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Biomedical subjects

M E Safar

Publications and source records attributed to M E Safar.

At least 109 records · Page 6Linked to original sources
PubMed1996

Antihypertensive therapy and wave reflections.

Studies of pulsatile arterial hemodynamics have emphasized that the pulsatile component of pulse pressure has two important characteristics: (i) it increases from central to peripheral arteries for a similar value of mean arterial pressure, and (ii) it is dominantly influenced by the amplitude and timing of the backward pressure wave. Although these important aspects of wave reflections have been poorly investigated in the field of hypertension, they may be easily studied noninvasively in humans on the basis of the analysis of the pulse wave contour of carotid and aortic blood pressure. Increased wave reflections returning toward the thoracic aorta during systole may have deleterious consequences on the structure and function of the heart. Some (but not all) antihypertensive drugs may contribute to decrease and/or to delay wave reflections in association with blood pressure reduction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Cardiac and arterial interactions in end-stage renal disease.

Although cardiac hypertrophy is a frequent complication of end-stage renal disease (ESRD), relatively little is known about large arterial geometry and function in vivo in these patients, and the relationship between arterial changes and cardiac hypertrophy is unknown. Common carotid artery (CCA) intima-media thickness and internal diameter and left ventricular geometry and function were determined by ultrasound imaging in 70 uncomplicated ESRD patients and in 50 age-, sex-, and blood pressure-matched controls. Arterial distensibility and compliance were determined from simultaneously recorded CCA diameter and stroke changes in diameter and CCA pressure waveforms, obtained by applanation tonometry, and also by the measurement of carotid-femoral pulse wave velocity. Compared with control subjects, ESRD patients had greater left ventricular diameter (P < 0.01), wall thicknesses and mass (P < 0.001), increased CCA diameter (6.25 +/- 0.87 vs. 5.55 +/- 0.65 mm; P < 0.001), larger CCA intima-media thickness (777 +/- 115 vs. 678 +/- 105 microns; P < 0.001) and intima-media cross-sectional area (17.5 +/- 4.5 vs. 13.4 +/- 3.3 mm2; P < 0.001). In uremic patients, arterial hypertrophy was associated with decreased CCA distensibility (17.8 +/- 8.8 vs. 24.0 +/- 12.7 kPa-1.10(-3); P < 0.001) and compliance (5.15 +/- 2 vs. 6.0 +/- 2.5 m2.kPa-1.10(-7); P < 0.05), accelerated carotid-femoral pulse wave velocity (1055 +/- 290 vs. 957 +/- 180 cm/seconds; P < 0.001), early return and increased effect of arterial wave reflections (20.5 +/- 15.4 vs. 9.2 +/- 18.4%; P < 0.001). The latter phenomenons were responsible for increased pulsatile pressure load in CCA (58.3 +/- 21 vs. 48 +/- 17 mm Hg; P < 0.01) and were associated with a decreased subendocardial viability index (157 +/- 31 vs. 173 +/- 30%; P < 0.001). The CCA diameter was correlated with the left ventricular diameter (P < 0.01), and a significant correlations existed between CCA wall thickness or CCA intima-media cross-sectional area and left ventricular wall thicknesses and/or left ventricular mass (P < 0.01). In multivariate analysis, these relationships were independent regarding age, sex, blood pressure and body surface area. The present study documents parallel cardiac and vascular adaptation in ESRD, and demonstrates the potential contribution of structural and functional large artery alterations to the pathogenesis of left ventricular hypertrophy and functional alterations.

Adult↗
PubMed1996

Structural changes of large conduit arteries in hypertension.

