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Biomedical subjects

G M London

Publications and source records attributed to G M London.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1995

Effect of hemodialysis on cardiovascular rhythms in end-stage renal failure.

The purpose of this investigation was to determine non-invasively the alteration in autonomic cardiovascular control observed in end-stage renal disease (ESRD) patients submitted to a hemodialysis (HD) treatment. The effect of HD on finger blood pressure (BP) and heart rate (HR) variability was studied by means of spectral analysis in 12 ESRD patients at supine and during 45 degrees head-up tilt. Amplitude spectra of BP and HR rhythmicity were estimated and integrated amplitudes of the low (60 to 140 mHz, Mayer waves) and high frequency (area under the curve at mean respiration rate +/- 50 mHz) components were computed. The overall variability of a signal was given by the total area under the curve of the spectrum between 20 and 500 mHz. The transfer function was calculated between systolic BP and HR fluctuations using cross-spectral analysis. The principle findings are as follows: (1) Before HD, overall variability in systolic and diastolic BP as well as in the low frequency component in BP spectra were markedly reduced in ESRD patients compared to control subjects. Dialysis produced an immediate improvement in overall BP variability and the LF BP rhythmicity. (2) Before HD, there was an alteration of the HR spectral profile in uremic patients. (3) Chronic uremia and HD induced no changes in the transfer gain characteristic of modulation of HR by systolic BP. Taken together, these findings suggest that volume depletion in ESRD patients during a dialysis treatment is responsible for the improvement of overall BP variability and its spectral components.

Adult↗
PubMed1995

Effect of head-down tilt on cardiovascular control in healthy subjects: a spectral analytic approach.

1. The purpose of this investigation was to determine non-invasively the changes in autonomic cardiovascular control observed in normal subjects submitted to acute cardiopulmonary blood volume expansion by 100 degrees head-down tilt. The effect of head-down tilt on finger blood pressure and heart rate fluctuations was studied by means of power spectral analysis in 12 healthy men. 2. Amplitude spectra of heart rate and blood pressure rhythmicity were estimated at the low-frequency (60-140 mHz, 10-s rhythm) and high-frequency (area under the curve at mean respiration rate +/- 50 mHz) component. Transfer gain and phase were calculated between systolic blood pressure and heart rate. Forearm vascular resistance was estimated to validate the head-down procedure. 3. Forearm vascular resistance decreased significantly from 19.82 (16.34-26.46) mmHg ml-1 min 100 ml to 18.05 (13.69-22.88) mmHg ml-1 min 100 ml (P < 0.01) during head-down tilt (values are medians and 25 and 75 percentiles). The overall variability (total area under the curve of the spectrum from 20 to 500 mHz) of blood pressure and heart rate time series was consistently reduced with head-down tilt. 4. The spectral pattern of systolic blood pressure showed a diminution of the absolute and relative low-frequency component during head-down tilt: absolute log-transformed values, 2.86 (2.80-2.94) mmHg/Hz1/2 versus 2.77 (2.72-2.82) mmHg/Hz1/2 (P < 0.05); relative values, 35% (32-37%) versus 32% (29-32%) (P < 0.05). In heart rate spectra only the absolute low-frequency component decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Large artery function and alterations in hypertension.

HYPERTENSION AND ARTERIAL HEMODYNAMICS: One of the characteristics of hypertension is an impairment in arterial hemodynamics. Any definition of hypertension has to take account of oscillatory fluctuations during the cardiac cycle, that is, fluctuations in systolic and diastolic blood pressure around mean arterial pressure. These fluctuations are determined by ventricular ejection, arterial distensibility and the timing of arterial wave reflections. EFFECTS OF AGING ON LARGE ARTERIES: Larger arteries stiffen progressively with age, due to medial and intimal thickening. This alteration can be described as a decrease in arterial distensibility (Di = delta D/delta P x D, where D is the diameter of the artery and P is the blood pressure). The most obvious consequence of arterial stiffening is an increase in the amplitude of pulse pressure, caused by an increase in systolic pressure and a decrease in diastolic pressure. Two mechanisms underlie this increase in pulse pressure: a higher incident pressure wave generated by the left ventricle into a stiffened aorta and an increase in the velocity of the pressure wave traveling forward and back in the arterial tree. In young subjects, the reflected wave causes an increase in the early diastolic wave, but in older people the reflected wave is summed with a late systolic wave, causing a dramatic increase in central systolic pressure. These phenomena affect left ventricular function adversely, increasing myocardial oxygen consumption and tending to decrease coronary blood flow. Furthermore, the increased systolic blood pressure induces left ventricular hypertrophy. EFFECTS OF ANTIHYPERTENSIVE DRUGS: Although all classes of antihypertensive drugs can reduce blood pressure, only some can decrease arterial distensibility. Angiotensin converting enzyme inhibitors and calcium antagonists have been shown to decrease the stiffness of conduit arteries and dilate peripheral arteries. This may account for the superiority of these drugs in regressing left ventricular hypertrophy.

