental thrombosis induced by laser beams, according to its in vivo plasma concentration. Experiments were done on nine groups of seven Wistar male rats. The groups are defined by the delay between aspirin administration time and the laser-induced thrombosis time. Results from this study showed an enhancement of thromboembolic complications when thrombosis was induced 8 or 10 days after aspirin administration; the number of emboli and the duration of embolization are increased, compared to the control group. The prothrombotic properties of ASA demonstrated in this study, might limit its therapeutic benefit and might explain thromboembolic complications observed in some ASA-treated patients. These results also suggest a biological monitoring several days after aspirin administration to patients.

Administration, Cutaneous↗
PubMed1997

Action of neurotransmitters: acetylcholine, serotonin, and adrenaline in an experimental arterial thrombosis induced by oxygen free radicals.

It is well known that high stress and particularly an enhancement of plasma catecholamines and myocardial infarction have a close relation. In addition, adrenaline is presented as a prothrombogenic agent in vivo. The role of the other agents such as serotonin or acetylcholine, in the development of arterial thrombosis is somewhat uncertain, although, the role of each of them is often considered at the level of vascular regulation only. Therefore, the present study was designed to investigate the effects of three neurotransmitters on experimental arterial thrombosis model induced by generation of free radicals. The results demonstrate that intravenously injection of adrenaline or serotonin (1 ng/kg) stimulated arterial thrombosis formation, whereas injection of high dose of acetylcholine (5 mg/kg) slackened the thrombosis formation.

Acetylcholine↗
PubMed1996

Action of neurotransmitters: acetylcholine, adrenaline and serotonin on arterial thrombosis induced by a laser beam.

The releasing of catecholamines is increased in stress situation which promotes the formation of circulating platelet aggregates, and could participate in the arterial thrombosis formation in coronary diseases. The purpose of this study is to evaluate the thrombogenic action of some neurotransmitters, and their participation through the vessel's vasomotoricity, in the growth of an arteriolar thrombosis. Endothelial cells destruction, induced by a laser beam in mesenteric arteriole of the rat were observed to determine changes in thrombus growth, through the embolization and variation of vessel diameter. It is desirable to get insight into the interrelation of thrombus formation and local vasomotoricity in the presence of acetylcholine, adrenaline and serotonin. The administration of acetylcholine (5mg/kg) increases the number of emboli which detached from thrombus, and decreases the thrombus area. Therefore, acetylcholine induces a variation of the vessel's diameter, a vasodilation in the intact vessel and a vasoconstriction when the endothelium is removed. Two vasoconstrictor agents are used: adrenaline and serotonin which increase the number of laser injuries required to induce thrombus formation, decrease the number of emboli and the duration of embolization (p < 0.05). They cause a potent vasoconstriction. These neurotransmitters seem to be involved in the arterial thrombosis induced by laser beam, promoting or not the platelet aggregation, and modulating the vascular tone by the endothelium.

Acetylcholine↗
PubMed1996

New class of heparin derivatives with a potent antithrombotic effect and a very limited hemorrhagic activity.

Eight heparin derivatives (HD1 to HD8) were prepared by mixing various doses of protamine with a fixed amount of heparin. After centrifugation and elimination of the formed complex, the supernatant was lyophilized and titrated. A dose of 5 mg (dry weight)/kg of these heparin derivatives was injected subcutaneously to rats in classical thrombosis model induced by stasis. Antithrombotic, hemorrhagic and anticoagulant activities are investigated and compared to those of Unfractionated Heparin (UFH) and LMWH (Enoxaparin). Seven rats in each group were studied. Significant antithrombic effect was exhibited by HD1, HD2, HD3, and HD4 which decreased progressively. Only HD1, HD2, and HD3 augmented hemorrhagic activity but to a lower degree than UFH and LMWH. No change was observed by coagulation assays; Activated Partial Thromboplastin Time (APTT) and Diluted Thrombin Time (dTT) and there was no effect on platelet aggregation except for UFH. These heparin derivatives might present advantages over UFH and LMWH in the treatment of thrombosis.

Animals↗
PubMed1996

Antithrombotic effects of aspirin and LMWH in a laser-induced model of arterials and venous thrombosis.

