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Biomedical subjects

Alain Poncelet

Publications and source records attributed to Alain Poncelet.

10 recordsLinked to original sources
PubMed2006

Fractional flow reserve of pedicled internal thoracic artery and saphenous vein grafts 6 months after bypass surgery.

BACKGROUND: Although the internal thoracic artery was proven superior to saphenous vein graft in long-term patency, it is thought to be a more resistive conduit than the vein graft. Moreover, patency studies comparing both left and right internal thoracic arteries have provided results favoring the former. Fractional flow reserve is an established functional index of coronary blood flow. METHODS: To compare the fractional flow reserve between both internal thoracic arteries and saphenous vein grafts, 43 bypass grafts were studied 6 months after revascularization. Intra-graft pressures were measured during cardiac catheterization using a pressure-wire advanced to the first distal anastomosis of 12 left internal thoracic arteries (ITAs), 10 right ITAs and of 21 vein grafts. Pressure gradients between the aorta and the graft were measured at baseline and during a maximal hyperemia. RESULTS: At baseline, pressure gradient was recorded in the left ITA (2.9+/-2.2 mmHg), in the right ITA (1.2+/-1.2 mmHg) and in the vein graft (0.4+/-0.7 mmHg). During maximal hyperemia, pressure gradient increased to 9.6+/-3.2 mmHg in left ITA, to 4.5+/-2.0 mmHg in the right ITA (p<0.001 vs left ITA) and to 3.3+/-2.7 mmHg in vein (p<0.001 vs left ITA; NS vs right ITA). Fractional flow reserve was 0.90+/-0.04 in left ITA, 0.95+/-0.03 in right ITA (p<0.01 vs left ITA) and 0.96+/-0.03 in vein (p<0.001 vs left ITA). CONCLUSION: Internal thoracic arteries and saphenous vein grafts allow myocardial revascularization with minimal resistance to maximal blood flow. The resistance appears significantly higher in left ITA compared to both the right ITA and venous grafts.

Blood Pressure↗
PubMed2006

Repair of bicuspid aortic valves in patients with aortic regurgitation.

BACKGROUND: Bicuspid aortic valve regurgitation can be caused by a defect in the valve itself or by dysfunction of one or more components of the aortic root complex. A successful repair thus requires correction of all aspects of the problem simultaneously. We review our experience addressing both the valve and the aortic root when correcting bicuspid valve regurgitation. METHODS AND RESULTS: Between 1996 and 2004, we treated 68 patients for aortic regurgitation. Thirty patients had isolated aortic regurgitation, and 38 had an associated ascending aortic aneurysm. All patients were treated using a standardized and integrated surgical technique, which included resection of the median raphe or leaflet plication, subcommissural annuloplasty, reinforcement of the leaflet free edge, and sinotubular junction plication. In the 38 patients with proximal aortic dilatation, reimplantation or remodeling of the aortic root was performed. Immediate postoperative echocardiography showed grade < or = 1 aortic regurgitation in all patients. Three patients nonetheless needed an early re-operation because of recurrent regurgitation. No hospital mortality was observed. At a mean follow-up of 34 months after surgery, all patients were in New York Heart Association (NYHA) class 1 or 2. Two patients needed a re-operation (23 and 92 months, respectively). Echocardiographic follow-up showed no progression of the regurgitation in 58 surviving patients. Four patients progressed to grade 2 regurgitation. CONCLUSIONS: Our data indicate that regurgitant bicuspid aortic valves, whether alone or in association with a proximal aortic dilatation, can be repaired successfully provided that both the valve and the aortic root problems are treated simultaneously.

Adolescent↗
PubMed2006

Characterization of acute and chronic myocardial infarcts by multidetector computed tomography: comparison with contrast-enhanced magnetic resonance.

BACKGROUND: We evaluated whether contrast-enhanced multidetector computed tomography (CE-MDCT) might characterize myocardial infarct (MI) with patterns similar to those obtained by contrast-enhanced magnetic resonance (CE-MR) and studied the underlying mechanisms. METHODS AND RESULTS: In vivo infarct characterization by CE-MDCT was shown to be feasible between 4 and 20 minutes after contrast injection in 7 pigs with MI. Subsequently, in 16 patients with acute MI and 21 patients with chronic MI, contrast patterns by CE-MDCT were related to CE-MR. Eighteen patients had hypoenhanced regions on early CE-MDCT images at the time of coronary imaging, and 34 patients had hyperenhanced regions on images acquired 10 minutes later. On a segmental basis, there was moderately good concordance of early hypoenhanced regions (92%, kappa=0.54, P<0.001) and late hyperenhanced regions (82%, kappa=0.61, P<0.001) between CE-MDCT and CE-MR. Absolute sizes of early hypoenhanced (6+/-16 versus 7+/-16 g, P=0.25) and late hyperenhanced (36+/-34 versus 31+/-40 g, P=0.14) regions were similar on CE-MDCT and CE-MR and were highly correlated (r=0.93, P<0.001 and r=0.89, P<0.001 respectively). In 8 retrogradely perfused infarcted rabbit hearts, contrast kinetics of iomeprol were similar to gadodiamide, ie, slow wash in (8.7+/-6.7 versus 1.2+/-0.3 minutes, P<0.001) in infarct core and slow washout (20+/-12 versus 2.5+/-0.5 minutes, P<0.001) in both infarct core and rim compared with the remote region. CONCLUSIONS: Because iodated contrast agents have similar kinetics in infarcted and noninfarcted myocardium as gadolinium DPTA, CE-MDCT can characterize acute and chronic MI with contrast patterns similar to CE-MR. CE-MDCT may thus provide important information on infarct size and viability at the time of noninvasive coronary imaging.

