References of "Dogné, Jean-Michel"
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See detailStructure-based pharmacophore of COX-2 selective inhibitors and identification of original lead compounds from 3D database searching method
Michaux, C.; De Leval, X.; Julémont, F. et al

in European Journal of Medicinal Chemistry (2006), 41

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See detailEffects of BM-573, a thromboxane A(2) modulator on systemic hemodynamics perturbations induced by U-46619 in the pig
Tchana-Sato, Vincent ULg; Dogné, Jean-Michel ULg; Lambermont, Bernard ULg et al

in Prostaglandins & Other Lipid Mediators (2005), 78(1-4), 82-95

The aim of our study was to evaluate the effects of thromboxane A(2) (TXA(2)) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA(2) receptor ... [more ▼]

The aim of our study was to evaluate the effects of thromboxane A(2) (TXA(2)) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA(2) receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group (n=6), the animals received six consecutive injections of U-46619 at 30 min interval, while in Anta group (n = 6) they received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. The effects of each dose of BM-573 on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were also evaluated. Vascular properties such as characteristic impedance, peripheral resistance, compliance, arterial elastance were estimated using a windkessel model. Intravenous injections of 0.500 mg/ml of BM-573 and higher doses resulted in a complete inhibition of platelet aggregation induced by arachidonic acid. In the same conditions, BM-573 completely blocked the increase of arterial elastance, and stabilized both mean aortic blood pressure and mean systemic blood flow. In conclusion, BM-573 could therefore be a promising therapeutic approach in pathophysiological states where TXA(2) plays it main role in the increase of vascular resistance like in pathologies such as systemic hypertension. (c) 2005 Published by Elsevier Inc. [less ▲]

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See detailCharacterisation of an original model of myocardial infarction provoked by coronary artery thrombosis induced by ferric chloride in pig
Dogné, Jean-Michel ULg; Rolin, S.; Tchana-Sato, Vincent ULg et al

in European Heart Journal (2005, September), 26(Suppl. 1), 455-456

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See detailEffects of dobutamine on left ventriculoarterial coupling and mechanical efficiency in acutely ischemic pigs
Kolh, Philippe ULg; Lambermont, Bernard ULg; Ghuysen, Alexandre ULg et al

in Journal of Cardiovascular Pharmacology (2005), 45(2), 144-152

This study investigated the effects of dobutamine on left ventriculoarterial (VA) coupling and mechanical efficiency in acutely ischemic pigs. Experiments were performed in 12 pigs in which vascular ... [more ▼]

This study investigated the effects of dobutamine on left ventriculoarterial (VA) coupling and mechanical efficiency in acutely ischemic pigs. Experiments were performed in 12 pigs in which vascular properties, including peripheral resistance (R-2), compliance (C), and arterial elastance (E-a), were estimated with a windkessel model, and left ventricular (LV) function by the slope (E-es) of the end-systolic pressure-volume relationship (ESPVR) and stroke work (SW). VA coupling was defined as E-es/E-a, and mechanical efficiency as SW/pressure-volume area (PVA). In all animals, the left anterior descending coronary artery was ligated after basal measures. The animals were then randomly divided into 2 groups: group CTRL (n = 6) was followed for 180 minutes without other intervention, whereas group DOBU (n = 6) was infused with dobutamine (5 mug(.)kg(-1.)min(-1)) starting after T60 measures. Coronary occlusion induced a rightward shift of ESPVR and a decrease in E-es from 3.67 +/- 0.33 to 1.92 +/- 0.20 mm Hg(.)mL(-1), while E-a changed from 3.33 +/- 0.56 to 4.65 +/- 0.29 mm Hg(.)mL(-1), R-2 from 1.72 +/- 0.30 to 2.38 +/- 0.16 mm Hg(.)s(.)mL(-1), and C from 0.78 +/- 0.16 to 0.46 +/- 0.08 mL(.)mm Hg-1. This altered VA coupling from 1.22 +/- 0.11 to 0.44 +/- 0.07. SW decreased from 4056 +/- 223 to 2372 +/- 122 mm Hg(.)mL, and PVA and SW/PVA decreased from 5575 +/- 514 to 4830 +/- 3.17 mm Hg(.)mL, and from 0.76 +/- 0.04 to 0.49 +/- 0.03, respectively. In group DOBU, dobutamine restored E-es and the position of ESPVR to baseline values, while E-a decreased to 3.39 +/- 0.34 mm Hg(.)mL(-1) because of an R-2 decrease to 1.60 +/- 0.24 mm Hg(.)s(.)mL(-1). VA coupling was restored. SW and PVA increased to 3833 +/- 180 mm Hg(.)mL and to 7498 +/- 442 mm Hg(.)mL, respectively, while SW/PVA was unchanged. In ischemic pigs, dobutamine restored VA coupling through an increase in LV contractility and decrease in arterial elastance as a result of peripheral vasodilatation. However, myocardial oxygen consumption was increased, and mechanical efficiency impaired. [less ▲]