Aged↗
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

Influence of sex on arterial hemodynamics and blood pressure. Role of body height.

Systolic pressure is lower in premenopausal women than in age-matched men, but underlying alterations are not well characterized. Aging and body size alter arterial function, influencing pressure wave propagation and amplification in peripheral and central arteries. To assess the possibility that systolic pressure differences in women are related to smaller body size, we studied arterial function in 119 men and 104 women. Premenopausal and postmenopausal women were compared with age-matched men. The following parameters were measured: ankle-arm pressure index (Doppler), aortic and arterial distensibility (pulse wave velocity), systolic pressure and the effect and time delay of arterial wave reflections in the common carotid artery (applanation tonometry), and diameters of the abdominal aorta and aortic bifurcation and their ratio (aortic tapering, echography). Premenopausal women had lower brachial (P < .05) and ankle (P < .01) systolic pressures than age-matched men, whereas the ankle-arm pressure index was higher in men (P < .01). In the overall population the ankle-arm index was positively correlated with body height (P < .001). Carotid systolic pressure was similar in women and men, with an increased effect and earlier return of wave reflections in women (P < .01). The effect of wave reflections was inversely correlated with body height (P < .001) and positively associated with aortic tapering (P < .001), which was increased in women (P < .01). In premenopausal women the distensibility of brachial and femoral arteries was higher than in age-matched men (P < .01), whereas aortic distensibility was not different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Proximal and distal pulse pressure after acute antihypertensive vasodilating drugs in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: In a previous study (J Hypertens 1993, 11:135-139) our group showed that in anaesthetized rats, although pulse pressure increased from the proximal (common carotid artery) to the distal (terminal aorta) portion of the aorta in normotensive Wistar-Kyoto (WKY) rats, such a pulse pressure gradient was not observed in spontaneously hypertensive rats (SHR) which had identical values of proximal and distal pulse pressure. The purpose of the present study was to show, in awake SHR, in comparison with awake WKY rats, that the lack of pulse pressure gradient might be functionally reversed after acute administration of vasodilating agents. METHODS: The drugs (administered intra-arterially) were an angiotensin converting enzyme inhibitor (perindoprilat; 2 mg/kg), a calcium antagonist (nicardipine; 30 micrograms/kg), a peripheral vasodilator (hydralazine; 200 micrograms/kg) and placebo (isotonic saline). Blood pressure was evaluated invasively. RESULTS: In untreated rats it was noticed that pulse pressure increased physiologically from the proximal to the distal part of the aorta for the same mean arterial pressure in WKY rats, whereas no pulse pressure gradient was observed in SHR. With acute drug administration, marginal modifications were observed in WKY rats, but mean arterial pressure was reduced significantly in SHR (hydralazine > perindoprilat > nicardipine). Proximal pulse pressure was decreased significantly with perindoprilat or nicardipine but was unchanged with hydralazine. Distal pulse pressure was unchanged, except for an increase in the nicardipine-treated group. Heart rate was increased significantly by hydralazine. CONCLUSION: The results show that, although all of the drugs studied decreased mean arterial pressure in SHR, only the calcium antagonist nicardipine and the angiotensin converting enzyme inhibitor perindoprilat reduced proximal pulse pressure. This dissociation between the effects on mean arterial pressure and proximal and distal pulse pressure can be explained by the preferential action of the different antihypertensive agents on large arteries and wave reflections, producing different patterns in the pulsatile component of the heart load.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Arterial stiffness and wave reflections following acute calcium blockade in essential hypertension.