Acute Disease↗
PubMed2006

Replacement of chordae tendineae with polytetrafluoroethylene (PTFE) sutures in mitral valve repair: early and long-term results.

BACKGROUND AND AIM OF THE STUDY: A variety of reliable techniques are now available for chordal disease management and repair of the anterior mitral valve leaflet prolapse. The study aim was to review the authors' experience with polytetrafluoroethylene (PTFE), using a standardized technique for length adjustment, and to analyze the long-term results in patients who underwent mitral valve repair. METHODS: A total of 111 patients (mean age 56.2 +/- 16.1 years) underwent mitral valve repair with PTFE neochordae, in addition to a variety of other surgical procedures. Etiologies were degenerative in 82 patients (73.9%), Barlow disease in 13 (11.7%), rheumatic in 10 (9%), and infection in six (5.4%). Prolapse of the anterior leaflet was present in 78 patients (70.3%), of the posterior leaflet in 15 (13.5%), a bileaflet prolapse was present in 12 (10.8%), and a commissural prolapse in six (5.4%). In all cases the anterior annulus was used as the reference level in order to assess the appropriate length of the PTFE neochordae. RESULTS: The mean number of PTFE neochordae used was 6 +/- 4 per patient. In-hospital mortality was 1.8% (n = 2); mean follow up was 36.8 +/- 25.6 months (range: 12-94 months). There were no late deaths. At five years postoperatively the patient overall survival was 98.2 +/- 1.8%, freedom from reoperation rate 100%, and freedom from grade 1+ mitral regurgitation rate 97.2 +/- 2.8%. There were no documented thromboembolism or hemorrhagic events. CONCLUSION: In degenerative and myxomatous mitral valve disease, leaflet prolapse can be successfully repaired by implantation of PTFE neochordae. Both immediate and long-term results proved the versatility, efficiency and durability of this technique.

Adult↗
PubMed2005

Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: a new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains.

In the treatment of AIDS, the efficacy of all drugs, including non-nucleoside inhibitors (NNRTIs) of HIV-1 reverse transcriptase (RT), has been limited by the rapid appearance of drug-resistant viruses. Lys103Asn, Tyr181Cys, and Tyr188Leu are some of the most common RT mutations that cause resistance to NNRTIs in the clinic. We report X-ray crystal structures for RT complexed with three different pyridinone derivatives, R157208, R165481, and R221239, at 2.95, 2.9, and 2.43 A resolution, respectively. All three ligands exhibit nanomolar or subnanomolar inhibitory activity against wild-type RT, but varying activities against drug-resistant mutants. R165481 and R221239 differ from most NNRTIs in that binding does not involve significant contacts with Tyr181. These compounds strongly inhibit wild-type HIV-1 RT and drug-resistant variants, including Tyr181Cys and Lys103Asn RT. These properties result in part from an iodine atom on the pyridinone ring of both inhibitors that interacts with the main-chain carbonyl oxygen of Tyr188. An acrylonitrile substituent on R165481 substantially improves the activity of the compound against wild-type RT (and several mutants) and provides a way to generate novel inhibitors that could interact with conserved elements of HIV-1 RT at the polymerase catalytic site. In R221239, there is a flexible linker to a furan ring that permits interactions with Val106, Phe227, and Pro236. These contacts appear to enhance the inhibitory activity of R221239 against the HIV-1 strains that carry the Val106Ala, Tyr188Leu, and Phe227Cys mutations.

Crystallography, X-Ray↗
PubMed2005

4-Benzyl and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones: in vitro evaluation of new C-3-amino-substituted and C-5,6-alkyl-substituted analogues against clinically important HIV mutant strains.

