Biomedical subjects

C Dubray

Publications and source records attributed to C Dubray.

At least 55 records · Page 3Linked to original sources

PubMed1991

Influence of pentobarbital and chloralose anesthesia on quinidine-induced effects on atrial refractoriness and heart rate in the dog.

The effects of pentobarbital and chloralose on the atrial effective refractory period (AERP), atrial and ventricular rates, and mean blood pressure and also on the effects of quinidine on the same parameters were investigated in dogs with chronic atrioventricular block and implanted atrial pacing electrodes. Pentobarbital (30 mg/kg) increased the AERP by up to 12%, atrial and ventricular rates by 39 and 40%, respectively, and after initial lowering (48%) it increased the mean blood pressure (46%). Chloralose (100 mg/kg) increased the AERP (less than 30 min) by up to 7%, the atrial rate by 49%, the ventricular rate (less than 5 min) by 18%, and the mean blood pressure by 47%. In conscious dogs, quinidine at cumulative doses of 2, 4, and 8 mg/kg, i.e., at plasma levels between 2.7 +/- 0.6 and 6.3 +/- 1.3 micrograms/ml, increased the AERP by up to 21, 28, and 46%, the atrial rate by 49, 65, and 72%, and the ventricular rate (less than or equal to 5 min) by 17, 14, and 14%, and lowered the mean blood pressure by 19, 33, and 43%, respectively. Pentobarbital increased the quinidine-induced lengthening of the AERP by up to 10, 21, and 25 ms, respectively, and reduced the corresponding atrial (38, 53, and 67 beats/min) and ventricular (4, 4, and 5 beats/min) chronotropic effects. In contrast, chloralose reduced the quinidine-induced lengthening of the AERP (5, 12, and 22 ms, respectively), but did not modify the corresponding atrial and ventricular chronotropic effects. Neither pentobarbital nor chloralose altered quinidine plasma levels or the hypotensive effects of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

PubMed1990

Modulation by external Ca2+ and nicardipine of Ca2+ influx and cytosolic concentration in human erythrocytes.

Variations of Ca2+ influx (evaluated by the initial rate of 45Ca2+ uptake) and cytosolic free Ca2+ concentration ([Ca2+]i, measured with fura-2) were investigated in human erythrocytes. When external Ca2+ concentration ([Ca2+]o) rose from 1 to 2 mM, the initial rate of Ca2+ influx nearly doubled whereas [Ca2+]i increased only by 15%. Nicardipine dose-dependently decreased both initial rate of Ca2+ influx and [Ca2+]i (up to 53 and 18%. respectively at 10(-6) M). The less marked changes in [Ca2+]i than in Ca2+ influx indicate a partial adjustment of the Ca2+ extruding-pump activity to of Ca2+ influx. In vivo administration of nicardipine reduced [Ca2+]i only when its initial value exceeded 80 nM and prevented the rise in [Ca2+]i induced by the increase in [Ca2+]o. Our results indicate that nicardipine may reduce Ca2+ influx in human erythrocytes and participate in the control of [Ca2+]i when elevated.

Calcium↗

PubMed1990

Chronic treatment by the calcium channel blocker +/- PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo.

In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with +/- PN 200-110 (3 mg.kg-1.day-1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 +/- 4.9 vs 95.0 +/- 9.1 micrograms/l, p less than 0.0001) and pituitary weight (19.9 +/- 0.4 vs 23.0 +/- 0.6 mg, p less than 0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

Animals↗

PubMed1989

Cardiac electrophysiological effects of cibenzoline in the conscious dog: plasma concentration-response relationships.

The cardiac electrophysiological effects of cibenzoline were studied in the conscious dog. Sinus rate, corrected sinus recovery time (CSRT), and Wenckebach point (WP) were measured in six intact dogs. Atrial and ventricular rates, and atrial effective refractory period (AERP) were measured in seven atrioventricular (AV)-blocked dogs. In both groups, blood pressure and cibenzoline plasma concentrations were also monitored. Each dog received three intravenous injections of 0.75, 1.5, and 3 mg base/kg cibenzoline 30 min apart. Cibenzoline increased sinus and atrial rates from the second dose onward, and ventricular rate slightly at the third dose. It lengthened CSRT and decreased WP at the first two doses only, and increased AERP from the first dose onward. In both groups, cibenzoline increased mean blood pressure at each dose. Taken together, these results indicate that in the conscious dog, cibenzoline at low plasma concentrations exhibits electrophysiological effects (lengthening of CSRT and AERP, and decrease in WP) attributable to its antiarrhythmic properties, and that at increasing concentrations it produces effects (increase in sinus rate, no effect on CSRT nor WP) which reflect competition between the effects related to its antiarrhythmic properties and those resulting from its direct vagolytic effect.

