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Biomedical subjects

A Berdeaux

Publications and source records attributed to A Berdeaux.

142 records · Page 8Linked to original sources
PubMed1977

[Determination of plasma digoxin in newborn infants. Practical applications].

Measurement of plasma digoxin concentrations in infants after three increasing dosage levels shows that the optimal dose of this glycoside in 20 microgram/kg/day, i.e. a loading dose of 20 microgram/kg followed every 8 hours by a maintenance dose of 7 microgram/kg. The plateau concentration achieved is 3.0 +/- 0,5 ng/ml 8 hours after the last administration. When digoxin levels exceed 5 ng/ml (overdosage, renal failure or low body weight), toxic manifestations occur.

Digoxin↗
PubMed1977

Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man.

1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man.

Adrenergic beta-Antagonists↗
PubMed1976

Influence of sex on the clinical pharmacology of flutiorex, a new anorectic drug.

The effects of flutiorex, a new anorectic agent, and of a placebo on food intake and the activity of the sympathetic and central nervous systems have been compared in a double blind trial in two groups of healthy volunteers, one of five males and the other of five females. Flutiorex 20 mg orally had a significant anorectic effect both in males and females, the observed reduction in food intake being 34.0 and 27.5%, respectively. It caused alpha-adrenergic stimulation (blood pressure and pupil diameter) and central nervous system excitation (critical flicker frequency), both of which were more marked in males than in females. Flutiorex was better tolerated by women than by men. Measurement of the blood level of flutiorex and its de-ethylated metabolite, norflutiorex, showed that both compounds were detectable in four of the five male subjects, but in only one of the five females. Sex-linked differences in the pharmacokinetics of flutiorex may explain the greater intensity of its effects in males.

Adult↗
PubMed1976

Effects of verapamil on regional myocardial blood flow and ST segment. Role of the induced bradycardia.

The effects of verapamil on regional myocardial blood flow and on the ST segment were studied in both normal and ischemic regions in dogs with and without cardiac pacing. In the absence of cardiac pacing, verapamil (0.05 mg/kg/min/10 min) induced marked bradycardia, a drop in blood pressure and an increase in epicardial and endocardial flows both in normal and ischemic regions of the heart. However, in ischemic regions, redistribution was favorable since the endo/epi ratio increased from 0.46 to 0.61 (p less than 0.01) whereas this ratio did not vary in normal regions (0.94 vs. 0.92). This increase is accompanied by less marked ST segment elevation during coronary occlusion in dogs treated with verapamil. In dogs with cardiac pacing, administration of verapamil under the same conditions again induced a drop in blood pressure and, in normal regions only, a homogeneous but less marked increase in epicardial and endocardial flows, the endo/epi ratio varying from 0.94 to 0.98. In contrast, in ischemic regions, blood flow was not modified by verapamil, but the endo/epi ratio dropped from 0.46 to 0.31 (p less than 0.01), while the ST segment elevation observed did not differ from that recorded during the control occlusion. These results demonstrate the major role of verapamil-induced bradycardia in the anti-anginal affects of this drug.

Animals↗
PubMed1976

Preliminary assessment of flutiorex, a new anorectic drug, in man.

1 The effects of +/--flutiorex, a new anorectic agent, on food intake, the sympathetic nervous system and the central nervous system were compared to those of fenfluramine and a placebo in a double-blind trial involving six healthy volunteers. 2. Flutiorex exerts a singificant anorectic effect and was shown to be approximately twice as potent as fenfluramine in this regard. 3 Flutiorex induces a definite alpha-adrenergic sympathomimetic stimulation as was shown by a rise in systolic blood pressure and the development of marked mydriasis. 4 Flutiorex is a central nervous system stimulant producing an increase in critical flicker frequency. It does not, however, influence psychomotor coordination as reflected in the pursuit rotor test. 5 Serial determinations of blood and urine levels of flutiorex and its deethylated metabolite, norflutiorex, showed that flutiorex is rapidly absorbed and deethylated, accumulates in large quantities in the tissues and, like its metabolite, is excreted in the urine in very small quantities. Blood levels of norflutiorex appear to remain elevated longer than those fo flutiorex.

