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P Duchene-Marullaz

Publications and source records attributed to P Duchene-Marullaz.

At least 19 recordsLinked to original sources
PubMed1994

Seven-day antinociceptive effect of a sustained release vapreotide formulation.

This work studies the antinociceptive effect of a sustained (7 day) release dosage form of vapreotide, a peptidic analogue of somatostatin, in rats submitted to a nociceptive mechanical stimulus (paw pressure). One intramuscular injection (0.6 mg/animal) induced a significant antinociceptive effect for 7 complete days with a maximal increase in vocalization thresholds of 68 +/- 5% and a plateau of activity during the first 4 days. This action was totally inhibited by naloxone (1 mg kg-1, s.c.) injected 24 h or 6 days after vapreotide, suggesting an opioidergic involvement throughout the antinociceptive effect. These findings suggest potential interest in human therapy.

Analgesics↗
PubMed1994

Evidence for a central long-lasting antinociceptive effect of vapreotide, an analog of somatostatin, involving an opioidergic mechanism.

The antinociceptive effect of the octapeptide vapreotide, an analog of somatostatin, was studied after systemic injection in normal mice using the hot plate and abdominal stretching assays, and in normal rats using the paw pressure analgesiometric assay. Vapreotide was ineffective at 1 microgram/kg s.c. in the hot plate test in mice, but 30 min after injection it induced an antinociceptive effect at s.c. injected doses of 8, 64, 512 and 4096 micrograms/kg, with an ED50 of 213 +/- 5 micrograms/kg. For the three highest doses this effect persisted 24 hr after the injection (maximal increase: +80 +/- 23% for 512 micrograms/kg) and disappeared at 48 hr. In the phenylbenzoquinone stretching test, in mice, the ED50 was 186 +/- 6 micrograms/kg (maximal decrease: -63 +/- 5%); the effect persisted 24 hr only for the same two highest doses. Using the paw pressure test, in rats, a dose-dependent increase in paw withdrawal and vocalization thresholds was observed for 21 and 24 hr, respectively, after s.c. injections of 16, 64 and 512 micrograms/kg. Global scores obtained for vocalization thresholds were significantly increased (vs. paw withdrawal thresholds) for 64 and 512 micrograms/kg. Carrageenan-induced nociception in rats was reduced for 21 hr by 64 and 512 micrograms/kg s.c.; scores of the contralateral noninflamed paw were also increased. Vapreotide administered locally in the inflamed paw was inactive. No change in edema volume was obtained after systemic injection of vapreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Arrhythmogenic potencies of amrinone and milrinone in unanesthetized dogs with myocardial infarct.

1. In dogs with a 2-4 day old myocardial infarct and a predominantly sinus heart rhythm, we examine arrhythmogenic potencies of amrinone (0.5 mg/kg/min, 1 and 3 mg/kg) and milrinone (10 micrograms/kg/min, 75 and 100 micrograms/kg). 2. Amrinone and milrinone significantly reinduced ventricular ectopic beats on day 2 after coronary occlusion. 3. These effects were preceded by a cardioacceleration which intensified as the ventricular arrhythmias developed. 4. Over the following days the arrhythmogenic potencies of these inotropic drugs were modest. 5. Thus, amrinone and milrinone can impair heart rhythm chiefly in a recent myocardial infarct.

Amrinone↗
PubMed1991

Time course of spontaneous ventricular arrhythmias following acute coronary occlusion in the dog.

In this study, the arrhythmias occurring in dogs between 4 and 15 hr after occlusion of the left anterior descending coronary artery were continuously monitored by recording the electrocardiogram from bipolar leads. At 4.5 hr the number of dogs with less than 50% of sinus beats had increased and at 5 hr 15 min sinus beats represented on average 80% of total heart beats. In the period up to 6 hr isolated ventricular beats and ventricular salvos were seen in 95% and 63% of the dogs respectively and at 7 hr there were, on average, 50% of sinus beats and monomorphic ventricular rhythm was observed in 58% of the dogs. From 7 hr half the dogs had over 50% of ventricular ectopic beats and by 9 hr ventricular rhythm disturbances were permanently present in all the dogs. The ventricular arrhythmias reached a peak at about 11-12 hr (mean % sinus beats less than 10) when all dogs had a predominantly monomorphic (42%) and/or polymorphic (63%) ventricular heart rhythm. The characteristic time course of these cardiac disturbances suggest that it may form the basis for an experimental model that may be useful in analyzing the effects of potential antiarrhythmic drugs.

