Search PubMed⌕ Search

Biomedical subjects

H R Brunner

Publications and source records attributed to H R Brunner.

At least 199 records · Page 11Linked to original sources
PubMed1992

Conduit artery compliance and distensibility are not necessarily reduced in hypertension.

The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance-pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure.

Animals↗
PubMed1992

Non-invasive determination of arterial diameter and distensibility by echo-tracking techniques in hypertension.

METHODOLOGY: A new non-invasive ultrasonic device was developed to characterize the biomechanical properties of medium and large peripheral arteries. Simultaneous recordings of internal diameter and blood pressure over the whole cardiac cycle are used to establish compliance-pressure curves. Since blood pressure, which is an inherent co-determinant of arterial compliance, is taken into account, the comparison of arteries from patients with markedly different blood pressures has become possible. In a first study, the effects of three different antihypertensive drugs (20 mg lisinopril, 100 mg atenolol, 20 mg nitrendipine administered once a day) on arterial compliance and distensibility were investigated in young healthy volunteers. RESULTS: After 8 days of treatment, lisinopril induced a significant increase in arterial compliance. Subsequently, we compared the mechanical behaviour of arteries from newly diagnosed hypertensive patients (radial artery) or the carotid artery from spontaneously hypertensive rats (SHR) with that of corresponding arteries in normotensive counterparts. No decrease in arterial distensibility was found in the hypertensive groups over the measured blood pressure range. This result is not totally consistent with previous in vitro or in situ localized studies. Methodological differences, the absence of blood flow and/or denervation may partly explain these contradictory results. Finally, we tested the effects of hydralazine (5 mg/day) and captopril (25 mg/day), administered for 6 weeks in drinking water, on the behaviour of the carotid arteries of 16-week-old SHR. The two drugs effectively reduced blood pressure while shifting the distensibility-pressure curves upward in comparison to the placebo-treated animals, suggesting an improvement in arterial compliance. CONCLUSIONS: While hypertension does not itself appear to alter the elastic behaviour of large peripheral arteries, antihypertensive treatment may increase the compliance of these blood vessels.

Adult↗
PubMed1992

Chronic adriamycin treatment and its effect on the cardiac beta-adrenergic system in the rabbit.

Treatment of male rabbits with adriamycin at a cardiotoxic dose (1 mg/kg intravenously, i.v., twice a week for 9 weeks) caused cardiovascular disturbances characteristic of chronic heart failure. The severity of symptoms varied, indicating differences in the individual sensitivity of the animals to adriamycin. Thus, cardiac output (CO) was decreased by greater than 40% in only 4 of the 7 animals in which it was measurable at 9 weeks. Elevated levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA), as well as pulmonary congestion, hydrothorax, and ascites were also evident. The baroreflex response to sodium nitroprusside (NPS) was blunted. The response to the inotropic drug dobutamine was depressed by 50% as compared with the control animals. Right ventricular beta-adrenoceptor density was significantly reduced in these animals (22.9 +/- 3.1 as compared with 31.8 +/- 1.0 fmol/mg protein in control animals) owing to a selective downregulation of the beta 1-adrenoceptor population. The loss of beta-adrenoceptors was highly correlated with severity of heart failure symptoms: i.e., baroreflex dysfunction as indicated by the NPS slope (r = 0.91), decrease in CO during the previous weeks (r = 0.88), and plasma norepinephrine (NE) levels (r = 0.96). However, when all adriamycin-treated animals were compared collectively regardless of the severity of heart failure, with the controls, no difference in the beta-adrenoceptor density was detectable, a finding in agreement with previous observations in this model. Chronic treatment of rabbits with adriamycin thus causes low-output failure, reflecting some of the findings reported for the human disease; however, individual sensitivity to adriamycin varies considerably between rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Dynamic non-invasive measurements of arterial diameter and wall thickness.

