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Biomedical subjects

B Dupuis

Publications and source records attributed to B Dupuis.

At least 19 recordsLinked to original sources
PubMed1992

Oxidized low density lipoproteins exert arrhythmogenic effects in rabbit Purkinje fibers.

The electrophysiological effects of oxidized low density lipoproteins (ox-LDLs) have been studied in rabbit Purkinje fibers using standard microelectrode techniques, in comparison with native LDLs (n-LDLs) and lysophosphatidylcholine (LPC). At the concentration of 100 micrograms protein/ml, ox-LDL but never n-LDL induced the abrupt occurrence of abnormal electrical activities during the basic stimulation of 1 Hz (6/13 fibers) and the development of either early afterdepolarizations (6/13 fibers) or abnormal automaticity (4/13 fibers) at low frequencies (0.1 and 0.03 Hz). Short trains of rapid stimulation (2, 3, 4 and 5 Hz) did not trigger delayed afterdepolarizations. However, early afterhyperpolarizations were commonly seen after each action potential. 30 microM LPC caused quite similar electrophysiological derangements. The results suggest that ox-LDLs may exert arrhythmogenic effects partly explained by their LPC content.

Action Potentials↗
PubMed1992

Proto-oncogene expression in rabbit aorta after wall injury. First marker of the cellular process leading to restenosis after angioplasty?

In order to study the earliest phenomenons occurring in the arterial wall after balloon angioplasty, the level of expression of the proto-oncogenes, c-fos and c-myc, was studied in rabbit aorta after balloon denudation by using Northern blot analysis. Both c-fos and c-myc are rapidly and transitorily induced (maximal at 30 min and 2 h after mechanical injury for c-fos and c-myc respectively). By comparison, infusion of norepinephrine increases oncogene expression in normal non-denuded rabbit aorta after 1 h, but the combination of both mechanical and hormonal stimuli do not lead to a more important induction than balloon denudation alone.

Angioplasty, Balloon↗
PubMed1991

[The excitation-contraction coupling of the vascular smooth muscle cells].

Two phenomena may lead to an increase in intracellular calcium concentration of vascular smooth muscle cells: an increase in the permeability of the cell membrane to Ca2+ ions; liberation of Ca2+ ions from the intracellular reservoirs. The calcium channels of smooth muscle are varied. There are two types of voltage operated calcium channels: the fast (T) and the slow (L) channels. The calcium channels activated by extracellular membrane receptors are not voltage dependent. Only the L calcium channels are sensitive to dihydropyridines. The liberation of Ca2+ from the sarcoplasmic reticulum which is the intracellular reservoir of calcium can be controlled by two different mechanisms: a direct mechanism by the influx of Ca2+ into the cell through the voltage-operated channels; by the intermediary of a second intracellular messenger. High conductance calcium channels controlled by cytosolic Ca2+ and by IP2 have been demonstrated on the membrane of the sarcoplasmic reticulum. The contraction of smooth muscle may therefore be regulated directly through control of the phosphorylation of the contractile proteins by the intermediary of the systems of adenylate and guanylate cyclase.

Calcium↗
PubMed1991

[Methodology in clinical trials of anti-arrhythmia agents in ventricular arrhythmias. Analysis and perspective following results of the CAST study].

The results of the Cardiac Arrhythmia Suppression Trial (CAST) have not finished modifying the methodology and strategy of development of new antiarrhythmic agents for the treatment of ventricular arrhythmias. The demonstration of a dissociation between a proved antiarrhythmic effect and increased mortality in coronary patients treated with encainide or flecainide, means that, in this situation, antiarrhythmic efficacy cannot be considered to be a substitute criterion of therapeutic benefit. The consequences of these results are as follows: in phase II, the dose-effect relationships should be studied in patients with chronic ventricular extrasystole without ischemic heart disease. This model is sufficiently predictive for the selection of the dosage to be tested in phase III; in phase III, studies of benign ventricular arrhythmias, antiarrhythmic efficacy is demonstrated by ambulatory ECG recordings. If these studies include patients with ischemic heart disease, the patients must be placed on betablocker therapy and the benefits in terms of reduction of mortality have to be shown by controlled trials versus placebo. In malignant life-threatening arrhythmias, open clinical trials may be performed using provocative electrophysiological studies. The inclusion of patients with implanted automatic defibrillator devices could constitute control groups for the placebo group. The future of antiarrhythmic agents for the treatment of ventricular arrhythmias greatly depends on the search for criteria of severity of arrhythmias and the validation of intermediate criteria of efficacy.

Anti-Arrhythmia Agents↗
PubMed1991

[Dobutamine: mechanisms of action and use in acute cardiovascular pathology].

