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Biomedical subjects

P Duchêne-Marullaz

Publications and source records attributed to P Duchêne-Marullaz.

At least 19 recordsLinked to original sources
PubMed1994

Cardiac electrophysiological effects of rilmenidine, a novel antihypertensive agent, in the conscious dog: comparison with clonidine.

The cardiac electrophysiological effects of rilmenidine, a novel antihypertensive agent, and clonidine were studied in the conscious dog. Sinus rate, corrected sinus recovery time (CSRT) and Wenckebach point (WP) were measured in seven intact dogs. Atrial rate and atrial effective refractory period (AERP) were measured in six atrioventricular (AV)-blocked dogs with ventricular pacing. In both groups, blood pressure was also monitored. Each dog received with at least a three-day interval rilmenidine as dihydrogen phosphate and clonidine as hydrochloride in four successive intravenous injections, 30 min apart. In intact dogs, rilmenidine was administered at 50, 50, 100 and 200 micrograms/kg and clonidine at 2.5, 2.5, 5 and 10 micrograms/kg. In AV-blocked dogs, doses of rilmenidine were 25, 25, 50 and 100 micrograms/kg, those of clonidine 5, 5, 10 and 20 micrograms/kg. Rilmenidine and clonidine decreased sinus rate and atrial rate from the first dose. In this regard, rilmenidine was respectively 24 and 23 times less potent than clonidine. A lengthening of CSRT was observed at all doses with rilmenidine and at the last three doses with clonidine (ratio: 17) and a lowering of WP at all doses with rilmenidine and clonidine (ratio: 22). A shortening of AERP was also seen with rilmenidine and clonidine from the second dose (ratio: 6). All these effects may at least partly be explained by a cholinergic activation mechanism. In intact dogs both drugs produced a lowering of mean blood pressure (ratio: 17), whereas in AV-blocked dogs, in which ventricular rate was kept constant by pacing, pressure effects were more complex, being the resultant of hypotensive and hypertensive effects, the latter due to alpha vascular stimulation. Taken together, these results indicate that in the conscious dog, rilmenidine and clonidine exert qualitatively identical electrophysiological effects, but with different potency ratios.

Animals↗
PubMed1994

Chronotropic cardiac effects of falipamil in conscious dogs: interactions with the autonomic nervous system and various ionic conductances.

The chronotropic cardiac effects of falipamil were studied in conscious dogs with chronic atrioventricular (AV) block. Falipamil (0.5-2 mg/kg) initially increased atrial rate dose dependently. After atropine and atropine-pindolol, falipamil (2 mg/kg) decreased atrial rate, but after pindolol, it did not modify atrial rate. After atropine-pindolol-phenoxybenzamine, atropine-pindolol-yohimbine, atropine-pindolol-verapamil, and atropine-pindolol-quinidine pretreatment, falipamil produced atrial bradycardia. Falipamil dose-relatedly decreased ventricular rate. Falipamil (2 mg/kg) decreased ventricular rate after atropine, pindolol, and atropine-pindolol more than under basal conditions. After the other four pretreatments, it also produced ventricular bradycardia. Falipamil did not affect mean blood pressure (MBP) at any dose. These results (a) show that the initial atrial cardio-acceleration produced by falipamil results from its direct vagolytic action; (b) show that absence of atrial bradycardia results from buffering by the vagolytic effect and/or a relatively low basal atrial rate; (c) suggest that the falipamil ventricular bradycardia is partly buffered by the vagolytic effect, norepinephrine (NE) release, and involvement of alpha 2-adrenoceptors; (d) exclude involvement of postsynaptic muscarinic, alpha- and beta-adrenoceptors, and of the slow calcium current in the mechanism(s) by which falipamil decreases cardiac automaticity; and (e) suggest possible involvement of a quinidine-sensitive current in this (these) mechanism(s).

Animals↗
PubMed1992

Membrane stabilizing activity and beta-adrenoceptor antagonist-induced bradycardia in conscious dogs.