Animals↗

PubMed1989

Effects of propranolol and pindolol on plasma ANP levels in humans at rest and during exercise.

In attempt to elucidate whether the beta-adrenoceptor is involved in the control of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP level was measured at rest, in recumbent and upright positions, and during graded maximal ergocycle exercise in nine healthy male subjects (23 +/- 0.5 years of age) treated for 3 days with nonselective beta-blockers propranolol (150 mg/day) or pindolol (15 mg/day) or with placebo. The effects of beta-blockers, which differ by their hemodynamic actions at rest because of the intrinsic sympathomimetic activity of pindolol, were compared. Maximal O2 consumption (VO2max) during beta-blockade was not significantly different from the placebo value. Resting heart rate was not affected by pindolol treatment but was decreased with propranolol (-10 beats/min). Both beta-blockers caused a reduction in heart rate at all the exercise intensities. Mean blood pressure was not affected by beta-blockade at rest but was significantly reduced during exercise. During placebo treatment, plasma ANP increased in response to exercise intensities greater than 65% of VO2max. At 100% VO2max plasma ANP was nearly doubled (101.5 +/- 14 pg/ml) compared with the basal value in upright position (56.6 +/- 15 pg/ml). beta-Blockade caused a marked elevation in plasma ANP at all the levels of activity. Despite different hemodynamic responses to pindolol and propranolol, both beta-blockers produced similar increases in the basal level of plasma ANP. These rises were maintained in the course of exercise tests, and no significant difference was found between propranolol and pindolol. We conclude that beta-adrenoceptor mechanisms are not directly responsible for tonic and exercise-induced ANP secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Effect of beta-adrenoceptor blockade on renin-aldosterone and alpha-ANF during exercise at altitude.

The renin-aldosterone system may be depressed in subjects exercising at high altitude, thereby preventing excessive angiotensin I (ANG I) and aldosterone levels, which could favor the onset of acute mountain sickness. The role of beta-adrenoceptors in hormonal responses to hypoxia was investigated in 12 subjects treated with a nonselective beta-blocker, pindolol. The subjects performed a standardized maximal bicycle ergometer exercise with (P) and without (C) acute pindolol treatment (15 mg/day) at sea level, as well as during a 5-day period at high altitude (4,350 m, barometric pressure 450 mmHg). During sea-level exercise, pindolol caused a reduction in plasma renin activity (PRA, 2.83 +/- 0.35 vs. 5.13 +/- 0.7 ng ANG I.ml-1.h-1, P less than 0.01), an increase in plasma alpha-atrial natriuretic factor (alpha-ANF) level (23.1 +/- 2.9 (P) vs. 10.4 +/- 1.5 (C) pmol/1, P less than 0.01), and no change in plasma aldosterone concentration [0.50 +/- 0.04 (P) vs. 0.53 +/- 0.03 (C) nmol/1]. Compared with sea-level values, PRA (3.45 +/- 0.7 ng ANG I.ml-1.h-1) and PA (0.39 +/- 0.03 nmol/1) were significantly lower (P less than 0.05) during exercise at high altitude. alpha-ANF was not affected by hypoxia. When beta-blockade was achieved at high altitude, exercise-induced elevation in PRA was completely abolished, but no additional decline in PA occurred. Plasma norepinephrine and epinephrine concentrations tended to be lower during maximal exercise at altitude; however, these differences were not statistically significant. Our results provide further evidence that hypoxia has a suppressive effect on the renin-aldosterone system. However, beta-adrenergic mechanisms do not appear to be responsible for inhibition of renin secretion at high altitude.

Adult↗

PubMed1989

The stimulated C-kinase activity in estradiol-treated rat pituitaries is reduced by chronic treatment with the dopamine agonist CV 205-502.