AIM: Non-invasive measurements of arterial diameter and wall thickness are critical in characterizing the onset and development of vascular disease. A precise dynamic method was proposed and tested for this purpose. DESIGN: A non-invasive method of measuring the variations in diameter and thickness of human arteries throughout the cardiac cycle was developed, using a high-precision ultrasonic echo-tracking system. An adaptive filtering technique was used to suppress artefacts caused by the layered tissue structure of the vessel wall. RESULTS: Based on decorrelation of microstructure noise, this technique improved the detectability of the wall interfaces, which allowed a determination of thickness and diameter. The accuracy and reproducibility of the method were tested by measurements of plastic films with known thicknesses. The discrepancies between standard micrometer and pulse-echo measurement were consistently less than 5 microns for film thicknesses ranging from 220 to 800 microns. The difference between two successive measurements was less than 2 microns. The identity of the measured vascular interfaces was checked in two ways. First, experiments on fixed bovine carotid arteries showed that the identified echogenic interfaces corresponded to the actual anatomical structure, as obtained by acoustic microscopy. Second, the radial artery thickness and diameter were extrapolated to obtain the change in wall volume over one cardiac cycle. The volume was found to be nearly constant, indicating incompressibility. CONCLUSION: This method will make it possible to obtain new information on atherogenesis and other vascular diseases.

Acoustics↗
PubMed1992

Non-invasive method for the assessment of non-linear elastic properties and stress of forearm arteries in vivo.

AIM: To propose a method for obtaining non-invasive highly accurate measurements of arterial diameter, thickness and pressure at a single location on a peripheral arm artery, and use this data to estimate the status of the arterial wall. METHODS: Diameter and thickness were measured with an A-mode ultrasonic echo-tracking device, with a precision of close to 1 micron. Pressure was measured with a photoplethysmograph at the finger level. A simple hemodynamic model was used to estimate, from the measured pressure pulse, the pressure waveform at the diameter-measuring site. RESULTS: The collected data made it possible to assess (1) the elastic response of the artery, through the compliance and distensibility, (2) the loading conditions, through the average stress-diameter curve and (3) the elastic properties of the wall material, through the incremental modulus of elasticity. CONCLUSION: This information can be used to assess the overall status of the arterial wall.

Blood Pressure↗
PubMed1992

Effect of mental stress on the tone of a medium-sized muscular artery.

AIM: We studied the effects of mental stress on the tone of the radial artery, a medium-sized muscular artery. METHODS: Using an A-mode echo-tracking device coupled to a photoplethysmograph, we took continuous measurements of the radial artery diameter, heart rate and finger arterial pressure in six healthy young volunteers. RESULTS: Under mental stress, the heart rate increased from 63 +/- 4 to 74 +/- 4 beats/min (mean +/- SEM, P < 0.01) and systolic pressure from 123 +/- 5 to 140 +/- 6 mmHg (P < 0.05). No consistent modification in the arterial diameter was observed at this time. CONCLUSION: The activation of sympathetic nerve activity induced by mental stress does not cause a significant contraction in the radial artery.

Adolescent↗
PubMed1992

Arterial dilatory reserve in congestive heart failure.

AIM: The purpose of this study was to determine whether there are abnormalities in flow-mediated large vessel relaxation in patients with congestive heart failure (CHF). METHODS: The radial arterial diameter and flow responses upon the release of 10 min of forearm arterial occlusion (reactive hyperemia) were measured with ultrasound and Doppler devices. RESULTS: In patients with CHF there was a 26% reduction in peak blood flow (P = 0.09) compared to age-matched controls. However, the increase in arterial diameter that followed the peak blood flow was reduced by 49% in CHF (P < 0.01). CONCLUSIONS: The causes of the abnormal flow-mediated large artery relaxation in CHF are unclear; both structural and endothelial abnormalities may contribute.

Blood Flow Velocity↗
PubMed1992

Arterial compliance and distensibility in spontaneously hypertensive rats.

AIM: These studies were undertaken in intact spontaneously hypertensive rats (SHR) to assess whether the elastic behavior of conduit arteries changes as a function of age. METHODS: We studied 16-week-old (n = 10) and 36-week-old (n = 10) SHR under fluothane anesthesia. Diameter-, compliance-, and distensibility-pressure curves were established non-invasively for the carotid artery by means of a high-precision ultrasonic echo-tracking device. Intra-arterial pressure was monitored simultaneously in the contralateral carotid artery. RESULTS: Mean blood pressure was 197 +/- 6 and 185 +/- 3 mmHg (mean +/- SEM) in the younger and older SHR, respectively. No significant difference was observed between the two groups of rats in the diameter-, compliance- and distensibility-pressure curves. CONCLUSIONS: These results suggest that the elastic behavior of elastic arteries is not necessarily altered with aging in rats with genetic hypertension.