Adult↗
PubMedDate not supplied

[Therapeutic perspectives in the treatment of stable angina].

Five groups of drugs are presently available to reduce the symptoms associated with angina pectoris: beta-blockers, calcium channel antagonists, nitrates, potassium channel agonists and trimetazidine. beta-blockers remain the drugs of first strategy since they are unique in reducing major cardiac events. Angiogenesis and gene therapy are still in the field of research. The second therapeutic goal is to reduce cardiovascular morbi-mortality. Inhibitors of platelet aggregation, hypolipemic agents and converting enzyme inhibitors have proved their efficacy in these fields. Conversely, vitamins C, E and B, antibiotics against intra-cellular germs and substitutive hormonotherapy of post-menopausal women must yet prove their efficacy.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Cardiovascular interactions of local anesthetics and calcium entry blockers in conscious dogs.

To assess the pharmacologic risk of regional anesthesia in patients treated with calcium entry blockers (CEBs), the cardiovascular effects of 30-minute infusions of lidocaine (60 micrograms.kg-1.minute-1 after an intravenous bolus of 1.5 mg.kg-1), bupivacaine (15 micrograms.kg-1) or normal saline (1 ml.minute-1) were studied with concurrent 40-minute infusions of equihypotensive doses of verapamil (25 micrograms.kg-1.minute-1) and diltiazem (20 micrograms.kg-1.minute-1) in seven conscious dogs chronically instrumented for continuous recording of arterial pressure and left ventricular (LV) contractility assessed by the peak of LV dP/dt. The effects of CEBs alone (saline group) were stable throughout the infusion time. Besides a 10% decrease in mean arterial pressure, verapamil increased heart rate, prolonged atrioventricular (AV) conduction and decreased LV dP/dt, whereas a lesser and isolated tachycardia was observed in the case of diltiazem. At the end of a 30-minute concomitant infusion: (1) bupivacaine (1.4 micrograms/ml) further decreased arterial pressure (with verapamil and diltiazem; -8% and -11%, respectively) and LV dP/dt (with verapamil, -13%), whereas PR interval was further lengthened with verapamil and diltiazem (+36% and +17%, respectively) without change in heart rate; (2) lidocaine (approximately 3.5 micrograms/ml) increased heart rate (with verapamil and diltiazem; +19% and +14%, respectively) and arterial pressure (with verapamil, +8%) without change in LV dP/dt, while the PR interval was further lengthened during verapamil infusion (+34%). Second-degree AV blocks appeared with lidocaine (one of seven dogs) and bupivacaine (three of seven dogs) during verapamil infusion. Caution should therefore be exercised when patients under effective verapamil or diltiazem treatment are given regional anesthesia resulting in significant plasma levels of local anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Interaction of intravenous diazepam and bupivacaine in conscious dogs.

The cardiac and hemodynamic effects of bupivacaine, diazepam and their coadministration were evaluated in six mongrel dogs chronically instrumented for recording of mean arterial pressure (MAP), left ventricular (LV) pressure, and cardiac output (CO, electromagnetic flow probe around the ascending aorta). LVdP/dt was derived from the LV pressure signal, and its positive peak was used as an index of myocardial contractility. Heart rate (HR), RR, PR and QT intervals were measured from ECG. At weekly intervals, each dog received in a random order one of the following treatments: (1) saline as control, (2) diazepam (0.2 mg/kg, intravenous, bolus), (3) bupivacaine (0.4 mg/kg intravenous bolus, followed by 15 micrograms/kg/minute, during 30 minutes), and (4) a combination of diazepam and bupivacaine, as in (2) and (3), respectively. Despite its intrinsic cardiodepressant effects, bupivacaine induced a delayed (30-minute) compensatory increase in HR (+ 11%, p less than 0.05) and LVdP/dt (+ 10%, p less than 0.05). Diazepam decreased systemic vascular resistance (SVR; -16%, p less than 0.05) with concomitant increases in HR and CO. After diazepam pretreatment, LVdP/dt did not rise after bupivacaine administration, whereas SVR decreased (-14%, p less than 0.05) and HR increased (+19%, p less than 0.05). The QT-RR relationship remained unchanged regardless of the treatment administered. Thus, diazepam might blunt the compensatory effects of bupivacaine on cardiac function and may decrease the margin of safety of this local anesthetic agent during major neural blockade procedure.