BACKGROUND: Structural alterations of large conduit arteries are a common pathway for any complication of hypertensive vascular disease. Whether increased arterial wall thickness occurs at an early phase in uncomplicated hypertension has remained largely ignored until recent years. METHODS: Sophisticated echo-Doppler techniques with a high degree of resolution and reproducibility have been developed to obtain reliable non-invasive determinations of intima-media thickness of superficial arteries such as the radial and the common carotid arteries. RESULTS: In uncomplicated hypertension, a significant increase in intima-media thickness is observed at the sites both of the radial and of the carotid arteries. The former is known to be constantly undamaged by atheroscierosis and is composed almost exclusively of arterial smooth muscle; operational arterial stiffness is found to be normal. The latter is strongly affected by atheroscierosis and predominantly composed of elastin and collagen fibres; operational arterial stiffness is found to be increased. In old subjects with systolic hypertension, radial artery hypertrophy is significantly reversed by drug therapy involving diuretics, converting enzyme inhibitors or both. This change occurs in parallel with the reduction in blood pressure. CONCLUSION: In sustained essential hypertension, arterial wall hypertrophy can be demonstrated in the absence of organ damage. Operational arterial elasticity is maintained in peripheral but not in central arteries. Structural changes of the large conduit arteries are substantially reversed by drug therapy together with a reduction in blood pressure.

Animals↗
PubMed1996

Antihypertensive effects and arterial haemodynamic alterations during angiotensin converting enzyme inhibition.

OBJECTIVE: To assess the respective roles of the anti-hypertensive and blood pressure-independent effects of angiotensin converting enzyme (ACE) inhibition in the changed arterial haemodynamics observed in hypertensive patients with end-stage renal disease (ESRD) treated by haemodialysis. DESIGN AND METHODS: Twelve hypertensive patients with ESRD were included in a double-blind, cross-over study comparing a single 20 mg dose of the ACE inhibitor quinapril versus placebo. Two study periods each of 172 h duration were separated by a 2-week placebo period. Repeated measurements of the following parameters were performed: brachial artery systolic blood pressure (SBP); diastolic blood pressure and mean blood pressure (using a mercury sphygmomanometer); carotid artery SBP and pulse pressure (by applanation tonometry); aortic stiffness (by pulse wave velocity); and the effect of arterial wave reflections in the common carotid artery (the augmentation index, by applanation tonometry). A radioimmunoassay was used to determine plasma angiotensin II levels. Quinaprilat pharmacokinetics were studied using a specific assay. Two-way (time-treatment) analysis of variance for repeated measures, analysis of covariance for two within-factors and a covariate changing with the level of the factor time (pressures measured at each time) and baseline values of the studied parameter as a second covariate were used for statistical analysis. RESULTS: Quinapril treatment induced a long-lasting decrease in arterial wave reflections, which was still observable 172 h after quinapril administration and still present after removing the effect of the decrease in blood pressure. The effect on wave reflections was associated with a more pronounced and sustained decrease in carotid SBP and pulse pressure than that in brachial SBP and pulse pressure. Quinapril administration also induced a long-lasting decrease in aortic pulse wave velocity, but this effect was entirely dependent on parallel changes in blood pressure. Arterial haemodynamic changes were not related to plasma angiotensin II or quinaprilat levels. CONCLUSIONS: The results of this controlled study indicate that, in ESRD patients, ACE inhibition results in a long-lasting, blood pressure-independent decrease in arterial wave reflections. The consequence of this was a decrease in pulsatile pressure load in the central arteries with increased aortic distensibility. The increased aortic distensibility resulted from the decrease in blood pressure. The observed arterial haemodynamic alterations suggest that ACE inhibition induced alterations in arterial wave reflections in the distal parts of the arterial tree.

Adult↗
PubMed1996

Arterial alterations in hypertension with a disproportionate increase in systolic over diastolic blood pressure.

