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Biomedical subjects

C Thuillez

Publications and source records attributed to C Thuillez.

At least 109 records · Page 6Linked to original sources
PubMed1990

[The humeral artery and clinical pharmacology].

Regional haemodynamic parameters such as blood flow, brachial artery diameter and forearm resistances may be measured or calculated non-invasively by pulsed Doppler techniques, and, in the absence of blood pressure changes, provide a method of observing and quantifying the vasomotor tone of small or large arteries. This type of study therefore allows characterisation of the vascular effects of drugs whether they be vasodilators or substances with a preferential mode of action on the myocardium. These effects can be situated with respect to the central hemodynamics in order to determine the presence of phenomena of regional redistribution of cardiac output, the regional vascular changes observed after taking a meal or in cardiac failure, with and without treatment; this should lead to a better understanding of the mode of action of drugs used in cardiovascular disease and also of the underlying physiopathological mechanisms.

Arm↗
PubMed1990

[Role of the enoximone-dobutamine combination in the treatment of congestive cardiac insufficiency].

Theoretically, there are two reasons for using the association of dobutamine and enoximone in patients with acute cardiac failure; the powerful vasodilator effect of enoximone and the different biochemical actions of the two drugs on the myocardial fibre affecting the production (dobutamine) or the degradation (enoximone) of cyclic AMP. The combined effects of beta adrenergic agonists and phosphodiesterase III inhibitors in vitro and in vivo have been previously reported. An increased contractile response to dobutamine has been demonstrated with enoximone on isolated human ventricle obtained during cardiac transplantation. We confirmed the additive effect of dobutamine (5 to 10 micrograms/kg/min) and enoximone (1 mg/kg/bolus IV) in 8 patients with acute cardiac failure with each molecule used alone. Mild changes in heart rate (+19 bpm) and in systolic blood pressure (-3 mmHg) were observed simultaneously. The absence of an increase in SvO2 compared to the use of each molecule in monotherapy is probably related to a tendency to increase myocardial oxygen consumption which may be potentially deleterious in terms of gas exchange. Having demonstrated the additive effects of the association of dobutamine and enoximone, there is probably a place for this therapeutic association in the management of acute cardiac failure. However, the potential risk of inducing an atrial and/or ventricular tachyarrhythmia and the consequences of lowering ventricular filling pressures and systemic vascular resistances should be born in mind; when using this therapeutic association, the authors suggest starting treatment with low doses of dobutamine (5/kg/min) and enoximone (0.5 - 1 mg/kg) with haemodynamic control and steadily increasing the doses, depending on the results obtained.

Cardiotonic Agents↗
PubMed1990

[Modeling of the relation between plasma concentration of the active metabolite of perindopril and inhibition of the activity of plasma converting enzyme in healthy volunteers].

UNLABELLED: The purpose of this study was to investigate the relationship between plasma concentration (Cp) of perindoprilat (P), the active metabolite of perindopril, and plasma converting enzyme activity (CEA) after a single oral administration of perindopril. CEA and Cp were investigated before, and, 1, 2, 3, 4, 6, 8, 10, 24 and 48 hours after a random administration of a placebo or 4, 8, 16 mg perindopril in a double-blind and crossover study performed in 6 healthy male volunteers. Effect on CEA was expressed as the percentage of inhibition of pretreatment value (CEA0): CEI = 100 (CEA0 = CEA)/CEA0. The CEI-Cp relationship was non linear and displayed an hysteresis loop. Following Sheiner et al. (Clin Pharmacol Ther, 1979; 25: 358-71), we used an effect compartment in which drug dissipation is governed by a first-order rate constant keo. Concentration of P in the effect compartment (Ce) was related to CEI by the Hill equation CEI = 100 Emax Cen/(EC50n + Cen), where Emax (expressed as a percentage) is the theoretical maximum effect, EC50 the Ce which produces 50 p. 100 of Emax, and n the Hill coefficient. Pharmacodynamic parameters were estimated by the non parametric approach proposed by Unadkat et al. (Clin Pharmacol Ther, 1986; 40: 86-93). The Hill equation was fitted to the data for 3 different values of n: 1, 2, and 3. RESULTS: for all the 3 doses, the best curve fitting was achieved for n = 1 or 2. We obtained keo = 0.60 +/- 0.30 h-1 (mean +/- s.d.), Emax = 90 +/- 10 p. 100, EC50 = 1.30 +/- 0.95 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Functional antagonism between PK 11195, a peripheral benzodiazepine receptor antagonist, and nicardipine at the vascular level in healthy subjects: a peripheral hemodynamic study.