Age Factors↗
PubMed1991

[ACE inhibitors in the treatment of hypertension in elderly patients].

Recent epidemiological studies clearly indicate that blood pressure rises with age and that hypertension remains a major risk factor for cardiovascular morbidity and mortality in the elderly. An accurate antihypertensive therapy reduces in these patients the incidence of stroke and heart failure. Because of their clinical efficiency and good therapeutic tolerance, the angiotensin-converting enzyme (ACE) inhibitors are first-line drugs for the treatment of elderly hypertensive patients. ACE inhibitions is expected to normalize blood pressure in approximately 40-60% of the patients. When needed, they can be combined with other drugs of different antihypertensive properties. In these cases, the most rational combination therapy consists of an ACE inhibitor with a diuretic or a calcium antagonist.

Aged↗
PubMed1991

Effects of SCH 34826, an orally active inhibitor of atrial natriuretic peptide degradation, in healthy volunteers.

Atrial natriuretic peptide is cleared from plasma by clearance receptors and by enzymatic degradation by way of a neutral metalloendopeptidase. Inhibition of neutral metalloendopeptidase activity appears to provide an interesting approach to interfere with metabolism of atrial natriuretic peptide to enhance the renal and haemodynamic effects of endogenous atrial natriuretic peptide. In this study, the effects of SCH 34826, a new orally active neutral metalloendopeptidase inhibitor, have been evaluated in a single-blind, placebo-controlled study involving eight healthy volunteers who had maintained a high sodium intake for 5 days. SCH 34826 had no effect on blood pressure or heart rate in these normotensive subjects. SCH 34826 promoted significant increases in excretion of urinary sodium, phosphate, and calcium. The cumulative 5-hour urinary sodium excretion was 15.7 +/- 7.3 mmol for the placebo and 22.9 +/- 5, 26.7 +/- 6 (p less than 0.05), and 30.9 +/- 6.8 mmol (p less than 0.01) for the 400, 800, and 1600 mg SCH 34826 doses, respectively. During the same time interval, the cumulative urinary phosphate excretion increased by 0.3 +/- 0.4 mmol after placebo and by 1.5 +/- 0.3 (p less than 0.01), 1.95 +/- 0.3 (p less than 0.01), and 2.4 +/- 0.4 mmol (p less than 0.001) after 400, 800, and 1600 mg SCH 34826, respectively. There was no change in diuresis or excretion of urinary potassium and uric acid. The natriuretic response to SCH 34826 occurred in the absence of any change in plasma atrial natriuretic peptide levels but was associated with a dose-dependent elevation of urinary atrial natriuretic peptide and cyclic guanosine monophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Non-invasive estimate of the mechanical properties of peripheral arteries from ultrasonic and photoplethysmographic measurements.

The non-linear elastic response of arteries implies that their mechanical properties depend strongly on blood pressure. Thus, dynamic measurements of both the diameter and pressure curves over the whole cardiac cycle are necessary to characterise properly the elastic behaviour of an artery. We propose a novel method of estimating these mechanical properties based on the analysis of the arterial diameter against pressure curves derived from ultrasonic and photoplethysmographic measurements. An ultrasonic echo tracking device has been developed that allows continuous recording of the internal diameter of peripheral arteries. It measures the diameter 300 times per second with a resolution of 2.5 microns. This system is linked to a commercially available light-plethysmograph which continuously records the finger arterial pressure (0.25 kPa accuracy). Because of the finite pulse wave velocity, the separation between the diameter and the pressure measurement sites causes a hysteresis to appear in the recorded diameter-pressure curve. Using a model based on haemodynamic considerations, the delay between the diameter variations and the finger arterial pressure is first eliminated. As the pulse wave velocity depends on the pressure, the delay is determined for each pressure value. The relationship between pressure and diameter is then described by a non-linear mathematical expression with three parameters, which best fits the recorded data. The dynamic local behaviour of the vessel is fully characterised by these parameters. Compliance, distensibility and pulse wave velocity can then be calculated at each pressure level. Thus, the mechanical behaviour of peripheral human arteries can now be characterised non-invasively over the pressure range of the whole cardiac cycle. The results obtained in vivo on human radial and brachial arteries show that a thorough analysis of the compliance-pressure curves and their modifications (curving, shift) is needed in order to compare two different vessels in a meaningful way.