BACKGROUND: Although systolic and diastolic blood pressure and cardiovascular risk are directly related in epidemiologic studies, the results of large therapeutic trials in mild to moderate hypertension have indicated that the prevention of cerebrovascular accidents was much more effective than that of coronary ischemic accidents. Actually, a significant decrease in coronary events was observed only in aged populations in which systolic (and not diastolic) blood pressure was chosen as criterion of entry. Whether the choice of the mechanical factor (systolic or diastolic blood pressure or both) used to define hypertension might have created a bias in the studied populations remains an important question. FINDINGS: Above 50 years of age, most hypertensive populations are characterized by a disproportionate increase in systolic over diastolic blood pressure, so that the pulsatile component of blood pressure is strikingly augmented. This pattern is commonly observed in old people with essential hypertension, in hypertensive subjects with advanced renal failure undergoing hemodialysis and in atherosclerotic subjects with hypertension, particularly those with atherosclerosis of the lower limbs and cerebral vessels. In all these populations, the disturbed pulse pressure is associated with significant alterations in large conduit arteries involving hypertrophy of central and peripheral large vessels and increased values of operational stiffness and altered wave reflections which return during the systolic (and not the diastolic) component of the aortic blood pressure curve. Sodium sensitivity is commonly observed in these patients, so that low doses of diuretics correct the increased pulse pressure, particularly in those with normal or low plasma renin activity. CONCLUSIONS: Although strong interactions may be observed between the pulsatile component of blood pressure and the arterial changes in hypertension, much more research is required before a clear-cut cause-effect relationship can be established between these two variables. With the exception of diuretic therapy in the elderly, there are at present no treatments that can selectively reduce pulse pressure or reverse the arterial changes or both in patients with essential hypertension and a disproportionate increase in systolic blood pressure.

Arteries↗
PubMed1996

Arterial wall remodelling and stiffness in hypertension: heterogeneous aspects.

1. Hypertension is associated with hypertrophy and decreased operating distensibility of the large artery wall. Because similar pathological and functional changes are observed with ageing, hypertension is often looked upon as an accelerated form of aging. 2. Considering the decrease in arterial distensibility observed with both ageing and hypertension, whether the change is due to age, an increase in distending pressure or to hypertension-induced changes in large artery structural properties may be much debated. 3. The purpose of the present review is to study the effects of aging and hypertension on structural (lumen diameter and arterial wall thickness) and functional (distensibility) properties of large central and medium-sized arteries in humans. 4. From clinical studies in subjects with hypertension with or without advanced renal disease, it is suggested that age- and hypertension-induced structural arterial changes are quite heterogeneous, depending on the topography of the vessel and on the severity of the underlying disease.

Aging↗
PubMed1996

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Adipose Tissue↗
PubMed1996

Arterial stiffness, hydrochlorothiazide and converting enzyme inhibition in essential hypertension.

In a randomized double blind study, the arterial changes produced either by hydrochlorothiazide plus amiloride (Group I), or by hydrochlorothiazide plus captopril (Group II) were investigated in two territories of the arterial tree, the common carotid artery and the terminal aorta. Arterial echo-tracking techniques of high resolution and applanation tonometry were used to evaluate non-invasively the indices of arterial stiffness and carotid wave reflections. In Group I and II, there was a similar significant decrease in brachial blood pressure (BP) and carotid diastolic diameter and an increase in aortic compliance and distensibility. Groups I and II differed significantly in aortic diastolic diameter which decreased in Group I but not in Group II, and in carotid wave reflections which were modified in Group II but not in Group I. Thus, captopril associated with hydrochlorothiazide resulted in a shift in the carotid arterial reflection wave from systole to diastole with no reduction in the aortic diastolic dimension. For similar BP reduction, the combination of hydrochlorothiazide and amiloride had no significant effect on the carotid reflection wave, but caused a significant reduction in the aortic diastolic diameter. These intergroup differences were related to the presence or absence of converting enzyme inhibition.

Adult↗
PubMed1996

Aortic collagen, aortic stiffness, and AT1 receptors in experimental and human hypertension.

