Late streptokinase therapy in thrombotic microangiopathy: a case study.

A 42 year woman presented with malignant hypertension, anuria and hemolytic anemia with schistocytosis. The diagnosis of thrombotic microangiopathy was confirmed by early renal biopsy. Purely symptomatic treatment (peritoneal dialysis and hypotensive drugs) was supplemented by administration of heparin and Dipyridamole. Gastro-intestinal bleeding prevented early thrombolytic therapy. Microangiopathic anemia rapidly disappeared but anuria persisted. Three months later a second renal biopsy showed persistence of active lesions and absence of irreversible parenchymal damage. Streptokinase treatment was then instituted and followed by a rapid return of urinary output. Hemodialysis was stopped and renal function continued to improve over the following months. Two years later the patient remains well despite persistence of hypertension difficult to control. Creatinine clearance is stable at 20 ml/min. This observation suggests that late thrombolytic therapy may be effective in patients with thrombotic microangiopathy when histological findings do not indicate extensive irreversible lesions.

[Hemodynamic and hormonologic basis of the treatment of arterial hypertension]. / Bases hémodynamiques et hormonologiques du traitement de l'hypertension artérielle

The efficiency and the variety of drugs used in the treatment of arterial hypertension demand that the various disorders responsible for the blood pressure increase be well individualized. The study of the haemodynamic and hormonal factors and of their interelations in the patients provides interesting informations which make it possible to classify the hypertensive subjects according to physiopathological criteria. Starting from these data, it is possible to consider a rational treatment by selecting the drugs acting specifically on the anomalies to be corrected.

[Renal effects of intravenous tertatolol in essential arterial hypertension]. / Effets rénaux du tertatolol intraveineux dans l'hypertension artérielle essentielle.

The acute renal effects of intravenous tertatolol were studied in eight patients with moderate essential hypertension: the study included a 100 mmol/day sodium intake during 3 days. Then, tertatolol was infused after a water load during 2 consecutive periods of 30 min (priming dose followed by constant infusion) in order to obtain plasma concentrations of tertatolol at 2 different levels: 10 ng/ml, then 40 ng/ml successively; the measurements were obtained at 15, 30, 45 and 60 min. The renal plasma flow (RPF) and the glomerular filtration rate (GFR) were calculated from the 131I-Hippuran clearance and the 125I-Iothalamate clearance respectively; a bladder catheter allowed a precise urine collection. The results indicate that intravenous tertatolol, at low dose, induced a marked and early renal vasodilatation; higher dose of tertatolol attenuated the vasodilator response, probably because of a decrease in cardiac output (suggested by the decrease in heart rate); thus, the systemic effects would hide the direct renal hemodynamic effects of tertatolol. Natriuresis and kaliuresis were unchanged by intravenous tertatolol.

[Acute effects of metoprolol on blood pressure and heart rate. Value of the nitroglycerin test]. / Effets aigus du métoprolol sur la pression artérielle et la fréquence cardiaque. Intérêt du test à la trinitrine.

The acute effects of Metoprolol on blood pressure and heart rate were studied with reference to the plasma level of the betablocker in 10 patients (6 male and 4 female) with permanent moderate uncomplicated hypertension. Each patient was given a single oral dose of 200 mg Metoprolol: blood samples were taken over a 12 hour period at given times for Metoprolol estimation. The blood pressure was measured with a mercury manometer; heart rate was measured lying and during a stress test (glyceryl trinitrate). The antihypertensive effect of Metoprolol was significant from the 4th hour; at the 8th hour the systolic pressure was reduced by 15% and the diastolic pressure by 17% (p less than 0.001). The blood pressure then rose progressively. The heart rate in the recumbent position fell 10 to 15% during the study. The heart rate during the trinitrin test varied linearly with time (r = 0.991, p less than 0.001). The variation in systolic and diastolic blood pressure did not correlate with the plasma Metoprolol level (r = 0.03, and 0.19); no correlation was found between the fall in lying heart rate and the plasma betablocker level. On the other hand, the trinitrin heart rate (at the end of the test) correlated negatively with the logarithm of the plasma Metoprolol (n = 56, r = 0.688, p less than 0.001). These results confirm that the antihypertensive effect of Metoprolol is not directly related to the plasma level of the betablocker. On the other hand, the betablocker effect assessed by the trinitrin test, correlated with the plasma Metoprolol level. This relationship is similar to those previously observed with other betablockers; atenolol and oxprenolol.

