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Biomedical subjects

P Chatelain

Publications and source records attributed to P Chatelain.

At least 19 recordsLinked to original sources
PubMed1995

Effects of irbesartan (SR47436/BMS-186295) on angiotensin II-induced pressor responses in the pithed rat: potential mechanisms of action.

The effects of two new non-peptide angiotensin receptor antagonists, irbesartan (SR 47436/BMS-186295, (2-n-butyl-4-spirocyclopentane-1-[((2'-tetrazol-5-yl)bipheny l-4-yl)methyl]2 - imidazolin-5-one) and SR 47155A (2-n-butyl-4-spirocyclopentane-1-[((2'-carboxy)biphenyl-4-yl)methy l]2- imidazolin-5-one, trifluoroacetate), on angiotensin II-induced pressor responses were studied in the pithed rat in comparison to losartan, EXP 3174 and [Sar1,Val5,Ala8]angiotensin II. SR 47155A (1-10 mg/kg i.v.) and losartan (1-10 mg/kg i.v.) shifted dose dependently the dose-response curve of angiotensin II to the right without affecting the maximal response. SR 47436 (0.3-10 mg/kg i.v.), EXP 3174 (0.03-1 mg/kg i.v.) and [Sar1,Val5,Ala8]angiotensin II (0.03-1 mg/kg i.v.) induced, at least at high doses, a non-parallel shift to the right of the angiotensin II dose-response curve and this was associated with a reduction of the maximal response. During a 70 min period, the effect of [Sar1,Val5,Ala8]angiotensin II (1 mg/kg i.v.) on the angiotensin II (0.3 microgram/kg i.v.)-induced pressor response was shown to be reversible, the effect of SR 47155A (10 mg/kg i.v.) was partially reversible and the effect of SR 47436 (3 mg/kg i.v.), EXP 3174 (1 mg/kg i.v.) or losartan (6 mg/kg i.v.) was not reversed at the end of this 70 min period. Administration of SR 47155A (10 mg/kg i.v.) before SR 47436 (1-10 mg/kg i.v.) reversed the reduced angiotensin II-maximal response induced by SR 47436. Administration of SR 47436 (10 mg/kg i.v.) before SR 47155A (1-10 mg/kg i.v.) prevented the full development of the pressor response as observed in the absence of SR 47436. In the pithed rat, SR 47436 (30 mg/kg i.v.) and losartan (30 mg/kg i.v.) reduced the change in diastolic blood pressure induced by electrical stimulation of the spinal cord only at low stimulation rates. Taken together these results indicate that SR 47436, under in vivo conditions, is a potent non-peptide angiotensin receptor antagonist. The type of antagonism (partially insurmountable but selective) can be explained by different theoretical models which are discussed.

Angiotensin II↗
PubMed1995

Effect of SR 33805 on arterial smooth muscle cell proliferation and neointima formation following vascular injury.

The possible activity of SR 33805 ([[N-[dimethoxy-3,4-phenethyl]-N- methylamino-propoxyl]-4-benzenesulfonyl]-2-isopropyl-3-methyl-1-in dole), a novel Ca2+ channel blocker, in early atherogenesis was investigated. In vitro, SR 33805 strongly inhibited fetal calf serum-induced proliferation of cultured human aortic smooth muscle cells with an IC50 value of 0.3 +/- 0.1 microM (n = 3). In this respect, SR 33805 was several fold more active than the reference compounds: diltiazem, verapamil, nifedipine and fantofarone. SR 33805 was also a potent inhibitor of platelet-derived growth factor- or basic fibroblast growth factor-induced proliferation of human smooth muscle cells. SR 33805 inhibited serum-stimulated 45Ca2+ uptake in these cells, with an IC50 value of 47 +/- 18 nM. The effect of SR 33805 on intimal smooth muscle hyperplasia in rabbit carotid arteries subjected to air-drying endothelial injury was then investigated. After a 16-day treatment, SR 33805 (6.0 mg/kg/day p.o.) inhibited the development of intimal thickening. Under the same experimental conditions, nifedipine, verapamil, diltiazem (2 x 6 mg/kg/day p.o.--16 days) and fantofarone (12 mg/kg/day p.o.--16 days) were inactive. These results show that SR 33805, a novel and potent Ca2+ channel blocker, can reduce myointimal thickening following endothelial injury.

