Search PubMed⌕ Search

Biomedical subjects

P Chatelain

Publications and source records attributed to P Chatelain.

At least 91 records · Page 5Linked to original sources

The Magnum wire for percutaneous coronary balloon angioplasty in 723 patients.

The experience of the use of the Magnum wire in a single center is reported. Percutaneous balloon coronary angioplasty, using the Magnum 0.021 inch wire, was attempted in 723 patients with 850 lesions; of these, 453 (53%) were chronic total occlusions and 50 (7%) recent occlusions of less than 24 hours (patients presenting with acute myocardial infarction). The overall technical success rate per lesion was 655/850 (77%). It was 255/280 (91%) for non-total lesions, 311/453 (69%) for chronic total occlusions, 53/67 (79%) for functional (TIMI grade I) occlusions, and 36/50 (72%) for recent occlusions. Clinical success was achieved in 196/232 patients (84%) with non-total lesions, in 292/436 (67%) with total chronic occlusions, in 49/65 (75%) with functional occlusions, and in 34/50 (68%) with recent occlusions. Complications (significant creatine kinase rise, new Q-wave infarction, need for coronary bypass surgery or in-hospital death) occurred in 7% (3% if patients presenting with unstable ischemic syndromes were excluded from the analysis). These data confirm that the use of the Magnum wire has success rates competitive with other systems both in setting of chronic total occlusion and in that of routine percutaneous transluminal coronary angioplasty.

Adult↗

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↗

SR 33589, a new amiodarone-like agent: effect on ischemia- and reperfusion-induced arrhythmias in anesthetized rats.

We have assessed the ability of the new amiodarone-like antiarrhythmic agent, SR 33589, to reduce the incidence of ischemia- and reperfusion-induced arrhythmias, in comparison to amiodarone, D-sotalol, and lignocaine. Rats were anesthetized, artificially ventilated, and the thorax opened by a left thoracotomy. Ischemia was induced by left coronary artery ligation, and reperfusion was achieved (after a 5-min period of ischemia) in a separate group of rats by removing the ligature. Agents were given intravenously 5 min before occlusion or orally 4 h before study. During a 20-min period of ischemia, SR 33589 reduced significantly the incidence of ventricular fibrillation (VF) from 80 to 30% (p < 0.05) at 3 mg/kg i.v. and eliminated VF and mortality at 10 mg/kg i.v. In contrast, amiodarone at 10 mg/kg i.v. reduced significantly only the incidence of mortality during ischemia (from 60 to 0%, p < 0.01), while having no significant effect on 3 mg/kg i.v. On reperfusion (after a 5-min period of ischemia), SR 33589 reduced significantly the incidence of mortality (from 90 to 20%, p < 0.01) at 1 mg/kg and eliminated VF and mortality when administered at 3 and 10 mg/kg. Against both ischemia- and reperfusion-induced arrhythmias, approximately 20% of animals showed AV block at the highest dose of SR 33589 tested. This was not observed with lower doses. Amiodarone (10 mg/kg i.v.) eliminated completely reperfusion-induced VF and mortality while having no significant effect at 1 and 3 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Vascular calcium overload produced by vitamin D3, in rats. Effect of treatment with SR 33805, a novel calcium entry blocker.

The effect of SR 33805, a novel calcium entry blocker, on calcium overload was studied in six vascular beds in rat. Fantofarone, a parent compound, and verapamil were used as reference calcium entry blockers. Calcium overload induced with a single dose (300,000 IU, i.m. of vitamin D3) was measured by means of atomic absorption and histological techniques. From the time-course of calcium overload, a treatment period of 3 days was selected to determine the effects of drug treatment. The compounds were given orally twice a day in the following dose ranges: SR 33805 2-100 mg/kg, fantofarone 10-300 mg/kg, verapamil 100 mg/kg. SR 33805 significantly decreased the calcium content beginning at the dose of 2 mg/kg in the thoracic aorta, 5 mg/kg in the mesenteric artery and 30 mg/kg in the heart. Fantofarone and verapamil had the same effect at the dose of 100 mg/kg. Histological assessment of the heart revealed that lesions appearing in the tissue adjacent to the arteries were significantly diminished by treatment with SR 33805 at a dose which produced a significant decrease in the arterial calcium content. Thus, SR 33805 can inhibit both calcium overload and its deleterious consequences and its actions are evident at doses as low as 2 mg/kg.