In a program to optimize the anti-HIV activity of the 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 9 and 10, lead compounds in a new class of highly potent non-nucleoside type inhibitors of HIV-1 reverse transcriptase, modification of the alkyl substitutents at the C-5 and C-6 positions on the pyridinone ring and of the substitutents on the C-3 amino group has been studied. Of the 17 new 5/6-modified analogues prepared, compounds 31b and 32b substituted at C-5 by an extended nonpolar chain containing an ether function and a C-6 methyl group and compound 35 bearing a C-5 ethyl/C-6 hydroxymethyl substituent pattern were selected on the basis of their in vitro activity against wild-type HIV and the three principle mutant strains, K103N, Y181C, and Y188L. When tested further, it was shown that these molecules, and in particular compound 35, are globally more active than 9, 10, and efavirenz against an additional eight single [L100I, K101E, V106A, E138K, V179E, G190A/S, and F227C] and four double HIV mutant strains [L100I + K103N, K101E + K103N, K103N + Y181C, and F227L + V106A], which are clinically relevant. Concerning modulation of the N-3 substituent, 36 new analogues were prepared. Of these, the N-methyl-N-(2-methoxyethyl)-substituted compounds 40, 42, and 62, as well as the doubly modified compounds 77a and 77b, were selected from the initial screen and were subsequently shown to be active at sub-micromolar concentrations (IC(50)'s) against all the other mutant strains except K103N + Y181C and F227L + V106A. Two possible, but distinct, modes of binding of these analogues in RT were suggested from molecular modeling studies. The preferred mode of binding for compound 62, corresponding to the predicted "orientation 1", was revealed in the X-ray crystal structure of the compound 62-RT complex.

Anti-HIV Agents↗
PubMed2005

Synthesis, structure-activity relationship, and receptor pharmacology of a new series of quinoline derivatives acting as selective, noncompetitive mGlu1 antagonists.

We describe the discovery and the structure-activity relationship of a new series of quinoline derivatives acting as selective and highly potent noncompetitive mGlu1 antagonists. We first identified cis-10 as a fairly potent mGlu1 antagonist (IC(50) = 20 nM) in a cell-based signal transduction assay on the rat mGlu1 receptor expressed in CHO-K1 cells, and then we were able to design and synthesize highly potent compounds on both rat and human mGlu1 receptors as exemplified by compound cis-64a, which has an antagonist potency of 0.5 nM for the human mGlu1 receptor. We briefly present and discuss the in vitro metabolic stability of the compounds in human liver microsomes. We finally report the pharmacokinetic properties of our lead compound cis-64a.

Animals↗
PubMed2005

Gastroepiploic artery minimally invasive grafting in reoperative patients with patent mammaries.

BACKGROUND: Patients with patent grafted bilateral internal thoracic arteries may require repeat myocardial revascularization because of either progression of disease in a nongrafted native vessel or failure of a saphenous vein graft. In order to avoid extensive dissection and possible damage of the internal thoracic arteries, we elected to proceed with an off-pump minimally invasive direct coronary artery bypass grafting (MIDCABG) approach using the pedicled right gastroepiploic artery. This paper summarizes our midterm angiographic results. METHODS: From 1996 to 2003, 15 patients were reoperated on using this approach in our department. Internal thoracic artery grafts always revascularized the anterior and lateral territories and were angiographically patent. Indications for repeated surgery were: (1) coronary disease progression in 8 patients; (2) occlusion of the saphenous vein graft in 6 patients; and (3) anastomotic stenosis of a pedicled right gastroepiploic artery in 1 patient. Off-pump grafting of the pedicled right gastroepiploic artery was targeted at the posterior descending artery in 14 patients, and at the left anterior descending artery in 1 patient. RESULTS: Thirty-day mortality was 6.5% (1 of 15 patients). With a mean follow-up of 56 +/- 20 months, angina-free survival was 79%. At angiographic control (mean, 38 months), the pedicled right gastroepiploic artery was patent in 13 patients. One patient had an occluded right gastroepiploic artery graft at 23 months and another patient showed progression of disease distal to the right gastroepiploic artery anastomosis at 28 months. CONCLUSIONS: Off-pump MIDCABG repeat revascularization with a pedicled right gastroepiploic artery is an effective method of revascularization for patients with patent bilateral internal thoracic arteries.

Breast↗
PubMed2004

4-benzyl- and 4-benzoyl-3-dimethylaminopyridin-2(1H)-ones, a new family of potent anti-HIV agents: optimization and in vitro evaluation against clinically important HIV mutant strains.

The 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 13 and 14 are representatives of a new class of highly potent non nucleoside type inhibitors of HIV-1 reverse transcriptase. To conduct SAR studies on these two lead compounds, 102 new analogues were prepared. Thirty-three compounds displayed nanomolar range activity in vitro against wild-type HIV-1, and among these, 18 were active against the 103N, Y181C, and Y188L mutant strains with IC50 values inferior to 1 microM. Evaluation of this group of analogues against an additional eight single [100I, 101E, 106A, 138K, 179E, 190A, 190S, 227C] and four double HIV mutant strains [100I + 103N, 101E + 103N, 103N + 181C, and 227L + 106A], which are often present in HIV infected patients, permitted the selection of eight compounds, 17x, 18b, 18c, 18f, 18g, 27, 30, and 42, which are globally more active than the lead molecules 13/14, emivirine and the currently used NNRTI, nevirapine. Further comparison of the 3'-CN-substituted benzoylpyridinone compound 18c, and the corresponding 3'-acrylonitrile-substituted analogue 30, to efavirenz, the reference molecule in anti-HIV therapy today, revealed that the pyridinone analogues displayed a superior inhibition profile in the in vitro cellular assay system. These results form a solid basis for continued optimization of the pyridinone series.

Alkynes↗