References of "Ghuysen, Alexandre"
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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 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 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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See detailPharmacological characterization of N-tert-butyl-N’-[2-(4’-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a novel thromboxane A2 receptor antagonist and thromboxane synthase inhibitor in a rat model of arterial thrombosis and its effects on bleeding time
Dogné, Jean-Michel ULg; Hanson, Julien ULg; De leval, X. et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2004), 309(2), 498-505

The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], an original combined ... [more ▼]

The present study was undertaken to characterize the antiplatelet and antithrombotic effects of BM-573 [N-tert-butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl] urea], an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor in rats, and to determine its effects on mice bleeding time. Intraperitoneal injection of a single dose of 5 mg/kg BM-573 to rats inhibited U-46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin F-2)-induced washed platelet aggregation 30 min and 1, 2, and 4 h after drug administration with a maximum antiplatelet effect observed after 1 and 2 h. In a rat model of thrombosis induced by ferric chloride application on the abdominal aorta, BM-573 significantly reduced the thrombus weight by 92.53, 80.20, 64.75, and 18.21% at doses of 5, 2, 0.5, and 0.2 mg/kg, respectively. Time to occlusion of abdominal aorta in the BM-573-treated group (41.50+/-5.21 min) was significantly prolonged compared with the vehicle-treated rats (16.16+/-0.79 min). Like furegrelate, seratrodast, and acetylsalicylic acid, BM-573 did not affect the tail bleeding time induced by tail transection in mice compared with vehicle-treated mice. Moreover, BM-573, a close derivative of the loop diuretic torasemide, failed to induce a significant increase in diuresis in rat and did not produce a decrease in blood glucose concentration as observed with the sulfonylurea glibenclamide. In conclusion, we have demonstrated that the nitrobenzenic sulfonylurea BM-573, an original combined thromboxane receptor antagonist and thromboxane synthase inhibitor, is a potent antithrombotic agent that does not affect bleeding time. Moreover, BM-573 lost the diuretic property of torasemide and has no impact on glycemia. [less ▲]

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See detailEffect of hemodiafiltration on pulmonary hemodynamics in endotoxic shock
Lambermont, Bernard ULg; Kolh, Philippe ULg; Ghuysen, Alexandre ULg et al

in Artificial Organs (2003), 27(12), 1128-1133

Hemofiltration can improve pulmonary hemodynamics during septic shock. The main objective of the study was to determine whether hemodiafiltration (HDF) would also have beneficial effects on pulmonary ... [more ▼]

Hemofiltration can improve pulmonary hemodynamics during septic shock. The main objective of the study was to determine whether hemodiafiltration (HDF) would also have beneficial effects on pulmonary hemodynamics during septic shock. In the Endo group, six anesthetized pigs received a 0.5 mg/kg endotoxin infusion over 30 min. In the HDF group (n = 6), HDF was started 30 min after the end of the endotoxin infusion, while in the Control group (n = 4) they received HDF but no endotoxin infusion. Pulmonary hemodynamics were analyzed in detail with a four-element windkessel model. Although in the Control group, HDF did not alter pulmonary hemodynamic parameters, in the HDF group, it was responsible for an amplification of the deleterious pulmonary vascular response to endotoxin insult. Our results show that HDF must be used cautiously in septic shock since it can precipitate right heart failure by increasing pulmonary vascular resistance. [less ▲]

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See detailEffects of increased afterload on left ventricular performance and mechanical efficiency are not baroreflex-mediated
Kolh, Philippe ULg; Ghuysen, Alexandre ULg; Tchana-Sato, Vincent ULg et al

in European Journal of Cardio - Thoracic Surgery (2003), 24(6), 912-919

Objective: To assess baroreflex intervention during increase in left ventricular afterload, we compared the effects of aortic banding on the intact cardiovascular system and under hexamethonium infusion ... [more ▼]

Objective: To assess baroreflex intervention during increase in left ventricular afterload, we compared the effects of aortic banding on the intact cardiovascular system and under hexamethonium infusion. Methods: Six open-chest pigs, instrumented for measurement of aortic pressure and flow, left ventricular pressure and volume, were studied under pentobarbital-sufentanil anesthesia. Vascular arterial properties were estimated with a four-element windkessel model. Left ventricular contractility was assessed by the slope of end-systolic pressure-volume relationship. Results: The effects of aortic banding on mechanical aortic properties were unaffected by autonomic nervous system inhibition. However, increase in peripheral arterial vascular resistance and in heart rate were prevented by hexamethonium. Aortic banding increased left ventricular contractility and stroke work. Left ventricular-arterial coupling remained unchanged, but mechanical efficiency was impaired. These ventricular changes were independent of baroreflex integrity. Conclusions: Our results demonstrate that an augmentation in afterload has a composite effect on left ventricular function. Left ventricular performance is increased, as demonstrated by increase in contractility and stroke work, but mechanical efficiency is decreased. These changes are observed independently of baroreflex integrity. Such mechanisms of autoregulation, independent of the autonomic nervous system, are of paramount importance in heart transplant patients. (C) 2003 Elsevier B.V. All fights reserved. [less ▲]