Animals↗

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↗

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↗

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↗

Effect of SR 47436, a novel angiotensin II AT1 receptor antagonist, on human vascular smooth muscle cells in vitro.

Proliferation of smooth muscle cells within the intima plays a key role in vascular occlusive disorders such as atherosclerosis and restenosis following balloon angioplasty. Among the factors that may be important in the development of vascular lesions, several authors have reported that the local angiotensin system participates in modulating the proliferation of smooth muscle cells after arterial injury. This study was therefore designed to characterize the antagonistic properties and to investigate the antiproliferative effect of a newly developed non-peptide angiotensin II AT1 receptor antagonist, SR 47436. This compound is a potent and competitive antagonist of the binding of [125I]angiotensin II to its receptor on cultured human aortic smooth muscle cells, exhibiting an IC50 value of 1.7 +/- 0.6 nM. SR 47436 was 10-fold more potent than DuP 753 (Losartan) (IC50 = 20.8 +/- 3.7 nM). In these same cells, SR 47436 potently inhibited the angiotensin II-induced [Ca2+]i increase (IC50 = 0.53 +/- 0.13 vs. 7.4 +/- 1.3 nM for DuP 753). Angiotensin II is a potent mitogen for human aortic smooth muscle cells in culture, exhibiting a maximum proliferative response at 1 microM. SR 47436 and Losartan prevented angiotensin II-induced proliferation of these cells in a dose-dependent manner (IC50 = 0.32 +/- 0.09 and 0.71 +/- 0.08 microM, respectively). SR 47436 displayed a marked in vitro inhibition of serum-induced smooth muscle cell proliferation (IC50 = 5.5 +/- 0.8 microM). A selective AT2 receptor antagonist, PD 123177 did not affect angiotensin II-induced responses in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

31P nuclear magnetic resonance study of the effects of the calcium ion channel antagonist fantofarone on the rat heart.

The biochemical and mechanical effects of a new calcium ion channel antagonist, fantofarone ((2-isopropyl-1-((4-(3-(N-methyl-N-(3,4-dimethoxy-beta-phenethyl)-amino) propyloxy)benzenesulfonyl))-indolizine), on isovolumic perfused rat heart have been assessed by using 31P nuclear magnetic resonance (NMR) spectroscopy together with simultaneous monitoring of myocardial mechanical function. Cytosolic pH and phosphocreatine, adenosine triphosphate and inorganic phosphate contents were monitored by using 31P NMR. Heart rate, coronary flow and left ventricular developed pressure were measured routinely to assess mechanical function. Perfusion with 10 nM, 100 nM or 1 microM fantofarone for a period of 48 min did not cause any measurable metabolic changes. However, coronary vasodilatation and a partial positive inotropic effect were noted. A 15-min pretreatment with 100 nM did not protect against the deleterious effects of an 18-min period of normothermic, zero-flow ischemia. In contrast, a 20-min pretreatment period with 1 microM fantofarone significantly improved the recovery of mechanical performance, metabolic activity and pH after the same 18 min of ischemia. While only a slight protection of the ATP pool was noted during the ischemic period, major beneficial effects were observed during the reperfusion period, such that reflow was characterized by high recoveries of left ventricular pressure and rate pressure product (70-80%), low end diastolic pressure (< 10 mm Hg), significant recovery of ATP content (to 55%), a complete repletion of the phosphocreatine pool and a fast return of cytosolic pH to normal value.

Adenosine Triphosphate↗

Evaluation of the systematic use of a new type of diagnostic/interventional 6F catheters for coronary angiography and angioplasty.

