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Biomedical subjects

M Safar

Publications and source records attributed to M Safar.

At least 19 recordsLinked to original sources
PubMed1992

[Effects of aging on arterial function in man].

The structure of arteries changes with age. Gradual disappearance of elastic fibres facilitates dilatation of the arterial lumen and increase in length of the vessels. Simultaneously, the arterial wall becomes thicker, but it is often difficult to distinguish the changes due to ageing from those caused by atherosclerosis. These structural alterations result in a greater rigidity of the arteries, which can now be evaluated by non-invasive segmental methods. This shows that ageing does not have the same functional effects on wide-caliber elastic arteries and on middle-sized muscular arteries. The increase of systolic arterial pressure observed in the elderly is a consequence of structural and functional changes in the arterial system.

Aged↗
PubMed1992

Acute changes in forearm haemodynamics produced by cigarette smoking in healthy normotensive non-smokers are not influenced by propranolol or pindolol.

The aim of the present study was to examine the effect of cigarette smoking in healthy non-smokers on blood pressure and forearm haemodynamics after acute oral administration of non-selective beta-adrenoceptor blockers with and without intrinsic sympathomimetic activity, viz. pindolol 15 mg and propranolol 80 mg. A preliminary study was done to compare cigarette smoking and sham smoking to evaluate the time-course of the haemodynamic effects of cigarette smoking. The second experiment was then carried out in the same six volunteers, according to a double-blind randomized placebo-controlled crossover design, to evaluate the possible effect of pre-treatment with beta-adrenoceptor blockers on blood pressure, heart rate and forearm haemodynamics (forearm blood flow, brachial artery diameter and brachio-radial pulse-wave velocity) measured at baseline, during smoking and every five minutes up to 1 h afterwards. No major difference from placebo in blood pressure or forearm haemodynamics was found and pre-treatment with beta-blockers did not prevent the acute vascular effects of cigarette smoking.

Adult↗
PubMed1992

Rilmenidine: a novel approach to first-line treatment of hypertension.

Rilmenidine (RIL) is a novel antihypertensive drug selectively acting at the sites of imidazoline receptors. Compared with diuretics, beta-blockers, Ca2+ antagonists and angiotensin converting enzyme inhibitors, the four major groups recommended by the US Joint National Committee as first-line antihypertensive drugs, RIL appears to meet the same criteria of efficacy, safety, and acceptability. Rilmenidine dose-dependently decreases blood pressure (BP), acting as a vasodilator by decreasing vascular resistance through inhibition of the adrenergic nervous system, even while the BP changes due to standing and exercise. In comparison with placebo, RIL significantly decreased BP. In double-blind comparative trials versus first-line diuretics and beta-blockers, RIL normalized BP in approximately 60% patients, showing a similar efficacy to other drugs. In contrast with hydrochlorothiazide, RIL decreased total cholesterol and did not change plasma potassium levels. No tachyphylaxis was observed during long-term treatment. Central side effects, which have contributed to the limitation of the use of alpha 2-agonists as second- or third-line therapy for hypertension, were significantly less frequent with RIL than with clonidine or methyldopa. Indeed, the incidence of dry mouth and drowsiness during double-blind comparative trials versus clonidine and methyldopa was significantly lower with RIL. This absence of central side-effects was confirmed in double-blind comparative trials versus hydrochlorothiazide and atenolol. In contrast with clonidine, no sodium retention or weight gain were observed during chronic treatment with RIL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Arterial effects of salt restriction in hypertensive patients. A 9-week, randomized, double-blind, crossover study.

OBJECTIVE: To investigate the hemodynamic effects of a moderately low-salt diet in a 9-week, randomized, double-blind, crossover study in 20 hypertensive, ambulatory patients. METHODS: All subjects followed a 9-week, low-salt diet. During this period, they received capsules containing either lactose or salt in 4-week treatment periods, separated by a 1-week washout period. Hemodynamic and biological parameters were evaluated on the day of randomization and at the end of weeks 4 and 9. We defined a low-sodium diet (LSD) as a salt-restriction period with lactose capsules, and a normal-sodium diet (NSD) as a salt-restriction period with capsular salt supplementation. RESULTS: Blood pressure was significantly lower during LSD compared with NSD. This fall in blood pressure was associated with a decrease in peripheral resistance in carotid and forearm circulation. Brachial artery diameter was larger during LSD whereas carotid artery diameter remained unchanged. The changes in brachial artery were: (1) not related to blood pressure changes; (2) positively related to age, and (3) negatively correlated with baseline intracellular sodium content. CONCLUSIONS: These results suggest that moderate low-salt restriction is capable of decreasing blood pressure and peripheral resistance in carotid and forearm circulation. The increase in brachial, but not carotid, artery diameter following salt restriction suggests a difference in salt dependence among different arteries.