Animals↗
PubMed1995

SR 33589, a new amiodarone-like antiarrhythmic agent: anti-adrenoceptor activity in anaesthetized and conscious dogs.

We have assessed the ability of amiodarone and the new amiodarone-like antiarrhythmic agent, SR 33589 (N,N-dibutyl-3-[4-((2-butyl-5-methylsulphonamido)benzofuran-3-yl-c arbonyl) phenoxy]propylamine), to inhibit the effects of adrenoceptor stimulation in anaesthetized and conscious dogs. In anaesthetized, atropinized dogs, adrenoceptor stimulation was achieved (i) by i.v. administration of adrenaline and measurement of increased blood pressure (ii) by i.v. administration of isoprenaline and measurement of increased heart rate and decreased blood pressure. In conscious dogs, adrenoceptor stimulation was achieved by i.v. administration of isoprenaline and measurement of increased heart rate. In anaesthetized, atropinized dogs, both amiodarone and SR 33589 inhibited to similar extents, alpha-adrenoceptor stimulation (as indicated by attenuation of adrenaline-induced increases in blood pressure). The beta 1-adrenoceptor inhibitory activity of SR 33589 (as demonstrated by blockade of isoprenaline-induced increases in heart rate) was significant, but less marked than amiodarone (heart rate elevation reduced by 39%, P < 0.001 with 10 mg/kg SR 33589 and by 52%, P < 0.01 with 10 mg/kg amiodarone). In contrast, its beta 2-adrenoceptor antagonistic activity (as demonstrated by blockade of isoprenaline-induced reduction in blood pressure) was more marked (mean blood pressure decrease reduced by 69%, P < 0.01 with 10 mg/kg SR 33589 and by 31%, P < 0.05 with 10 mg/kg amiodarone). In conscious dogs, both SR 33589 and amiodarone (12.5, 25 and 50 mg/kg p.o.) inhibited isoprenaline-induced increases in heart rate by approximately the same amount for varying durations depending on the dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

[Percutaneous valvuloplasty in the treatment of mitral stenosis: results in Geneva].

Percutaneous balloon valvotomy is a recognized form of treatment of mitral stenosis. In Geneva between 1986 and 1993, 62 procedures were attempted in 60 patients (87% females) aged 48 +/- 17 years (12 to 80 years). Patient selection was based on symptoms (NYHA class), echocardiography (valve area, Boston score), and hemodynamics. 11 patients (18%) had undergone surgical commissurotomy in the past, 28 patients (47%) were in atrial fibrillation, and 12 patients (30%) had a history of peripheral emboli. Mild or moderate mitral insufficiency was present angiographically in 17 patients (28%) and echographically in 42 patients (70%). Esophageal echocardiography was performed in 37 patients (62%) before the procedure. In 52 patients (84%) a single balloon (Inoue technique) was used. Technical success was obtained in 59 procedures (95%). Following the procedure, mitral valve area increased from 1.1 +/- 0.3 to 1.8 +/- 0.3 cm2 (p < 0.0001) at echocardiography and from 1.1 +/- 0.3 to 1.9 +/- 0.5 cm2 (p < 0.0001) based on invasive hemodynamic data. There were 5 complications directly related to the procedure. In two cases cardiac tamponade developed, one after pericardial perforation during the transseptal approach and one because of left ventricular perforation. The second patient required surgical treatment. In two other cases, a moderate pericardial effusion without clinical consequences was observed. In one case the venous sheath malfunctioned, rendering surgical repair of the right femoral vein necessary. A residual atrial septal defect was observed at echography in 13 patients (22%). Mitral insufficiency was increased in 6 patients (10%) angiographically and in 9 patients (15%) at echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Stenting with the half (disarticulated) Palmaz-Schatz stent.