Coronary angioplasty performed immediately after coronary angiography has raised interest to develop diagnostic catheters potentially usable for interventions (i.e. Diaventional catheters). To evaluate the performance and cost-effectiveness of such material, we performed a prospective study in 100 consecutive patients with a > 50% pre-angiographic likelihood of coronary angioplasty in 85 of them. Angioplasty was actually performed in 61 patients. Of the 56 (92%) immediate angioplasty procedures, 33 (59%) were performed successfully with the Diaventional catheter chosen initially. In 23 cases, another guiding catheter was used for technical failure (2 cases) or because of operator's choice (21 cases). Angiographic success of angioplasty procedures was 97% with Diaventional and 91% with "standard" guiding catheters. Based on current market prices, the costs of the systematic use of such diagnostic/interventional catheters were 11% less than the projected costs of the standard strategy. Thus, this new type of catheter is both safe and cost-effective for the majority of coronary angioplasty procedures "at first sight." It could become a logical first choice for diagnostic coronary angiography, when the likelihood of immediate subsequent angioplasty is high and at relatively low risk.

Adult↗

Improving results of bailout coronary stenting after failed balloon angioplasty.

Stent implantation can be a valuable alternative to emergent bypass surgery to treat established or threatening abrupt closure following coronary balloon angioplasty. To evaluate several sequentially introduced changes in our practice of bail-out stenting, we compared the first (group I) and second half (group II) of our single center experience (n = 88). Use of bailout stenting increased over time (2% of all angioplasty procedures in group I vs. 6% in group II, P < 0.001), more often to prevent rather than to reverse abrupt closure. Technical success of stent implantation was unchanged (95% vs. 93%), and there was a decreasing trend for stent thrombosis (14% vs. 5%), in-hospital death (5% vs. 2%), Q-wave myocardial infarction (9% vs. 7%), and requirement for surgery (9% vs. 7%). The incidence of non-Q-wave myocardial infarction (29% vs. 7% P < 0.01), bleeding complications (27% vs. 7% P < 0.01), and hospital stay duration (11 +/- 11 vs. 8 +/- 5 days P < 0.05) decreased. Our data suggest that coronary stent implantation is currently an effective stand-alone bailout procedure for a large majority of failed angioplasty procedures.

Aged↗

Binding of fantofarone, a novel Ca2+ antagonist, to serum albumin: a fluorescence study.

Using the fluorescent properties of fantofarone, we have studied the interactions between this novel calcium entry blocker and human and bovine serum albumins. Binding of fantofarone, which is poorly fluorescent in aqueous buffer, resulted in a large increase in the fluorescent signal (lambda ex = 335 nm, lambda em = 395 nm). Fantofarone bound to a single site with a dissociation constant (Kd) of 11-12 x 10(-6) M. The number of sites and the Kd value were not modified by either NaCl (134 mM) or Ca2+ (10 mM). Two values of fluorescence lifetime (tau 1 = 12.8 ns and tau 2 = 3.5 ns) with respective fractional contributions (chi 1 = 0.79 and chi 2 = 0.21) were determined. Quenching by iodide resulted in a downward curved Stern-Volmer plot, where 36% of the fluorescence was quenched with a quenching constant (KQ) of 11.4 M-1. From the measured degree of fluorescence depolarization and fluorescence lifetime, a value of rotational relaxation time of 109 ns was calculated.

Animals↗

Present and potential uses of growth hormone in therapeutics.

In the first weeks of 1993, the accepted indications of growth hormone remain limited to the treatment of severe growth failure resulting directly from pituitary somatrotropic deficiency and to the improvement of height in Turner syndrome. Various other indications of GH may be considered as "potential". Each one has still to prove its real usefulness at more or less long term. Moreover, for all of them there will have to largely take into account the ethical side, mainly the ratio between the expected beneficial effects and the costs and burden, even if no serious inconveniences are presently known. The possible increase in the use of growth hormone is an extremely serious scientific question. It is important to keep it out from the changes in subjective opinions, the medical faschions, and the influences of public opinion or media.