Adult↗
PubMed1992

Mechanism of nitrate-induced improvement on arterial compliance depends on vascular territory.

The link between arterial caliber and distensibility has been studied extensively, with conflicting results. As have other researchers, we previously showed evidence of an increase in arterial diameter and a decrease in arterial stiffness with use of nitrates at the site of the brachial artery (BA) and the aorta. Whether these results would apply to other large superficial arteries remained to be established. In the present study, by means of an original pulsed ultrasound echo-tracking system based on Doppler shift, we measured internal diastolic diameter and stroke change in diameter of the common carotid artery (CCA), the femoral artery, and the BA in patients with essential hypertension and determined the acute effects of administration of isosorbide dinitrate (ISDN 20 mg). Twenty untreated hypertensive patients entered this randomized, placebo-controlled, double-blind, parallel study. No significant change occurred during placebo. During ISDN therapy, blood pressure (BP) decreased significantly; cross-sectional compliance increased at the site of the CCA, the BA, and the common femoral artery (CFA). The increase in cross-sectional compliance was mainly due to an increase in internal diameter for CCA and to an increase in distensibility coefficient (DC) for BA. The pattern of cross-sectional compliance was intermediate for CFA. During ISDN therapy, the augmentation index of the CCA distension waveform was significantly reduced, whereas no change occurred during placebo, suggesting a reduction in wave reflection by nitrates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Arterial and antihypertensive effects of nitrendipine: a double-blind comparison versus placebo.

Arterial effects evaluated by carotid-femoral, brachial-radial, and femoral-tibial pulse wave velocity and antihypertensive effect evaluated by 24-h ambulatory blood pressure (BP) monitoring were measured in 17 hypertensive patients before and 24 h after once-daily nitrendipine (20 mg) administration. After a 15-day placebo period, a double-blind study of nitrendipine versus placebo was performed for 1 month. After nitrendipine dosing, BP measured by sphygmomanometer 24 h after the last drug intake showed a significant decrease as compared with the pretreatment period. Ambulatory BP mean values were also significantly decreased for systolic and diastolic BP (SBP, DBP). This decrease predominated during the day but was observed nocturnally only after 6 a.m. Twenty-four hours after the last tablet intake of nitrendipine, carotid-femoral and brachial-radial pulse wave velocities were significantly reduced, whereas femoral-tibial wave velocity was unchanged, indicating that markers of arterial rigidity might be substantially modified and that the modifications were partly unrelated to BP changes. The results provide evidence that in hypertensive subjects nitrendipine 20 mg given once daily for 1 month produces an arterial effect for 24 h, in association with BP reduction.

Adult↗
PubMed1992

Hemodynamic effects of carvedilol after acute oral administration in hypertensive and normal subjects.

Forearm hemodynamics using pulsed Doppler flowmetry were studied in nine healthy volunteers and 12 patients with mild-to-moderate hypertension before and after acute oral administration of the beta-blocking and vasodilating agent carvedilol. Both the 25- and the 50-mg dose produced a significant blood pressure reduction by comparison with placebo in normotensive and hypertensive subjects. Only the 50-mg dose caused a decrease in forearm vascular resistance in hypertensive subjects. The decrease disappeared after wrist occlusion. Although brachial artery diameter did not change, a significant decrease in tangential tension was observed. This study provides evidence that carvedilol produced arteriolar dilation within the forearm of hypertensive subjects in association with a decrease in brachial artery tangential tension.

Administration, Oral↗
PubMed1992

Increased systolic pressure in chronic uremia. Role of arterial wave reflections.

To assess the role of arterial wave reflections in the mechanism of systolic hypertension and altered pulsatile arterial dynamics in patients with end-stage renal disease (ESRD), 79 ESRD patients were compared with 73 age-matched control subjects with normal renal function and similar mean blood pressure. Wave reflections were investigated from the carotid pulse contour recorded by applanation tonometry using a Millar micromanometer-tipped probe. Wave reflections were quantified as the ratio (augmentation index, %) of the height of the late systolic peak to the total height of carotid pulse wave. Travel time of the reflected wave was timed from the foot of the pressure wave to the foot of the late systolic peak. Systolic and pulse pressure were increased in ESRD patients (p less than 0.001) and was not attributable to differences in left ventricular ejection pattern. The augmentation index was increased in ESRD patients (23.2 +/- 15.0 versus 9.8 +/- 15.6%; p less than 0.001) in association with a shorter travel time of reflected wave (109 +/- 24 versus 131 +/- 30 msec; p less than 0.001). Multiple regression analysis showed two principal factors associated (p less than 0.001) with the increase in augmentation index and shortened travel time of reflected wave: increased aortic pulse wave velocity and smaller stature with shorter body height in ESRD patients. The study points to the role of arterial wave reflections in the mechanisms producing alterations in pulsatile arterial dynamics in ESRD and is the first, through the mechanisms of early wave reflections, to show in humans that the increase in systolic and pulse pressures is associated with lesser body size.