The atrial effective refractory period (AERP) and atrial and ventricular chronotropic effects of the stereoisomers of propranolol, pindolol, metoprolol and penbutolol were studied in conscious atrio-ventricular blocked dogs. Atrial beta-adrenoceptor blocking activity was assessed for all the drugs against isoprenaline. All the drugs except dextro-pindolol lengthened AERP and decreased ventricular rate dose relatedly. At comparable levels of atrial beta-adrenoceptor blockade, dextro-propranolol, dextro-metoprolol and dextro-penbutolol were more potent to induce AERP lengthening than their respective levo-isomers, whereas dextro-pindolol was less potent than levo-pindolol. In addition, levo-pindolol and levo-metoprolol were more potent to produce ventricular bradycardia than the corresponding dextro-isomers, whereas the levo- and dextro-isomers of propranolol and penbutolol were equipotent. These results confirm that the ventricular bradycardia induced by the different beta-adrenoceptor antagonists is partly due to ventricular beta-adrenoceptor blockade and to the membrane stabilizing activity of these drugs, and partly to another as yet unknown factor seen especially with the levo-isomers and particularly marked with metoprolol.

Adrenergic beta-Antagonists↗
PubMed1992

Interactions with the cardiac cholinergic system: effects of disopyramide and its mono-N-dealkylated metabolite.

The cardiac vagolytic effects of disopyramide and its mono-N-dealkylated metabolite (MND), and their interactions with the cardiac cholinergic system, were assessed using in vivo and in vitro experiments. In chloralose anesthetized dogs, disopyramide phosphate (0.25 mg/kg/min) and MND at equimolar dose (0.173 mg/kg/min) reduced vagal bradycardia. As indicated by the ED80, MND exhibits a vagolytic activity 1.5-2 times less potent than disopyramide. Concomitantly, increases in heart rate and mean blood pressure were observed with disopyramide, whereas with MND only a rise in mean blood pressure occurred. In conscious dogs, where vagal tone is fully expressed, disopyramide and MND increased heart rate and, interestingly, prevented any atropine-induced additional tachycardia, though heart rate was relatively low. Binding studies on rat heart membranes yielded Ki values 2-2.5 times higher for MND than for disopyramide, and demonstrated that neither disopyramide nor MND binding modified the cardiac muscarinic receptor sites. Taken together, these results show that disopyramide exhibits a more potent cardiac vagolytic action than MND, very likely linked to a greater ability to bind to cardiac muscarinic receptors. They also show that disopyramide and MND are very potent in preventing atropine-induced "excess tachycardia", very likely by inhibiting the ionic pacemaker current(s) involved in its genesis.

Animals↗
PubMed1992

Contribution of vagal blockade to the tachycardia induced by the antimuscarinic agents atropine and pirenzepine.

1. The cardiac cholinergic blockade and the chronotropic effect of the widely differing antimuscarinic drugs atropine and pirenzepine were investigated in the dog. 2. In conscious dogs, suppression of the parasympathetic system with atropine (0.2 mg kg-1 h-1) causes marked brief cardioacceleration (234 +/- 13 beats min-1) while pirenzepine (3 mg kg-1 h-1) causes moderate but persistent cardioacceleration (179 +/- 13 beats min-1). After suppression of the influence of the cardiac sympathetic system these cardioaccelerator effects are attenuated, particularly those of pirenzepine. 3. The effects of vagal stimulation are blocked completely and persistently by both agents. 4. When the cardioinhibitory action of the vagus nerve is blocked by pirenzepine the induced tachycardia can be increased by atropine, which causes an additional cardioacceleration (25 +/- 9 beats min-1). 5. These results show that the tachycardia induced by antimuscarinic agents is not only due to vagal blockade. The different mechanisms which may be involved are discussed. The results suggest that pirenzepine can suppress cholinergic influence on the heart more electively than atropine, which induced an 'excess tachycardia'. Also, intrinsic heart rate can be approached more closely when pirenzepine is used to suppress the parasympathetic system, than with atropine.

Animals↗
PubMed1991

Long-lasting antinociceptive effect of RC-160, a somatostatin analog, in mice and rats.