Antihypertensive agents are routinely studied in terms of changes in the level of systolic, diastolic, and mean arterial pressure. Pulse pressure may be independently modified from these parameters as a consequence of specific changes in the mechanical properties of the large arteries and in the timing of incident and reflected pressure waves. The aim of this study was to evaluate the changes in pulse pressure produced by acute calcium blockade by the dihydropiridine derivative, lacidipine, in a double-blind design versus placebo in 18 subjects with mild to moderate hypertension. Carotid and femoral pressure waveforms were recorded noninvasively by applanation tonometry using a Millar micromanometer-tipped probe. Early (Pi) and mid-to-late (Ppk) systolic peaks of carotid pressure waveform were evaluated, enabling the effect of incident pressure wave to be quantified as the ratio of Pi to the total height of carotid pulse wave (PP) (Pi/PP) and the effect of wave reflections as the ratio (Ppk-Pi)/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. Pulsatile changes in diameter were studied using noninvasive echo-tracking techniques. Whereas mean arterial pressure significantly decreased following lacidipine, pulse pressure measured at three different sites (brachial, carotid, and femoral arteries) was unchanged. Carotid-femoral pulse wave velocity, carotid and femoral arterial stiffness, and delta tp were not modified, whereas the (Ppk-Pi)/PP ratio and left ventricular ejection time was significantly reduced and the Pi/PP ratio was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1994

Arterial pulse wave and calcium-channel blockers in hypertension.

In contrast to mean blood pressure, arterial pulsatility represented by pulse pressure (PP) varies from heart to periphery. It depends on the stiffness of large arteries and the degree of arteriolar vasoconstriction. The central pulsatility, directly linked to left ventricular work, cannot be accurately evaluated by measurement of brachial PP. Moreover, the pulse wave reflection, when arriving in systole, increases the late-systolic pressure and the left ventricular afterload, particularly in older and hypertensive subjects. Analysis of the central pressure curve recorded by an accurate noninvasive method (applanation tonometry) may improve the hemodynamic evaluation of antihypertensive drugs. Calcium blockers reduce cardiac afterload in hypertension by their arteriolar vasodilating properties, by improving the compliance of large arteries, and also by reducing the central influences of the reflection wave, as shown after single administration and particularly after chronic treatment with calcium blockers.

Arteries↗
PubMed1994

Pathophysiology of left ventricular hypertrophy in dialysis patients.

Left ventricular hypertrophy is a frequent cardiovascular alteration in end-stage renal disease patients on hemodialysis which is associated with increased morbidity and mortality. Hypertrophy results from chronic flow and pressure overload and from poorly understood neurohumoral alterations. Clinical symptomatology associated with ventricular hypertrophy is related to diastolic dysfunction which characterizes this condition. The symptoms are (1) an unusual sensitivity to volume changes such that hypotension and hemodynamic instability and/or pulmonary edema occur with small volume variations and (2) a high frequency of supraventricular arrhythmias.

Anemia↗
PubMed1994

Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease. Comparative effects of ACE inhibition and calcium channel blockade.

BACKGROUND: We wished to assess the respective roles of the antihypertensive and blood pressure (BP)-independent effects of antihypertensive drugs on arterial hemodynamics and left ventricular hypertrophy (LVH) in end-stage renal disease (ESRD) patients. METHODS AND RESULTS: In a double-blind study, 24 ESRD patients with LVH were randomized to 12 months' administration of either the angiotensin-converting enzyme (ACE) inhibitor perindopril (n = 14) or the calcium channel blocker nitrendipine (n = 10). Repeated measurements of the following parameters were performed: BP (mercury sphygmomanometry), left ventricular mass (LVM, echocardiography), cardiac output (aortic cross-section and velocity integral), total peripheral resistance (cardiac output and mean BP), aortic and large-artery compliance (pulse wave velocity, Doppler flowmeter), and arterial wave reflections (augmentation index, applanation tonometry). Radioimmunoassay was used to determine plasma renin activity, aldosterone, and plasma catecholamine levels. Two-way (time-treatment) ANOVA for repeated measures was used for statistical analysis. Perindopril and nitrendipine induced significant and similar decreases in BP, total peripheral resistance (P < .001), aortic and arterial pulse wave velocities (P < .001), and arterial wave reflections (P < .01). At baseline, the two groups had LVH mostly due to increased LV end-diastolic diameter (LVEDD) (perindopril, 54.3 +/- 1.4 and nitrendipine, 54.3 +/ 2.4 mm) with near-normal mean LV wall thickness (perindopril, 11.4 +/- 0.3 and nitrendipine, 11.2 +/- 0.4 mm). A decrease in LVM was observed only in patients receiving perindopril (from 317 +/- 18 to 247 +/- 21 g) (time-treatment interaction, P = .036). Nitrendipine had no significant effect on LVM (314 +/- 29 versus 286 +/- 32 g). The decrease in LVM observed with perindopril was associated with a reduction in LVEDD (49.9 +/- 1.6 versus 54.3 +/- 1.4 mm after 12 months) (time-treatment interaction, P = .04), while the mean LV wall thickness was unchanged (11.4 +/- 0.3 versus 10.5 +/- 0.5 mm). Cardiac alterations were not correlated with changes in BP or with alterations in plasma renin activity or aldosterone or catecholamine levels. CONCLUSIONS: In ESRD patients with LVH, ACE inhibition decreases LVM independently of its antihypertensive effect and of associated alterations in arterial hemodynamics. The decrease in LVM was due primarily to a decrease in LV volume, which may have resulted in these patients from chronic volume overload.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