Converting-enzyme inhibitors decrease the collagen content of the arterial wall in various models of hypertension in rats. Angiotensin II induces collagen production in culture cells. Whether the decrease in collagen induced by converting-enzyme inhibition is due in vivo to pressure mechanisms or to nonhemodynamic factors or a combination of both remains the subject of discussion. In this review, it will be shown that (i) converting-enzyme inhibition prevents the accumulation of aortic collagen in hypertensive rats independently of blood pressure changes, (ii) prevention of aortic collagen accumulation in hypertensive rats is obtained through blockade of angiotensin II formation involving AT1 receptors, and (iii) in hypertensive humans, increased aortic stiffness is associated with AGTR1 receptor polymorphism independently of age and blood pressure.

Angiotensin II↗
PubMed1995

Effects of antihypertensive drugs on large artery compliance.

The changes in arterial compliance following drug treatment have been studied mainly in hypertension. Physiologically, reduced arterial compliance independently affects blood pressure through an increase in systolic pressure and a decrease in diastolic pressure at any given value of mean arterial pressure. This review summarizes the pharmacological studies performed in recent years on the ability of antihypertensive drugs to modify arterial compliance. For the same decrease in mean arterial pressure, antihypertensive drugs may have differential effects improving arterial compliance (calcium channel blockers, converting enzyme inhibitors, alpha-blockers and some beta-blockers) or causing no change (dihydralazine, diuretics, propranolol) with resulting consequences on cardiac structure and function.

Antihypertensive Agents↗
PubMed1995

Distension capacity of the carotid artery and ambulatory blood pressure monitoring. Effects of age and hypertension.

In hypertension, the principal components of the mechanical stress acting on the arterial wall may be evaluated not only from the level of peak systolic and end-diastolic blood pressure but also by the level of pulse pressure and variability of blood pressure measured by ambulatory monitoring. The purpose of the present study was, in a population of 51 subjects with essential hypertension, to determine the influence of these parameters and of heart rate on the distension capacity of the common carotid artery, measured noninvasively by high-resolution echo-tracking techniques. The pulsatile change in diameter of the carotid artery diameter, estimated either in absolute or relative values, was shown to be significantly and independently correlated with four mechanical parameters deduced from daytime ambulatory blood pressure measurements: baseline diastolic blood pressure (the lower the diastolic blood pressure, the higher the distension capacity; r = -0.44; P < .001); pulse pressure (the higher the pulse pressure, the higher the distension capacity; r = 0.32; P < .024); variability of diastolic blood pressure (the higher the variability, the higher the distension capacity; r = 0.37; P < .008); and mean heart rate (the higher the heart rate, the more reduced the distension capacity; r = -0.28; P < .05). Multiple regression analysis indicated that mean diastolic blood pressure and its variability, mean heart rate, and pulse pressure acted independently on carotid artery distension, even after adjustment for age. The present study suggests for the first time that, in humans, hypertension may act on the arterial wall not only through the amplitude of peak systolic and end-diastolic blood pressure but also through several other mechanical factors involving the level of pulse pressure and heart rate and also blood pressure variability. Thus, in addition to the level of blood pressure, carotid artery distension is specifically influenced by two factors independently implicated in the epidemiologic cardiovascular risk: pulse pressure and heart rate.

Adult↗
PubMed1995

Carotid arterial changes produced by a centrally mediated antihypertensive agent in hypertensive rats.