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See detailEffects of reperfusion on left ventricular hemodynamics and ventriculo-arterial coupling in acutely ischemic pigs
Lanoye, Lieve; KOLH, Philippe ULg; Rolin, Stéphanie et al

in Computer Methods in Biomechanics & Biomedical Engineering (2005), 8(suppl. 1), 169-170

Rapid restoration of coronary blood flow following a period of myocardial ischemia (due to coronary occlusion) is mandatory to preserve the cardiac muscle. Reperfusion, however, not necessarily restores ... [more ▼]

Rapid restoration of coronary blood flow following a period of myocardial ischemia (due to coronary occlusion) is mandatory to preserve the cardiac muscle. Reperfusion, however, not necessarily restores cardiac function, and cellular damage of the cardiac muscle cells following reperfusion (reperfusion injury) is well documented. The aim of this study was to investigate the effects of reperfusion on left ventricular (LV) hemodynamics and on left ventriculo-arterial (VA) coupling in acutely ischemic pigs. [less ▲]

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See detailCharacterization of an original model of myocardial infarction provoked by coronary artery thrombosis induced by ferric chloride in pig
Dogné, Jean-Michel ULg; Rolin, Stéphanie; Petein, Michel et al

in Thrombosis Research (2005), 116(5), 431-442

Background: Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely ... [more ▼]

Background: Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely contributed to the discovery and to the validation of original treatments. The purpose of the present work was to develop and validate an original model of acute myocardial infarction provoked in pig by thrombosis of the left anterior descending (LAD) coronary artery induced by topical application of ferric chloride solution. Methods and results: Myocardial infarction, resulting from an occlusive and adherent mixed thrombus formed in the LAD coronary artery, was examined at macroscopic level using dual staining technique (Evans blue dye; triphenyltetrazolium chloride) and at microscopic level using conventional histological analyses and immunohistochemical detection of desmin. Biochemical markers (troponin T and ATP), platelet reactivity and standard hemodynamic parameters (such as stroke volume, ejection fraction, stroke work and cardiac output) have also been evaluated. From these analyses, it was demonstrated that each pig developed a transmural area of irreversible damage mainly located in the anteroseptal region of the left ventricle. The more progressive development of coronary artery occlusion, as compared to an abrupt Ligation, was accompanied by a correspondingly progressive impairment in hemodynamics. Conclusion: We conclude that this original porcine model of myocardial infarction is quite close to clinical pathophysiological conditions, such as thrombus formation occurring after atherosclerotic plaque rupture. This certainly constitutes a further argument in favour of this model to assess pharmaceutical or mechanical support of an acutely ischemic heart. (c) 2005 Elsevier Ltd. All rights reserved. [less ▲]

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See detailIn vitro and in vivo pharmacological characterization of BM-613 [N-n-pentyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea]
Hanson, Julien ULg; Rolin, Stéphanie; Reynaud, Denis et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2005), 313

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See detailA new potential cyclooxygenase-2 inhibitor, pyridinic analogue of nimesulide
Michaux, C.; Charlier, C.; Julémont, F. et al

in European Journal of Medicinal Chemistry (2005), 40

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See detailEffect of BM-573[N-terbutyl-N '-[2-(4 '-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, in a porcine model of acute pulmonary embolism
Ghuysen, Alexandre ULg; Lambermont, Bernard ULg; Dogné, Jean-Michel ULg et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2004), 310(3), 964-972

The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane A(2) synthase inhibitor and receptor antagonist, on ... [more ▼]

The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane A(2) synthase inhibitor and receptor antagonist, on the hemodynamic response to acute pulmonary embolism. Six anesthetized pigs were infused with placebo ( placebo group) and compared with six other pigs receiving a continuous infusion of BM-573 ( BM group). Pulmonary embolization with 0.3 g/kg autologous blood clots was carried out 30 min after the start of the infusion. Right ventricular pressure-volume loops were recorded using a conductance catheter, and end-systolic ventricular elastance was periodically assessed by varying right ventricular preload. Pulmonary vascular properties were studied by use of a four-element wind-kessel model. Hemodynamic data, including assessment of right ventricular-arterial coupling, were collected at baseline and every 30 min for 4 h. Blood samples were collected to assess gas exchange, thromboxane A(2), and prostacyclin plasma levels and to evaluate platelet aggregation. Mean pulmonary arterial pressure in the placebo group increased significantly more than in the BM group, mainly because of an additional increase in pulmonary vascular resistance. Arterial and end-systolic ventricular elastances increased also more in the placebo group, whereas right ventricular efficiency decreased. BM-573 prevented both platelet aggregation induced by U-46619 (9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F-2alpha) or by arachidonic acid, and thromboxane A(2) overproduction, whereas prostacyclin liberation was preserved. Oxygenation, however, was not significantly improved. We conclude that in this animal model of acute pulmonary embolism, infusion of BM-573 reduced pulmonary vasoconstriction. As a result, right ventricular-vascular coupling values were maintained at a maximal efficiency level. [less ▲]

