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C Thuillez

Publications and source records attributed to C Thuillez.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Role of nitric oxide in flow-dependent vasodilation of human peripheral arteries in vivo].

Experiments performed in isolated arteries or in animals suggested that flow-dependent dilatation of conduit arteries is mediated through the release of endothelium-derived nitric oxide (NO). The present study was designed to assess whether NO also contributes to flow-dependent dilatation of conduit arteries in humans. Radial artery internal diameter was measured in 8 healthy volunteers (age 22 +/- 1 years), using a transcutaneous A-mode echo-tracking system, coupled to a Doppler device for the measurement of radial blood flow. A catheter was inserted in the brachial artery for measurement of arterial pressure and infusion of the L-arginine analogue NG-monomethyl L-arginine (L-NMMA (8 mumol/min for 7 min, infusion rate 0.8 ml/min). Flow-dependent dilatation was evaluated before and after L-NMMA as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3 min distal cuff occlusion). Release of the occlusion induced a significant increase in radial blood flow (from 27 +/- 4 to 82 +/- 13 ml/min; p < 0.01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.77 +/- 0.13 to 2.85 +/- 0.13 min; p < 0.01), without any change in heart rate or arterial pressure. L-NMMA induced a significant decrease in basal forearm blood flow (from 27 +/- 4 to 14 +/- 2 ml/min; p < 0.05), without affecting basal radial artery diameter, heart rate or arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Reading of the trials in cardiac insufficiency; preliminary and experimental studies (phases I-II)].

In addition to general consideration concerning the justification and methodology of therapeutic trials, the interpretation of the results of evaluation of new products in the field of cardiac failure poses a number of problems. In experimental studies in the animal, the choice of model of cardiac failure, the mode of evaluation of the parameters and the justification of the choice of dosage studied require particular attention. In preliminary clinical trials (Phases I and II), the choice and number of subjects, the dosage and methodology both for recensement and interpretation of data, are factors which influence the quality of the information obtained. When these studies have been completed, the decisions whether to develop the product and the recommended dosage have to be taken. The importance of these decisions justifies the extreme attention which has to be taken in the elaboration of these studies and in their interpretation.

Animals↗
PubMed1994

A comparison of the hemodynamic effects of urapidil, prazosin, and clonidine in healthy volunteers.

Urapidil is an antihypertensive agent known to have central 5HT1A agonistic properties in addition to alpha-1 blocking effects. To assess the importance of these effects, we compared the hemodynamic effects of a single oral dose of urapidil (U, 60 mg) with those of prazosin (Pr, 2 mg), clonidine (Cl, 0.15 mg), and placebo (Pl), at rest, during orthostatic tilt, and during submaximal graded bicycle exercise tests, in a double-blind randomised crossover study in 24 healthy male volunteers. The variables studied were heart rate, mean blood pressure, cardiac index by bioimpedance, systemic vascular resistance index (SVRI), and plasma norepinephrine. Baseline values before drug administration were identical. At rest, during tilt, and during identical exercise, compared to placebo, urapidil and prazosin caused similar decreases in SVRI, with a smaller increase in HR after urapidil than after prazosin (p < 0.01), and without any difference in BP. Both drugs increased norepinephrine in a similar manner. In contrast, clonidine decreased blood pressure (p < 0.01) and norepinephrine (p < 0.01) with no difference in heart rate or SVRI. In conclusion, at rest, during tilt and during exercise, urapidil and prazosin have similar vasodilating effects, but the sympathetic stimulation is less and the parasympathetic stimulation greater after urapidil than after prazosin, probably indicating a centrally acting effect of urapidil. However, the sympathoinhibitory effect of urapidil is less marked than that of clonidine.

Adult↗
PubMed1993

Arterial hemodynamics and cardiac effects of enoximone, dobutamine, and their combination in severe heart failure.