We studied the effects of centrally mediated reduction of sympathetic outflow on the mechanical properties of the carotid arterial wall in spontaneously hypertensive rats (SHR) as compared with matched Wistar-Kyoto rats (WKY). Ascending aortic pressure and flow were recorded in open-chest anesthetized rats, and the systemic arterial compliance (SAC) was calculated. Intravenous injection of rilmenidine induced a transient increase in blood pressure (BP) in WKY and SHR, followed by a long-lasting reduction in SHR, together with a decrease in cardiac output (CO) and heart (HR) and a significant increase in SAC. Serial measurements of internal carotid artery diameter made with a newly described echo-tracking technique showed a significant, rapid, and long-lasting constriction in both strains. In this set of experiments, the carotid compliance was determined from the arterial volume-pressure relation under control conditions and after administration of intravenous (i.v.) rilmenidine. In both WKY and SHR, carotid compliance increased, but the increase was observed only at the higher transmural pressure ranges and not at the operating systemic BP of the corresponding animals. Simultaneous recordings of the carotid arterial diameter made with the echo-tracking technique indicated that these compliance changes occurred in the presence of carotid arterial constriction at any given value of transmural pressure. Distensibility was increased in a higher pressure range: from 100 to 200 mm Hg transmural pressure. The centrally mediated antihypertensive agent rilmenidine produced carotid arterial constriction independent of BP changes and, in in vivo in situ carotid preparations, arterial constriction was associated with a decrease in the stiffness of the arterial wall.

Analysis of Variance↗
PubMed1995

Influence of graded changes in vasomotor tone on the carotid arterial mechanics in live spontaneously hypertensive rats.

1. The contribution of vasomotor tone to the increased stiffness of carotid arteries in living spontaneously hypertensive rats (SHR) is largely unknown. Whether a reduced vascular tone is associated with an increase or a decrease in arterial stiffness in vivo remains to be determined. The goal of the present investigation was to show that a decrease in vascular tone is associated with a decrease in arterial stiffness, independent of the structural composition of the arterial wall. 2. New high resolution echo-tracking techniques were used to evaluate pulsatile changes of carotid blood pressure and diameter following transient and graded changes of vasomotor tone produced by the dihydropyridine derivative, isradipine. Treatment for 8 weeks was given to groups of SHR rats either with a low (0.6 kg day-1) or a high (2.6 mg kg-1 day-1) dose. Another SHR group received an acute dose of 2.6 mg kg-1 day-1. Results were compared to those of placebo-treated Wystar-Kyoto (WKY) and SHR rats. Whatever the dosage, acute or chronic calcium blockade caused a decrease in blood pressure which was maximal 1 h after administration and disappeared after the 16th h. Carotid arterial thickness and the composition of the arterial wall was determined from histomorphometry. 3. In placebo-treated SHR, the inverse relationship relating blood pressure to carotid arterial distensibility was significantly shifted toward higher values of blood pressure compared to the curve of normotensive placebo-treated WKY rats. The curve of SHR receiving chronically a non antihypertensive (0.6 mg kg-1 day-1) isradipine dose prolonged that of placebo-treated SHR toward lower values of blood pressure, so that carotid distensibility was significantly higher than in WKY for the same diameter and blood pressure level (145 mmHg). With administration of a chronic antihypertensive dose (2.6 mg kg-1 day-1) causing a significant decrease in arterial function. Acute antihypertensive calcium blockade with a single isradipine dose (2.6 mg kg-1 day-1) caused a similar shift in the pressure-distensibility curve toward the WKY curve although the histomorphometric composition of the arterial wall differed significantly from that of chronically treated animals. 4. The study provides evidence that, in living SHR submitted to calcium blockade, (i) a low dose of isradipine causing no substantial antihypertensive effect is associated with a significant elevation of carotid arterial distensibility for the same pressure and diameter as normotensive controls, and (ii) an acute or chronic dose causing a substantial antihypertensive effect is associated with a transient shift of the SHR distensibility-pressure curve toward a physiological arterial function, increasing carotid distensibility for the same pressure and diameter as WKY controls. Since such findings were observed independently of the histomorphometric composition of the arterial wall, they imply that the transient decrease in arterial stiffness produced by calcium blockade should involve specific changes in the connections between arterial smooth muscle and extracellular matrix.

Animals↗
PubMed1995

Carotid arterial hemodynamics in response to LBNP in normal subjects: methodological aspects.