The effects of PK 11195, a peripheral benzodiazepine receptor antagonist (200 mg orally), of nicardipine (20 mg orally), of their combination, and of a placebo on brachial and carotid arteries, diameters, and flows were determined and compared over a period of 8 h after drug intake during a double-blind and cross-over study performed on six healthy volunteers. Simultaneously, plasma concentrations of both drugs were measured. PK 11195 significantly increased carotid and more markedly brachial arteries, flows (20 and 39%, respectively), and diameters (4 and 7%, respectively) and decreased forearm vascular resistance. Thus, PK 11195 preferentially affected the resistance vascular beds where it dilated both large arteries and arterioles. The intensity and duration of the peripheral vasodilating effects of PK 11195 were similar to those of nicardipine. Simultaneous administration of PK 11195 and nicardipine abolished almost all the peripheral vasodilating effects of both drugs. This finding, which was not related to a pharmacokinetic interaction between PK 11195 and nicardipine, demonstrates that in humans a functional antagonism develops between these two drugs at the vascular level.

Adult↗
PubMed1989

Relationship between mixed venous oxygen saturation and cardiac index in patients with chronic congestive heart failure.

The use of mixed venous oxygen saturation (SvO2) in patients with chronic congestive heart failure (CHF) has been advocated to analyze the action of therapy on cardiac index (CI). To evaluate the relationship between CI and SvO2, ten CHF patients (mean age 65 years) were studied before and one, two, three, four (T4), six, eight and 24 hours after oral administration of an angiotensin converting enzyme (ACE) inhibitor (perindopril, 4 mg). At T4, a 12 percent increase in CI (p less than 0.01) was associated with a 16 percent decrease in arteriovenous oxygen difference (p less than 0.01), a 13 percent increase in mixed venous oxygen pressure (PvO2) (p less than 0.01), and a 9 percent increase in SvO2 (p less than 0.05) with no significant change in arterial oxygen pressure. There was no correlation between CI and SvO2 (r = 0.22) and between CI and PvO2 (r = 0.23). Individual analyses were performed and patients were divided into two groups based on CI versus SvO2 r value; group 1, n = 6, r greater than 0.65 (0.65-0.90), group 2, n = 4, r less than 0.65 (0.14-0.20). The lack of correlation in group 2 was due to a drug-dependent increase in oxygen consumption (VO2) +18 percent vs -3 percent in group 1 (p less than 0.05) associated with a lack of increase in PvO2 +3 percent vs +14 percent in group 1 (p less than 0.05) despite a similar increase in oxygen availability +19 percent versus +16 percent. It was concluded that (1) a correlation between CI and SvO2 is not found in every patient with CHF; (2) the lack of correlation in four out of our ten patients was due to an associated and significant increase in CI and VO2 in group 2; (3) group 2 patients probably had an important oxygen debt before treatment; (4) SvO2 cannot be used instead of CI to determine the hemodynamic consequences of the use of cardiovascular drugs.

Administration, Oral↗
PubMed1989

[Non-invasive regional and cardiac output determination in healthy volunteers. Predictive value].

