To determine the pharmacokinetic, subjective effects of a single 20 mg dose of nefopam administered either intravenously or orally in healthy volunteers, twenty-four healthy Caucasian men received 20 mg nefopam orally+placebo intravenous infusion and placebo orally+intravenous infusion of 20 mg nefopam with one week interval, in a double-blind, double-dummy cross-over study. Nefopam and desmethyl-nefopam plasma concentrations were measured by HPLC with UV detection up to 48 hr after drug administration. Self-rating questionnaires (Mood and vigilance Visual Analogue Scales, Addiction Research Centre Inventory) and drug safety were investigated. The F value (bioavailability) of the parent drug was 0.36+/-0.13. The AUCoral/AUCiv ratio of nefopam+desmethyl-nefopam was 0.62+/-0.23. The half-life of nefopam was similar whether administered orally (5.1+/-1.3 hr) or intravenously (5.1+/-0.6 hr). The half-life of desmethyl-nefopam was two to three times longer than that of the parent molecule (orally: 10.6+/-3.0 versus 5.1+/-1.3 hr, P<10(-4) and intravenously: 15.0+/-2.4 versus 5.1+/-0.6 hr, P<10(-4)). As assessed by the Addiction Research Centre Inventory, no evidence of abuse liability in healthy, drug-naive volunteers was observed. On visual analogue scales, volunteers rated themselves as more drowsy, less alert, less energetic and less anxious after oral compared to intravenous administration. The AUC0-->24 hr of anxiety and energy parameters were not different after oral and intravenous administration: 90+/-142 versus 35+/-84 (P=0.27) and 66+/-74 versus 46+/-54 mm x hr (P=0.36), respectively. The AUC0-->24 hr of drowsiness and alertness parameters were significantly greater after oral than after intravenous administration: 68+/-65 versus 27+/-30 (P=0.005) and 54+/-63 versus 28+/-48 mm x hr (P=0.03), respectively. A clockwise hysteresis loop was observed for drowsiness in 16 out of 24 volunteers after oral administration. The results suggest that in healthy volunteers desmethyl-nefopam may contribute to the pharmacodynamic effects of single dose nefopam solution administered orally. This study shows a rather low bioavailability of nefopam given in intravenous solution when administered orally. Nevertheless, when the main metabolite desmethyl-nefopam is taken into account, the ratio of the areas under the curves is almost doubled.

Nefopam (NEF) and desmethyl-nefopam (DMN) were assayed simultaneously in plasma, globule and urine samples using imipramine as internal standard. A liquid-liquid extraction procedure was coupled with a reverse phase high-performance liquid chromatography system. This system requires a mobile phase containing buffer (15 mM KH(2)PO(4) with 5 mM octane sulfonic acid: pH 3.7) and acetonitrile (77:33, v/v) through (flow rate=1.5 ml/min) a C(18) Symmetry column (150x4.6 I.D., 5 micrometer particle size: Waters) and a UV detector set at 210 nm. Internal standard was added to 1 ml of plasma or globule sample or 0.5 ml of urine sample, prior to the extraction under alkaline ambiance with n-hexane. The limits of quantification were 1 and 2 ng/ml for both molecules in plasma and globule, respectively; 5 and 10 ng/ml for NEF and DMN in urine, respectively. The method proved to be accurate and precise: the relative error at three concentrations ranged from -13.0 to +12.3% of the nominal concentration for all molecule and biological fluid; the within-day and between-day precision (relative standard deviation %) ranged from 1.0 to 10.1% for all the molecules and biological fluids. The method was linear between 1 and 60 ng/ml for both molecules in the plasma; 2 and 25 ng/ml for both molecules in the globule; 25 and 250 ng/ml for NEF and 50 and 500 ng/ml for DMN in the urine: correlation coefficients of calibration curves (determined by least-squares regression) of each molecule were higher than 0.992 whatever the biological fluid and during the pre-study and in-study validations. This method was successfully applied to a bio-availability study of NEF in healthy subjects.