Adult↗
PubMed1992

Effects of antihypertensive agents on carotid pulse contour in humans.

The aim of this study was to assess the influence of antihypertensive agents on arterial wave reflections (AWR) and carotid pulse pressure (PP) in humans. Twenty patients with hypertension (predominantly systolic) were studied. After one month of placebo therapy they were randomly assigned to atenolol (At) 50 mg/day or to nitrendipine (Ni) 40 mg/day. Carotid pressure waveform was recorded noninvasively by applanation tonometry using a Millar micromanometer-tipped probe. Arterial wave reflections were quantified as the ratio of the height of the late systolic peak (delta P) to the total height of carotid pulse pressure wave as an augmentation index (delta P/PP). Travel time of the reflected wave (delta tp) was timed from the foot of the pressure wave to the foot of the late systolic peak. Atenolol and Ni were equally effective in reducing sphygmomanometric brachial artery blood pressure (BP). Whereas At (p < 0.05) and Ni (p < 0.01) reduced the carotid PP, Ni (p < 0.01) but not At significantly reduced delta P/PP. Both agents increased the delta tp (p < 0.01) and decreased aortic PWV (p < 0.01). Nitrendipine was associated with a decrease in left ventricular ejection time (LVET) (p < 0.01), while At increased heart period (p < 0.01) and LVET. The LVET/delta tp ratio decreased after Ni (from 3.25 +/- 0.77 to 2.42 +/- 0.73; p < 0.01) but did not change after At. The study shows, that for the same effect on peripheral BP, Ni has a more pronounced effect on pressure wave in central arteries, resulting from an improvement in the timing between the ventricular ejection and AWRs.

Antihypertensive Agents↗
PubMed1992

[Absence of labetalol interference on urine metanephrine determination in hypertensive patients].

The dosage of urinary catecholamines and their metabolites is a main element of diagnosis in the research of a pheochromocytoma in patients with high blood pressure. The literature reports high values of these compounds in patients treated with labetalol (an alpha/beta-blocker). An analytical interference has been evoked to explain these misleading results, which have not been observed with other beta-blockers. The goal of this work was to look for this eventual analytical interference in the dosage of urinary metanephrine by reversed phase liquid chromatography coupled with electrochemical detection, in patients with high blood pressure. Eighteen hypertensive patients, 52 +/- 14 years old, were included in the study. In 8 patients, a dosage of metanephrine, normetanephrine and creatinine on a 24 hours urine sample was performed before (D1) and 24 hours after (D3) the prescription of labetalol (200 mg twice a day). In the other group, labetalol was not prescribed but dosage was made in the same conditions. Urinary excretion of these compounds (metanephrine+normetanephrine) divided by urinary creatinine was not modified in the treated group (0.16 +/- 0.08 vs 0.14 +/- 0.04), nor in the reference group (0.17 +/- 0.08 vs 0.17 +/- 0.08). This study shows that administration of labetalol in patients with essential hypertension does not interfere with urinary metanephrine and normetanephrine determination after 48 hours of treatment. This implies that research for a pheochromocytoma is possible in patients with hypertension and receiving labetalol, by using reversed phase liquid chromatography coupled with an electrochemical detector for the dosage of urinary metanephrine and normetanephrine.

Adrenal Gland Neoplasms↗
PubMed1992

[Nitrate derivatives and compliance of large arteries].

Nitrate derivatives are useful drugs because of their direct vasodilating properties even in the presence of abnormal endothelial function. This is particularly true of the great arteries, explaining the improvement in arterial compliance regularly observed. The corollary of this effect is an improvement in systolic blood pressure and arterial pulsatility with little change in mean arterial pressure. The improved systolic but unchanged mean blood pressures reduce myocardial systolic stress and ensure relative preservation of coronary perfusion pressure which is particularly important in the treatment of systolic hypertension of the elderly.

Blood Pressure↗
PubMed1992

[Non-invasive methods in the study of the elastic properties of the thoracic aorta. Effect of isosorbide dinitrate].