To investigate whether the modulation of lactotrope cell multiplication and prolactin secretion in rat pituitary glands implicated the phosphoinositide C-kinase system, female Wistar rats were treated or not-with the dopamine agonist CV 205-502 or 8 days or with estradiol cervical implants for 8 for 15 days, alone or in combination with CV 205-502 for the last 8 days. CV 205-502 treatment induced a significant reduction in plasma PRL levels and in pituitary weights, whereas estradiol treatment induced a significant increase in both parameters. CV 205-502, in association with estradiol, counteracted estradiol stimulation of PRL levels and of pituitary weights. Total C-kinase activity in controls was 29.8 +/- 9.9 pmol 32phosphorus/min (N = 7, mean +/- SEM), mainly found in the soluble fraction (84%). When administered alone, CV 205-502 induced a significant reduction (-58%, p less than 0.02) in C-kinase activity in the particulate fraction with no modification in the soluble fraction. Both 8 and 15 days estradiol treatment induced a significant stimulation of total C-kinase activity, 74% and 155% respectively. When combined with estradiol, CV 205-502 significantly (p less than 0.02) counteracted the estradiol increase in total C-kinase activity, which was only 45% over control values. We conclude that treatment with a dopamine agonist and estradiol, which have antagonistic effects on the pituitary, exerts an opposite regulation of C-kinase activity. Whether this may be one of the mechanisms involved in their interaction on pituitary lactotropes remains to be determined.

1-Phosphatidylinositol 4-Kinase↗

PubMed1989

[Effect of beta-adrenergic receptors blockade on auricular natriuretic factor, aldosterone and renine blood activity during physical exercise].

Physical exercise stimulates the renin-angiotensin-aldosterone system. However several factors affect the control of mineralocorticoid secretion. In this study, eight healthy volunteers performed maximal exercise on cycle ergometer after being pretreated for 3 days with placebo (P) or with a non selective beta-blocker (B) (pindolol 15 mg/day). Plasma reinin activity (PRA), aldosterone (ALD), atrial natriuretic factor (ANF), and kalemia (K+) were measured at rest (R) and during exercise until exhaustion (E). (table; see text) These results confirm the role of beta-adrenoceptor activation in the increased PRA during exercise. It appears an exercise-induced increase in plasma ANF which was more elevated in subjects treated with pindolol, but which had no inhibitory effect on ALD secretion in theses conditions. K+ rose during exercise and this hyperkalemia tended to be higher with a beta-blocker. It is suggested that K+ elevation counterbalance both PRA decrease and ANF increase to be responsible for the absence of change in plasma ALD during beta-blockade.

Adult↗

PubMed1988

Influence of digestive secretions and food on intestinal absorption of nicardipine.

The role of digestive absorption in the pharmacokinetics of nicardipine has been studied by the perfusion technique. Nicardipine (40 mg) was perfused in six healthy subjects at 5 ml/min for 2 h either in isotonic saline with (Experiment A) or without (B) an occlusive balloon isolating the test segment from digestive secretions, or in a nutrient solution (Experiment C). In Experiments A and B, 100% of nicardipine was absorbed from the jejunal lumen in a 25 cm test segment and in Experiment C it was slightly lower (94%). There was no relationship between the absorption of nicardipine and water movement or bile salt concentration in the jejunum. Nicardipine was already present in the first plasma sample taken after 15 min and the peak level was found at the end of the perfusion. The areas under the curves differed widely between subjects, because of interindividual variation in the first pass effect, but they were similar in Experiments A, B and C. The experimental data showed a good fit to a mode involving a two-phase absorption process. The first phase was associated with intestinal perfusion (zero order process) and the second with passage across the intestinal wall (1st order process). In three further healthy subjects, nicardipine in saline was perfused in the jejunum and then in the ileum on consecutive days. Mean plasma levels over time were similar. The study showed that absorption of nicardipine both from the jejunum and the ileum was complete and was especially rapid. The food-induced change in the kinetics of absorption from the jejunum was too small to affect the pharmacokinetic parameters of nicardipine.

Adult↗

PubMed1987

Comparative effects of procainamide and its N-acetylated metabolite in conscious dogs with atrioventricular block: plasma concentration-response relationships.

