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Biomedical subjects

M Safar

Publications and source records attributed to M Safar.

At least 253 records · Page 14Linked to original sources

[Arterial pressure, heart rate and systolic time intervals in patients on long-term hemodialysis dialyzed with a bath containing acetate or bicarbonate].

UNLABELLED: Blood pressure (BP), body weight, heart rate and systolic time intervals (STI) were measured every 6 months during 18 months in a group of 25 patients hemodialyzed with bicarbonate (B), as compared with 25 patients dialyzed with acetate (A). Dialysate Na remained at 140mmol/l. During the dialysis session, the decrease in BP were similar in the 2 groups but tachycardia was observed exclusively with A. The ratio between pre-ejection period (PEP) and left ventricular ejection time (LVET) increased during dialysis similarly in both groups. However predialytic PEP/LVET increased in the A group and decreased in the B group, becoming significantly lower in the Bi group at 18 months. With Bi, the loss of weight was significantly greater during the Hd session for the same decrease in blood pressure. CONCLUSION: 1) During dialysis, the increase of PEP and PEP/LVET seems to be directly connected with the weight loss, and is the same in both groups. 2) The long term decrease of predialysis PEP and PEP/LVET seen with the B group can be explain by a greater degree of water inflation and by an improvement of myocardial contractility.

Acetates↗

[Pharmacokinetics of isosorbide dinitrate administered by intravenous infusion to hypertensive patients (author's transl)].

The pharmacokinetics of intravenous isosorbide dinitrate was investigated in 11 patients with labile hypertension and with normal renal and hepatic functions. The mode of administration (constant rate infusion without loading dose) was chosen in order to minimize side-effects and to approximate clinical conditions. Isosorbide dinitrate levels were measured by electron-capture gas chromatography. The volume of distribution during steady state (Vd beta = 318 +/- 117 I) and the elimination half-life (t1/2 beta = 64.8 +/- 30.5 min) were similar to those found after perlingual and oral administration. Systemic clearance (Cls = 3.80 +/- 1.48 I/min) was high for a drug given intravenously, presumably because of active hepatic extraction, intensive pre-systemic degradation and very active extra-hepatic metabolism. These findings should be compared with the considerable inter-individual variations observed in theoretical plasma concentrations during steady state and with the presence of two pharmacokinetic models (one -- and two -- compartments) in the patients under study. Comparison of the results obtained by the intravenous route with previously published results after perlingual and oral administration indicates the following bioavailability ratios: perlingual/i.v. = 31%, oral/i.v. = 20%, and oral/perlingual = 63%.

Female↗

Effects of captopril on prostaglandin and natriuresis in patients with essential hypertension.

The antihypertensive, renal and hormonal effects of captopril were studied in 10 patients with essential hypertension. Captopril significantly decreased arterial blood pressure with a concomitant increase in glomerular filtration rate, natriuresis and kaliuresis and a significant selective increase in urinary (renal) prostaglandin E2; other plasma and urinary prostaglandin (F2 alpha, 6-keto-prostaglandin F1 alpha; thromboxane B2) were not significantly changed. The urinary prostaglandin E2 increase was observed even in patients with pretreatment subnormal prostaglandin E2 excretion. Increases in urinary prostaglandin E2 were significantly positively correlated with increases in urinary sodium concentration. It is concluded that the antihypertensive effect of captopril is mediated, at least partially, by prostaglandin E2 release from renal and extrarenal tissues. Captopril enhances natriuresis at a lower perfusion pressure.

Blood Pressure↗

[Urinary thromboxane B2 in hypertensive patients].

UNLABELLED: Thromboxane A2 (TxA2) is a vasoconstrictor synthetized by the kidney. Its role in hypertension is unknown. We measured urinary TxB2 (the metabolite of renal TxA2) by radioimmunoassay and studied renal functions in 15 borderline, 15 sustained essential hypertensive patients and 12 age-matched normotensive subjects (6 young and 6 older adults). Results were as follows: Normotensive subjects: Mean arterial blood pressure (MBP) 97 +/- 2 mmHg, urinary TxB2 (UTxB2V) 159 +/- 12 pg/min, glomerular filtration rate (GFR) 120 +/- 8 ml/min, sodium excretion (UNaV) 73 +/- 9 mueq/min. Hypertensive patients: MBP 115 +/- 2 mmHg (p less than 0,001 vs controls), UTxB2V 298 +/- 24 pg/min (p less than 0,005), GFR 128 +/- 6 ml/min, UNaV 51 +/- 4 mueq/min (p less than 0.02). There was a positive significant correlation between UTxB2V and GFR (p less than 0,005) and between UTxB2V and UNaV (p less than 0,005) in hypertensive but not in normotensive subjects. There was no correlation between GFR and UNaV in either group. CONCLUSION: 1. Urinary (i.e. renal) TxB2 is significantly elevated in hypertensive patients; 2. TxA2 may be a mediator of pressure natriuresis.

Adolescent↗

[Systolic arterial hypertension: demonstration and mechanism in obliterating arteriopathy of the lower extremities].

Hemodynamic parameters were measured in 24 patients with arteriosclerosis obliterans of the lower limbs, in comparison with 16 normal subjects of same age. Systemic arterial compliance was estimated from a simple visco-elastic model. In patients with arteriosclerosis obliterans, systolic pressure was significantly increased (P less than 0.001) while diastolic pressure remained within normal ranges. Arterial compliance was reduced (P less than 0.01) and was negatively correlated with systolic pressure (r = -0.72). Intravenous administration of nitroglycerin significantly decreased systolic pressure (P less than 0.05) and increased arterial compliance (P less than 0.01) without any change in mean arterial pressure. This study provided evidence that, in patients with arteriosclerosis obliterans of the lower limbs, the reduced systemic arterial compliance contributes in the increase in systolic pressure.