The role of the great arteries is to distribute and stock blood. Pulsatile discontinuous flow is transformed to a continuous flow system. The elastic properties of the aorta play a major role in these functions. It is generally agreed that changes in these elastic properties may lead to the development of left ventricular hypertrophy. The evaluation of the aorta has, until recently, depended on invasive hemodynamic and angiographic techniques. In addition, the measurement of pulse wave velocity, though useful, is a global and only an approximate method. Transoesophageal echocardiography (TEE) enables accurate measurement of the aortic diameter and its systolo-diastolic variations. The accuracy of these measurements has been validated in vitro and the reproducibility is much better than with previously used techniques. Previous studies have shown an improvement of the elastic properties of the great arteries with nitrate derivatives. In recent studies using TEE, isosorbide dinitrate caused dilatation of the descending thoracic aorta and thereby improved its elastic properties. The development of tonometry techniques in our department has resulted in the finding of excellent correlations between carotid and aortic pulse pressures measured non-invasively. The association of TEE and tonometry thereby provides a direct approach to the evaluation of aortic compliance. It has then become possible to study the effects of nitrate derivatives on the aortic compliance of elderly patients in whom it is the most reduced.

Aorta, Thoracic↗
PubMed1992

Potential role of the renal tubule in fixing the level of plasma sulfoconjugated catecholamines in the dog.

Plasma levels of sulfoconjugated catecholamines in human subjects and in dogs are usually much higher than those of native amines. Their origins and the mechanism(s) involved in fixing their plasma concentrations are not well known; however, several lines of clinical evidences indicate a major role for the kidney. Thus this study was undertaken to measure the renal fractional excretion--used as an overall index of kidney mechanisms involved in the handling of catecholamines and their sulfoconjugates in the dog--and to look for any possible relationships between plasma concentration and urinary excretion. This was carried out in 36 anesthetized hydropenic mongrel dogs. The mean values of the renal fractional excretion of sulfoconjugated dopamine, norepinephrine, and epinephrine were shown to be statistically greater than 100%, suggesting a predominant secretion by the renal tubules of hydropenic dogs. Statistically significant correlations between plasma concentration and urinary excretion of sulfoconjugates--independent of blood pressure, cardiac output, clearance of para-aminohippuric acid, glomerular filtration rate, and sodium excretion are reported. Thus any change in the tubular handling of sulfoconjugates is likely to have a direct consequence in the fixation of their plasma concentrations.

Animals↗
PubMed1991

[Validation of Oscillomat, a device for self-measurement of blood pressure. Comparison with mercury sphygmomanometers].

Self-measurement of arterial blood pressure (BP) is a valuable aid in the follow-up of hypertensive patients. Unfortunately, the devices utilized are not subject to certification and therefore must be validated. In this study, the accuracy and precision of BP measurement with the Oscillomat device were measured and simultaneously compared with those of a standard mercury sphygomomanometer in 60 subjects and with a random zero mercury sphygmomanometer in 44 subjects. The Oscillomat device correctly explored systolic and diastolic BP within a 55 to 210 mmHg range. Compared with the auscultatory method, it tended to underestimate systolic BP values by + 3 to -15 mmHg and diastolic B.P. values by + 1 to -15 mmHg.

Adult↗
PubMed1991

Arterial distensibility and left ventricular hypertrophy in patients with sustained essential hypertension.

Reduced aortic distensibility and compliance may participate in the genesis of cardiac hypertrophy in patients with hypertension. In these patients the increase in end-systolic stress, a determinant factor contributing to the development of cardiac hypertrophy, is influenced not only by the geometric properties of the ventricle but also by the level of systolic pressure. In patients with sustained essential hypertension, the degree of cardiac hypertrophy correlates significantly with the increase in aortic rigidity, which is assessed by the calculation of the characteristic impedance, by the measurement of carotid-femoral pulse-wave velocity, or by the calculation of the Peterson elastic modulus at the level of the aortic arch. Dihydralazine-like substances are unable to modify arterial stiffness, whereas calcium-entry blockers and converting-enzyme inhibitors improve arterial stiffness when achieving the same degree of blood pressure reduction. Modifications in the stiffness of the aorta and other large arteries must be considered to understand reversion of cardiac hypertrophy as a result of antihypertensive treatment.

Antihypertensive Agents↗
PubMed1991

Central hypotensive effects of nicardipine in conscious freely moving spontaneously hypertensive rat.

The central cardiovascular effects of the calcium channel blocker nicardipine was studied in conscious freely moving normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Nicardipine was administered in a 1.5 microliters volume into the lateral ventricle of the brain (i.c.v.) or intravenously (i.v.). The injection of vehicle alone did not significantly change mean arterial pressure (MAP) or heart rate (HR). Nicardipine (10, 30, 100 and 300 micrograms/kg) intravenously administered, dose-dependently decreased MAP and increased HR in WKY and SHR. However, when administered i.c.v., nicardipine (10 micrograms/kg) increased MAP and HR in WKY and decreased MAP without any significant change in HR in SHR. These results are consistent with previous work reporting an exaggerated hypotensive response to i.c.v. administration of dihydropyridine calcium channel blockers in anesthetized SHR as compared to WKY. They suggest that a 1,4-dihydropyridine-sensitive pressor system is present in the SHR but not in the WKY.

Animals↗