The acute systemic and regional hemodynamic effects of dobutamine (5, 10, and 15 micrograms/kg/min intravenously), of enoximone (1, 1.5, and 2 mg/kg intravenously), and of the dobutamine-enoximone combination were compared in eight patients with severe congestive heart failure. Dobutamine and enoximone similarly and dose-dependently increased cardiac index and decreased systemic vascular resistance, right atrial pressure, and mean capillary wedge pressure. Dobutamine, but not enoximone, increased heart rate after 10 and 15 micrograms/kg/min. The combination of the two drugs caused a greater increase in cardiac index and a greater decrease in total peripheral resistance than did each drug alone. In the forearm vascular bed, brachial blood flow and brachial artery diameter were increased by enoximone significantly and dose-dependently and by dobutamine only at 5 micrograms/kg/min. Finally, the combination of the two drugs increased brachial blood flow but not brachial artery diameter to a larger extent than enoximone alone. Hepatosplanchnic and renal blood flows were not altered by any of the treatments. These results indicate that (1) enoximone exerts a significantly greater muscular vasodilator action than dobutamine; (2) the dobutamine-enoximone combination potentiates the systemic and brachial vasodilator effects of each drug; and (3) high doses of dobutamine (10 and 15 micrograms/kg/min) improve hemodynamics through their positive inotropic and chronotropic effects, whereas at low doses (5 micrograms/kg/min) a peripheral vasodilation also contributes.

Adult↗
PubMed1993

Regional hemodynamic effects of perindopril in congestive heart failure.

The onset of heart failure is associated with complex neurohumoral, cardiac, and vascular changes. These disorders partly explain that, in this situation, regional distribution of blood flows is hardly modified with stability or increase in heart and brain flows and impairement of limb, renal, and splanchnic blood flows. Using the bidimensional Doppler technique to measure brachial blood flow and diameter and standard clearance techniques to determine renal and hepatic blood flows, we studied the effects of perindopril, a long-lasting angiotensin-converting enzyme inhibitor, on regional hemodynamics. We demonstrated that perindopril produces a very marked increase in forearm and kidney flows but a very minor increase in the hepatosplanchnic territory, resulting in a regional distribution of cardiac output that favors the renal and musculocutaneous territories. This mechanism of action might be an important contribution to clinical improvement observed with perindopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Ischaemic preconditioning is not mediated by oxygen derived free radicals in rats.

OBJECTIVE: Although several studies have shown that ischaemic preconditioning greatly limits myocardial infarct size in the rat, the mechanisms of the beneficial effect of preconditioning in this species are not known. Experiments in dogs and rabbits have suggested that this effect could be related in part to the production of oxygen derived free radicals, as free radical scavengers partially prevent the limitation of infarct size induced by preconditioning. This study was designed to assess the contribution of oxygen derived free radicals in the infarct size limiting effects of preconditioning in rats, using the cell diffusible free radical scavenger N-2-mercaptopropionyl glycine (MPG). METHODS: Open chest rats underwent 20 minutes of coronary occlusion followed by one hour of reperfusion. Preconditioning was elicited by three cycles of five minutes ischaemia and five minutes reperfusion. MPG (20 mg.kg-1) was infused for 60 minutes starting 30 minutes before preconditioning. Control hearts (with or without MPG) were treated identically but without ischaemic preconditioning. Area at risk and infarct size were determined by India ink injection and triphenyltetrazolium chloride stain, with computerised analysis of enlarged sections after colour video acquisition. RESULTS: During preconditioning, reperfusion after the first episode of ischaemia was associated with a high occurrence of severe ventricular arrhythmias, and this was reduced by MPG. Preconditioning, however, reduced arrhythmias and mortality during subsequent episodes of ischaemia and reperfusion. In the absence of MPG, preconditioning greatly limited infarct size (from (mean (SEM)) 59.8(3.9)% to 1.2(0.6)% of the area at risk; p < 0.01). MPG alone did not affect infarct size (60.5(6.1)%), and did not modify the infarct size limiting effect of preconditioning (infarct size: preconditioning 1.2(0.6)%; preconditioning + MPG 2.9(1.2)%. CONCLUSIONS: Preconditioning greatly reduced infarct size, and this was not affected by MPG. These experiments suggest that production of oxygen derived free radicals does not contribute to preconditioning in the rat heart.

Animals↗
PubMed1993

[Mechanical adaptation of muscular arteries to acute increase of blood pressure in man. Contribution of the measurement of arterial wall thickness].

