F Duclos

Unité Inserm U1077, Caen, Lower Normandy, France

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Publications (6)54.34 Total impact

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    ABSTRACT: P. Dos Santos, M. K. Aliev, P. Diolez, F. Duclos, P. Besse, S. Bonoron-Adèle, P. Sikk, P. Canioni and V. A. Saks. Metabolic Control of Contractile Performance in Isolated Perfused Rat Heart. Analysis of Experimental Data by Reaction:Diffusion Mathematical Model. Journal of Molecular and Cellular Cardiology (2000) 32, 1703–1734. The intracellular mechanisms of regulation of energy fluxes and respiration in contracting heart cells were studied. For this, we investigated the workload dependencies of the rate of oxygen consumption and metabolic parameters in Langendorff-perfused isolated rat hearts.31P NMR spectroscopy was used to study the metabolic changes during transition from perfusion with glucose to that with pyruvate with and without active creatine kinase system. The experimental results showed that transition from perfusion with glucose to that with pyruvate increased the phosphocreatine content and stability of its level at increased workloads. Inhibition of creatine kinase reaction by 15-min infusion of iodoacetamide decreased the maximal developed tension and respiration rates by a factor of two.31P NMR data were analyzed by a mathematical model of compartmentalized energy transfer, which is independent from the restrictions of the classical concept of creatine kinase equilibrium. The analysis of experimental data by this model shows that metabolic stability—constant levels of phosphocreatine, ATP and inorganic phosphate—at increased energy fluxes is an inherent property of the compartmentalized system. This explains the observed substrate specificity by changes in mitochondrial membrane potential. The decreased maximal respiration rate and maximal work output of the heart with inhibited creatine kinase is well explained by the rise in myoplasmic ADP concentration. This activates the adenylate kinase reaction in the myofibrillar space and in the mitochondria to fulfil the energy transfer and signal transmission functions, usually performed by creatine kinase. The activity of this system, however, is not sufficient to maintain high enough energy fluxes. Therefore, there is a kinetic explanation for the decreased maximal respiration rate of the heart with inhibited creatine kinase: i.e. a kinetically induced switch from an efficient energy transfer pathway (PCr–CK system) to a non-efficient one (myokinase pathway) within the energy transfer network of the cell under conditions of low apparent affinity of mitochondria to ADP in vivo. This may result in a significant decrease in the thermodynamic affinity of compartmentalized ATPase systems and finally in heart failure.
    No preview · Article · Oct 2000 · Journal of Molecular and Cellular Cardiology
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    ABSTRACT: In vivo endovascular ultrasonography has confirmed the extension of atheroma to angiographically normal segments. The authors set out to determine by endocoronary ultrasonography if the introduction of the atherotome changed the intimal thickness 20 mm proximal and distal to the site treated. The area circumscribed by the external elastic layer (EEL) and the surface area of the lumen was measured in 17 patients: 1) before atherectomy; 2) after atherectomy; 3) at control 6 months later. Atherectomy immediately increased the luminal area at the site dilated from 1.9 + 0.9 to 8.1 +/- 2mm (p < 0.001). At the proximal segment, the surface area of the lumen was unchanged (mean + 0.6 +/- 1.5 mm2; p = 0.13). Similarly the procedure did not change the surface circumscribed by the EEL (mean + 0.8 +/- 3.2 mm2; p = 0.32) in this zone. The same results were observed at the distal site. At 6 months, the areas under the EEL and those of the lumen were unchanged at the unoperated sites. The mean of the differences (+/- 1 SD) for the area under the EEL was respectively -0.2 +/- 1.5 mm2 proximally and +0.7 +/- 2.5 mm2 distally. The means for the luminal area were 0.2 +/- 1 mm2 proximally and -0.01 +/- 1.1 mm2; distally. At the site of atherectomy, the luminal surface increased (+2.0 +/- 2.6 mm2; p < 0.01) as did the area under the EEL (+2.0 +/- 3.5 mm2; p < 0.05). This preliminary series shows no significant progression of atherosclerosis at the sites not affected by atherectomy.
    No preview · Article · Nov 1997 · Archives des maladies du coeur et des vaisseaux
  • P Coste · P Dos Santos · S Sempe · A Moussari · C Jaïs · F Duclos · P Besse
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    ABSTRACT: The authors prospectively assessed 95 patients undergoing optimal guided atherectomy to assess the incidence of restenosis at 6 months. The coronary lesions were measured by a system of quantitative angiography to ensure reproducibility. Ventricular volumes, ejection fraction and segmental wall motion were assessed by ventriculography performed in the right anterior oblique projection. Sixty-three patients underwent atherectomy of the left anterior descending artery and 32 patients of the right coronary artery. The reference diameter was 3.58 +/- 0.65 mm. Atherectomy increased the minimal diameter of the lesion from 1.19 +/- 0.44 to 3.03 +/- 0.45 mm, with a residual stenosis of 14 +/- 10% of the diameter. At 6 months, 23% of patients had restenosed (> 50% stenosis) with a residual lumen at 1.16 +/- 0.39 mm. In the absence of restenosis, there was no significant change in left ventricular volumes or pressures and the global ejection fraction increased by +4 +/- 9% (p < 0.01), mainly in the group undergoing left anterior descending atherectomy. Moreover, fractional shortening increased in the anterior segments (+11 +/- 18%; p < 0.001). The authors conclude that optimal atherectomy is associated with acceptable rates of restenosis and that medium-term benefits of segmental wall motion are observed in patients without angiographic restenosis, mainly in those undergoing the procedure on the left anterior descending artery.