Animals↗
PubMedDate not supplied

Direct versus reflex activation of cardiac beta-adrenoceptors in the chronotropic and inotropic effects of isoprenaline and prenalterol in the conscious dog.

The mechanisms by which isoprenaline and prenalterol increase heart rate and myocardial contractile force were investigated in conscious instrumented dogs. Isoprenaline (0.1 micrograms/kg/min/10 min) increased both heart rate (+98 +/- 14%) and contractility (+36 +/- 5%) and decreased diastolic blood pressure. beta 1-Adrenoceptor blockade abolished the isoprenaline induced increase in contractility whereas the induced tachycardia was reduced by approximately 50%. Either beta 2-blockade, which abolished the hypotensive effect of isoprenaline or ganglionic blockade, which abolished the isoprenaline-induced activation of sino aortic baroreflexes, strongly reduced (-67 +/- 8%) the isoprenaline-induced tachycardia but did not markedly alter the increase in contractility. However, the isoprenaline-induced increase in contractility was potentiated by methylatropine (+83 +/- 12%) whereas the simultaneous tachycardia was less marked than before methylatropine. In the same dogs, prenalterol (2 micrograms/kg/min/5 min) increased contractility (+38 +/- 5%) to the same extent as isoprenaline but induced a lesser increase in heart rate (+23 +/- 3%) and had no effect on aortic pressure. These effects were not significantly modified by pretreatments with either ganglionic or beta 2-blockades but were abolished by beta 1-blockade. After methylatropine the prenalterol-induced increase in heart rate was not modified but the increase in contractility was potentiated (+63 +/- 11%). We conclude that whereas indirect activation of arterial baroreflexes through hypotension markedly contributes to the isoprenaline-induced increase in heart rate, the simultaneous increase in cardiac inotropism is only dependent upon direct beta 1-adrenoceptor activation by isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Effects of nicardipine on regional coronary deficit and the ST segment of the healthy and ischemic myocardium in dogs].

The effects of nicardipine, a phenyldihydropyridine calcium-channel antagonist agent, have been investigated on regional blood flow and epicardial ST-segment elevation in the nonischemic and ischemic myocardial zones after either intermittent, or permanent coronary artery occlusion in dogs. Whichever the experimental model used, nicardipine reduced heart rate and arterial blood pressure and increased regional myocardial blood flows (50 to 100% of control flow values). All these effects were dose-dependent. During intermittent coronary occlusion (a model that mimics angina pectoris), the nicardipine-induced myocardial vasodilation was homogeneous between the endocardium and the epicardium of the ischemic and nonischemic zones. During permanent coronary occlusion (a model that mimics myocardial infarction), the nicardipine-induced myocardial vasodilation mainly developed within the endocardium of the ischemic zone, leading thus to a beneficial transmural blood flow redistribution in that zone. Finally, and whichever the experimental model used, nicardipine did not reduce the ischemic injury as assessed by epicardial ST-segment elevation.

Animals↗
PubMedDate not supplied

[Bepridil: hemodynamic and coronary effects on normal and/or ischemic myocardium in dogs (author's transl)].