The effect of RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) was studied in mice by means of the hot plate test and in rats with the tail flick test. In mice, 512 micrograms/kg (s.c.) induced an antinociceptive effect maximal (+88 +/- 17%) at the 6th hour after injection but still significant at the 24th hour; 16 micrograms/kg (s.c.) was active for 3 h; 64, 256 and 1024 micrograms/kg were active 30 min, 3 and 24 h after injection. The effects of these last three doses were not different. The antinociceptive action was as high at 24 h as at 3 h (e.g. for 512 micrograms/kg, 44 +/- 9% and 51 +/- 12%, respectively); 48 h after injection the scores of the treated groups were not different from the score for saline treatment in the tail flick test, 512 micrograms/kg induced a significant antinociceptive effect for 12 h (maximal at the 3rd hour: +60%). No behavioral changes, and particularly no motor activity modifications were observed.

Amino Acid Sequence↗
PubMed1991

Effects of bepridil, diltiazem and verapamil on atrial refractoriness and heart rate in the conscious dog: comparison with quinidine.

1. Bepridil at cumulative doses between 1.25 and 8.75 mg/kg and quinidine between 2.5 and 17.5 mg/kg given in conscious dogs with chronic atrioventricular block and implanted atrial pacing electrodes, dose-relatedly lengthened atrial effective refractory period (AERP), as reflected by the decrease in maximal atrial frequency determined by pacing. 2. Diltiazem shortened AERP at 0.25 mg/kg and lengthened it at 1.75 mg/kg, but both effects were very slight. 3. Verapamil between 0.06 and 0.435 mg/kg did not alter AERP at all. 4. Except for diltiazem at 0.75 and 1.75 mg/kg and bepridil at 8.75 mg/kg, each dose of each drug increased atrial rate. Each drug produced an increase in ventricular rate and a short-lasting lowering in mean blood pressure. 5. Thus, these results indicate that bepridil exhibits more marked antiarrhythmic potentialities than quinidine and that the atrial and ventricular tachycardic effects observed are mainly baroreceptor reflex effects.

Animals↗
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

Comparison of anticholinergic effects of cibenzoline, disopyramide, and atropine.

The anticholinergic effects of cibenzoline, disopyramide, and atropine were compared on experimental models. Using inhibition of specific binding of 3H-quinuclidinyl benzylate (3H-QNB) in rat heart and cerebral cortex, Ki values were 15.8 +/- 1.6, 12 +/- 3.5, and 0.013 +/- 0.001 microM, respectively, for heart membranes and 31.6 +/- 1.5, 7.8 +/- 1.3, and 0.006 +/- 0.001 microM, respectively, for cerebral cortex membranes. In isolated guinea pig ileum, disopyramide was about 15 times more anticholinergic than cibenzoline but about 900 times less so than atropine. In anesthetized dogs, the three drugs administered by intravenous bolus reduced bradycardia caused by vagal stimulation. The effect of cibenzoline at 7 mg/kg i.v. (double the antiarrhythmic dose) was approximately the same as that of disopyramide at 2.5 mg/kg (half the antiarrhythmic dose). The drugs were infused for 1 h at 0.17 mg/kg/h for atropine, 11.6 mg/kg/h for disopyramide, and 5.5 mg/kg/h for cibenzoline. The maximal inhibition of the vagal stimulation was 98, 95, and 52%, respectively, for the three drugs. In nonanesthetized dogs, inhibition of the vagal-tone-induced tachycardia reached 33 +/- 4, 134 +/- 20, and 206 +/- 19% for cibenzoline, disopyramide and atropine, respectively. These results show cibenzoline to exert less potent anticholinergic effects than disopyramide.

Animals↗
PubMed1990

Comparison of standard one-minute treadmill exercise and strandness test (absolute walking distance) in relation to site of lesion, walking distance, and diastolic blood flow velocity (Doppler curves).