Although it was usually admitted that hypertension is associated with a reduction in conduit artery compliance and distensibility, recent experiments using newly developed high precision echo-tracking devices allowing simultaneous, non-invasive measurements of blood pressure and arterial diameter have suggested that compliance and distensibility, when calculated at equal transmural pressure, could indeed be maintained, or even increased, in hypertensive subjects. Such a maintained arterial compliance could be explained best by a decrease in wall stress despite the increase in arterial blood pressure, through either an increase in wall thickness or a decrease in arterial wall elastic modulus. Thus, the goal of the present study was to assess the role of the changes in these determinants of vessel compliance in the arterial response to an acute increase in arterial pressure in 7 healthy volunteers. Arterial pressure (AP, Finapress) as well as right radial artery internal diameter and wall thickness (Echo-Tracking, NIUS 2, Asulab) were measured continuously before and after a 2 min cold pressor test (CPT). The following parameters were then calculated at fixed (105 mmHg) pressure from the pressure/diameter curve: compliance (mm2/mmHg) and distensibility (mmHg-1) mid-wall stress (dynes/cm2) and incremental elastic modulus (dynes/cm2). During CPT, mean AP increased (from 83 +/- 4 to 106 +/- 8 mmHg; p < 0.01), compliance distensibility; and mean internal diameter (mm) decreased, mean wall thickness (mm) increased, whereas wall stress and elastic modulus remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

[Systemic and regional hemodynamic effects of a new angiotensin converting enzyme and neutral endopeptidase mixed inhibitor, alatriopril, in the dog].

Alatriopril is a dual inhibitor of two cell surface metallopeptidases which play important roles in the regulation of arterial blood pressure and renal function: the angiotensin I converting enzyme (ACE) which catalyses transformation of angiotensin I to angiotensin II, and the neutral endopeptidase (NEP; EC 3.4.24.11; atriopeptidase), responsible for the degradation of the atrial natriuretic factor (ANF). The purpose of the present study was to evaluate the systemic and regional hemodynamic effects of alatrioprilat, the active part of alatriopril, in 6 anesthetized, closed-chest beagle dogs instrumented for the measurement of arterial pressure (aortic catheter), cardiac output (thermodilution), as well as femoral and renal artery flows (Doppler). Animal received alatrioprilat at the doses of 1 and 10 mg/kg (i.v. bolus). Hemodynamic parameters were measured at baseline, then 15, 30, 45 and 60 min after administration of each dose. In addition, plasma ANF and ACE activity were determined at baseline and 30 min after administration. At the dose of 1 mg/kg, alatrioprilat dit not induce marked hemodynamic effects, except a transient hypotension which appeared within the first 10 min after administration and lasted less than 10 min. Neither plasma ANF nor angiotensin converting enzyme activity were affected by this dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1992

Systemic and regional hemodynamic effects of zabicipril in healthy volunteers.

The effects of two oral doses of zabicipril, a new angiotensin converting enzyme inhibitor, on systemic (arterial pressure, heart rate, and cardiac output) hemodynamic parameters and regional (brachial, carotid and femoral arteries' diameters and flows) hemodynamic parameters and on biologic (plasma-converting enzyme and renin activities, catecholamines, and atrial natriuretic factor) parameters were noninvasively investigated and compared with those of a placebo in a double-blind crossover study performed in six healthy male volunteers. Although it did not affect the systemic hemodynamic parameters, zabicipril induced a strong peripheral vasodilation, significantly reducing brachial, carotid, and femoral resistances and increasing the corresponding blood flows from 3 or 4 1/2 hours to 9 hours. This vasodilation affected only the arterioles, not the large arteries, and resulted in a redistribution of cardiac output toward the three regional vascular beds. Zabicipril induced an early, potent, and long-lasting converting enzyme inhibition. Furthermore, zabicipril did not affect plasma catecholamines and atrial natriuretic factor.

Analysis of Variance↗
PubMed1992

Effects of cardiovascular drugs on oxygen consumption/oxygen delivery relationship in patients with congestive heart failure.