1. The effects of bepridil, certain properties of which suggest antagonism of calcium flux, were studied: 1.1. On arterial blood pressure and heart rate in unanesthetized dogs. 1.2. On coronary and systemic hemodynamics in anesthetized dogs. 1.3. On regional blood flow (R.B.F.) in the myocardium of anesthetized dogs either normal or experimentally ischemic from temporary and/or permanent coronary occlusion. 2. Bepridil in unanesthetised dogs does not cause any significant change in heart rate or systolic blood pressure. Both the mean and diastolic blood pressures increase at the end of the observation period 20 minutes after the second injection. 3. In contrast, bepridil in anesthetized dogs induces a fall in peripheral resistance together with a drop in arterial blood pressure without any alteration in cardiac output. Both heart rate and contractile force are decreased while coronary flow is increased. 4. In models of localized transitory myocardial ischemia, bepridil (1 mg . kg-1 I.V.) induces a general increase in absolute R.B.F., particularly causing a favourable redistribution of coronary blood to the endocardium in ischemic areas, as evidenced by the improved endocardium/epicardium irrigation ratio. These favourable effects disappear when the dose of bepridil (3 mg . kg-1) used in this a preparation induces a marked drop in blood pressure and consequently a fall in coronary perfusion. 5. In models of localized permanent myocardial ischemia, bepridil has no effects either on R.B.F. in healthy or ischemic areas, or on the endocardium/epicardium irrigation ratios in these two types of areas.

Animals↗
PubMedDate not supplied

[Nitrates and coronary vascular endothelium dysfunction].

Since the classical studies by Furchgott and Zawadski (Nature, 1980, 286, 373-376), the vascular endothelium is known to play a fundamental role in the regulation of haemostasis and vasomotor activity. This is primarily due to its strategic interface position between the circulating blood and smooth muscle cells of the media. Due to the presence of specific receptors to mediators released during platelet aggregation (thrombin, ATP, serotonin, PAF, etc.), and the presence of mechanoreceptors sensitive to shearing forces generated by blood flow along the vessel wall, the endothelium is able to release, at the two poles of the cell, vasodilator and antiaggregant substances called "endothelium derived relaxing factors" (EDRFs), the best known for which are nitric oxide (NO) ans prostacyclin (PGl2). In the absence of endothelium (angioplasty), or in the case of endothelium dysfunction related to cardiovascular diseases such as hypertension, heart failure, atherosclerosis or diabetes, EDRF synthesis is absent or defective and its oxidative catabolism in increased (particularity by superoxide anion), resulting in varying degrees of disorders of haemostasis (thrombosis) and/or arterial and venous vasomotor activity. The only known effective treatment to palliate these dysfunctions is exogenous NO, supplied in the form of nitrate (nitroglycerin, isosorbide dinitrate, 5-mononitrate) or "NO donors" (Sin1, nitroprussate). The advantage of these substances is that their vasodilator effects (and, in some cases, their antiaggregant effects) are strictly endothelium-independent and they remain effective regardless of the causes and severity of endothelial dysfunction.

Coronary Vessels↗
PubMedDate not supplied

[Cell adhesion molecules and pharmacologic applications. Round Table No 3 at Giens XIII].

This workshop intended to perform a "state-of-the art" of current research on adhesion molecules in various pathophysiologies, and to determine pharmacological targets. Indeed, recent important progress concerning the cellular and molecular physiology of adhesion molecules led to the development of various integrin antagonists in several domains, like cardiovascular disease, inflammation and cancer. Integrins play a major role in numerous process like embryonic development, tumor growth and metastasis, apoptosis, hemostasis, leucocyte recruitment and activation, and bone resorption. The development of integrin antagonists is well advanced in the cardiovascular domain, since the first marketed drug (abciximax, Reopro) is an antibody directed against the GPIIb/IIIa complex (integrin alpha IIb/beta 3) involved in the final pathway of platelet aggregation. Another active domain of research in pharmacology is 'cardioprotection', i.e. the prevention of cardiac damages induced by the reperfusion of the coronary bed after an ischemia secondary to thrombolysis, angioplasty, of coronary bypass. The pharmacological targets of these antagonists are integrins involved in various process like leucocyte and platelet adhesion and endothelial function. Other potential indications in the cardiovascular field are restenosis after angioplasty, and atherosclerosis.

Cardiovascular Diseases↗