The effects of nifedipine (20 mg), propranolol (80 mg), the nifedipine (20 mg) + propranolol (80 mg) combination and a placebo on cardiac [heart rate (HR), cardiac output (CO, Doppler determination)] and systemic [mean arterial pressure (MAP), systemic vascular resistance (SVR)] and regional hemodynamic [brachial blood flow (BBF) and arterial diameter (BAD) (pulsed Doppler), forearm vascular resistance (FVR)] parameters were investigated during the 3 hours following their random administration in a double blind and cross over study performed in 6 healthy subjects. At their peak effects, (a) nifedipine decreased SVR (-17 p. 100, p less than 0.01), increased HR (+ 12p. 100, p less than 0.001) and CO (+ 18 p. 100, p less than 0.001), did not change MAP and increased BBF (+31 p. 100, p less than 0.001) with a vasodilating effect which affected both large and small arteries; (b) propranolol decreased HR (-14 p. 100, p less than 0.05) and CO (-25 p. 100, p less than 0.01), increased SVR (+25 p. 100, p less than 0.01), did not change MAP and decreased BBF (-28 p. 100, p less than 0.05) with a vasoconstrictor effect which affected both large and small arteries; (c) in the nifedipine-propranolol combination, nifedipine neutralized propranolol-induced systemic and regional vasoconstrictor effects while propranolol antagonized nifedipine-induced increases in HR and CO. Thus, the favorable synergistic effects of the nifedipine-propranolol combination in hypertensive patients could be demonstrated in healthy subjects inasmuch as MAP was decreased and peripheral vascular blood flows were preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Comparison of the effects of Bay K 8644 and aortic constriction on regional myocardial blood flow and function in canine nonischemic and ischemic myocardium.

The effects of Bay K 8644, aortic constriction, and a placebo on regional myocardial blood flows (RMBFs) and contractile function (RCF) were compared in three groups of open-chest anesthetized dogs during coronary stenosis. Bay K 8644 was investigated in two doses: 0.1 micrograms/kg, which exhibited no systemic hemodynamic effect, and 1 microgram/kg, which significantly increased arterial pressure. Aortic constriction was performed to raise afterload to the same extent as Bay K 8644 1 microgram/kg. As compared with placebo, Bay K 8644 0.1 microgram/kg, significantly increased coronary resistance, decreased RMBFs without changing RCF in nonischemic myocardial zones, and affected neither RMBFs nor RCF in ischemic zones. In nonischemic myocardium, Bay K 8644 1 microgram/kg increased RMBFs without affecting RCF, whereas aortic constriction did not modify RMBFs but decreased RCF. In ischemic myocardium, both Bay K 8644 1 microgram/kg and aortic constriction increased RMBFs but did not affect RCF. Thus, the low dose of Bay K 8644 exerts a direct and selective coronary vasoconstrictor effect that has no deleterious consequences on nonischemic RCF. Despite this intrinsic coronary vasoconstrictor effect, the high dose of Bay K 8644 increases RMBFs and maintains RCF in both ischemic and nonischemic zones in relation with the drug-induced increases in coronary perfusion pressure (both zones) and in contractility (nonischemic zones).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Peripheral haemodynamic effects of perindopril compared in patients with congestive heart failure and in normal volunteers.

The effects of perindopril, 4 mg orally, on brachial artery blood flow and diameter (pulsed Doppler) and on forearm vascular resistance were investigated and compared in six normal subjects and 10 congestive heart failure patients (New York Heart Association class III or IV). Pre-drug values of brachial artery blood flow and diameter were significantly lower in patients with congestive heart failure than in normal subjects, the reverse being true for forearm vascular resistance. In normal subjects perindopril increased brachial artery blood flow and decreased forearm vascular resistance, while in patients with congestive heart failure the same effects were observed but they were more pronounced and brachial artery diameter was increased. In patients with congestive heart failure, when perindopril effects were maximal, brachial artery blood flow remained below the baseline values of normal subjects but brachial artery diameter was normalized. Finally, there was a correlation between the drug-induced decrease in forearm vascular resistance and basal plasma noradrenaline values in all subjects taken together. These results indicate that: (1) the renin-angiotensin system plays a major role in vasoconstriction in patients with congestive heart failure; (2) this vasoconstriction affects both large arteries and arterioles; (3) perindopril is able to considerably improve peripheral haemodynamics in congestive heart failure; and (4) this improvement is linked to the initial sympathetic tone.