In 215 outpatients suffering from occlusive arterial disease of the lower limbs the authors compared the decrease in the ratio of ankle systolic pressure to brachial systolic pressure according to whether the treadmill exercise was limited to one minute or extended until pain forced the patient to stop. After a one-minute walk the pressure index always decreased significantly, especially when walking was restricted. The decrease in the pressure index was generally greater when the exercise was continued until the absolute walking distance, and the recovery time was usually twice as long. The fall in the pressure index was significantly greater for patients with single and multiple iliac stenoses than for those with stenoses at lower levels. In patients having a diastolic blood flow velocity on Doppler curves at rest, not modified by walking, a maximum drop in peripheral pressure was recorded after walking for one minute. In this instance there was no intensification of the decrease in peripheral pressure, unlike in patients without a diastolic blood flow velocity at rest. This one-minute test is not a maximal hemodynamic response, but it is sufficient for the appreciation of ischemia during exercise, according to the different parameters measured.

Arterial Occlusive Diseases↗
PubMed1989

Mechanisms of chronotropic cardiac effects of alinidine and plasma concentration-response relationships in the conscious dog with chronic atrioventricular block.

The chronotropic cardiac effects of alinidine were studied in the conscious dog with chronic atrioventricular block. Alinidine at 0.5 - 4 mg/kg, i.e., at plasma concentrations between 42 +/- 2 and 1625 +/- 371 ng/ml, initially increased atrial rate dose-dependently. This effect fell off rapidly, but atrial bradycardia was never observed. After atropine and pindolol, which raised basal atrial rate, alinidine (2 mg/kg) decreased atrial rate, whereas after phenoxy-benzamine, yohimbine or phentolamine, it produced atrial effects identical to those observed under basal conditions, i.e., initial tachycardia and no bradycardia. Alinidine dose-relatedly decreased ventricular rate. None of the pretreatments modified the maximal ventricular bradycardia, but interestingly after pindolol or yohimbine this effect developed more rapidly (maximal bradycardia between 3 and 5 against 30 min) and then declined progressively. Alinidine did not modify mean blood pressure at any dose. After atropine, phenoxybenzamine or phentolamine, alinidine remained without effect on mean blood pressure, but after pindolol or yohimbine, a hypotensive effect appeared concomitantly with the reduction of the ventricular bradycardia. These results show that the initial atrial cardioacceleration due to alinidine results from a direct vagolytic action of this drug and that the absence of atrial bradycardia results from buffering by the vagolytic effect and/or a relatively low basal atrial rate. They also suggest that the ventricular bradycardia does not involve either the muscarinic cholinoceptors or the alpha- or beta-adrenoceptors, though the results obtained after pindolol or yohimbine suggest possible involvement of a fall in sympathetic tone by stimulation of presynaptic or central alpha2-adrenoceptors, particularly in the persistence of the bradycardic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
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

[Therapeutics using plants: medications based on plants].

There has been renewed interest in the age-old practice of using plants to treat disease. The general public prefers to emphasize the side effects of modern drugs rather than consider the efficacy of the revolutionary changes in therapeutics over the past forty years. So the need to implement protective measures to prevent the uncontrolled use of herbal remedies is being discussed throughout Europe. It is impossible to confirm whether the suggested plants are just placebos but even if they were, the need for the doctor to resort to this form of therapy must be stressed because of its unquestionable success rate. However, it is vital that the doctor's and perhaps public education allow the precise recognition of cases in which this form of treatment should be formally prohibited.

Europe↗
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

Effects of sotalol on ambulatory electrocardiography in volunteers.

The effects of sotalol dosing, 160, 240, and 320 mg/day, for 10 days in seven healthy volunteers were studied. Twenty-four-hour ECG was recorded continuously under placebo and on days 2, 4, 6, 8, 10, 11, 13, and 14. Sotalol at the three doses significantly lowered mean heart rate, reducing mean diurnal heart rate significantly between noon and 6:00 PM and decreasing mean nocturnal heart rate between midnight and 6:00 AM at 320 mg/day. Although there was no change in plasma sotalol between days 4 and 10, at high doses a significant decrease in bradycardiac effect occurred. PR intervals and QTc intervals were lengthened at all doses during the daytime. At the highest dose, the PR interval was lengthened during the nighttime.

Adult↗
PubMed1986

Studies on the stereoisomers of beta-adrenoceptor antagonists in conscious A-V blocked dogs.