Pulsatile changes in blood pressure and arterial diameter were studied noninvasively with applanation tonometry and echo-tracking techniques at the sites of the common carotid artery (CCA) and the carotid arterial bulb (CAB) in 12 healthy volunteers. Determinations were performed before and during application of -10 and -40 mmHg lower body negative pressure (LBNP) to investigate noninvasively the tensile forces acting on the CAB. Together with significantly decreased mean arterial pressure, increased heart rate, forearm vascular resistance, and plasma norepinephrine, the -40 mmHg LBNP stimulus produced the following significant changes in CCA and CAB hemodynamics: 1) for the same decrease in mean arterial pressure, a greater decrease in carotid than in brachial pulse pressure was observed (P < 0.01) due to a significant change in pressure wave transmission and in the timing of the carotid backward pressure wave; and 2) a highly significant decrease in pulsatile changes in diameter and tangential tension occurred, with a greater decrease in systolic than in diastolic tangential tension. Subsequently, cyclic tangential tension decreased more substantially than mean tangential tension. The cyclic changes in tension were quite significant after -40 mmHg LBNP but were already observed for mild -10 mmHg LBNP in which mean systemic blood pressure and heart rate were not modified. During -10 and -40 mmHg LBNP, CCA and CAB compliance and distensibility were unchanged. This study provides evidence that the autonomic nervous system activation produced by the LBNP procedure is associated with significant changes in pressure-wave amplification and in cyclic tensile forces acting on the CAB. These changes, which may occur even for mild LBNP, should be taken into account when interpreting results of the LBNP procedure in humans.

Adult↗
PubMed1995

Carotid artery mechanical properties of Dahl salt-sensitive rats.

We evaluated the mechanical properties of the carotid artery in anesthetized Dahl rats with or without long-term treatment with the diuretic compound indapamide. The mechanical properties of the carotid artery were evaluated by establishing pressure-volume curves in situ in vivo before and after total relaxation of arterial smooth muscle by potassium cyanide. Dahl salt-sensitive and salt-resistant rats were fed either a low (0.4%) or high (7%) NaCl diet for 5 weeks. In each group, half the rats received for the same period of time oral treatment with indapamide (3 mg/kg per day). Blood pressure, heart rate, and pressure-volume curves were studied at the end of the 5-week period. In untreated Dahl salt-sensitive rats, the pressure-volume curve of the carotid artery was shifted to the right compared with that in untreated Dahl salt-resistant rats. The finding was observed even after potassium cyanide and regardless of the NaCl diet (P < .01 between Dahl salt-sensitive and -resistant rats). Indapamide was able to prevent the development of hypertension in Dahl salt-sensitive rats receiving a high NaCl diet (185 +/- 7 versus 146 +/- 8 mm Hg in untreated and treated Dahl salt-sensitive rats with a high NaCl diet, P < .0005). In the other groups, indapamide had no effect on blood pressure. Indapamide treatment increased carotid arterial static compliance in Dahl salt-sensitive rats with a high or low NaCl diet and to a lesser extent in Dahl salt-resistant rats. The increase was observed even after total relaxation of carotid arterial smooth muscle by potassium cyanide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The arterial system in hypertension. A prospective view.

Hypertension has long been considered a hemodynamic disorder, the hallmark of which is an increased total peripheral resistance that is more or less uniformly distributed in the arterioles of the component organ circulations. In recent years, because of the introduction of innovative technologies and methods, it is now possible to obtain a meaningful assessment of the physiological role of the larger arteries, thereby providing an index of arterial distensibility and compliance and a new means to assess the role of pulsatile pressure and arterial stiffening in hypertension and its comorbid diseases (eg, arteriosclerosis, diabetes mellitus). This discussion addresses these newer methodological aspects in assessing arterial stiffening in systemic hypertension and other cardiovascular disorders. In addition, the epidemiological, the molecular biological, and genetic, as well as certain therapeutic, aspects of pulse pressure in these circumstances are discussed.

Adult↗