PubMed Health⌕ Search

Biomedical subjects

O Aguejouf

Publications and source records attributed to O Aguejouf.

At least 19 recordsLinked to original sources

Effects of external electrical stimulation on laser-beam-induced experimental thrombosis.

External electrical stimulation (EES) has demonstrated venous antithrombotic properties. The aim of this investigation was to study its antithrombotic properties using unfractionated heparin (UFH) as a reference in arterial and venous mesenteric microvessels. For this purpose a rat model of laser-beam-induced thrombosis was used. Four groups of rats were investigated (n = 7): control, UFH (5 mg /kg), UFH (2.5 mg/kg) and electrical stimulation [e-vascular, E = 10, alternate polarity, in two protocols: (i) 30 min before and during thrombosis induction and (ii) only 30 min before thrombosis induction as preventive stimulation]. This effect was tested in arterial and venous microvessels in the four groups using the continuous protocol and only in arterial microvessels using the preventive protocol. Three parameters were studied: the number of laser beams needed to induce platelet thrombus formation, the number of emboli and the duration of embolization. Induced hemorrhagic time (IHT), platelet aggregation induced by ADP and coagulation tests (activated partial thromboplastin time, aPTT, prothrombin time, pTT, and fibrinogen level) were also determined. Continuous electrical stimulation decreased the number of emboli and the duration of embolization both in arterioles and in venules. It also significantly reduced the amplitude and velocity of the ex vivo platelet aggregation induced by ADP. Contrary to UFH, neither aPTT nor pTT were affected in platelet-poor plasma collected after the induction of thrombosis by laser beam, nor did it modify IHT. Preventive electrical stimulation produced similar results with fewer effects on induced venous thrombosis. These data suggest that EES has a potent antithrombotic effect on arterial and venous thrombosis without any hemorrhagic adverse effects, making it a very promising tool in the prevention and treatment of venous and arterial thromboembolic complications.

Animals↗

Increase of arterial thrombosis parameters in chronic Helicobacter pylori infection in mice.

An animal model was developed to study arterial thrombosis and determine if animals infected with Helicobacter pylori behave differently after induction of direct damage to blood vessels. Twenty-one C56/BL6 mice inoculated with the "Sydney strain" of H. pylori and 19 uninfected animals were kept for 1 year before testing. Vascular lesions were induced to mesenteric arterioles (15-25 microm diameter) by Argon laser. The dynamic course of thrombus formation was continuously monitored by a video camera for 10 min. Three parameters were assessed: (1) the number of laser pulses required to induce thrombus formation, (2) the number of platelet emboli removed by the blood flow and, (3) the duration of embolization. Additionally, blood was tested for platelet aggregation, fibrinogen, and cell count. Of the parameters measured, statistical differences between infected and uninfected mice concerned the number of emboli formed (6.00+/-2.18 infected vs. 3.89+/-1.37 non-infected, p=.0006) and the duration of embolization (2.41+/-0.73 min infected vs. 1.47+/-0.61 min non-infected p>.0001). A significant difference was also found in the fibrinogen levels between infected and uninfected mice. Chronic infection of mice with H. pylori leads to increased platelet embolization after damage to arterioles. These results are in favor of the possible involvement of H. pylori infection in the acute phase of coronary heart disease (CHD).

Animals↗

Vasoconstrictive response of rat mesenteric arterioles following infusion of cross-linked, polymerized, and conjugated hemoglobin solutions.

Infusion of hemoglobin-based oxygen-carrying solutions (HBOCs) produce an immediate rise in blood pressure with most solutions, both in animals and humans, as a result of systemic and pulmonary vasoconstriction. Autoregulation of the O2 supply by the microvasculature has been proposed as a phenomenon involved in the vasoconstriction elicited by HBOCs. Nevertheless, little is known about the ability of various HBOCs to induce constriction in the microcirculation according to their specific physicochemical properties (viscosity, molecular weight, P50, etc.). This study was therefore designed to assess the effects of three HBOCs, that is, bis(3.5-dibromosalicyl) fumarate-crosslinked hemoglobin (alphaalpha-Hb), dextran-benzene-tetracarboxylate-conjugated hemoglobin (Hb-Dex-BTC) and o-raffinose-oligomerized hemoglobin (o-raffinose-Hb), on the vascular tone of rat mesenteric arterioles (diameter, 15-25 microm) viewed microscopically in moderate hemodilution conditions. The effects of HBOCs were compared to those elicited by a reference solution of hydroxyethyl starch (HES-200) infused in the same conditions. In each experimental group, a fall in arteriolar diameter was observed 2 min and 5 min after infusion of the solution. The maximum changes were observed in Hb-Dex-BTC and o-raffinose-Hb groups, in which diameter decreased from 6.9 +/- 0.5% and 5.2 +/- 0.7%, respectively, 2 min after infusion. The changes in arteriolar diameter induced by Hb-Dex-BTC and o-raffinose-Hb were significantly higher than those elicited by HES-200 and alphaalpha-Hb. In conclusion, our data indicate that moderate hemodilution with HBOCs induces instantaneous constriction in rat mesenteric arterioles, with amplitudes depending on both pharmacological and physicochemical properties of the hemoglobin solution infused.

Animals↗

Time related neutralization of two doses acetyl salicylic acid.