Antiplatelet drug aspirin and anticoagulant low molecular weight heparin (LMWH) were compared as arterial and venous antithrombotic preparations in the rat experimental model of the laser induced thrombus formation. A method to induce microthrombi in small mesenteric vessel (15-25 microns) has been developed to investigate antithrombotic drugs and to study platelet reactions. Mesenteric injuries are induced in the vascular system of Wistar rats with an argon laser. The laser beam induced formation of the vessel wall injury with damage of endothelial cells. Thrombus was formed within seconds after laser injury and grew rapidly. The aggregate can be swept away by the flow and a new thrombus was formed again. This embolization began within the minute following the laser flash. Thrombus formation and embolization were repetitive phenoma. Aspirin (100 mg/kg) and LMWH (1 mg/kg) are approximately the same as to decrease the number of emboli detached from the thrombus and the duration of embolization; both in venules and in arterioles. This results suggest reflexion about the role of platelets in venous thrombosis induced by laser beam.

Administration, Cutaneous↗
PubMed1996

The arterial antithrombotic activity of thioxylosides in a rat model of laser-induced thrombosis.

beta-D xylosides have been shown to have venous antithrombotic properties after simple oral administration. Therefore, the arterial antithrombotic effect of these compounds was investigated in vivo, using the experimental thrombosis model induced by laser injury. The products tested were administered orally, 4 h before the thrombosis induction. Two beta-D xylosides were tested (LF 09-0055 and LP 05-0030), either after a simple oral administration at 50, 100, 200, and 400 mg/kg, or after repetitive oral administration at 200 mg/kg twice daily during 5 days. These compounds increased significantly the number of laser shots required to induce arterial thrombosis and decreased the number of emboli and the duration of embolization. At single-dose or repeated administrations, these xylosides did not affect diluted thrombin time in platelet-poor plasma collected after thrombosis inductions. They induced a dermatan sulfate-like activity in the plasma of treated rats, as measured by heparin cofactor II-mediated thrombin inhibition assay. These data suggest that these xylosides are potent arterial antithrombotic agents after single or repetitive oral administrations. beta-D xylosides constitute a very promising therapeutic class of orally active antithrombotic drugs.

Administration, Oral↗
PubMed1996

Effect of monoclonal and polyclonal antibodies against conjugated neurotransmitter on experimental venous thrombosis.

Vasomotoricity in veins is largely controlled by the sympathetic nervous system. Norepinephrine and acetylcholine modulate the vasoconstrictor effect mediated by alpha-adrenergic receptors. Our objective was to study the role of local vasomotoricity in venous thrombosis, and particularly to determine some of the factors regulating it. Although no attempt has been described until now, polyclonal and monoclonal antibodies against L-dihydroxyphenylalanine, acetylcholine, and dopamine were administered in an experimental model of venous thrombosis. In view of the rather high specific antibody recognition for each compound, the presence of endogenous epitopes of L-dopa-like molecules and acetylcholine-like molecules in the circulation can be postulated. The results of this study may open an important new approach in the treatment of vascular diseases.

Acetylcholine↗
PubMed1995

Experimental thrombosis model induced by free radicals. Application to aspirin and other different substances.

A large number of experimental studies suggests that oxygen free radicals play a major role in the pathogenesis of the myocardial lesions observed during the sequence ischemia-reperfusion. The purpose of this study was to determine whether oxygen free radicals can induce thrombosis. In so doing we have developed a new experimental thrombosis model. Reproducible focal thrombosis has been achieved by irradiating mesenteric arterioles of rat for variable time with green filtered light issuing from a mercury lamp after systemic injection of different rose bengal doses. The number of emboli that remove in the blood (N), the duration of total occlusion (T) and the number of emboli per minute were then measured. As control, no rose bengal administration was done and the vessels were exposed to the filtered light. In comparison with this control, results clearly showed that free radicals always induced thrombosis and the induced thrombus was mainly composed of platelets. In this new thrombosis model induced by free radicals antithrombotic drugs (aspirin, 200 mg/Kg, heparin, 2 mg/Kg) and antioxidants (vitamin C, 10 and 20 mg/Kg, allopurinol, 200 and 300 mg/Kg, vitamin E, 500 and 1000 mg/Kg) have been tested. Results have shown that only heparin and vitamin E had an antithrombotic effect on thrombus formation induced by free radicals. This model should be useful in studying the effects of different drugs and could lead to new treatment modalities for ischemic accident and other cardiovascular diseases.

Allopurinol↗
PubMed1995

Effect of the low molecular weight heparin/non steroidal anti-inflammatory drugs association on an experimental thrombosis induced by laser.