[Acute and chronic effects of a new calcium blocker, nicardipine, on renal hemodynamics in arterial hypertension]. / Effets aigus et chroniques d'un nouvel inhibiteur calcique, la nicardipine, sur l'hémodynamique rénale dans l'hypertension artérielle.

Renal hemodynamics and natriuresis were studied in 9 hypertensive patients without renal failure, 2 hours and 4 hours after oral intake of Nicardipine 30 mg; sodium intake was kept constant during the study (100 mmol per day). Then, Nicardipine was given at a dose of 30 mg three times a day and the hemodynamic study was repeated on the 6th day (2 hours after the morning dose). Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by the clearance methods using 131I-hippuran and 125I-iothalamate respectively. Results are as follows: (Table: see text). These results confirm the potent renal vasodilatory effect of Nicardipine; GFR was not significantly altered while RBF and FF returned to normal levels. An early and transient natriuretic effect was observed after the first dose of Nicardipine and body weight showed a significant decrease during the study indicating that no sodium retention was induced by Nicardipine.

[Comparative effects of nifedipine and indapamide in the treatment of arterial hypertension]. / Effets comparés de la nifédipine et de l'indapamide dans le traitement de l'hypertension artérielle.

A controlled multicentre trial was organised to compare the effects of 20 mg Nifedipine tablets (N) and 2,5 mg Indapamide tablets (I) during a 4 months' treatment period after a placebo period, in 59 patients with moderate essential hypertension (n = 59). The results of blood pressure measurements of 18 patients treated by nifedipine (1 tablet twice daily) and 22 patients treated by indapamide (1 tablet every morning) were compared. The systolic blood pressure, after 10 minutes recumbency, fell from 165 +/- 10 mmHg to 148 +/- 13 mmHg (p less than 0.01), and the diastolic pressure from 104 +/- 6 mmHg to 86 +/- 7 mmHg (p less than 0.01) in the patients treated with nifedipine. In the indapamide group, the SBP fell from 164 +/- 13 mmHg to 152 +/- 15 mmHg (p less than 0.01) and the DBP from 100 +/- 4 mmHg to 87 +/- 6 mmHg (p less than 0.01). There were no significant changes of heart rate with either drug; plasma creatinine, potassium and uric acid concentrations were also unchanged. There was a higher incidence of headaches and tiredness in the nifedipine group, whilst patients treated with indapamide complained more often of muscular cramps. Flushing was observed in nearly a quarter of the patients in both groups. These results confirm that both nifedipine and indapamide induce significant and persistant falls in systolic and diastolic blood pressure. Although the fall was greater with nifedipine than with indapamide, the difference was not statistically significant. The tolerance was satisfactory in both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Renovascular hypertension and beta blockers. Theoretical and practical implications]. / Hypertension réno-vasculaire et bêta-bloquants. Implications théoriques et pratiques.

Beta blockade was instituted in 10 patients with renovascular hypertension due to renal artery stenosis or thrombosis. The treatment was very effective in unilateral stenosis with a normal contralateral kidney (2 kidney Goldblatt) and in fibromuscular dystrophy of the renal artery. On the other hand many failures were observed in hypertension with a single kidney (1 kidney Goldblatt) and in renovascular hypertension with complex lesions or associated renal failure. Although a clear relationship was often observed between the increased plasma renin activity and the antihypertensive effect of beta blockade, this association was sometimes completely erroneous. Beta blockade, which is easy to perform, should be tried out systematically in renovascular hypertension, but, when no result is observed, this therapeutic test should not exclude surgical management thereafter.

[Acute hemodynamic effects of prostacyclin in severe or malignant hypertension]. / Effets hémodynamiques aigus de la prostacycline dans les hypertensions sévères ou malignes.