Adult↗
PubMed1991

Dose-response relationships following oral administration of DuP 753 to normal humans.

We assessed the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy volunteers. In a single dose study, doses of 2.5, 5, 10, 20, and 40 mg of DuP 753 or placebo were tested serially at one week intervals. In the multiple dose study, the administration of placebo or DuP 735 (5, 10, 20, or 40 mg, per os once daily) for eight consecutive days was evaluated. The blood pressure response to angiotensin I and II was inhibited in a dose-dependent fashion with a blocking effect still present 24 h post drug. DuP 753 also induced a dose-dependent compensatory rise in plasma renin. This new compound was well tolerated by these normal volunteers. Thus, DuP 753 appears to be a well tolerated, orally active, potent and long-lasting antagonist of angiotensin II in humans.

Administration, Oral↗
PubMed1991

In vitro effects of DuP 753, a nonpeptide angiotensin II receptor antagonist, on human platelets and rat vascular smooth muscle cells.

These experiments were designed to assess the ability of the new nonpeptide angiotensin II antagonist DuP 753 to inhibit the binding and, particularly, to antagonize the cellular response to angiotensin II in human platelets and primary cultures of rat aortic smooth muscle cells (SMC). The binding of 125I-angiotensin II was competitively inhibited by DuP 753 with a 50% binding inhibition (IC50) of 5 to 6 x 10(-8) mol/L in platelets and 1 x 10(-8) mol/L in vascular SMC as compared to an IC50 of 5 to 7.5 x 10(-9) mol/L with nonlabeled angiotensin II. In vascular SMC, DuP 753 completely abolished the effects of angiotensin II on 45CaCl2 efflux and 45CaCl2 uptake. Moreover, in these latter cells, DuP 753 prevented the angiotensin II but not the vasopressin induced increase in cytosolic calcium. These results demonstrate that DuP 753 competes with angiotensin II binding to its receptor in both animal and human cells and selectively blocks the cellular response to angiotensin II.

Angiotensin II↗
PubMed1991

Effect of the renin response during renin inhibition: oral Ro 42-5892 in normal humans.

The effect of the new renin inhibitor Ro 42-5892 was evaluated in healthy volunteers after both intravenous and oral administration. In a preliminary study, 14 subjects received a 10-min infusion of Ro 42-5892 at doses ranging from 0.001 to 1 mg/kg. Plasma renin activity (PRA) and angiotensin (Ang) II levels were maximally suppressed in a dose-dependent manner at the end of the infusion. Plasma active renin concentration increased up to threefold. In a second study, 24 volunteers received placebo or 100, 600, or 1,200 mg of Ro 42-5892 p.o. in a single-blind, randomized fashion. Within 30 min after drug intake, PRA and plasma Ang I and Ang II levels fell to their nadir. Both Ang I and Ang II were measured specifically after extraction on phenylsilylsilica and separation by isocratic HPLC. The degree as well as the duration of inhibition were dose related. The decrease in plasma Ang lasted maximally for 2 h. Active renin increased dose dependently and remained elevated for more than 8 h after the 1,200 mg dose. A theoretical generation rate of Ang I was calculated for individual plasma samples assuming Michaelis-Menten kinetics for competitive inhibition and steady-state conditions. This calculated Ang I generation rate, based on plasma active renin concentrations and drug levels, closely correlated with actually measured Ang I and Ang II levels (r = 0.90, n = 88) over the whole 8 h time period. Thus, a sustained renin inhibition by Ro 42-5892, as indicated by increased plasma active renin levels, induces a much shorter fall in plasma Ang I and II apparently because of a rise in renin secretion.

Administration, Oral↗
PubMed1991

Baroreflex and atrial natriuretic factor concentration correlate with myocardial infarct size and predict early death in rabbits: implications for drug studies.