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See detailLeft ventricular preload-adjusted maximal power: Clinically useful marker of LV contractility ?
Segers, P.; Tchana-Sato, Vincent ULg; Leather, H. A. et al

in Circulation (2003, October 28), 108(17, Suppl. S), 396-396

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See detailEffects of endotoxic shock on right ventricular systolic function and mechanical efficiency
Lambermont, Bernard ULg; Ghuysen, Alexandre ULg; Kolh, Philippe ULg et al

in Cardiovascular Research (2003), 59(2), 412-418

Objective: To investigate the effects of endotoxin infusion on right ventricular (RV) systolic function and mechanical efficiency. Methods: Six anesthetized pigs (Endo group) received a 0.5 mg/kg ... [more ▼]

Objective: To investigate the effects of endotoxin infusion on right ventricular (RV) systolic function and mechanical efficiency. Methods: Six anesthetized pigs (Endo group) received a 0.5 mg/kg endotoxin infusion over 30 min and were compared with six other anesthetized pigs (Control group) receiving placebo for 5 h. RV pressure-volume (PV) loops were obtained by the conductance catheter technique and pulmonary artery flow and pressure were measured with high-fidelity transducers. Results: RV adaptation to increased afterload during the early phase of endotoxin-induced pulmonary hypertension (T30) was obtained by both homeometric and hetereometric regulations: the slope of the end-systolic PV relationship of the right ventricle increased from 1.4+/-0.2 mmHg/ml to 2.9+/-0.4 mmHg/ml (P<0.05) and RV end-diastolic volume increased from 56+/-6 ml to 64+/-11 ml (P<0.05). Consequently, right ventricular-vascular coupling was maintained at a maximum efficiency. Ninety minutes later (T120), facing the same increased afterload, the right ventricle failed to maintain its contractility to such an elevated level and, as a consequence, right ventricular-vascular uncoupling occurred. PV loop area, which is known to be highly correlated with oxygen myocardial consumption, increased from 1154+/-127 mmHg/ml (T0) to 1798+/-122 mmHg/ml (T180) (P<0.05) while RV mechanical efficiency decreased from 63+/-2% (T0) to 45+/-5% (T270) (P<0.05). Conclusions: In the very early phase of endotoxinic shock, right ventricular-vascular coupling is preserved by an increase in RV contractility. Later, myocardial oxygen consumption and energetic cost of RV contractility are increased, as evidenced by the decrease in RV efficiency, and right ventricular-vascular uncoupling occurs. Therefore, therapies aiming at restoring right ventricular-vascular coupling in endotoxic shock should attempt to increase RV contractility and to decrease RV afterload but also to preserve RV mechanical efficiency. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailBM-573, a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, prevents pig myocardial infarction induced by coronary thrombosis
Rolin, S.; Petein, M.; Tchana-Sato, Vincent ULg et al

in Journal of Pharmacology and Experimental therapeutics (2003), 306(1), 59-65

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

The aim of this study was to characterize the effects of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a novel dual thromboxane A 2 receptor antagonist and thromboxane synthase inhibitor, on myocardial infarction induced by topical ferric chloride (FeCl3) application to the left anterior descending (LAD) coronary artery in anesthetized pigs. All control animals (n = 6) developed an occlusive thrombus in the LAD coronary artery. The mean infarct size, revealed by triphenyl tetrazolium chloride (TTC), and the area at risk, evidenced by Evans blue, corresponded to 35.3 +/- 2.2 and 36.9 +/- 2.1% of the left ventricular mass, respectively. In the BM-573-treated group (n = 6), a drug infusion (10 mg . kg(-1) . h(-1)) started 30 min before FeCl3 application and continued throughout the experimentation. Among the BM-573-treated group, four pigs did not develop coronary artery thrombus and their myocardium appeared healthy. Histopathological examination of FeCl3-injured coronary artery revealed an occlusive and adherent thrombus in control group, while pretreatment with BM-573 prevented thrombus formation. In infarcted zones, lack of desmin staining and muscle structure disorganization were obvious. Depletion of myocardial ATP content was observed in the myocardial necrotic region of the control group, but not in myocardial samples of BM-573-treated pigs that did not develop myocardial infarction. When BM-573 prevented LAD artery occlusion, the area under the curve of plasmatic troponin T was reduced by 77% over 6 h. These data suggest that BM-573 could be useful for the prevention of myocardial infarction. [less ▲]