Adult↗
PubMed1987

Pharmacokinetics, converting enzyme inhibition and peripheral arterial hemodynamics of ramipril in healthy volunteers.

The effects of a 10 mg dose of ramipril, a new angiotensin I converting enzyme (ACE) inhibitor, on systemic blood pressure, heart rate, brachial artery blood flow, brachial artery diameter, carotid artery blood flow, carotid artery diameter, forearm vascular resistance, plasma ACE and renin activities and plasma aldosterone were investigated. Ramipril's effects in 6 healthy volunteers on a normal sodium diet were compared with those of placebo over a 24-hour period after oral drug intake in an open cross-over trial. Ramipril inhibited plasma ACE activity, an effect that peaked at 3 to 4 hours and persisted up to at least 24 hours. Plasma renin activity increased from 4 to 12 hours after drug intake and plasma aldosterone was slightly decreased. Systemic blood pressure in the supine position was slightly decreased between 6 and 8 hours after drug intake but heart rate remained unaffected. Ramipril significantly increased brachial artery blood flow, brachial artery diameter and carotid artery blood flow and decreased forearm vascular resistance between 3 and 8 hours after drug administration. These peripheral arterial vasodilating effects were more marked in the muscular resistance vessels and affected both large arteries and arterioles in the brachial vascular territory. A correlation was found between the log of plasma concentrations of ramipril diacid metabolite and the drug-induced plasma ACE activity inhibition and increase in brachial artery blood flow. There was also a correlation between these 2 latter effects. A plasma ACE activity inhibition of 80% was required to induce significant increases in brachial artery blood flow and carotid artery blood flow.

Adult↗
PubMed1987

Arterial and venous effects of verapamil in normal volunteers.

1. The effects of verapamil (120 mg orally) and a placebo on arterial pressure, heart rate, PR interval, arterial flows and diameters of the brachial and carotid arteries (pulsed Doppler technique), forearm vascular resistance, and venous diameter and compliance (cutaneous microstrain gauge and plethysmography) have been compared over a 10-hr period in six healthy volunteers during a double-blind and cross-over study. 2. Verapamil reduced diastolic blood pressure by approximately 10 mm Hg, did not affect heart rate and increased PR interval by approximately 15%. 3. Verapamil significantly increased brachial and carotid arterial blood flows by 56% (P less than 0.01) and 16% (P less than 0.05), respectively, but the diameters of these vessels were not significantly modified (+7 and +4%, respectively, NS). Forearm vascular resistance decreased by 40% (P less than 0.01), indicating that verapamil preferentially dilates small arteries. All these effects peaked at 2 h after drug intake and lasted for 6 h. 4. Verapamil increased hand dorsal vein diameter and flow by 95% (P less than 0.05) and 80% (P less than 0.05), respectively, from 2 to 4 h after drug intake but venous compliance, assessed by the venous diameter/venous flow ratio, was not significantly modified (from 0.71 to 0.69, NS), thus indicating that veins are not directly affected by this drug.

Adult↗
PubMed1987

Perindopril, converting enzyme blockade, and peripheral arterial hemodynamics in the healthy volunteer.