Arterial Occlusive Diseases↗

[Comparative hemodynamic effects of 2 vasodilators: dihydralazine and diltiazem in permanent essential arterial hypertension].

Cardiac hemodynamic and diameter, blood flow velocity, volumic flow of the brachial artery measured by pulsed Doppler, were studied before and after diltiazem administration in comparison with dihydralazine in hypertensive patients. After diltiazem administration, blood pressure and total peripheral resistance significantly decreased (P less than 0.001) while cardiac index and heart rate increased (P less than 0.01). After 25 minutes perfusion cardiac output and heart rate returned toward control values, while blood pressure and total peripheral resistance remained decreased. The result contrasted with those observed after dihydralazine, which induced an increase in cardiac index and heart rate. The caliber of the brachial artery decreased significantly (P less than 0.001) after dihydralazine and increased after diltiazem (P less than 0.01). This study shows that 1). The antihypertensive effect of diltiazem was due to a fall in total peripheral resistance associated with a transient baroreflex mediated tachycardia, and 2) diltiazem dilated also large arteries.

Adult↗

[Anti-hypertensive action of Captopril. Hemodynamic study (author's transl)].

Hemodynamic parameters were studied before and after administration of SQ 14 225, an orally active converting enzyme inhibitor, in 6 sustained essential hypertensive patients. Blood pressure and total peripheral resistance significantly decreased while cardiac output and heart rate remained unchanged. Systolic time intervals and plasma volume were not modified. No correlation was observed between the basal value of plasma renin activity and the decrease in blood pressure. The study demonstrated the vasodilatator effect of SQ 14 225 and questionned the role of the renin-angiotensin system in the mechanism of the pressure decrease.

Adult↗

[Clinical pharmacology of the antihypertensive action of guanfacine].

The clinical pharmacology of a central antihypertensive drug, guanfacine, was studied in sustained essential hypertension. The study of the haemodynamics, performed in 7 patients demonstrated a significant decrease in blood pressure and a fall in heart rate (less than the one observed with clonidine): the peripheral resistances remained unchanged after 4 days treatment. A clinical trial was carried out in 20 patients with sustained essential hypertension. Guanfacine was given orally (2 to 4 mg/day) during 2 months; the results of this study confirmed the antihypertensive effect of the drug. The most frequent side effects were dryness of the mouth and sleepiness. Guanfacine kinetics were studied in patients after single and repeated oral doses. The plasma concentrations were fitted in a two compartments open model with first order absorption. Steady state plasma level during a long term treatment can be determined with the predicted values derived from simulation of the initial individual kinetic studies. For a 2 mg dosage the biological half-life was 22.8 +/- 3.6 h. Guanfacine kinetics were linear according to the dosage. In moderate permanent essential hypertension guanfacine can be easily prescribed in monotherapy at a posology of 2 to 4 mg/day.

Adult↗

Is low urinary prostaglandin concentration a stage in the development of essential hypertension?

Urinary prostaglandin E and F (PGE and PGF) concentrations, renal plasma flow (RPF), glomerular filtration rate (GFR), sodium excretion rate (UNaV), potassium excretion rate (UKV), urinary osmolarity (Uosm) and osmolar clearance (Cosm) were found to be higher, while mean blood pressure (MBP) was lower in a group of 15 normotensive subjects (15NS), compared to those values obtained in a group of 25 essential patients (25EHP) of the same mean age. After volume expansion, of the 25EHP, urinary PGE concentration, RPF, noncortical plasma flow (NCPF), UNaV, UKV, UNaV/UKV, Cosm and urine volume (UV) increased significantly, MBP, GFR, Uosm, free water reabsorption (Tc water) and urinary aldosterone concentration did not change, while plasma renin activity (PRA) decreased significantly. It was concluded that the deficiency in renomedullary PG synthesis in the EHP is accompanied by a decrease in RPF, NCPF and UNaV. This decrease in UNaV and renal hemodynamics could increase, in the long term, the BP in these patients. Nevertheless, these findings do not exclude the interpretation that the decrease in renomedullary PGE release in the EHP indicates an attempt to increase sodium excretion at the distal tubule by diminishing sodium reabsorption by this agent in order to prevent further increase in BP. In any case, it seems that renomedullary PGs play an important role in intra-renal control systems.

Adult↗

[Prostaglandins in renovascular arterial hypertension].

Prostaglandins (PG) A1, B1, E2, F2 alpha and plasma renin activity (PRA) were measured by radioimmunoassay in 8 patients with unilateral artery stenosis, 7 hypertensive patients with unilateral renal atrophy without stenosis ans 20 controls. The measurement of the PG and PRA in the hypertensive group was performed in the infra-renal inferior vena cava and in the two renal veins. PRA and PGA1 were significantly raised in the renovascular hypertensive patients but no significant change was observed in the group with unilateral renal atrophy. On the other hand, the PGE2 and PGF2 alpha were raised in both groups, especially in the renal veins on the stenosed or atrophic side. There was a positive significant correlation between PRA and PGA1 and PGB, but none with PGE2 or PGF2 alpha. This study suggests that the increase in PGA1 and PGE2 represents a secondary hypertensive mechanism which is diuretic and natiuretic. The increase of PGF2 alpha represents a direct mechanism of hypertension. Simultaneous measurement of the vasopressor (PRA and PGF2 alpha) and vasodepressor (PGA and PGE) systems may give a better diagnostic and prognostic approach to renovascular hypertension.

Adolescent↗