The effects of procainamide and its metabolite N-acetylprocainamide (NAPA) on atrial effective refractory period (AERP), atrial rate, ventricular rate, and mean blood pressure were investigated in conscious dogs with chronic atrioventricular block and implanted atrial pacing electrodes. Procainamide at cumulative doses of 4.3, 13.0, and 30.3 mg/kg and NAPA at equimolar doses of 5.1, 15.3, and 35.7 mg/kg (i.e., at plasma levels covering the assumed therapeutic range) concentration-relatedly lengthened AERP, as reflected by the decrease of maximal atrial frequency determined by pacing. Procainamide was 1.2-1.5 times more potent than NAPA in this regard. Both drugs increased atrial rate in relation to their plasma concentrations--procainamide 1.2 times more than NAPA. Procainamide decreased ventricular rate at the two highest doses, while NAPA decreased it only at the highest dose after having increased it at the lowest. Procainamide lowered mean blood pressure at the lowest dose and increased it 15 min after the highest, whereas NAPA produced an increase in mean blood pressure for each dose. Taken together, these results on atrial rate, ventricular rate, and mean blood pressure indicate that the two drugs possess distinct pharmacological properties--i.e., procainamide exhibits slightly more marked direct vagolytic and depressor effects than does NAPA and exerts quite different blood pressure effects from those of NAPA. Thus, these data suggest that NAPA, especially when present at high levels, may markedly affect expected responses in patients being treated with procainamide.

Acecainide↗

PubMed1986

Differing effects of spontaneous and atropine-induced variations of vagal tone on atrial refractoriness in the conscious dog.

The effects of spontaneous and atropine-induced variations of vagal tone on atrial refractoriness were studied in the conscious dog with complete atrioventricular block. Atrial rate and vagal tone, assessed with atropine, along with maximal paced atrial frequency were monitored for 90 days after the creation of atrioventricular block. The effects of atropine on maximal paced atrial frequency were also studied over the same period. Atrial rate was initially high and then fell back to values close to preoperative sinus levels. Vagal tone was first low and then rose back to values close to preoperative ones. The time-courses of atrial rate and vagal tone were correlated. The rise in vagal tone was accompanied by a correlated increase in maximal paced atrial frequency and thus a shortening of the atrial effective refractory period. However, atropine never significantly lengthened the atrial effective refractory period. This work clearly demonstrates the consistent shortening effect of vagal tone on the atrial effective refractory period in the conscious dog as well as the still unexplained inability of atropine to offset this effect, which may arise from a two-fold action of atropine on the heart.

Animals↗

PubMed1985

[Tangier disease. A rare thesaurismosis].

The authors report the case of a 15-year old boy with Tangier disease characterized clinically by grossly enlarged tonsils, liver and spleen. Blood counts showed signs of hypersplenism, and blood lipid assays disclosed hypercholesterolaemia with moderate hypertriglyceridaemia and very low levels of high density lipoproteins. The diagnosis was confirmed by biopsies of the liver, spleen, rectal mucosa, tonsils and bone marrow, all tissues which contained foamy histiocytic cells staining like adipose cells. Following splenectomy, the child developed an unexplained, persistent (6 months) fever, then died suddenly of digestive haemorrhage. A genetic study showed a high degree of inbreeding, with 2 deaths probably due to Tangier disease. The authors contrast the surprising severity of this case with the apparent benignity of the disease as described in other publications.

Adolescent↗

PubMed1984

Chronotropic effects of pindolol. Relation between ventricular effects and control resting ventricular rate values in conscious dogs with chronic A-V block.

The chronotropic effects of pindolol were studied in the conscious dog with chronic A-V block. Pindolol significantly increased atrial rate, probably through both its strong intrinsic sympathomimetic activity and reflex withdrawal of atrial vagal tone in response to its hypotensive effect. Pindolol did not alter ventricular rate overall. However, in individual dogs, pindolol caused ventricular chronotropic effects that were inversely related to resting ventricular rate: it increased ventricular rate when the resting ventricular rate was low and reduced it when it was high. In view of the fact that pindolol is a beta-adrenoceptor antagonist endowed with a strong intrinsic sympathomimetic activity, this finding contributes to a better understanding of how pindolol affects heart rate.

Animals↗

PubMed1984

Dopamine in the conscious dog with chronic heart-block. Mechanisms of chronotropic cardiac effects.