Self blood pressure measurement (SBPM) is not fully applied because of the cost of devices and the lack of efficient dedicated medical networks. The aim of the REVEIL study was to allow patients to freely rent SBPM devices by their pharmacist after initial medical prescription. Practitioners taught SBPM methods to the patients with a booklet and the pharmacist explained them how to use the device. This preliminary report focuses on the 428 first patients included from September 1999 to June 2000 by their general practitioner (n = 59) or cardiologist (n = 12) in the centre of the city of Reims (France), when he thought there was an indication for a SBPM period. The patient received a medical prescription and took a validated device (Omron 705CP) by one of the 44 pharmacists who accepted to participate. After 7 days the patient consulted his practitioner with the filled booklet. The prescription was for 7 days with 3 measurements each morning (before intake of antihypertensive drugs) and each evening (12 hours later). Patients reported the results on the booklet and enclosed the report printed by the device. From the 428 included patients, 362 (85%) gave analyzable data, the difference being explained by refusals (n = 39) and by the lag between inclusion and completion. Mean age was 55.2 (range 20 to 90). Education levels were: no graduation (n = 71), primary school (n = 172), college (n = 59), university (n = 86) [no answer in n = 40]. Seventy nine percent (n = 286) performed at least 12 measurements on three consecutive days. There is no significant difference between morning and evening completions. According to themselves, 294 patients fully succeeded in SBPM. Eighteen failed (6 reported a failure of the device, 2 had not understood the procedure, 5 had forgotten, 5 reported another cause), 50 did not answer. These results establish the fair applicability of SBPM under the realistic conditions of the REVEIL study (free rent of devices after medical prescription) as 85% of patients gave contributive information with a good quality in 79% of them.

The REVEIL study is a pilot studies to determine the feasibility of self blood pressure measurement (SBPM). Feasibility was assessed by the quality of measurements and the patient opinion. This preliminary report focused on the patient opinion. Patients were included in the study by their general practitioner or cardiologist when he thought there was an indication for SBPM. Patients were excluded if their physical or mental autonomy was not sufficient to perform SBPM or if they were arrhythmic. The lending of the device was free (against a guarantee of 800 F) and it was available in one of the 44 drugstores that participated to the study. The physician performed patient education about SBPM and the druggist explained the handling of the device. SBPM was performed over a 7-day period: every day two series of 3 consecutive measurements were requested in the morning before taking the antihypertensive treatment, and in the evening between dinner and bedtime. The device was the validated OMRON 705 CP. 428 patients were included in the study. Among them, 385 (90%) accepted to participate to the study and 43 refused (10%). Almost half of the refusals were due to patients that did not want to take care of them and 16% were justified by a technical problem. Preliminary data included 362 patients aged 55.2 years, 79 of them older than 70 years. 80 patients (22%) experienced difficulties to perform SBPM, 28 of them (7.3%) to perform measurements and 13 (3.4%) to understand how worked the device. At the end of the study, 82 patients (23%) had better understanding of their hypertension, 90 patients (25%) felt themselves more motivated to take their medication and 111 patients (31%) found that their physician took better charge of them. 286 patients (79%) evaluated the overall satisfaction at SBPM. Among them, 276 patients (97%) were very satisfied (57%) or satisfied (40%) with SBPM when only 3% of patients were not. In summary, SBPM was easily performed in the conditions of the REVEIL study, and the majority of patients was satisfied with this experience.

Self blood pressure measurement (SBPM) is not fully applied because of the cost of devices and the lack of efficient dedicated medical networks. The aim of the REVEIL study was to allow patients to freely rent SBPM devices by their pharmacist after initial medical prescription. Practitioners tought SBPM methods to the patients with a booklet and the pharmacist explained them how to use the device.This preliminary report focuses on the 428 first patients included from September 1999 to June 2000 by their general practitioner (n=59) or cardiologist (n=12) in the centre of the city of Reims (France), when he thought there was an indication for a SBPM period. The patient received a medical prescription and took a validated device (Omron 705CP) by one of the 44 pharmacists who accepted to participate. After 7 days the patient consulted his practitioner with the filled booklet.The prescription was for 7 days with 3 measurements each morning (before intake of antihypertensive drugs) and each evening (12 hours later). Patients reported the results on the booklet and enclosed the report printed by the device.From the 428 included patients, 362 (85%) gave analysable data, the difference being explained by refusals (n=39) and by the lag between inclusion and completion. Mean age was 55.2 (range 20 to 90). Education levels were: no graduation (n=71), primary school (n=172), college (n=59), university (n=86) [no answer in n=40].Seventy nine percent (n=286) performed at least 12 measurements on three consecutive days. There is no significant difference between morning and evening completions. According to themselves, 294 patients fully succeeded in SBPM. Eighteen failed (6 reported a failure of the device, 2 had not understood the procedure, 5 had forgotten, 5 reported another cause), 50 did not answer.These results establish the fair applicability of SBPM under the realistic conditions of the REVEIL study (free rent of devices after medical prescription) as 85% of patients gave contributive information with a good quality in 79% of them.