Animals↗
PubMed1991

[Silent ischemic heart diseases in patients with peripheral arterial diseases. Screening and 5-year prognosis in a population of 418 patients].

Silent ischaemic heart disease was looked for by exercise stress testing in 418 patients with chronic obliterative arterial disease of the lower limbs with no clinical or electrocardiographic signs of myocardial ischaemia. In the initial work-up, 6.2% of patients had a positive exercise test and the results were suspect in 9.2% of patients. These patients were followed up for 5 years. There were 42 deaths (10%). The cause of death was cardiovascular in 53.7% of cases (myocardial infarction 40.4%) and malignant disease in 35.7%. During the 5 year follow-up, ischaemic heart disease present as angina pectoris or myocardial infarction in 115 cases (27.5%). Patients who had a positive exercise stress test initially had a particularly high death rate (23%) and developed clinical signs of coronary insufficiency in 57.5% of cases. On the other hand, the peripheral vascular complications were relatively rare in this series: cerebrovascular accidents: 1.4%; retinal vascular accident: 1.1%; carotid surgery: 1.6%; lower limb amputation: 1.9%; lower limb vascular surgery: 17.7%. Silent ischaemic heart disease is very prevalent in patients with obliterative arterial disease of the lower limbs and is a main vital prognostic factor in these patients. These results confirm the need for a complete cardiovascular check-up in all patients with peripheral arterial disease.

Adult↗
PubMed1990

Evidence for postsynaptic alpha 1- and alpha 2-adrenoceptors mediating catecholamine-induced negative chronotropic ventricular responses in the conscious dog.

1. Adrenaline (0.25-1 microgram/kg), noradrenaline (0.125-0.5 microgram/kg) and dopamine (25-100 micrograms/kg) given in the conscious dog with chronic atrio-ventricular block after beta-adrenoceptor blockade, increased ventricular cycle length (VCL) and mean blood pressure (MBP). 2. Atropine (muscarinic receptor blocker) reduced the catecholamine-induced effects on VCL without modifying their hypertensive effects. 3. Phenoxybenzamine or phentolamine (alpha-adrenoceptor blockers) only decreased the effects of adrenaline on VCL but suppressed those of noradrenaline and dopamine. They only reduced the effects of adrenaline and noradrenaline on MBP, but reversed that of dopamine. 4. Yohimbine (alpha-adrenoceptor blocker) suppressed the catecholamine-induced effects on VCL, and reduced strongly the hypertensive effects of adrenaline and noradrenaline and reversed that of dopamine. 5. Thus, these results show the existence of negative chronotropic postsynaptic alpha-adrenoceptors in the ventricles.

Adrenergic alpha-Antagonists↗
PubMed1988

Effects of diproteverine, a new calcium antagonist on sinoatrial node and atrioventricular conduction in conscious unsedated dogs.

The electrophysiologic effects of diproteverine were studied in the conscious nonsedated chronically instrumented dog. Diproteverine at 0.25-0.75 mg/kg (i.e., at plasma levels within the assumed therapeutic range) dose-relatedly decreases heart rate, increases corrected sinus node recovery time, and decreases Wenckebach point. These effects are observed at plasma levels ranging between 16.2 +/- 4.1 and 144.7 +/- 12.5 ng/ml. After cholinergic blockade with N-methylscopolammonium, diproteverine lowers heart rate (greater than or equal to 0.25 mg/kg), increases corrected sinus node recovery time, and decreases Wenckebach point (greater than or equal to 0.5 mg/kg). After propranolol, diproteverine only significantly reduces corrected sinus node recovery time 5 min after the third administration (0.75 mg/kg). After pharmacologic autonomic blockade by N-methylscopolammonium propranolol combination, diproteverine lowers intrinsic heart rate (greater than or equal to 0.25 mg/kg) and Wenckebach point (greater than or equal to 0.5 mg/kg). Diproteverine does not modify mean blood pressure. These results show that diproteverine administered with and without pharmacologic autonomic blockade in the conscious dog causes dose-related depressant effects on sinus node function and atrioventricular conduction without producing significant vasodilatation.