Atrial and ventricular chronotropic effects of the individual stereoisomers of propranolol, pindolol, metoprolol and penbutolol were studied in conscious dogs with chronic atrio-ventricular (A-V) block. Ventricular beta-adrenoceptor blocking activity was assessed for all drugs against isoprenaline under the same experimental conditions. At low doses, the stereoisomers of propranolol and penbutolol decreased atrial rate, whereas those of pindolol and metoprolol produced an increase. At higher doses, all drugs increased atrial rate. All drugs decreased ventricular rate dose-dependently except (+)-pindolol. Relative ventricular beta-blocking potencies of the (-)-isomers of propranolol, pindolol, metoprolol and penbutolol were respectively 38, 21, greater than 43 and 31 times higher than those of their corresponding (+)-isomers. In addition, beta-blocking potencies of (-)- and (+)-pindolol were respectively 60 and 120 times higher, those of (-)- and (+)-penbutolol 7 and 8 times higher and those of (-)- and (+)-metoprolol 4 and greater than 4 times weaker than those of (-)- and (+)-propranolol. At comparable levels of ventricular beta-adrenoceptor blockade, (-)-pindolol and (-)-metoprolol were more potent in producing ventricular bradycardia than their respective (+)-isomers, whereas (-)- and (+)-propranolol and (-)- and (+)-penbutolol were equiactive. In addition, regardless of which isomer was being studied, the order of ventricular bradycardiac potencies, at comparable levels of beta-adrenoceptor blockade, was metoprolol greater than propranolol greater than penbutolol greater than pindolol. In addition, regardless of which isomer was being studied, the order of ventricular bradycardiac potencies, at comparable levels of beta-adrenoceptor blockade, was metoprolol > propranolol > penbutolol >pindolol. 5 These results show that antagonism of beta-adrenoceptors in the ventricle is at least partly responsible for the ventricular bradycardiac effect produced by these drugs, but also that some other factor, apparently distinct from the membrane stabilizing activity, is involved, suggesting the existence of some other as yet unknown pharmacological property of the beta-adrenoceptor blocking drugs, especially evident in metoprolol. Finally, these results demonstrate that the intrinsic sympathomimetic activity exhibited by some of these drugs attenuate their bradycardiac effect.

Adrenergic beta-Antagonists↗
PubMed1986

Comparative electrophysiologic effects of bepridil, verapamil and diltiazem in conscious and anesthetized dogs.

The electrophysiologic effects of bepridil (10 mg/kg), verapamil (0.15 mg/kg) and diltiazem (0.6 mg/kg) were studied in the chronically instrumented conscious and pentobarbital-anesthetized dog. Sinus node automaticity assessed by the corrected sinus node recovery time and atrio-ventricular conduction assessed by the Wenckebach phenomenon were evaluated by atrial pacing via electrodes placed in the wall of the right atrium, and exteriorized in the neck region. Nineteen dogs were studied and groups of 6 dogs were used for each experimental session. The calcium channel blocking drugs were administered by slow i.v. infusion (15 min). Effects were measured over 45-60 min and compared with the pretreatment value. In conscious dogs, heart rate was initially markedly increased by bepridil and diltiazem and only slightly increased by verapamil. These chronotropic responses were reversed to bradycardia by diltiazem only. Corrected sinus node recovery time measured at the end of infusion was decreased by verapamil and diltiazem and was unchanged by bepridil. Lengthening of corrected sinus node recovery time was observed with verapamil at the end of the experiment. All 3 calcium channel blocking agents produced negative dromotropic responses. To determine to what extent electrophysiologic effects of pentobarbital were involved in the cardiac responses measured in the anesthetized dog, pentobarbital was administered prior to injection of each calcium channel blocking agent. Pentobarbital produced positive chronotropic and dromotropic effects which were attenuated by the 3 calcium channel blocking agents. The reduction of corrected sinus node recovery time induced by pentobarbital was diminished by bepridil and diltiazem and unchanged by verapamil. Pentobarbital anesthesia thus has important electrophysiologic implications on the effects of calcium channel blocking agents on chronotropic and dromotropic variables on the heart.

Anesthesia, General↗