The REVEIL study is a pilot studes to determine the feasibility of self blood pressure measurement (SBPM). Feasibility was assessed by the quality of measurements and the patient opinion. This preliminary report focused on the patient opinion. Patients were included in the study by their general practitioner or cardiologist when he thought there was an indication for SBPM. Patients were excluded if their physical or mental autonomy was not sufficient to perform SBPM or if they were arrhythmic. The lending of the device was free (against a guarantee of 800 F) and it was available in one of the 44 drugstores that participated to the study. The physician performed patient education about SBPM and the druggist explained the handling of the device.SBPM was performed over a 7-day period: every day two series of 3 consecutive measurements were requested in the morning before taking the antihypertensive treatment. and in the evening between dinner and bedtime. The device was the validated OMRON 705 CR 428 patients were included in the study. Among them, 385 (90%) accepted to participate to the study and 43 refused (10%). Almost half of the refusals were due to patients that did not want to take care of them and 16% were justified by a technical problem. Preliminary data included 362 patients aged 55.2 years, 79 of them older than 70 years. 80 patients (22%) experienced difficulties to perform SBPM, 28 of them (7.3%) to perform measurements and 13 (3.4%) to understand how worked the device. At the end of the study, 82 patients (23%) had better understanding of their hypertension, 90 patients (25%) felt themselves more motivated to take their medication and 111 patients (31%) found that their physician took better charge of them. 286 patients (79%) evaluated the overall satisfaction at SBPM. Among them, 276 patients (97%) were very satisfied (57%) or satisfied (40%) with SBPM when only 3% of patients were not.In summary, SBPM was easily performed in the conditions of the REVEIL study, and the majority of patients was satisfied with this experience.

BACKGROUND AND OBJECTIVESHypertension is found in one‐third of acromegalic patients. An heterogenous distribution of cardiac output has been recently demonstrated in acromegalic patients with an increased blood flow at the level of the upper limb, suggesting that acromegalic patients may have some degree of endothelial dysfunction. Elsewhere, studies involving hypopituitary GH‐deficient adults have shown that GH and/or IGF‐I may have direct effect on endothelial function.SUBJECTS AND METHODSWe thus compared cutaneous vasoreactivity responses in 10 normotensive patients with active acromegaly (A) (six women and four men) aged 25–59 (mean, 43.2 years), whose basal GH and IGF‐I levels ranged from 7.4 to 158 mU/l and from 401 to 1690 μg/l, respectively, and in 10 normal age‐ and sex‐matched controls (NC) by means of Laser Doppler flowmetry at the levels of the palm and the dorsum of the right hand. Circulatory skin velocities were studied basally and after increasing skin temperature to 44 °C (in order to study direct nonspecific vasodilatation response which is independent of endothelial or autonomous nervous system and reflects normal vascular muscle function), after shear‐stress (known to produce flow‐dependent vasodilatation, mediated by nitric oxyde (NO) originating from endothelial cells) and after cold‐stress applied on the opposite hand (known to produce vaso‐constriction mediated by the sympathetic nervous system).RESULTSThe warm test induced a significant (P < 0.001) and similar increase in both dorsal and palmar skin perfusion in A (mean ± SD) (240 ± 96 and 238 ± 134%, respectively) and NC (232 ± 137 and 233 ± 73, respectively). Ischaemia release induced a significant increase in both dorsal and palmar skin blood flows in the two groups (P < 0.001), but reactivities in acromegalic patients were about one half of those measured in controls (22.9 ± 16.2% (A) vs. 46.9 25% (NC), 2P < 0.02, at the level of the dorsum; and 45.0 ± 43.6% (A) vs. 104.7 ± 40.1 (NC), 2P < 0.01, at the level of the palm). Cold pressor test resulted in significant decreases in both cutaneous flows (P < 0.01) in the two groups, with a larger vasoconstriction (that did not reach statistical significance) in acromegalic patients as compared with controls (P < 0.10).CONCLUSIONVascular smooth cell ability to produce skin vasodilatation is normal but endothelium‐dependent vasodilatation appears to be impaired while sympathetic‐mediated vasoconstrictive response might be increased in acromegaly. This endothelial dysfunction may contribute to hypertension and represent a risk factor for cardiovascular complications in acromegaly.