A total of 110 half (disarticulated) Palmaz-Schatz coronary stents were implanted in 102 patients. Procedural success rate was 98%. Elective stenting was performed in five patients. The others received half stents for bail-out situations, including short dissections, relapsing stenoses, dissections not adequately covered by a full stent, ostial stenoses, and thrombus containing lesions. Seventeen patients received no anticoagulation except aspirin. Complications included one procedural death, three acute occlusions (resulting in one Q and two non-Q wave myocardial infarctions), and one non-Q wave infarction related to side branch closure. Stenting with the half Plamaz-Schatz coronary stent is an effective technique. It allows stenting in situations where a full stent may not be ideally suited. Use of only half a stent reduces thrombogenicity and halves costs.

Adult↗
PubMed1995

Randomized evaluation of six French voda-type guiding catheters for left coronary artery balloon angioplasty.

In order to evaluate 6 French (6F) Voda-type guiding catheters for left coronary artery balloon angioplasty, we randomized the choice of the guiding catheter in 100 consecutive patients between a Voda (group 1, n = 50) and a Judkins or Amplatz curve (group 2) guiding catheter. Angioplasty success rate (98% for both), need for guiding catheter crossover exchange (2 in group 1 vs. 1 in group 2), fluoroscopy time, and volume of injected contrast were similar in both groups, but the operator's appreciation of good back-up support was better with the Voda-type guiding catheter (90% vs. 74%, P < 0.05). No complications attributed to the guiding catheter were noted in either group. Efficiency of the Voda-type guiding catheter appeared similar for both left anterior descending (n = 35, success rate 100%) and circumflex (n = 18, success rate 94%) coronary artery angioplasty. Voda-type guiding catheters are an efficient and safe approach to routine left coronary angioplasty. They appear to be as effective as a choice between a Judkins or an Amplatz configuration and could be of particular use when a double angioplasty of the left anterior descending and circumflex arteries is attempted during the same procedure.

Angioplasty, Balloon, Coronary↗
PubMed1995

Bailout coronary stenting with 6F guiding catheters for failed balloon angioplasty.

Between July 1992 and February 1994, we attempted bailout Palmaz-Schatz stent implantation through a 6F guiding catheter after 52 failed coronary balloon angioplasty procedures to reverse (14 [27%] cases) or prevent (38 [73%] cases) abrupt vessel closure. The stents or half-stents were manually crimped onto a monorail balloon catheter for delivery. Thirty-nine (75%) procedures involved a single stent, and 13 (25%) involved two or three stents. Technical success was achieved in 50 (96%) procedures, and clinical success without major complications was obtained in 45 (87%) cases. Target vessel occlusion was documented angiographically or suggested clinically in 2 (4%) cases. Two (4%) patients underwent semielective bypass surgery, and in 4 (8%) patients a non-Q-wave and in 1 (2%) a Q-wave myocardial infarction developed. There were no deaths. Major bleeding occurred in 2 patients: 1 had an important groin hematoma that was treated with local surgery followed by coronary bypass surgery, and one had macroscopic hematuria that required interruption of anticoagulation therapy on day 4. Three (6%) femoral pseudoaneurysms were diagnosed by ultrasound and could be obliterated by external compression alone. Bailout coronary stent implantation through 6F guiding catheters after failed balloon angioplasty is technically reliable, safe, and cost-efficient. As a consequence, use of 6F guiding catheters is a good option for a large majority of routine balloon angioplasty procedures.

Aged↗
PubMed1995

New drug binding sites in Ca2+ channels.

New classes of drugs modifying Ca2+ channel activity have become available, this may enlarge the clinical utilities that have been associated with established Ca2+ channel antagonists such as the dihydropyridines (for example, nifedipine). Two such classes are reviewed by Michael Spedding, Barry Kenny and Pierre Chatelain. Fantofarone is a non-dihydropyridine with a novel site of action in the L-type Ca2+ channel that appears to yield a distinct cardiovascular profile. In contrast, fluspirilene and related Na+ and Ca2+ channel inhibitors have a distinct site of action in Ca2+ channels, which is not specific for one channel type. The utility of Na+ and Ca2+ channel inhibitors in ischaemic stroke is compared with new and more selective Na+ channel inhibitors.