High levels of circulating catecholamines associated with heart failure down-regulate cardiac beta-receptors, with a more pronounced effect on beta-1 receptors, leading to impaired inotropic effect. The use of exogenous inotropic agents is therefore a logical therapeutic approach in heart failure. Dobutamine is a synthetic catecholamine that acts on alpha-1, beta-1 and beta-2 adrenergic receptors. In the heart, the stimulation of these receptors produces a relatively strong, additive inotropic effect and a relatively weak chronotropic effect. In the vasculature, alpha-1 agonist activity (vasoconstriction) balances the beta-2 agonist effect (vasodilatation). In clinical use, dobutamine has a rapid onset of action and a short half-life. It increases myocardial contractility, while the reflex reduction in sympathetic tone, in response to augmentation of stroke volume, leads to a decrease in total peripheral resistance. The expected hemodynamic effects are an increase in cardiac output and a decrease in systemic vascular resistance without significant change in arterial pressure or heart rate. In acute cardiac failure state with elevated afterload pressures, resulting from myocardial dysfunction, dobutamine therapy remains, nowadays, the reference.

Acute Disease↗
PubMed1991

[Continuous Holter cardiac monitoring and chemotherapy by combination with platinum and fluoro-uracil].

Thirty-three male patients (pts) were given cisplatin and fluoro-uracil (1 g/m2/d) in IV continuous infusion over 96 h, for the primary or palliative treatment of locally advanced head and neck cancer. The mean age was 52 +/- 7 years (range: 37-65). Patients underwent continuous ECG monitoring and were monitored for 22.4 +/- 1.5 h before FU infusion, 91.9 +/- 7.3 h during FU infusion and 18.5 +/- 2 h after 5FU infusion. Patients were given one cycle of chemotherapy (32 pts), two (25 pts) or three consecutive cycles (20 pts). Seventeen pts (53%) had supraventricular arrythmia, 15 pts (47%) had ventricular arrythmia and 10 pts (31%) had ST segment deviation. The ECG abnormalities were more frequent during the first cycle of chemotherapy. No previous clinical or ECG parameter was associated to ECG changes. Platin-induced hypomagnesemia and hypokaliemia probably increase incidence of cardiac abnormalities, during and after FU infusion.

Adult↗
PubMed1990

Inhibitory studies of mexiletine and dextromethorphan oxidation in human liver microsomes.

The cytochrome P-450dbl isozyme (P-450bdl) is responsible for the genetic sparteine-debrisoquine type polymorphism of drug oxidation in humans. To investigate the relationship between mexiletine oxidation and the activity of this isozyme, cross-inhibition studies were performed in human liver microsomes with mexiletine and dextromethorphan, a prototype substrate for P-450dbl. The formation of hydroxymethylmexiletine and p-hydroxymexiletine, two major mexiletine metabolites, was competitively inhibited by dextromethorphan. Mexiletine competitively inhibited the high affinity component of dextromethorphan O-demethylation. In addition, there was a good agreement between the apparent Km values for the formation of both mexiletine metabolites and the high affinity component of dextromethorphan O-demethylation and their respective apparent Ki values. Several drugs were tested for their ability to inhibit mexiletine oxidation. Quinidine, quinine, propafenone, oxprenolol, propranolol, ajmaline, desipramine, imipramine, chlorpromazine and amitryptiline were competitive inhibitors for the formation of hydroxymethylmexiletine and p-hydroxymexiletine as for prototype reactions of the sparteine-debrisoquine type polymorphism. Amobarbital, valproic acid, ethosuximide, caffeine, theophylline, disopyramide and phenytoin, known to be non-inhibitors of P-450dbl activity, were found not to inhibit the formation of these mexiletine metabolites. Moreover, the formation of both metabolites was strongly inhibited by an antiserum containing anti-liver/kidney microsomes antibodies type I (anti-LKMI) directed against P-450dbl. These data suggest that the formation of two major metabolites of mexiletine is predominantly catalysed by the genetically variable human liver P-450dbl.

Binding, Competitive↗
PubMed1990

Anal cloacogenic and squamous carcinomas. Comparative histologic analysis using in situ hybridization for human papillomavirus DNA.

In order to evaluate the morphologic and possible etiologic distinctions between anal cloacogenic and squamous carcinomas, we performed histologic examination and in situ hybridization for human papillomavirus (HPV) DNA on anal canal and anal verge carcinomas from 37 patients. Twenty-one neoplasms were invasive or in situ squamous carcinomas, 14 were invasive cloacogenic carcinomas, and two were unclassified. In situ hybridization was positive for HPV types 16/18 in 12 cases and for types 6/11 in two cases of anal squamous carcinoma (67% HPV positivity overall). All 14 cases classified as anal cloacogenic carcinoma were negative for HPV DNA by this technique. One of the two unclassified carcinomas was positive for type 16/18 DNA. We conclude that anal cloacogenic and squamous carcinomas are histologically similar but distinct neoplasms. Differential expression of HPV DNA in these lesions may be a manifestation of separate mechanisms of pathogenesis, or it may be due to varying degrees of tumor cell differentiation.