The oxygen consumption (VO2)/oxygen delivery (DO2) relationship was analyzed in ten patients with severe congestive heart failure (CHF) and normal blood lactate levels. First dobutamine and then enoximone, after a washout period, were administered to each patient to increase cardiac output by at least 15 percent. Similar increases in DO2 were obtained with both drugs: from 285 +/- 46 to 393 +/- 87 ml/min/m2 for dobutamine, and from 285 +/- 54 to 392 +/- 99 ml/min/m2 for enoximone. However, while VO2 did not change (132 +/- 24 vs 132 +/- 21 ml/min/m2) (VO2/DO2 independency) with a dobutamine infusion (mean dose of 10 +/- 2 micrograms/kg/min), a significant increase in VO2 from 134 +/- 22 to 157 +/- 21 ml/min/m2 was observed with a bolus infusion of enoximone (mean dose of 1.7 +/- 0.5 mg/kg). These results, observed in patients with CHF without patent oxygen debt, suggest that an artefactual VO2/DO2 dependency might be induced by the cardiovascular drug used to elevate DO2, probably because of a drug-induced oxygen demand increase.

Acute Disease↗
PubMed1992

Use of ultrasonic and microsphere techniques to evaluate regional aspects of vasodilator therapy in myocardial ischaemia, arterial hypertension and heart failure.

PURPOSE: To review regional aspects of vasodilator therapy in myocardial ischemia, arterial hypertension and heart failure. DATA IDENTIFICATION: Results were obtained from experiments (1) performed either in experimental animals or in human volunteers or patients; (2) using either ultrasonic or microsphere techniques; (3) on the effects of different drug classes, including angiotensin converting enzyme inhibitors, calcium antagonists, potassium channel openers and nitrates; and (4) on the arterial and arteriolar vasodilating effects of different drug classes. CONCLUSIONS: The regional vasodilator effects, both arteriolar and arterial, of the major classes of drugs used in the treatment of coronary insufficiency, arterial hypertension and cardiac failure appear to be heterogenous. This heterogeneity is seen with a given drug in different vascular beds; within a class of drugs in a single vascular region; and between the regional vasodilator profiles of different classes of drugs. From the clinical point of view, the consequences of this heterogeneous vasodilation may be either positive (increase in flow, favourable redistribution of flow) or negative (steal phenomenon, opening of shunts).

Animals↗
PubMed1991

Non invasive study of systemic and regional haemodynamic and cardiac effects of a new calcium antagonist, SR 33557, in healthy volunteers.

The systemic and regional haemodynamic and cardiac effects of two oral doses (100 and 300 mg) of a new sulphone-indolizine calcium antagonist SR 33,557 (SR) and a placebo were non invasively investigated in a double-blind, cross-over study in 6 healthy male volunteers. Arterial pressure, heart rate, cardiac output, brachial and carotid artery diameters and flows and PR and QT intervals were studied. Stroke volume, total peripheral and forearm vascular resistance, regional cardiac output distribution indices and corrected QT intervals were calculated. SR did not produce any significant modification in systemic haemodynamics, although arterial pressure and cardiac output tended to decrease slightly after 300 mg. In contrast, at the regional level, ST produced strong vasodilatation and significantly increased brachial and carotid blood flow. SR-induced vasodilation affected only the arterioles, as shown by a significant decrease in forearm vascular resistance, but not the large arteries, as shown by lack of change in the brachial and carotid artery diameters. SR-induced vasodilation preferentially affected the brachial rather than the carotid vascular bed, resulting in a redistribution of cardiac output towards the musculo-cutaneous territories. SR caused a marked and long-lasting decrease in heart rate, but it did not affect the auriculo-ventricular conduction time.

Adult↗
PubMed1991

Arterial vasodilating profile and biological effects of pinacidil in healthy volunteers.

1. The effects of pinacidil (25 mg, sustained release formulation) a) on systemic (arterial pressure, cardiac output) and regional (brachial and carotid arteries' diameters and flows) haemodynamics (pulsed Doppler techniques), b) on sympathetic (plasma noradrenaline) and renin-angiotensin (plasma renin activity) systems, and c) on atrial natriuretic factor have been investigated and compared with those of a placebo during the 12 h period following oral administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. Simultaneously, the plasma levels of pinacidil and of its active metabolite, pinacidil N-oxide, were determined. 2. As compared with placebo, pinacidil decreased systemic vascular resistance and arterial blood pressure but cardiac output was not modified. 3. Pinacidil significantly increased brachial and carotid arteries' diameters (by 7 and 8% respectively) and flows (by 60 and 17% respectively) and decreased forearm vascular resistance (by 43%). Thus, pinacidil dilates both large and small arteries, increases large vessels' compliance and redistributes blood flow towards the muscular vascular bed. These effects peaked at 4 h and their duration at the brachial level was 8 h. 4. Pinacidil administration resulted in a stimulation of both sympathetic (increases in heart rate and plasma noradrenaline) and renin-angiotensin systems, and induced a transient increase in atrial natriuretic factor. 5. The duration of pinacidil haemodynamic effects at the brachial level is consistent with the pharmacokinetic data which show that pinacidil and pinacidil N-oxide plasma levels almost plateaued between 3 and 8, and 2 and 8 h respectively after oral administration of the sustained release formulation used.