[Pressure-independent improvement of aortic distensibility in hypertensive hemodialysed patients].

Hypertensive patients undergoing hemodialysis (HPH) have a marked impairment of their large artery distensibility and an increased cardiovascular morbidity. We investigated twelve HPH (8 males, 4 females, 53 +/- 12 years of age, +/- SD) following a single dose of an ACE inhibitor (quinapril 20 mg) comparatively to a placebo in a randomised cross over study over a week (H0 to H172). We measured repeatedly blood pressure and aortic distensibility (carotid-femoral pulse wave velocity, PWV). Statistical analysis was made through repeated measure ANOVA and repeated measure analysis of covariance because of the tight link between pressure and arterial function. Blood pressure decreased (SAP: p < 0.01, DAP: p < 0.001), and PWV was significantly improved independently of the pressure decrease. ACE inhibitor reduces blood pressure in these patients and improves large arterial function independently of the blood pressure changes.

Adult↗
PubMed1994

Intrinsic modifications of the brachial and radial arteries in hypertensive humans.

The properties of vessel walls of brachial and radial arteries were studied noninvasively, using 2 original pulsed ultrasound echo-tracking systems based on Doppler shift, in an investigation comparing 32 normotensive controls and 50 age-matched hypertensive patients. The 2 groups did not differ with respect to sex, total and high-density lipoprotein cholesterol, blood glucose, and smoking habits. Whereas noninvasive measurements of blood pressure indicated that both mean arterial pressure and pulse pressure were significantly increased in the arterial tree of the hypertensive forearm, end-diastolic diameter and pulsatile changes of the brachial and radial arteries remained within the normal range. The finding was more pronounced at the site of the radial artery in which: (i) pulsatile changes of blood pressure (documented from Finapres method) were significantly higher than those of the brachial artery, yet (ii) indices of arterial stiffness (compliance and distensibility) remained within the normal range. For the branchial artery, distensibility was significantly reduced (p = 0.01), whereas no significant change in compliance was observed. The study provides evidence that, in subjects with essential hypertension, the mechanical properties of the brachial and the radial arteries are not exclusively related to the level of blood pressure, and differ according to the arterial segment studied.

Adult↗
PubMed1994

Sodium, large arteries, and diuretic compounds in hypertension.

Clinical and experimental data have shown that antihypertensive drugs do not cause the same change in arterial compliance for an equipotent blood pressure reduction. However, there is not clear data on the effect of sodium and diuretics on the visco-elastic properties of the hypertensive arterial wall. Cross-sectional epidemiologic studies suggest that, at any given value of age and blood pressure, pulse wave velocity is lower in the presence of decreased sodium intake. Longitudinal studies indicate that, in hypertensive subjects, low sodium intake is associated with a larger brachial artery diameter than is high sodium intake. In hypertension in the elderly and in severe hypertension with end-stage renal disease, sodium overload causes a reduction in arterial compliance and distensibility unrelated to blood pressure changes. In animal studies, the diuretic compounds cycletanine and indapamide were shown to increase systemic and carotid compliance independently of blood pressure changes. In contrast, a crossover study of hypertensive subjects showed that the diuretic agent hydrochlorothiazide did not change arterial compliance and pulse wave velocity, whereas the calcium entry blocker, felodipine, improved these parameters. Nevertheless, indapamide decreased the pulse pressure on stroke volume ratio, a parameter used as a marker of aortic distensibility. Taken together, such studies indicate that sodium may act on the arterial wall independently of blood pressure changes. The contribution of counter regulatory mechanisms, possibly related to the renin-angiotensin and sympathetic nervous systems, might explain the differences between the clinical and experimental changes observed with diuretic compounds. Of the various antihypertensive agents, diuretics seem to have the least effect on the arterial system.

Animals↗