Anus Neoplasms↗
PubMed1989

Effect of quinidine on the dextromethorphan O-demethylase activity of microsomal fractions from human liver.

1. The kinetics of dextromethorphan O-demethylation were measured in microsomes prepared from five human livers, both in the absence and in the presence of quinidine. 2. For each liver and over the concentration range of dextromethorphan examined (4.2-3400 microM), this reaction involved an enzymatic component of high affinity, with an apparent Michaelis-Menten constant (Km) of 4.6 +/- 1.8 microM (mean +/- s.d.) and a maximum velocity (Vmax) of 4.2 +/- 3.5 nmol mg-1 h-1 (mean +/- s.d.). 3. Quinidine was a potent and competitive inhibitor of the activity of this component (mean Ki +/- s.d. of 0.025 +/- 0.008 microM) as it is for other oxidation reactions which have already been found to co-segregate with the debrisoquine-type polymorphism. 4. With microsomes from four of the five livers studied, there was evidence of a second enzymatic component of activity characterized by a similar Vmax and about 20-fold higher Km compared with the high affinity component. The activity of this low affinity component was unaffected by quinidine in the concentrations studied.

Chromatography, High Pressure Liquid↗
PubMed1988

Electrophysiological effects of intravenous nicaïnoprol, a new antiarrhythmic agent, in 11 patients.

Nicaïnoprol, a new class 1 antiarrhythmic drug was given intravenously in a dose of 2 mg kg-1 of body weight (two patients) and 3 mg kg-1 of body weight (nine patients), and the clinical, electrocardiographic and electrophysiological effects were studied. Fifteen minutes after the end of drug administration, the PR interval was prolonged by 24.4% (P less than 0.001), and the QTc by 3.9% (P less than 0.01). The prolongation of QRS duration (+6%) was not significant. There was a slight (-3.9%) but non-significant decrease of the heart rate, with no alteration in sinus node function. Alteration of atrial conduction and atrioventricular (AV) conduction were due to an increase in the PA interval (+57.4%, P less than 0.05), the AH interval (+10.9%, NS) and the HV interval (+43.8%, P less than 0.01). The anterograde Wenckebach cycle length increased by 11% (P less than 0.01). The effective and functional atrial refractory periods increased respectively by 4.5% and 11.4% (P less than 0.05), and the effective refractory period of the AV node increased by 11.2% (P less than 0.05). None of the other electrophysiological variables changed significantly. A non-significant drop in blood pressure was noted between the second minute following injection (-9.4%) and the 15th minute (-3.4%), and two patients complained of dizziness; one of these two patients reported a heat flush with an oral burning. In conclusion, nicaïnoprol seems to possess the electrophysiological properties of some other class I antiarrhythmic drugs, and is clinically well tolerated.

Adult↗
PubMed1987

Propafenone versus disopyramide: a double-blind randomized crossover trial in patients presenting chronic ventricular arrhythmias.

In vitro and in vivo electrophysiological studies have shown that propafenone could be classified as a class I antiarrhythmic agent. The aim of this study was to investigate the short-term antiarrhythmic efficacy and safety of propafenone in 10 patients compared to disopyramide in a double-blind randomized protocol. Included patients suffered from ventricular arrhythmias with at least 60 ventricular premature beats (VPB) per hour refractory to at least two other antiarrhythmic agents. At the end of the control period and of the two treatment periods during which patients received either propafenone (300 mg three times a day) or disopyramide (200 mg three times a day), clinical examination, Holter recordings, electrocardiogram, and clinical laboratory tests were performed. The PR interval and the QRS interval were significantly increased with propafenone, but not with disopyramide. The cQT interval was not significantly changed by either propafenone or disopyramide. Heart rate was decreased with propafenone (p less than 0.05) with no change in the diurnal/nocturnal circadian ratio variation. Heart rate was significantly decreased with disopyramide only during the day. Five of nine patients in the propafenone group and two of nine patients in the disopyramide group showed a reduction in ventricular premature beats greater than 80%. Total resolution of severe arrhythmias (repetitive events) was seen in 5 of 8 patients with propafenone; 2 of 8 with disopyramide. Adverse events, when they occurred, were mild (visual disturbances, epigastric discomfort, changes in taste perception, transient atrioventricular block with propafenone, and photophobia with disopyramide), and did not require reduction or discontinuation of study drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Comparison of propranolol, sotalol, and betaxolol in the treatment of neuroleptic-induced akathisia.

In earlier open studies, beta-blockers were found to be effective in the treatment of neuroleptic-induced akathisia. In the present study, 16 patients with severe neuroleptic-induced akathisia successively received low doses of three beta-blockers--propranolol, sotalol, and betaxolol. There was rapid and complete improvement in seven of 16 patients (and partial improvement in three patients) treated with betaxolol. The efficacy of propranolol and betaxolol and failure of sotalol in treating neuroleptic-induced akathisia suggest a central mechanism of action.

Adult↗