Animals↗
PubMed1995

Acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway.

A case of asymptomatic acute coronary occlusion secondary to radiofrequency catheter ablation of a left lateral accessory pathway is reported. Due to post-procedural ST modifications of the surface ECG, a coronary angiography was performed which disclosed total occlusion of the first marginal branch of the left circumflex coronary artery. Acute myocardial infarction was confirmed by moderate cardiac enzyme release, abnormal myocardial perfusion scan and mild lateral hypokinesia at echocardiography. This rare but potentially harmful complication of interventional electrophysiology should be kept in mind and coronary angiography performed immediately when coronary occlusion related to radiofrequency application is suspected.

Catheter Ablation↗
PubMed1995

SR 33589, a new amiodarone-like antiarrhythmic agent: electrophysiological effects in anesthetized dogs.

We compared the electrophysiological effects of a new amiodarone-like agent, SR 33589, with those of amiodarone. Mongrel dogs were anesthetized with chloralose, and electrodes were implanted in right atrium and ventricle for electrical stimulation and regional ECG measurement. Sinus cycle length (CL), AH interval, Wenckebach CL (WCL), atrial, atrioventricular node, and ventricular effective refractory periods (AERP, AVNERP, VERP), and parameters calculated from surface ECG were measured. SR 33589 was administered intravenously (i.v.) at 1, 2.5, or 5 mg/kg followed 60 min later by a second similar dose. The same protocol was followed with amiodarone 5 mg/kg, which reduced heart rate (HR) by 19% (p < 0.05), increased WCL by 31% (p < 0.01), AH interval by 14% (p < 0.05) and AERP, AVNERP, and VERP by 13% (p < 0.05), 19% (p < 0.05), and 11% (p < 0.01) respectively. No effect was observed on HV or PQ intervals. A second administration of 5 mg/kg changed these indexes further. SR 33589 (2.5 mg/kg) reduced HR by 21% (p < 0.001), increased WCL by 44% (p < 0.001), AH interval by 24% (p < 0.01), and AERP, AVNERP, and VERP by 17% (p < 0.001), 63% (p < 0.01), and 15% (p < 0.01) respectively, with an 18% increase in PQ interval (p < 0.05) but no significant effect on HV interval. Higher doses (5 mg/kg) and/or administration of a second dose both resulted in greater changes. Both amiodarone and SR 33589 prolonged VERP more at longer CL than at shorter CL, but the degree of reduction at shorter CL was less with SR 33589 than with amiodarone. Results suggest that acute administration of SR 33589 results in electrophysiological actions similar to those produced by amiodarone.

Amiodarone↗
PubMed1995

Standard views in cardiac multimodality tomographic imaging.

In cardiology, it is often necessary to acquire more than one type of image to investigate a given clinical problem of a single patient. Images obtained from different imaging modalities are usually recorded and displayed in different orientations, at different positions, and at different scale factors. It is then necessary for the physician to mentally integrate the image information from the different imaging modalities. This phenomenon is particularly true with tomographic imaging techniques that allow complete freedom of the acquisition plane. In particular, when comparing images obtained from ultrasound, computed tomography, magnetic resonance imaging, positron-emission tomography, and single-photon emission computed tomography. The purpose of this article is to propose a standard set of slice orientations that could be easily applied to all modalities. Such common views could greatly facilitate the user's perception of the regional abnormalities observed in the different imaging modalities. This standardization is certainly useful for clinical application but also for every research study that requires a comparative evaluation of the different imaging modalities. Although exact registration of the images from the different modalities requires sophisticated computer programs, the simple reference method in plane positioning proposed here based on plane orientation according to the cardiac geometry can certainly provide a practical and convenient method for the reasonably accurate image registration required for visual comparative studies.

Diagnostic Imaging↗
PubMed1994

Interaction of the calcium antagonist fantofarone with phospholipids: electrostatic effects.