The aim of this study was to validate in rats an alternative to the radioactive microspheres (RM) reference technique, the fluorescent microspheres (FM), for the simultaneous determination of cardiac index (CI) and regional blood flows (RBF). Validation of the FM method was performed in three steps: (a) comparison of CI and RBF values obtained simultaneously by FM and RM, (b) determination of the repeatability of the measurements by using two successive injections of FM, and (c) evaluation of the ability of the FM method to assess vasodilating effects (by using dipyridamole). CI values (range, 242-513 ml/min x kg; n = 20) obtained with FM correlated with those obtained with RM (r = 0.82: p<0.001), and agreement was found between FM and RM (error 95% confidence interval for one pair, +/-125 ml/min x kg). FM RBF values, although smaller than corresponding RM RBF values, were correlated with the latter (range, 0.1-7 ml/min x g; n = 71; r = 0.99; p< 0.001). Agreement was dependent on RBF values, e.g., error 95% confidence intervals for one pair were 0.08-0.13 and 3.86-6.48 for 0.1 and 5 ml/min x g, respectively. Two successive FM injections at a 10-min interval (conscious rats) provided similar values (n = 14) for CI (306+/-24 vs. 346+/- 18 ml/min x kg), and renal (5.1+/-0.2 vs. 6.2+/-0.3 ml/min x g), left (6.1+/-0.3 vs. 5.8+/-0.4 ml/min x g) and right (4.8+/-0.4 vs. 4.7+/-0.3 ml/min x g) myocardial RBF. Corresponding error 95% confidence intervals were +/-187 ml/min x kg, +/-2.8, +/-2.2, and +/-2.0 ml/min x g, respectively. Dipyridamole (2, 4, 6, and 8 mg/kg x min for 10 min, i.v.; n = 9-13 per group, conscious rats) significantly and dose dependently increased left and right myocardial blood flows, whereas renal blood flow was not affected. We conclude that the FM technique (a) is reliable and in agreement with the RM method, (b) provides repeatable measurements of systemic and regional hemodynamics, and (c) allows detection and quantification of vasodilating effects in rats.

Fundamental & Clinical PharmacologyVolume 10, Issue 3 p. 319-320 Repeatability of laser Doppler measurements of cutaneous blood flow in clinical pharmacology studies P. Maison, P. Maison Service de Pharmacologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, FranceSearch for more papers by this authorP. Démolis, P. Démolis Service de Pharmacologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, FranceSearch for more papers by this authorJF Giudicelli, JF Giudicelli Service de Pharmacologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, FranceSearch for more papers by this author P. Maison, P. Maison Service de Pharmacologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, FranceSearch for more papers by this authorP. Démolis, P. Démolis Service de Pharmacologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, FranceSearch for more papers by this authorJF Giudicelli, JF Giudicelli Service de Pharmacologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, FranceSearch for more papers by this author First published: May‐June 1996 https://doi.org/10.1111/j.1472-8206.1996.tb00313.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume10, Issue3May‐June 1996Pages 319-320 RelatedInformation

Background and Purpose The technique of transcranial Doppler ultrasonography (TCD) is widely used for assessment of cerebral blood flow velocity. Whether measurement of changes in TCD velocity can be used for studying volumetric cerebral blood flow variations remains a matter of debate. We therefore investigated the relationship between flow velocity and volumetric cerebral blood flow before and during acetazolamide-induced vasodilation. Methods The middle cerebral artery mean blood how velocity (MV) measured by TCD and the corresponding regional and hemispheric cerebral blood flows assessed with Xe-133 single-photon emission CT were measured in 52 unselected patients. Absolute values of flow and velocity before and after stimulation and their reactivity to acetazolamide were compared. When the correlation was statistically significant, the linearity of the relationship was tested. Results Absolute values of hemispheric cerebral blood flow were correlated with MV both before (r=.315, P=.02) and after acetazolamide (r=.436, P=.001), whereas regional cerebral blood flow was correlated with MV only after acetazolamide (before, r=.262, P=.06; after, r=.446, P=.001). All these relationships fitted a linear model. In contrast, there was no correlation between acetazolamide-induced relative increments of flow and velocity. Conclusions Our results support a Linear model describing the relationship between absolute values of flow and velocity when arterial section is the slope and anastomotic blood flow is the intercept. In contrast, relative increments in volumetric flow and velocity may be proportional only if anastomotic flow is negligible, ie, in subjects without cerebrovascular disease. We conclude that, for patients with cerebrovascular disease, TCD does not satisfactorily model cerebral vasoreactivity in terms of volumetric cerebral blood how.