The chronotropic effects of dopamine were studied in the conscious dog with chronic A-V block. Dopamine at 12.5-200 micrograms/kg and 12.5-50 micrograms/kg/min lowered atrial rate independently of dose. After blockade of muscarine receptors or alpha-adrenoceptors, it raised atrial rate. After blockade of dopamine receptors, dopamine still lowered atrial rate, and did so dose-relatedly after blockade of beta-adrenoceptors. It raised ventricular rate, and at high doses also induced ventricular rhythm disorders. Blockade of muscarine receptors enhanced the ventricular cardioaccelerator effect of dopamine (P less than 0.025) at 100 micrograms/kg, while blockade of alpha-adrenoceptors reduced it (P less than 0.05). Blockade of dopamine receptors did not modify this effect, but blockade of beta-adrenoceptors reversed it. Dopamine at 25-200 micrograms/kg raised mean blood pressure. This effect was enhanced by blockade of muscarine receptors, reversed by blockade of alpha-adrenoceptors, and was unaffected by blockade of beta-adrenoceptors or dopamine receptors. These results show that the atrial cardiomoderator effect of dopamine is a vagal reflex response to its hypertensive action, and that it is limited by its direct beta-adrenergic stimulating action. They also show that the ventricular cardioaccelerator effect of dopamine is attenuated by a reflex vagal depressor effect consequent to the induced hypertension. No evidence was found for the existence of positive chronotropic dopamine receptors in either atria or ventricles.

Adrenergic alpha-Antagonists↗

PubMed1984

Pharmacological evidence for differences in the beta-adrenoreceptor populations mediating atrial and ventricular chronotropic responses in the unanaesthetized dog.

The beta-adrenoreceptor populations mediating atrial and ventricular chronotropic responses were studied comparatively in the unanaesthetized dog with chronic atrio-ventricular block. With this aim, we first compared the increases in atrial and ventricular rate induced by isoprenaline. We then compared the reductions of this isoprenaline-induced atrial and ventricular cardio-acceleration, observed after administration of cumulative doses of propranolol and alprenolol, both non-selective beta-adrenoreceptor blocking agents, and metoprolol, a blocking agent selective for beta 1-adrenoreceptors. Isoprenaline induced a much more intense stimulation of atrial chronotropic beta-adrenoreceptors than of ventricular chronotropic beta-adrenoreceptors, whether or not the cholinoreceptors were blocked. Similarly, all three beta-blocking agents induced a more intense blockade of atrial chronotropic beta-adrenoreceptors than of ventricular chronotropic beta-adrenoreceptors, whatever the dose of isoprenaline considered and whether or not the cholinoreceptors were blocked. These results cannot be readily explained by quantitative differences in the distribution of beta 1- and beta 2-adrenoreceptors in the heart, given the identical effects obtained with metoprolol, propranolol and alprenolol. Therefore, beta-adrenoreceptor populations are not identical throughout the nodal tissue, and in particular, differences occur between beta-adrenoreceptors in the sinus node mediating atrial chronotropic responses and those in the His bundle mediating ventricular chronotropic responses, which might be linked to differing sensitivities of these beta-adrenoreceptor populations.

Alprenolol↗

PubMed1984

Familial growth retardation with isolated thyroid-stimulating hormone deficiency.

Three brothers with isolated thyroid-stimulating hormone (TSH) deficiency were observed at ages 17, 15, and 10 years. They suffered from severely retarded growth, with a marked retardation in bone maturation. Their serum T4, T3, and TSH levels were low. Serum thyrotropin-releasing hormone (TRH) concentration was normal. No increases in TSH levels were elicited during the TRH test. The other pituitary hormones, adrenocorticotropic hormone, growth hormone, follicle-stimulating hormone, luteinizing hormone, and prolactin hormone, responded normally to stimulation. Thyroxin treatment triggered a growth acceleration. Genetic investigation revealed several instances of small stature on the father's side.

Adolescent↗

PubMed1983

A method for determining the atrial effective refractory period in the unanesthetized dog.

Extension to the unanesthetized dog with chronic A-V block of the method of determination of the atrial effective refractory period described in vitro by Dawes provides a useful model for the study in atria of potential antiarrhythmic agents. This model, which comes fairly close to physiological conditions, is capable of furnishing reproducible results which correlate well with those obtained by other techniques, as shown by a study of quinidine chosen as reference. It also makes possible long-term studies of the effects of prolonged administration of antiarrhythmic agents on atrial effective refractory period, under conditions close to those of therapeutic practice, and so is likely to have predictive value.

Animals↗

PubMed1983

Spontaneously acquired factor VIII inhibitor in a non-haemophiliac child.

A three-year-old girl who had for two months suffered bruising after minimal injury was admitted because of diffuse ecchymoses and a large haematoma hindering elbow movement. These symptoms were attributable to the development of antifactor VIII inhibitor. No definite etiology was evident despite repeated immunological investigation. Although the inhibitor still persisted at high levels after two years, no further haemorrhage occurred, excepted haematomas three months after the onset of symptoms, in association with mumps.

Antibodies↗