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See detailEffects of U-46619 on Pulmonary Hemodynamics before and after Administration of Bm-573, a Novel Thromboxane A2 Inhibitor
Lambermont, Bernard ULg; Kolh, Philippe ULg; Dogné, Jean-Michel ULg et al

in Archives of Physiology & Biochemistry (2003), 111(3), 217-23

We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A2 (TXA2) agonist, before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Six ... [more ▼]

We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A2 (TXA2) agonist, before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Six anesthetized pigs (Ago group) received 6 consecutive injections of U-46619 at 30-min interval and were compared with six anesthetized pigs (Anta group) which received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. Consecutive changes in pulmonary hemodynamics, including characteristic resistance, vascular compliance, and peripheral vascular resistance, were continuously assessed during the experimental protocol using a four-element Windkessel model. At 2 mg/kg, BM-573 completely blocked pulmonary hypertensive effects of U-46619 but pulmonary vascular compliance still decreased. This residual effect can probably be explained by a persistent increase in the tonus of the pulmonary vascular wall smooth muscles sufficient to decrease vascular compliance but not vessel lumen diameter. Such molecule could be a promising therapeutic approach in TXA2 mediated pulmonary hypertension as it is the case in pulmonary embolism, hyperacute lung rejection and endotoxinic shock. [less ▲]

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See detailEffects of Bm-573, a Novel Thromboxane A2 Inhibitor, on Pulmonary Hemodynamics in Endotoxic Shock
Lambermont, Bernard ULg; Ghuysen, Alexandre ULg; Dogné, Jean-Michel ULg et al

in Archives of Physiology & Biochemistry (2003), 111(3), 224-31

Thromboxane A2 is considered to be partially responsible for the increase in pulmonary vascular resistance observed after endotoxin administration and to participate in proinflammatory reactions. The ... [more ▼]

Thromboxane A2 is considered to be partially responsible for the increase in pulmonary vascular resistance observed after endotoxin administration and to participate in proinflammatory reactions. The effects of a novel dual TXA2 synthase inhibitor and TXA2 receptor antagonist (BM-573) on pulmonary hemodynamics were investigated in endotoxic shock. 30 mins before the start of a 0.5 mg/kg endotoxin infusion, 6 pigs (Endo group) received a placebo infusion and 6 other pigs (Anta group) received a BM-573 infusion. In Endo group, pulmonary artery pressure increased from 25 +/- 1.8 (T0) to 42 +/- 2.3 mmHg (T60) (p < 0.05) after endotoxin infusion while, in Anta group, it increased from 23 +/- 1.6 (T0) to 25 +/- 1.5 mmHg (T60). This difference is due to a reduction in pulmonary vascular resistance in Anta group while pulmonary arterial compliance changes in Endo group remained comparable with the evolution in Anta group. In Endo group, PaO2 decreased from 131 +/- 21 (T0) to 74 +/- 12 mmHg (T300) (p < 0.05), while in Anta group, PaO2 was 241 +/- 31 mmHg at the end of the experimental period (T300). These results demonstrate that TXA2 plays a major role in pulmonary vascular changes during endotoxin insult. Concomitant inhibition of TXA2 synthesis and of TXA2 receptors by BM-573 inhibited the pulmonary vasopressive response during the early phase of endotoxin shock as well as the deterioration in arterial oxygenation. [less ▲]

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See detailAlteration of left ventriculo-arterial coupling and mechanical efficiency during acute myocardial ischemia
Kolh, Philippe ULg; Lambermont, Bernard ULg; Ghuysen, Alexandre ULg et al

in International Angiology (2003), 22(2), 148-158

AIM: Myocardial revascularisation being frequently performed during acute myocardial ischemia, in a hostile hemodynamic environment, we evaluated left ventriculo-arterial (VA) coupling, left ventricular ... [more ▼]