Animals↗
PubMed1988

Comparative effects of acebutolol and labetalol on peripheral hemodynamics in healthy volunteers.

1. During a 28-day treatment period, 10 healthy volunteers in a cross-over, double-blind study received at random 200 mg of either acebutolol or labetalol twice a day. Each treatment period was followed by administration of a placebo over an equal length of time. 2. Only acebutolol reduced heart rate measured in the supine position significantly at rest, whereas acebutolol and labetalol reduced it significantly after exercise on the treadmill. 3. Only acebutolol lowered humeral pressure at rest but not after exercise. Neither drug produced a change in blood pressure in the ankle or in the first toe at rest or after exercise. 4. Blood flow measured by plethysmography was increased by labetalol in the calf by comparison with placebo and in the first toe by comparison with placebo and acebutolol. 5. Labetalol lowered peripheral resistance significantly in comparison with placebo in the calf and first toe. Acebutolol tended to lower the resistance insignificantly in the calf but to increase resistance in the first toe.

Acebutolol↗
PubMed1986

Findings on ambulatory electrocardiographic monitoring in subjects older than 80 years.

Twenty-four-hour electrocardiograms were recorded in 50 subjects (44 women, 6 men) older than 80 years without cardiovascular disease and with normal standard electrocardiographic responses. During waking and sleeping periods, the mean sinus rates were, respectively, 78 +/- 3 and 64 +/- 1 beats/min; heart rate ranged from 43 to 180 beats/min over 24 hours. Supraventricular tachycardia (SVT) was present in 28% of the subjects. Nocturnal sinus arrhythmia was only noted in 12% of the patients; it was accompanied by sinus pauses of 1.8 to 2 seconds, and 1 woman had a transient pattern compatible with atrioventricular dissociation. Supraventricular ectopic contractions (SVECs) were present in all cases. The frequency was less than 1 per hour in 25% and more than 20 per hour in 65%. Serious supraventricular tachyarrhythmias included an episode of ectopic atrial tachycardia (1 subject), a short run of atrial fibrillation (1 subject) and of flutter (1 subject), and several episodes of supraventricular tachycardia (2 subjects), all accompanied by more than 50 SVECs per hour. The number of ventricular premature contractions (VPCs) exceeded 10 per hour in 32% and were multifocal in 18%. There were couplets in 8% and a run of 6 VPCs in 1 subject (2%). In conclusion, sinus pause and atrioventricular block are unusual in people older than 80 years without apparent heart disease. In contrast, frequent SVECs and VPCs are more common. This study stresses the difficulty of evaluating the normality of the electrocardiogram with portable monitoring in the older population.

Aged↗
PubMed1986

Comparison of verapamil and bepridil, two slow channel inhibitors, in protection against calcium-induced arrhythmias.

Verapamil and bepridil share the common property of antagonizing the slow inward calcium-mediated current, but bepridil has some additional antiarrhythmic properties. The efficacy of these two compounds against CaCl2-induced arrhythmias has been compared in rats. CaCl2 was administered i.v. by continuous infusion until death (25 mg X kg-1 X min-1 or 40 mg X kg-1 X min-1) or by bolus injection (160 mg X kg-1). Bepridil (5, 10 mg X kg-1) or verapamil (2.5, 5 mg X kg-1) were injected 10 min before CaCl2. Bepridil (10 mg X kg-1) or verapamil (5 mg X kg-1) prolong the survival time during CaCl2 infusion. After pretreatment, the injection of 160 mg X kg-1 CaCl2 is less toxic: 25% of animals are protected by bepridil (5 mg X kg-1), 41% by bepridil (10 mg X kg-1) or verapamil (5 mg X kg-1). At death the myocardial Ca2+ level is not different in controls and pretreated animals, thus, the ratio myocardial Ca2+/total injected Ca2+ is significantly lowered by bepridil (10 mg X kg-1) or verapamil (5 mg X kg-1). The efficacy of the two drugs on this model appears related solely to inhibition of slow inward current despite the additional antiarrhythmic profile of bepridil.

Animals↗
PubMed1986

Chronotropic cardiac effects of histamine in the conscious dog with chronic atrioventricular block: interactions with the autonomic nervous system.