The influence of local resistance and cardiac performance on peripheral blood acceleration was investigated in 14 healthy male volunteers. Steady and pulsatile flow was studied in the brachial and in the common carotid arteries, ie, two territories that exhibit marked differences in resistive characteristics. Instantaneous blood velocity (V), mean blood velocity (Vm) and artery diameter (D) were evaluated at rest by an ultrasonic range-gated pulsed Doppler flowmeter using a double transducer probe, thus allowing the calculation of mean blood flow (Q). Mean local resistance (R) was obtained by dividing the mean arterial pressure by Q. The peak value of the local acceleration of the blood was obtained by computer-assisted calculation of the first derivative of instantaneous blood velocity (Gmax = +dV/dtmax). Peak aortic blood acceleration (GAo) was simultaneously measured from the suprasternal notch using a pulsed Doppler velocity meter. In the branchial and the common carotid arteries, Gmax was of a similar magnitude (551 +/- 30 and 555 +/- 44 cm/s2, respectively) despite major differences in the respective D, Vm, Q and R values. In neither artery was there a relationship between Gmax and either resting Q or R. At the brachial artery level, Gmax was positively related to GAo (r = 0.79, P = 0.0008). At the common carotid artery level, there was a weak, although non significant relationship between Gmax and GAo (P = 0.08). Our results indicate that the local acceleration of peripheral blood flow in the brachial artery is related rather to upstream central impulse than to downstream hemodynamics, and suggest some regional differences in the hemodynamic determinants of the local acceleration of peripheral blood flow.

Acetazolamide (ACTZ) vasodilating properties are used for the assessment of cerebral vasodilatory reserve not only in cerebral pathology investigation, but also in clinical pharmacology studies. However, the kinetics of these vasodilating properties are not clearly established; moreover, the cerebral selectivity of ACTZ-induced vasodilation has not been demonstrated. To address these issues, we performed an ACTZ test in 9 healthy volunteers and measured noninvasively the effects exerted by the drug simultaneously on common carotid artery blood flow (CCABF), middle cerebral artery mean blood flow (BF) velocity (MV) (transcranial Doppler technique), and facial cutaneous BF (CutBF). The time of the peak increase in MV was variable, occurring between 20 and 40 min after ACTZ, and brief. In addition, simultaneous increases (with variable mean peak times) occurred in flows in the CCA (+11% at 20 min) and in its intracranial (+25% at 30 min) and extracranial (+134% at 50 min) branches. The first finding suggests that the cerebral effects of ACTZ should be measured repeatedly to detect in each individual subject the time of MV peak increase; the transcranial Doppler is particularly suitable for such an approach. The second finding suggests that, especially in patients, extracranial actions of ACTZ must be taken into account for estimation of the cerebral vasodilatory reserve.

Summary— The effects of two single oral doses (5 mg and 20 mg) of a new angiotensin I‐converting enzyme inhibitor, imidapril, on a) systemic hemodynamics (arterial pressure, heart rate, cardiac output), b) brachial and common carotid arteries' hemodynamics (diameter and blood flow, pulsed Doppler technique), c) cerebral hemodynamics (middle cerebral artery mean blood flow velocity, transcranial Doppler technique), and d) biological parameters (plasma converting enzyme activity, active plasma renin, plasma aldosterone, catecholamines, and atrial natriuretic factor) were investigated and compared with those of a placebo during the 24 h period following administration in a randomized, double‐blind, cross‐over study performed in six healthy volunteers. Imidapril induced a strong, dose‐dependent and sustained inhibition of plasma converting enzyme activity and at the 20 mg dose an increase in active plasma renin. Other investigated biological parameters were not drug‐affected. Imidapril, whatever the dose, did not significantly affect systemic hemodynamic parameters. Imidapril, 20 mg, significantly increased common carotid artery blood flow and diameter and brachial artery diameter. Brachial blood flow also tended to increase but this was not significant. The middle cerebral artery mean blood flow velocity investigated in only five volunteers, underwent spontaneous variations after placebo, and these variations were not affected by imidapril, suggesting that imidapril, whatever the dose, does not influence cerebral blood flow. Thus, imidapril's vasodilating properties apparently affect only the muscular (brachial artery) and cutaneous (external carotid artery) territories, but do not influence the cerebral vascular bed.