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See detailComparison of the effects of propofol and pentobarbital on left ventricular adaptation to an increased afterload
Kolh, Philippe ULg; Lambermont, Bernard ULg; Ghuysen, Alexandre ULg et al

in Journal of Cardiovascular Pharmacology (2004), 44(3), 294-301

The purpose of this study was to compare the hemodynamic effects of pentobarbital and propofol and their effects on cardiovascular adaptation to an abrupt increase in left ventricular afterload ... [more ▼]

The purpose of this study was to compare the hemodynamic effects of pentobarbital and propofol and their effects on cardiovascular adaptation to an abrupt increase in left ventricular afterload. Experiments were performed in 12 open-chest pigs instrumented for measurement of aortic pressure and flow, and left ventricular pressure and volume. In one group (n = 6), anesthesia was obtained with sodium pentobarbital (3 mg x kg(-1) x h(-1)), and, in the second group B (n = 6), with propofol (10 mg x kg(-1) x h(-1)). Both groups received sufentanil (0.5 microg x kg(-1) x h(-1)) and pancuronium bromide (0.1 mg x kg(-1)). Left ventricular function was assessed by the slope of end-systolic pressure-volume relationship and stroke work. After baseline recordings, left ventricular afterload was increased by aortic banding. The cardiovascular adaptations triggered by the aortic banding, such as tachycardia, vasoconstriction, and augmentation of myocardial contractility were prevented with propofol, suggesting interference with the baroreflex. Increase in left ventricular afterload decreased mechanical efficiency, regardless of anesthetic agent. These results showed that pentobarbital at 3 mg x kg(-1) x h(-1) has less deleterious hemodynamic effects than propofol at 10 mg x kg(-1) x h(-1). [less ▲]

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See detailModulation of the arachidonic cascade with omega 3 fatty acids or analogues: Potential therapeutic benefits
Roland, Isabelle ULg; de Leval, X.; Evrard, Brigitte ULg et al

in Mini-Reviews in Medicinal Chemistry (2004), 4(6), 659-668

Increasing interest in the role of omega 3 fatty acids has arisen in these latest years since evidence of their implication in the cardioprotective fish based diet of the Inuit has been demonstrated ... [more ▼]

Increasing interest in the role of omega 3 fatty acids has arisen in these latest years since evidence of their implication in the cardioprotective fish based diet of the Inuit has been demonstrated. Furthermore, several in vitro, in vivo and epidemiological studies support the benefit of this fatty acids intake in various pathological states such as in the cardiovascular, cancer, inflammation, psychiatric, paediatric, pulmonary, dermatological and ophthalmologic fields. This review will focus on metabolism and pharmacological implication of w3 fatty acids intake as well as its interest in the prevention or treatment of the above-mentioned pathologies. [less ▲]

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See detailEffect of a novel thromboxane A(2) inhibitor on right ventricular-arterial coupling in endotoxic shock
Lambermont, Bernard ULg; Kolh, Philippe ULg; Ghuysen, Alexandre ULg et al

in Shock (2004), 21(1), 45-51

We investigated the effects of a dual thromboxane (TX)A(2) synthase inhibitor and TXA(2) receptor antagonist (BM-573) on right ventricular-arterial coupling in a porcine model of endotoxic shock. Thirty ... [more ▼]

We investigated the effects of a dual thromboxane (TX)A(2) synthase inhibitor and TXA(2) receptor antagonist (BM-573) on right ventricular-arterial coupling in a porcine model of endotoxic shock. Thirty minutes before the onset of 0.5 mg/kg endotoxin infusion, six pigs (Endo group) received an infusion with a placebo solution, and six other pigs (Anta group) with BM-573. Right ventricular pressure-volume loops were obtained by the conductance catheter technique. The slope (E-es) of the end-systolic pressure-volume relationship and its volume intercept at 25 mmHg were calculated as measures of right ventricular systolic function. RV afterload was quantified by pulmonary arterial elastance (E-a), and E-es/E-a ratio represented right ventricular-arterial coupling. Mechanical efficiency was defined as the ratio of stroke work and pressure-volume area. In this model of endotoxic shock, BM-573 blunted the early phase of pulmonary hypertension, improved arterial oxygenation, and prevented a decrease in right ventricular myocardial efficiency and right ventricular dilatation. However, the drug could not prevent the loss of homeometric regulation and alterations in right ventricular-arterial coupling. In conclusion, dual TXA(2) synthase inhibitor and receptor antagonists such as BM-573 have potential therapeutic applications, improving right ventricular efficiency and arterial oxygenation in endotoxic shock. [less ▲]