LMWH (Fraxiparine), and NSAIDs (Aspirin, Feldene, Indocid and Profenid) injected together in doses, 1 mg/kg (Aspirin was used at 100 mg/kg), subcutaneously into rats 30 minutes before the thrombosis induction by LASER beams, increased the number of LASER beams required to induce platelet thrombus formation, decreased the number of emboli and reduced the duration of embolization, compared with control (p < or = 0.05). Of all the studied NSAIDs being injected either with LMWH or separately 30 minutes before the thrombosis stimulation by LASER only Aspirin appeared to potentiate the antithrombotic effect of Fraxiparine. Neither LMWH nor NSAIDs (except for Aspirin) at the dosages used modified aggregatory parameters compared with control. But it was observed the inhibition of platelet aggregation by the associations of Fraxiparine with Aspirin, Feldene or Profenid, tested in the whole blood 90 minutes after the drug injections.

Animals↗
PubMed1995

Thrombogenicity of ionic and nonionic contrast media tested in a laser induced rat thrombosis model.

Contrast media are used as substances for visualization of vascular system. But, their administration is often associated with thromboembolic complications. The purpose of this study is to evaluate the thrombogenic action of ionic and non-ionic contrast media on thrombus formation. The experimental destruction of endothelial cells by Laser injury leads to thrombus and emboli formation. Two ionic and two non-ionic contrast media were injected intravenously via penis vein and tested at various dosages (1.0 and 2.5 ml/kg) 5, 30, 45 and 65 minutes after injection. The administration of these contrast media decreases the number of Laser injuries required to induce thrombus formation, increases the number of emboli which detached from thrombus and prolongs duration of embolization (p < or = 0.05). These experimental results suggest that ionic and non-ionic contrast media induce thrombogenic effects. This thrombogenicity was the greatest for non-ionic contrast media. It was observed the decrease of the white cells, red cells and platelets.

Animals↗
PubMed1995

[Experimental models of arterial thrombosis].

Arterial thrombosis is clearly responsible for a very wide range of cardiovascular diseases, which is why many models of arterial thrombosis have been developed. These models are based on various techniques such as electrical, mechanical, biochemical, photochemical induction. They are an essential prerequisite to the understanding of molecular and cellular phenomena and are also essential to test the antithrombotic activity of new molecules before the first clinical trials in man. The large range of models means that the most appropriate model can be selected for the study of the test substance. However, the antithrombotic activity of a substance needs to be studied by several models. Most of these models induce total occlusion in which the number of parameters studied is limited. As a result of technological progress and the development of techniques such as laser and image analysers, new perspectives are now available for both basic and pharmacological research. Consequently, the already major value for these models should continue to grow over the years to come.

Animals↗
PubMed1993

Influence of heparin on the chemotactic activity of human thrombin.

Chemoattractant properties of human thrombin have been studied, by polymorphonuclear leucocyte migration under agarose gel, in the presence of various sulphated macromolecules such as standard heparins, low molecular weight heparins, CY216, K2165, PK10169 and pentosane polysulphate. These compounds did not attract polymorphonuclear leucocytes within the range of concentrations used, whilst thrombin alone is a cytotaxin for these cells. Addition of heparins to thrombin led to an increase in the chemoattractant activity of this enzyme for at least one of the doses studied. Augmentation of the chemoattractant activity of thrombin by heparins was shown at concentrations equivalent to those found in-vivo after administration of therapeutic doses of heparin. Pentosane polysulphate, at the studied concentrations, did not lead to a significant rise in the chemoattractant activity of thrombin.

Chemotaxis, Leukocyte↗
PubMed1993

Effects of aspirin on embolization in an arterial model of laser-induced thrombus formation.

This model of arterial thrombosis induced by laser was used to evaluate the effect of aspirin (Aspegic) on embolization. A partial occlusion was induced in small mesenteric arterioles (diameter 35-40 microns) with an Argon Laser. The laser induced the formation of a vessel wall lesion with damage of endothelial cells. Thrombus formed within seconds after the laser lesion and grew rapidly. Embolization began within the minute following the laser flash. Thrombus formation and embolization were repetitive phenomena. The duration of embolization was 6.50 +/- 0.84 min in the control group. Then the thrombus became stable and partially obstructed the vessel lumen. The administration of aspirin at three doses (50, 100, 200 mg/kg) by intramuscular injection, 15 min before the laser injury, induced three different phenomena: (1) an increase of the number of laser injuries required for the thrombus formation; (2) a dose-dependent decrease in the duration of embolization, and (3) a dose-dependent decrease in the number of emboli. The highest dose injected induced the strongest reduction in the duration of embolization and the number of emboli.

Animals↗