The effects of a single oral dose (20 mg) of lisinopril on systemic, carotid (pulsed Doppler), and cerebral (middle cerebral artery, transcranial Doppler) hemodynamics have been investigated over an 8-h period in eight healthy volunteers in a double-blind placebo-controlled crossover study. In addition, cerebral vasodilatory reserve was measured (acetazolamide test). Lisinopril did not affect systemic hemodynamics but it increased both common carotid artery blood flow (+26.2%, p < 0.01) and diameter (+4.5%, p < 0.05) after 8 h. Lisinopril did not affect middle cerebral artery mean blood flow velocity but increased cerebral resistance index (+8.1%, p < 0.05) at 4 h and cerebral vasodilatory reserve (+24.8%, p < 0.05). These data suggest that lisinopril produces a paradoxical vasoconstriction of the small cerebral arterioles. This vasoconstriction might be a compensatory mechanism to a dilation of large cerebral arteries, thus resulting in an unchanged cerebral blood flow.

1. Transcranial Doppler measurements of the mean blood flow velocity and the resistance index in the middle cerebral artery are used to assess cerebral haemodynamics. The prerequisite for the use of these parameters in clinical pharmacology studies is an evaluation of their repeatability and spontaneous variation with time.2. Repeatability of transcranial Doppler measurements of mean blood flow velocity and resistance index was investigated in healthy subjects by calculation of the repeatability coefficient as defined by the British Standards Institution. Intra-observer repeatability (comparison of two successive determinations by one observer, n=30 subjects), between-observer repeatability (comparison of two successive measurements each performed by a different observer, n=30) and long-term repeatability (comparison of two determinations performed at the same hour with a 1 week interval by one observer, n=14) were assessed. In addition, the spontaneous evolution with time of mean blood flow velocity and resistance index was determined over an 8 h period (n=14).3. Repeatability coefficients for intra-observer repeatability, between-observer repeatability and long-term repeatability were 4.83, 4.59 and 3.32 cm/s for mean blood flow velocity (normal value = 61.2+/-10.2 cm/s) and 2.62, 3.12 and 3.49% for resistance index, respectively (normal value = 53.6+/-5.9%), indicating that transcranial Doppler measurements are repeatable enough to be used over periods of time of up to 1 week in clinical pharmacology studies.4. Finally, a time effect was detected for mean blood flow velocity, indicating that this parameter undergoes diurnal variation.

1. The effects of a single oral dose (10 mg) of ramipril on (a) systemic haemodynamics (arterial pressure, cardiac output), (b) carotid artery haemodynamics (blood flow and diameter, pulsed Doppler technique), (c) intracranial haemodynamics (middle cerebral artery mean blood velocity, transcranial Doppler technique), and (d) renin-angiotensin system (plasma converting enzyme and renin activities) have been investigated and compared with those of a placebo during the 24 h period following administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. 2. Ramipril induced a strong and sustained inhibition of plasma converting enzyme activity (-96% at 4 h, -63% at 24 h) and an increase in plasma renin activity (+993% at 8 h). 3. As compared with placebo, ramipril did not significantly affect arterial blood pressure, heart rate, cardiac output and total peripheral resistance. 4. Ramipril significantly increased carotid blood flow (by 27% at 8 h) without significantly changing carotid artery diameter, indicating, given the unchanged arterial pressure, an arteriolar vasodilation in the carotid territory. 5. The middle cerebral artery mean blood flow velocity underwent spontaneous modifications during the placebo period but these changes were not affected by ramipril. This lack of influence of ramipril on intracranial haemodynamics suggests that the drug-induced arteriolar vasodilation and increase in carotid blood flow only concern the extracranial, musculo-cutaneous part of the carotid territory.

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.