The effects of three doses (4, 8, and 16 mg) of perindopril, a new angiotensin I converting enzyme inhibitor, on systemic blood pressure, heart rate, brachial and carotid artery flow and diameter (assessed by the pulsed Doppler technique), forearm vascular resistance, plasma converting enzyme and renin activities, and plasma aldosterone were investigated in the normal volunteer and compared with those of a placebo over a 24-h period following oral drug intake in a double-blind, crossover trial. Perindopril dose-dependently decreased plasma converting enzyme activity, an effect that peaked at 3-4 h and persisted up to at least 48 h. Plasma renin activity increased for 12 h and plasma aldosterone was slightly decreased. Systemic blood pressure and heart rate were not drug-affected but perindopril dose-dependently augmented brachial and carotid artery flow, indicating an increase in peripheral arterial compliance. These vasodilating effects, which lasted up to 10 h after drug intake, affected both large arteries and arterioles, the latter being more sensitive, however, and were more marked in the muscular resistance vessels.

Adult↗
PubMed1986

[Peripheral hemodynamic and biological effects of perindopril in the healthy subject. Dose-effect relationship].

The effects of three doses of perindopril (4.8 and 16 mg), a new angiotensin I-converting enzyme inhibitor, and of a placebo on systemic blood pressure, heart rate, brachial artery flow and diameter, forearm vascular resistance and the renin angiotensin system biological parameters (plasma converting enzyme activity PCEA, renin activity PRA and aldosterone PA) were compared during a double-blind cross-over study performed in six healthy volunteers. Perindopril dose-dependently inhibited PCEA, increased PRA, augmented brachial artery flow and diameter and decreased forearm vascular resistance, whereas it did not affect systemic blood pressure and heart rate. The perindopril-induced increase in brachial artery flow was related (a) at the low dose to the sole arteriolar and (b) at the two highest doses to both arteriolar and large vessels dilatation. Finally, during the ten first hours following drug intake, there was a significant correlation between perindopril-induced PCEA inhibition and brachial artery flow increase.

Adult↗
PubMed1985

Beta-adrenoceptor blocking effects and plasma levels of bornaprolol and propranolol in man.

The beta-adrenoceptor blocking effects and pharmacokinetics of bornaprolol (FM 24), a new beta-adrenoceptor blocking agent, have been compared with those of propranolol and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate, systolic and diastolic blood pressures and peak expiratory flow rate were measured at rest and at the end of 3 min vigorous exercise on a bicycle ergometer, before and 2,24 and 48 h after single oral doses of bornaprolol (120, 240 and 480 mg) and propranolol (40, 80 and 160 mg). Plasma renin activity at rest and the plasma concentrations of the two drugs were determined. Bornaprolol significantly reduced resting heart rate, dose-dependently lowered exercise-induced tachycardia and decreased peak expiratory flow rate and plasma renin activity. In addition, exercise-induced tachycardia was significantly reduced by bornaprolol up to 48 hours after drug intake (pharmacodynamic half-life approximately 63-86 h) and there was a correlation between this reduction and the log plasma bornaprolol concentration over the 48-h period. Thus, bornaprolol behaved in man as a non-cardioselective and long-lasting beta-adrenoceptor blocking drug, probably devoid of intrinsic sympathomimetic activity.

Adult↗
PubMed1984

Attenuation by diltiazem of arterial baroreflex sensitivity in man.

The effect of oral diltiazem 120 mg, on the responses to baroreflex activation and deactivation by phenylephrine and nitroglycerin, respectively, were investigated in normotensive subjects, with simultaneous measurement of plasma catecholamine levels. Diltiazem significantly reduced the tachycardia induced by bolus injections of nitroglycerin and abolished the concomitant increase in plasma noradrenaline. It also significantly decreased the bradycardiac response to phenylephrine infusion. Diltiazem reduced, although not significantly so, the bradycardia induced by boluses of phenylephrine. The overall reduction in baroreflex sensitivity, which might contribute to the limited tachycardiac effect of diltiazem in man, is consistent with the drug-induced attenuation of the sympathetic and also of the parasympathetic components of the baroreceptor reflex.

Adolescent↗
PubMed1984

Nicardipine: pharmacokinetics and effects on carotid and brachial blood flows in normal volunteers.