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis has become an important issue. In fact, hemorrhage complications are often associated with its use. On the other hand, previous studies showed unexpected thrombotic potencies associated with the presence of this drug at ultra low doses (ULD) in the circulation. In this study, we aimed to evaluate the effect of aspirin at ULD, injected 1, 2, or 3 hours after the administration of aspirin at 100 mg/kg, on hemostasis and bleeding in rats. We used an experimental model of thrombosis induced by laser beams to evaluate these effects. Platelet aggregation was determined by Cardinal and Flower method. Results from this investigation demonstrate that the neutralizing effect of aspirin at ULD did not operate significantly 1 hour after the injection of aspirin at 100 mg/kg. This effect was observed 2 and 3 hours after. The use of aspirin at ULD to neutralize the side effects of aspirin at high doses will reduce the hemorrhagic risk during extra corporeal circulation. The therapeutic benefit and safety of aspirin therapy in the treatment of cardiovascular diseases can be obtained.

Animals↗

Thrombogenic potential of contrast media in an experimental model of laser-induced thrombosis.

Controversy still exists about the pro- or antithrombotic side effects of contrast media used in daily medical practice. Recent reports have shown that various contrast media, including ionic compounds, have deleterious prothrombotic actions. A new evaluation of these adverse side effects is reported here, with the study of the dose-effect relationship. Two ionic (ioxaglate and diatrizoate) and two non-ionic contrast media (iopamidol and iohexol) were studied. Experiments were done on 22 groups of 5 Wistar male rats each, using a Laser Argon-induced thrombosis model in mesenteric microvessels. Three parameters were studied: the number of laser beams needed to induce platelet thrombus formation, the number of emboli, and the duration of embolization. Platelet count and platelet aggregation also were determined. Iopamidol and iohexol induced a significant rise in both the number of emboli and the duration of embolization in mesenteric microvessels at doses up to 1 mL/kg. Ioxaglate and diatrizoate also significantly increased these parameters at doses up to 2 mL/kg. All the products tested decreased platelet count, inducing a -17 to -30% variation from control values. Diatrizoate and ioxaglate inhibited platelet aggregation, while iopamidol and Iohexol behaved as activators. All non-ionic, and to a lesser extent, all ionic contrast media demonstrated prothrombotic properties.

Animals↗

Effects of acetyl salicylic acid therapy on an experimental thrombosis induced by laser beam.

Aspirin inhibits the synthesis of both platelet and vascular arachidonic acid metabolism which have opposite effects on platelet functions. The rationale for its clinical use as an antithrombotic drug has therefore been questioned. Therefore, we investigated the effects of acetylsalicylic acid (ASA) at 100 mg/kg on an experimental thrombosis induced by laser beams using different groups of rats that were previously treated with the same dose (100 mg/kg), according to the delay between the first and second injections. A partial occlusion was induced by laser beams in the rat mesenteric microvessels (15-25 m). The thrombus formed within seconds after the laser lesion; both it and the embolization which began within minutes after, were continuously accounted. Experiments were done on 11 groups of 5 animals each: 45 rats received a first injection of ASA at j(0) and a second injection 30 minutes before thrombosis induction at j(0)+x (x=2, 4, 6, 8, 9, 10, 12, 14 and 16 days). Different groups are defined according to the x value. The rats receiving NaCl 0.9% or a single injection of ASA at 100 mg/kg 30 minutes before thrombosis induction were used as control (Group I) and reference group (Group II) respectively. In this study, ASA treatment showed two types of results. The administration of ASA (100 mg/kg) 30 minutes before laser-induced thrombosis prevented thrombus formation. In the same way, ASA injected to rats already treated with the same dose 2 or 4 day later also demonstrated a potent antithrombotic effect. The same trends were observed with animals receiving the second injection (100 mg ASA) at j(0+8), j(0+12), j(0+14), and j(0+16). However, when injected to rats at j(0+6) and at j(0+10), ASA did not shown any effects on thrombus formation compared to the control (p>/=0.05). The same phases of ASA action were observed on the induced hemorrhagic time. The antithrombotic effects of the later second injection of ASA (100 mg/kg) were neutralized in rats previously receiving the same dose of this drug. This phenomenon seems to be periodic and is of great importance for the observance of ASA treatment.

Adenosine Diphosphate↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Effects of ultra-low-dose aspirin on embolization in a model of laser-induced thrombus formation.

A laser-induced rat mesenteric vessel thrombosis model was used to evaluate the effect of acetylsalicylic acid (ASA) at ultra-low doses. A partial occlusion was induced in small mesenteric vessels (diameter 40-50 microns) by an argon laser. The laser induced damage of endothelial cells. Thrombi formed within seconds after the laser lesion and grew rapidly. Embolization began during the minute following the laser injury. Compared to placebo, the administration of ASA at ultra-low doses (334 x 10(-11) mol/mL) by subcutaneous injection in the thorax region (0.2 mL) induced three different phenomena: (1) a decrease in the number of laser injuries required to induce thrombus formation, (2) an increase in number of emboli removed by the blood stream, and (3) an increase in the duration of embolization. The ultra-low doses of ASA showed a strong increase in the number of emboli and in the duration of embolization.

Animals↗

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↗