The severity of myocardial infarction (MI) and its functional consequences are difficult to assess in small animals. We searched for criteria to achieve such an assessment in rabbits 1 week after MI. Thirteen large mongrel rabbits (3-4 kg) were anesthetized with pentobarbitone for ligating a branch of the circumflex coronary artery and 7 rabbits were subject to a sham operation without ligation. All sham-operated rabbits and 12 MI animals survived for 1 week, when blood was obtained for biochemical analyses and the baroreflex was tested. Six animals survived to the third week (survivors) and six died earlier (nonsurvivors). The MI size, measured immediately after death, was 42 +/- 3% of the left ventricular mass in nonsurvivors and 20 +/- 7% in survivors. The plasma atrial natriuretic factor (ANF) concentration was correlated linearly with MI size (r = 0.77) over the whole range of infarct sizes and, like the MI size itself, was associated with the risk of early death (critical limit: 80 pM). Plasma renin activity and catecholamines yielded less prognostic information. The baroreflex control of the heart rate (tested using phenylephrine and nitroprusside) of nonsurvivors was severely impaired and the slopes correlated with MI size (r = 0.90 for phenylephrine and r = 0.67 for nitroprusside). The plasma ANF concentration and the baroreflex both accurately reflected MI size and also correctly classified 11/12 rabbits into survivors and nonsurvivors. An ANF- and baroreflex-based stratification of animals for future studies on therapeutic interventions after MI will reduce the number of animals required by at least 65%, making such studies far more feasible than in the past.

Animals↗
PubMed1991

Effect of weight reduction in moderately overweight patients on recorded ambulatory blood pressure and free cytosolic platelet calcium.

Although platelet cytosolic calcium has been shown to decrease during pharmacological treatment of hypertension, there is no evidence that cytosolic calcium also falls during a nonpharmacological reduction in blood pressure. To provide such evidence, we examined prospectively the relation between platelet cytosolic calcium and ambulatory blood pressure during weight reduction in moderately overweight (body mass index [BMI] greater than 25), mildly hypertensive individuals. The experimental group (responders: BMI reduction greater than 5%) consisted of 19 patients who lost 8.5 +/- 2.9 kg (mean +/- SD, p less than 0.05) during a 10-week hypocaloric diet, whereas the control group (nonresponders: BMI reduction less than 5%) consisted of 12 patients who showed no relevant change in body weight (-2.0 +/- 1.3 kg) during the same period of time. The moderate weight loss of the responders decreased blood pressure by 14/5 mm Hg (p less than 0.05), as measured by ambulatory monitoring, which renders a placebo effect unlikely. This nonpharmacological reduction in blood pressure was accompanied by a proportional 11% decrease (p less than 0.05) in platelet cytosolic calcium and also by significant (p less than 0.05) decreases in plasma catecholamines and serum cholesterol. These findings establish the concept of a nonpharmacological reduction in free cytosolic platelet calcium in humans and add further evidence suggesting a link between intracellular calcium homeostasis and blood pressure regulation.

Blood Platelets↗
PubMed1991

Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers. Inhibition of pressor response to exogenous angiotensin I and II.

BACKGROUND: The purpose of the present study was to assess the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy male volunteers. METHODS AND RESULTS: In the first study (single-dose study), eight volunteers were included in a 2-day protocol repeated four times at 1-week intervals. In each phase, a different dose of drug (2.5, 5, 10, 20, or 40 mg) or placebo was given. The peak systolic blood pressure response to a test-dose of angiotensin I was determined serially before and after oral administration of DuP 753 by continuously monitoring finger blood pressure using a photoplethysmographic method. DuP 753 reduced the systolic blood pressure response to angiotensin I in a dose-dependent fashion. Three, 6, and 13 hours after the 40-mg dose, blood pressure response decreased to 31 +/- 5%, 37 +/- 6%, and 45 +/- 3% of the control values (mean +/- SEM, n = 7), respectively. In the second study, 29 volunteers were treated for 8 days with either a placebo or DuP 753 (5, 10, 20, or 40 mg p.o. q.d.) and challenged on the first, fourth, and eighth days with bolus injections of angiotensin II. Again, the inhibitory effect on the systolic blood pressure response to angiotensin II was clearly dose dependent. Six hours after 40 mg DuP 753, the systolic blood pressure response to the test-dose of angiotensin II was reduced to 37 +/- 7%, 40 +/- 4%, and 38 +/- 6% of baseline values (mean +/- SEM, n = 6) on days 1, 4, and 8, respectively. With this latter dose, there was still a blocking effect detectable 24 hours after the drug. Similar to angiotensin converting enzyme and renin inhibitors, DuP 753 induced a dose-dependent increase in plasma renin that was more pronounced on the eighth than on the first day of drug administration. In these normal volunteers, no consistent clinically significant side effects were observed. There was no evidence for an agonist effect. CONCLUSIONS: DuP 753 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of angiotensin II in men.

Administration, Oral↗