Chronotropic effects of histamine and dimaprit were studied in the conscious dog with chronic atrioventricular block. Histamine at 0.2-5 micrograms/kg and dimaprit at equimolar doses (i.e. 0.25-6.25 micrograms/kg) increased atrial rate dose-relatedly. Blockade of muscarinic receptors reduced these effects and simultaneous blockade of muscarinic and beta-adrenergic receptors abolished them. Histamine and dimaprit moderately increased ventricular rate. Blockade of muscarinic receptors did not modify these effects, but blockade of beta-adrenoceptors with or without simultaneous blockade of muscarinic receptors suppressed them. After blockade of beta-adrenoceptors, histamine and more rarely dimaprit sometimes decreased atrial and ventricular rates. These effects were prevented by additional muscarinic blockade. Histamine and dimaprit lowered mean blood pressure to the same degree before and after each antagonist. The positive chronotropic effects of histamine and dimaprit, at these doses, are probably reflex responses to their hypotensive effects. The negative chronotropic effects of histamine after pindolol are due to muscarinic receptor activation. No evidence was found to implicate histamine-specific receptors in any of the chronotropic effects of histamine and dimaprit.

Adrenergic beta-Antagonists↗
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

Sudden death and experimental acute myocardial infarction.

Acute myocardial ischemia was produced by ligature of the anterior descending coronary artery on 658 dogs in 3 separate laboratories. Overall, 12% of the dogs died within the first hour (instantaneous death) and 25% within the first 24 hours (sudden death). The sudden death rate was significantly related to the logarithm of the weight of the dogs in the range studied. It varied widely if values from small series, comprising the same number of dogs, were considered. Values became less dispersed as the size of the series increased. In series of 10 dogs, sudden death rates ranged from 0 to 70%, whereas in series of 100 dogs the range was 14 to 36%. Stable values were obtained for 50 to 60 dogs per series. Accordingly, reliable assessment of preventive measures can be made only with experimental series of at least this size.

Animals↗
PubMed1985

Chemical structure and hemodynamic effects of two new pyridazinone derivatives.

Two new pyridazinone derivatives were selected among two series and assayed for their hemodynamic effects. Their synthesis is described and their chemical structure confirmed by I.R. and N.M.R. data. The 5-arylhydroxymethyl-3-pyridazinone did not induce any significant hemodynamic changes. However, the 5-dichlorobenzylidene-3-pyridazinone, intravenously injected, was active in anesthetized dogs. Moderate doses induced modifications in the heart rate, left ventricular dP/dt max and femoral blood flow and resistance.

Animals↗
PubMed1985

Use of experimental myocardial infarct to demonstrate arrhythmogenic activity of drugs.

Ligature of the anterior interventricular coronary artery in the dog is a model that is used, classically, to study antiarrhythmic properties of drugs. It can also be used to demonstrate arrhythmogenicity. In this study, twenty hours after coronary ligature, cardiac arrhythmia was reduced by oral administration of quinidine and phenytoin. This effect lasted over several days after the coronary occlusion. By Day 2, more than 60% of the treated dogs had a predominantly sinus heart rhythm, compared with 20% of the controls. This antiarrhythmic treatment also seemed to reduce mortality. Dipyridamole was subsequently injected i.v. at 0.5 and 1 mg/kg on Days 2, 3, and 4 after coronary ligature. On Day 2, dipyridamole significantly increased the proportion of ectopic beats and significantly lowered the proportion of sinus beats. This drug can thus worsen arrhythmia induced by coronary occlusion. On Days 3 and 4, dipyridamole showed no arrhythmogenic effects, but there was a significant increase in sinus automaticity.

Animals↗
PubMed1985

Methods for producing experimental complete atrioventricular block in dogs.

This paper reviews methods for producing experimental complete atrioventricular (A-V) block in dogs, with emphasis on those methods that enable chronic A-V block to be obtained. The dog with chronic complete A-V block, particularly when unanesthetized, is a useful experimental model, and the production of complete A-V block is an approach to the clinical treatment of certain supraventricular arrhythmias. Criteria for the choice of method are discussed, and the results obtained to date in the unanesthetized dog with chronic A-V block are briefly described to illustrate the usefulness of this experimental model.

Animals↗