The binding of fantofarone, a novel calcium channel antagonist, to cytoplasmic membranes and lipid vesicles has been studied by means of its fluorescence. The binding characteristics (dissociation constant Kd and total number of binding sites Bmax) were determined using saturation isotherms. In brain synaptic and cardiac sarcolemmal membranes, fantofarone binds to a single site with a Kd value of approximately 1.4 x 10(-6) M and a Bmax value of approximately 13 fantofarone molecules bound per 100 lipid molecules. Using vesicles made from egg phosphatidylcholine (PC), fantofarone was shown to possess a Kd approximately 7.5 x 10(-6) M and a Bmax approximately 15. When other classes of naturally-found lipids were incorporated into PC vesicles, a decrease in Kd with no modification in Bmax was observed for all acidic lipids studied. The decrease in Kd was inhibited by sodium and calcium. None of the experimental conditions modified the spectral properties or lifetimes of fantofarone. We conclude that an electrostatic interaction between fantofarone and negatively charged lipids takes place at the surface of the membrane and this interaction explains the decreased Kd value (increase in affinity) observed in cytoplasmic membranes.

Animals↗
PubMed1994

Characterization of the binding of [3H]SR 33805 to the slow Ca2+ channel in rat heart sarcolemmal membrane.

SR 33805 is a representative of a new class of compounds (indole sulfone) that inhibits L-type Ca2+ channels. [3H]SR 33805 has been shown to bind with a high affinity (Kd approximately 20 pM calculated from saturation isotherms and association/dissociation kinetics) to a single site in a purified preparation of rat cardiac sarcolemmal membranes. The binding was found to be saturable and reversible. The maximal binding capacity was in approximately 1:1 stoichiometry with that of other Ca2+ channel antagonists. Various cations (Na+, Ca2+, Cd2+, and La3+) were shown to inhibit specific [3H]SR 33805 binding, with La3+ being the most potent. Using a range of receptor or channel ligands (including omega-conotoxin and Na+ and K+ channel modulators), only the L-type Ca2+ channel antagonists were found to displace [3H]SR 33805. However, dihydropyridines, phenylalkylamines, benzothiazepines, and diphenyl-butylpiperidines were found to inhibit [3H]SR 33805 in a non-competitive manner as demonstrated by displacement experiments in addition to dissociation kinetics. In contrast, the interaction of SR 33805 with fantofarone has been found to be competitive. Binding of [3H]SR 33805 (and [3H]fantofarone) is entropy driven as opposed to that of the [3H]nitrendipine which is enthalpy driven. From these results we suggest that SR 33805 binds with a high affinity to a unique site on the L-type Ca2+ channel found in rat cardiac sarcolemmal membranes. This site is equivalent to that of fantofarone and in allosteric interaction with that of the dihydropyridines, phenylalkylamines and benzothiazepines.

Animals↗
PubMed1994

Coronary angioplasty for isolated non-dominant left circumflex coronary artery disease.

The study describes the clinical findings and results of coronary balloon angioplasty in 134 patients with non-dominant left circumflex coronary artery disease. The immediate angiographic success rate was 97% versus 95% for left anterior descending (P = NS), and 90% for right coronary lesions (P < 0.002). There was no hospital mortality in the circumflex group versus 1.2% in the left anterior descending (P < 0.01), and 0.4% in the right coronary artery group (P = NS). Major non-fatal cardiac complications were significantly lower in the non-dominant left circumflex coronary artery patients (no new Q-wave versus 3% in the left anterior descending, P < 0.0002, and 3% in the right coronary artery group, P < 0.01; no urgent coronary artery bypass grafting versus 2% in the left anterior descending, P < 0.001, and 1% in the right coronary artery group, P = NS). The freedom from chest pain was 63% in 112 patients (84%) with follow-up data available at 24 +/- 18 months, and mean angina class diminished to 0.7 +/- 1.3 (P < 0.001). Consumption of antianginal and other cardiac drugs was diminished during follow-up, and the number of patients on no such drugs increased from 5 to 32% (P < 0.001). Restenosis was found in 19 of 32 patients with repeat coronary angiography (59%). Repeat angioplasty was required in 22 patients during follow-up and in 4 of them (18%) it was done for new lesions. Angioplasty for isolated non-dominant left circumflex coronary artery disease yields excellent immediate and long-term results.

Angioplasty, Balloon, Coronary↗