Adult↗
PubMed1991

Angiotensin converting enzyme inhibition. Systemic and regional hemodynamics in rats and humans.

The systemic and regional hemodynamic effects of angiotensin I converting enzyme inhibitors (ACEIs) have been investigated using different experimental methods (pulsed Doppler, radioactive microspheres), either in rats (normotensive NT or genetically hypertensive SHRs) or in humans (healthy volunteers or patients with congestive heart failure CHF). All ACEIs decreased systemic vascular resistance but the profile of their peripheral vasodilating properties was heterogeneous. ACEI-induced vasodilation primarily affected the kidney in rats and in humans and this effect was accompanied by a strong and consistent increase in renal blood flow. This occurred even at non-hypotensive doses in SHRs and CHF patients and resulted in a favorable redistribution of cardiac output towards the kidney. In the muscular vascular bed, ACEIs also decreased local vascular resistance in rats and in humans, whether normotensive or hypertensive. In humans, this vasodilation affected both the arterioles and the large conductance vessels, more markedly in CHF patients than in normotensive subjects. Muscular blood flow was increased and a favorable redistribution of cardiac output towards the muscle occurred. Cerebral blood flow in SHRs and carotid blood flow in humans were augmented, whereas hepatosplanchnic blood flow was increased in rats but not modified in humans. There was no major difference between the regional vasodilating profiles of the different ACEIs, but captopril was somewhat less active at the muscular level. In conclusion, ACEI-induced regional vasodilation is heterogeneous, preferentially affecting the kidney and the muscle. In the latter, both arterioles and large conductance vessels are dilated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

[Mechanisms and consequences of changes of the vasomotor activity in cardiac insufficiency].

Changes in vasomotor tone in cardiac failure are related to the severity of the cardiac failure. The causative factors include dysfunction of the baroreceptor reflex, abnormal stimulation of the normal physiological regulators of cardio-circulatory function such as the sympathetic nervous and the renin-angiotensin-aldosterone system, and certain local factors characteristic of cardiac failure such as salt and water retention at vascular wall and interstitial level or changes in the metabolism of certain tissues. These changes are variable according to the region perfused and their interaction results in preferential redistribution of blood flow to the coronary and cerebral circulations at the expense of other regions such as the splanchnic and cutaneous vessels. In addition, they play a key role in the adaptive peripheral mechanisms to left ventricular failure and to the modulation of the vascular effects of drug therapy. An improvement in our understanding of these mechanisms and their consequences is important from the physiopathological, prognostic and therapeutic points of view.

Cardiac Output↗
PubMed1990

Systemic and regional hemodynamic effects of perindopril in congestive heart failure.

The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right atrial pressure (-60%), and mean pulmonary capillary wedge pressure (-28%), whereas it significantly increased cardiac index (+ 12%). Brachial (+ 130%, pulsed Doppler technique) and renal (+ 34%) blood flows were also significantly increased whereas hepatic blood flow remained unchanged. Brachial flow/cardiac output and renal flow/cardiac output ratios increased significantly from 0.8 to 1.6 and from 13.2 to 16.5, respectively. The maximal decreases in forearm and renal (but not in systemic) vascular resistances were correlated with the basal plasma norepinephrine concentrations but not plasma epinephrine concentrations or plasma renin activity. We conclude that in severe heart failure (a) perindopril considerably improves systemic hemodynamics and exerts an inhomogeneous vasodilating effect, resulting in a redistribution of flows toward the forearm and renal territories, (b) norepinephrine is a major determinant of the arteriolar tone in these two vascular beds, and (c) the pulsed Doppler is a particularly suitable method to non-invasively detect and assess hemodynamic improvements in heart failure patients.

Administration, Oral↗