AIM: Myocardial revascularisation being frequently performed during acute myocardial ischemia, in a hostile hemodynamic environment, we evaluated left ventriculo-arterial (VA) coupling, left ventricular (LV) mechanical efficiency, and the mechanical properties of the systemic vasculature during acute myocardial ischemia. METHODS: In 6 pigs, vascular properties [characteristic impedance (R(1)), peripheral resistance (R(2)), compliance (C), inductance (L), arterial elastance (E(a))] were estimated with a windkessel model. LV function was assessed by the slope (E(es)) of end-systolic pressure-volume relationship (ESPVR), and stroke work (SW) - end-diastolic volume (EDV) relation. Pressure-volume area (PVA) was referred to as myocardial oxygen consumption. VA coupling was defined as E(es)/E(a), and mechanical efficiency as SW/PVA. After baseline recordings, the left anterior descending coronary artery was ligated and hemodynamic measures obtained every 30 minutes for 3 hours. Data are expressed as mean (SEM). RESULTS: Coronary occlusion induced an ESPVR rightward shift, and decreased E(es) from 3.67 (0.33) to 1.92 (0.20) mmHg/ml and the slope of the SW - EDV relationship from 72.3 (3.4) to 40.4 (4.5) mmHg (p<0.001), while E(a) increased from 3.33 (0.56) to 4.65 (0.29) mmHg/ml (p<0.005). This was responsible for a dramatic alteration of VA coupling from 1.22 (0.11) to 0.44 (0.07), (p<0.001). While R2 increased from 1.72 (0.30) to 2.38 (0.16) mmHg x s x ml(-1) (p<0.05) and C decreased from 0.78 (0.16) to 0.46 (0.08) ml/mmHg (p<0.05), R(1) and L were unchanged. Coronary occlusion decreased SW from 4056 (223) to 2580 (122) mmHg.ml (p<0.001), while PVA and SW/PVA decreased from 5575 (514) to 4813 (317) mmHg x ml (NS), and from 0.76 (0.04) to 0.57 (0.03) (p<0.001), respectively. CONCLUSION: Acute myocardial ischemia severely altered left ventriculo-arterial coupling and LV mechanical efficiency. Impaired left VA coupling was due to a combination of augmented arterial elastance, secondary to early vasoconstriction later associated with decreased arterial compliance, and decreased LV contractility. [less ▲]

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See detailDeterminants of left ventricular preload-adjusted maximal power
Segers, Patrick; Tchano-Sato, Vincent; Leather, H. Alex et al

in American Journal of Physiology - Heart and Circulatory Physiology (2003), 284(6), 2295-2301

Maximal left ventricular (LV) hydraulic power output (PWRmax), corrected for preload as PWRmax/(V-ed)(beta) (where V-ed is the end-diastolic volume and beta is a constant coefficient), is an index of LV ... [more ▼]

Maximal left ventricular (LV) hydraulic power output (PWRmax), corrected for preload as PWRmax/(V-ed)(beta) (where V-ed is the end-diastolic volume and beta is a constant coefficient), is an index of LV contractility. Whereas preload-adjusted maximal power (PAMP) is usually calculated with beta = 2, there is uncertainty about the optimal value of beta (beta = 1 for the normal LV and 2 for the dilated LV). The aim of this work is to study the determining factors of beta. The data set consisted of 245 recordings (steady state and vena cava occlusion) in 10 animals in an ischemic heart pig model. The occlusion data yielded the slope (E-es; 2.01 +/- 0.77 mmHg/ml, range 0.71-4.16 mmHg/ml) and intercept (V-0; -11.9 +/- 22.6 ml; range -76 to 39 ml) of the end-systolic pressure-volume relation, and the optimal beta-factor (assessed by fitting an exponential curve through the V-ed-PWRmax relation) was 1.94 +/- 0.88 (range 0.29-4.73). The relation of beta with V-ed was weak [beta = 0.60 + 0.02(V-ed); r(2) = 0.20]. In contrast, we found an excellent exponential relation between V-0 and beta [beta = 2.16e(0.0189(V0)), r(2) = 0.70]. PAMP, calculated from the steady-state data, was 0.64 +/- 0.40 mW/ml(2) (range 0.14-2.83 mW/ml(2)) with a poor correlation with E-es (r = 0.30, P < 0.001). An alternative formulation of PAMP as PWRmax/(V-ed - V-0)(2), incorporating V-0, yielded 0.47 +/- 0.26 mW/ml(2) (range 0.09-1.42 mW/ml(2)) and was highly correlated with E-es (r = 0.89, P < 0.001). In conclusion, correct preload adjustment of maximal LV power requires incorporation of V-0 and thus of data measured under altered loading conditions. [less ▲]

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See detailRight ventricular diastolic function in acute pulmonary embolism
Morimont, Philippe ULg; segers, P.; Ghuysen, Alexandre ULg et al

Poster (2003)

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