    No preview · Article · Sep 1997 · Archives des maladies du coeur et des vaisseaux
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    ABSTRACT: Background Platelet aggregation is a dominant feature in the pathophysiology of unstable angina. Percutaneous transluminal coronary angioplasty (PTCA) in patients with this disorder carries an increased risk of thrombotic complications. Abciximab (c7E3) blocks the platelet glycoprotein IIb/IIIa receptor, thus preventing platelet adhesion and aggregation. The CAPTURE study was a randomised placebo-controlled multicentre trial to assess whether abciximab can improve outcome in patients with refractory unstable angina who are undergoing PTCA. Methods The study recruited patients with refractory unstable angina, defined as recurrent myocardial ischaemia under medical treatment including heparin and nitrates. Predefined stopping rules were met at a planned interim analysis of data for 1050 patients, and recruitment was stopped. Data for 1265 patients (of 1400 scheduled) are presented here. After angiography, patients received a randomly assigned infusion of abciximab or placebo for 18-24 h before PTCA, continuing until 1 h afterwards. The primary endpoint was the occurrence within 30 days after PTCA of death (any cause), myocardial infarction, or urgent intervention for recurrent ischaemia. Analyses were by intention to treat. Findings By 30 days, the primary endpoint had occurred in 71 (11.3%) of 630 patients who received abciximab compared with 101 (15.9%) of 635 placebo recipients (p=0.012). The rate of myocardial infarction was lower in the abciximab than in the placebo group before PTCA (four [0.6%] vs 13 [2.1%], p=0.029) and during PTCA (16 [2.6%] vs 34 [5.5%], p=0.009). Major bleeding was infrequent, but occurred more often with abciximab than with placebo (24 [3.8%] vs 12 [1.9%], p=0.043). At 6-month follow-up, death, myocardial infarction, or repeal intervention had occurred in 193 patients in each group. Interpretation In patients with refractory unstable angina, treatment with abciximab substantially reduces the rate of thrombotic complications, in particular myocardial infarction, before, during, and after PTCA. There was no evidence that this regimen influenced the rate of myocardial infarction after the first few days, or the need for subsequent reintervention.
    No preview · Article · May 1997 · The Lancet
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    ABSTRACT: To assess the effect of optimal directional coronary atherectomy (DCA) on restenosis and left ventricular (LV) function, 95 patients who underwent DCA and adjunctive balloon angioplasty for de novo lesions were prospectively followed for 6 months. Absolute and relative coronary lumen measurements were analyzed with online quantitative coronary angiography. LV volumes, ejection fraction, and segmental wall motion were measured off-line according to the radial method for LV cineangiograms acquired in a right anterior oblique projection. Target vessels were the left anterior descending artery in 63 patients and right coronary artery in 32. Mean (+/- SD) reference diameter was 3.58 +/- 0.65 mm. Mean lumen diameter improved significantly after DCA from 1.19 +/- 0.44 to 3.03 +/- 0.45 mm, yielding a 14 +/- 10% residual stenosis. Overall angiographic restenosis rate (> 50% stenosis in diameter) at control was 23%. In patients without restenosis, there were no significant changes in LV volumes or in LV pressures. In this subgroup, ejection fraction improved significantly in the left anterior descending group (mean difference 3 +/- 10%, p < 0.04). Moreover, there was an increase in fractional shortening of all anterior segments (mean difference 11 +/- 16%, p < 0.005). Improvement in fractional shortening was less marked in the right coronary artery group even without restenosis. We conclude that: (1) optimal DCA can achieve a low restenosis rate in selected large vessels, (2) long-term beneficial effects on regional LV function are possible, particularly in patients with left anterior descending disease and in the absence of coronary restenosis.
    No preview · Article · Apr 1997 · The American Journal of Cardiology
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    ABSTRACT: The authors studied 102 patients prospectively who were undergoing coronary atherectomy optimised by balloon dilatation in order to assess the restenosis rate at 6 months. The coronary lesions were measured in a reproducible manner by quantitative angiography. The vessels dilated were the left anterior descending in 66 patients and the right coronary artery in 36 patients. The reference diameter was on average of 3.57 +/- 0.64 mm. Atherectomy increased the minimal diameter of the lesion of 1.20 +/- 0.44 to 3.01 +/- 0.44 mm giving a residual stenosis of 15 +/- 11%. At six months, 25% of patients had developed a restenosis (> 50% stenosis) with a residual lumen of 2.15 +/- 0.77 mm. The predictive factors of restenosis were the initial absolute gain, the length of the lesion, the reference diameter of the vessel and the presence of an endoluminal thrombus. In multivariate analysis, a small initial gain (p < 0.02) and length of stenosis (p < 0.02) were independently correlated with restenosis. The authors conclude: 1) that optimal atherectomy is associated with acceptable restenosis rates in selected vessels, 2) that short stenoses of large diameter arteries may be a privileged indication of the technique if the best results are obtained.
    No preview · Article · Feb 1997 · Archives des maladies du coeur et des vaisseaux