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See detailNew developments on thromboxane modulators
Dogné, Jean-Michel ULg; Hanson, Julien ULg; De leval, X. et al

in Mini Reviews in Medicinal Chemistry (2004)

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See detailComparison between single-beat and multiple-beat methods for estimation of right ventricular contractility.
Lambermont, Bernard ULg; Segers, Patrick; Ghuysen, Alexandre ULg et al

in Critical Care Medicine (2004), 32(9), 1886-90

OBJECTIVE: It was investigated whether pharmacologically induced changes in right ventricular contractility can be detected by a so-called "single-beat" method that does not require preload reduction ... [more ▼]

OBJECTIVE: It was investigated whether pharmacologically induced changes in right ventricular contractility can be detected by a so-called "single-beat" method that does not require preload reduction. DESIGN: Prospective animal research. SETTING: Laboratory at a large university medical center. SUBJECTS: Eight anesthetized pigs. INTERVENTIONS: End-systolic elastance values obtained by a recently proposed single-beat method (Eessb) were compared with those obtained using the reference multiple-beat method (Eesmb). MEASUREMENTS AND MAIN RESULTS: Administration of dobutamine increased Eesmb from 1.6 +/- 0.3 to 3.8 +/- 0.5 mm Hg/mL (p =.001), whereas there was only a trend toward an increase in Eessb from 1.5 +/- 0.2 to 1.7 +/- 0.4 mm Hg/mL. Esmolol decreased Eesmb from 1.7 +/- 0.3 to 1.1 +/- 0.2 mm Hg/mL (p =.006), whereas there was only a trend for a decrease in Eessb from 1.5 +/- 0.2 to 1.3 +/- 0.1. CONCLUSIONS: The present method using single-beat estimation to assess right ventricular contractility does not work as expected, since it failed to detect either increases or decreases in right ventricular contractility induced by pharmacologic interventions. [less ▲]

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See detailEffects of COX-2 inhibitors on ROS produced by Chlamydia pneumoniae-primed human promonocytic cells (THP-1)
Mouithys-Mickalad, Ange ULg; Deby, Ginette ULg; Dogné, Jean-Michel ULg et al

in Biochemical and Biophysical Research Communications (2004), 325(4), 1122-1130

Chronic inflammation through foam cells and macrophages is important in atherosclerosis development, and can be considered as therapeutic targets. Cyclooxygenase and NADPH-oxidase were expressed within ... [more ▼]

Chronic inflammation through foam cells and macrophages is important in atherosclerosis development, and can be considered as therapeutic targets. Cyclooxygenase and NADPH-oxidase were expressed within atherosclerotic lesions. Reactive oxygen species produced by NADPH oxidase were found to trigger the cyclooxygenase-2 expression. The effects of preferential COX-2 inhibitors on ROS produced by Chlamydia-primed human monocytes (THP-1 cells) were evaluated by fluorescence, chemiluminescence, oxymetry, and EPR spin trapping. Fluorescence assays showed an increased production of ROS with Chlamydia versus cells primed by 10(-8) M PMA. COX-2 inhibitors inhibited in a dose-dependent manner the luminol-enhanced CL while ibuprofen and diclofenac increased the chemiluminescence response. By EPR spin trapping, COX-2 inhibitors, ibuprofen, and diclofenac, exhibited a dose-dependent inhibiting effect (10 and 100 muM) on the EPR signal appearance. Our cell model combining EPR, chemiluminescence, and oxymetry appeared relevant to study the modulating effects of preferential COX-2 inhibitors on the cell oxidant activity and chronic inflammatory diseases. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

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See detailNew developments on thromboxane and prostacyclin modulators. Part II: prostacyclin modulators
De Leval, X.; Hanson, Julien ULg; David, Jean-Louis ULg et al

in Current Medicinal Chemistry (2004), 11

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See detailCharacterization of preferential activity on platelet thromboxane A2 receptors of BM-613, a new thromboxane A2 antagonist
Hanson, Julien ULg; Rolin, S.; De Leval, X. et al

in Fundamental & Clinical Pharmacology (2004)

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See detailNew developments on thromboxane and prostacyclin modulators. Part I: thromboxane modulators
Dogné, Jean-Michel ULg; De leval, X.; Hanson, Julien ULg et al

in Current Medicinal Chemistry (2004), 11

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