The effects of nicardipine, 20 mg, three times daily, nicardipine slow release, 30 mg, twice daily and a placebo on brachial and carotid arteries diameters and flows have been investigated by the pulsed Doppler technique during a single blind and cross-over study performed in six healthy volunteers. Simultaneously, nicardipine plasma levels and relative bioavailability were determined. Nicardipine significantly increased brachial and carotid arteries diameters (by 16 and 10% respectively) and flows (by 60 and 35% respectively). These effects peaked after 4 h and lasted no longer than 6 h. Forearm vascular resistance was significantly decreased. Hence nicardipine dilated both large and small arteries. Nicardipine slow release elicited the same effects on brachial and carotid arteries diameters and flows as nicardipine. These effects peaked at 6 h and lasted up to 10 h. Although the profiles of the pharmacodynamic effects and of the kinetics of nicardipine were almost parallel in each individual after administration of both nicardipine formulations, there was no correlation between the nicardipine plasma relative bioavailability and its effects on brachial and carotid arteries blood flows when considering all subjects together.

Adult↗
PubMed1984

Influence of heart rate on the effects of prenalterol on regional myocardial blood flow and function during coronary stenosis in dogs.

The effects of prenalterol, a selective beta 1-adrenoceptor agonist with potent cardiac positive inotropic properties have been investigated on regional myocardial blood flow (RMBF) (microspheres) and contractile function (ultrasonic crystals) during partial circumflex coronary artery stenosis in 8 open-chest anaesthetized dogs. Prenalterol was investigated at two intravenous doses: 5 micrograms kg-1, which increased myocardial contractility (dP/dt max: +29%) more than heart rate (+12%, up to 150 beats min-1) and 20 micrograms kg-1 which induced almost similar increases in contractility (+35%) and heart rate (+31% up to 175 beats min-1). The induced modifications of regional flow and function were then compared to those produced in another series of 6 dogs by atrial pacing at 150 and 175 beats min-1 respectively. Prenalterol significantly increased RMBF and segment length (SL)-shortening in a dose-dependent manner in the nonischaemic zone. In the ischaemic zone, RMBF was maintained and SL-shortening increased with prenalterol, 5 micrograms kg-1 whereas both RMBF and contractile function were severely decreased with prenalterol, 20 micrograms kg-1. Atrial pacing had almost no effect on RMBF and SL-shortening in the nonischaemic zone. In the ischaemic zone, atrial pacing rate-dependently decreased both RMBF and SL-shortening. Thus, a significant increase in contractility, associated with little tachycardia (prenalterol, 5 micrograms kg-1), induces beneficial effects on RMBF and function in both the nonischaemic and ischaemic myocardium. In contrast, a strong tachycardia, whether accompanied by positive inotropic effects (prenalterol, 20 gig kg-') or not (atrial pacing at 175 beats min-1) induces deleterious effects on RMBF and cardiac function in the ischaemic myocardium.

Adrenergic beta-Agonists↗
PubMed1983

Effects of propranolol on regional myocardial blood flow and function during severe coronary stenosis in dogs.

The effects of propranolol alone or associated with atrial pacing were studied on regional myocardial blood flows (RMBF) and regional contractility (sonocardiometry) in non-ischemic, moderately and severely ischemic areas of the canine myocardium. In non-ischemic areas, propranolol reduced both epicardial and endocardial flows, increased the endo/epi ratio and decreased regional contractility. The reductions in subendocardial flow and function were correlated. In moderately and severely ischemic areas, propranolol increased subendocardial flow, reduced subepicardial flow, increased the endo/epi ratio and preserved or even slightly improved regional contractility. There was a good correlation between the propranolol-induced protective effects on regional contractility and the drug-induced increase in subendocardial flow since under atrial pacing subendocardial flow no longer increased and regional function dropped dramatically.

Animals↗