Fetal Growth Retardation↗

Fantofarone (SR33557): effects on myocardial oxygen consumption and coronary blood flow.

We have investigated the effects of a novel calcium antagonist, fantofarone (SR 33557) on myocardial oxygen consumption (MO2C) and coronary blood flow in anaesthetized dogs during periods of normal and elevated heart rate. 25 micrograms/kg i.v. fantofarone induced a transient increase in coronary blood flow (+25% after 2 min; p < 0.05) and a more sustained decrease in MO2C (-50% after 5 min; p < 0.05). During the periods of pacing, these alterations on cardiac function were not evident. Administration of 50 micrograms/kg i.v. resulted in similar modifications of cardiac function; however, these changes were apparent for a longer duration. Coronary blood flow was still significantly elevated by 29% 2 min after drug administration (p < 0.01) and MO2C was reduced by 67% after 5 min (p < 0.01) and by 56% after 30 min (p < 0.05). Most importantly, a significant decrease in MO2C was observed during the pacing periods (32% after 10 min; p < 0.01). Thus fantofarone can significantly modify cardiac function and in particular, decrease MO2C consumption during periods of elevated heart rate.

Animals↗

Dose-dependent catch-up growth after 2 years of growth hormone treatment in intrauterine growth-retarded children. Belgian and French Pediatric Clinics and Sanofi-Choay (France).

This study reports the results of a 2-yr clinical trial with GH in 95 short prepubertal children with non-GH-deficient intrauterine growth retardation. This randomized, double blind, controlled study compared the effects of placebo (restricted to the first 6 months) and two doses of GH (0.4 and 1.2 IU/kg.week) given sc 6 days/week for 2 yr. A significant GH dose-dependent growth acceleration was observed. Mean height gain (SDS/CA) was 0.66 +/- 0.07 in group I (low dose, 0.4 IU/kg.week) compared to 1.25 +/- 0.07 in group II (high dose, 1.2 IU/kg.week). Mean bone maturation progression (expressed in months) was 26.2 +/- 1.7 and 30.2 +/- 1.5 over 24 months in groups I and II, respectively. Onset of puberty was observed in some patients of both groups. Whether chronic use of a high GH dose will advance the onset of puberty remains to be established. A great variability of growth acceleration was seen among GH dose groups, suggesting that factors in addition to GH dose might modulate individual responses to treatment. In conclusion, it is suggested that in these patients, dose-dependent catch-up growth could be induced by GH treatment.

Analysis of Variance↗

Lack of predictors of left ventricular functional improvement following coronary angioplasty.

Coronary angioplasty is frequently performed in a vessel with corresponding regional wall motion abnormalities. However, late improvement of left ventricular function remains questionable in many cases and is difficult to predict. A retrospective analysis of 115 patients with single vessel disease and corresponding abnormal regional left ventricular function at the time of coronary angioplasty was performed. All patients had control coronary angiography and a new contrast ventriculography 5.6 +/- 3.1 months later (range 0.8-11.8 months). Among those patients, 61 (53%) showed improvement of regional left ventricular function, which was not seen in the 54 (47%) others. Global ejection fraction increased significantly in the former group, whereas it remained unchanged in the later group. Before angioplasty, patients with and without improvement of systolic left ventricular function were indistinguishable in terms of history, medication, rest and stress electrocardiogram, and angiographic characteristics. During angioplasty, angina was more frequent (65% vs. 44%, p < 0.02) in patients with subsequent left ventricular functional improvement. At follow-up study, significant angiographic restenosis was more frequently encountered (68% vs. 43%, p < 0.05) in patients with no evidence of functional improvement. Thus, coronary angioplasty in a vessel responsible for left ventricular systolic dysfunction is followed in only half the cases by improvement of this parameter. No predictor of the functional outcome of the myocardium can be pointed out before the procedure is performed.

Aged↗