The antihypertensive effect of Prostacyclin (PGI2) was investigated in 7 patients with severe or malignant hypertension. Cardiac output (dilution method), arterial blood pressure and total blood volume (TBV, radio-albumin dilution method) were measured before and during a PGI2 infusion, the effective dose ranging from 10 to 20 ng/kg/min. Cardiac index(CI) rose from 2.8 to 3.9 1/min/m2 and heart rate (HR) from 75 to 94 beats/min (p less than 0.01) Mean blood pressure decreased from 154 to 120 mmHg (p less than 0.001) and total peripheral resistances from 4650 to 2540 dynes.s.cm-5 (p less than 0.001). The ratio: central blood volume/total blood volume increased from 0.21 to 0.26 (p less than 0.001). The results confirm that PGI2 produces a potent vasodilatation of the systemic compartment with a marked decrease in blood pressure; however the antihypertensive effect is blunted by the increase in CI mainly related to the increase in HR; significant central translocation of blood suggests that PGI2 does not produce dilatation of the capacitance vessels. Sympathetic nervous system is highly stimulated by PGI2 very likely through the baroreceptor system.

[Renal effects of captopril in hypertension with renal artery stenosis. Comparison between Tc-99m-DTPA scintigraphy and clearance method]. / Effets rénaux du captopril dans l'hypertension avec sténose d'artère rénale. Comparaison entre scintigraphie au Tc-99m-DTPA et méthode des clairances.

In eleven hypertensive patients with renal artery stenosis, the acute renal effects of captopril were investigated using two methods: 1) the Tc99m-DTPA renography with determination of an index of renal perfusion (IP), an index of glomerular filtration (IF) and the ratio of these indices (F/P); 2) the renal hemodynamics obtained by the clearance method using a continuous infusion of I131-hippuran and I125-iothalamate for calculation of renal blood flow (RBF), glomerular filtration rate (GFR) and filtration fraction (FF). The studies were performed before and after captopril treatment. Patients were classified according to the acute response to captopril as responders (R; n = 6) and non responders (NR; n = 5). Results are as follows: (B: basal, C = captopril). (table; see text) These data confirm that captopril produced a significant decrease in F/P and FF in R whereas these indices did not change in NR; it was found that IF and GFR decreased in R whereas IF increased and GFR did not change in NR; a significant correlation was observed between delta IF and delta GFR in R (r = 0.834, p less than 0.05). These results indicate that 1) data obtained before and after captopril by renography and by clearance methods are in good correlation either in Ror in NR patients; 2) Captopril test including renography or renal hemodynamic measurements is useful for selection of R patients.

[Clinical pharmacology of prazosin in arterial hypertension with chronic renal insufficiency]. / Pharmacologie clinique de la prazosine dans l'hypertension artérielle avec insuffisance rénale chronique.

The pharmacokinetics of prazosin were studied in 10 patients (7 male and 3 female, Group I) with permanent hypertension and chronic renal failure (serum creatinine 40,5 +/- 5,9 mg/l) and in 10 normal subjects (10 male, Group II). Each patient received a single oral dose of 2 mg of prazosin; serum levels were studied at regular intervals over a ten hour period by spectrofluorometry Clinostatic blood pressure was measured with a mercury manometer in the patients in Group I. The rate of absorption of prazosin was identical in the two groups (t max: I,3 +/- 0,2 h and I,6 +/- 0,4 h). Maximal serum concentrations were significantly higher in Group I (33,5 +/- 3,7 microgram/1 compared to 22,0 +/- 2.5 microgram/l, p less than 0,02) as was the surface under the serum concentration curve plotted against time (206,I +/- 31.I microgram.h.l-1 compared to 99,9 +/- 12,3 microgram.h.l-1, p less than 0,01). Prazosin induced a significant fall in systolic and diastolic blood pressure (-19% and -23% respectively, p less than 0.001) in Group I, 90 minutes after administration, associated with a moderate rise in heart rate (+16%, p less than 0.01). The variation of blood pressure induced by prazosin correlated closely with its serum concentration (p less than 0.001). These results suggest that the bioavailability of prazosin is significantly higher in chronic renal failure and that a reduction of the daily dose should be envisaged in these patients on long-term therapy.

[Spectrofluorimetric estimation in biological fluids of a new beta-blockader: atenolol. Application to its pharmacokinetic study (author's transl)]. / Dosage spectrofluorimétrique dans les milieux biologiques d'un nouveau bêtabloquant, l'aténolol. Application à son étude pharmacocinétique.

The authors describe a simple method of fluorimetric estimation of atenolol, applicable to blood and urine, sufficiently sensitive to permit a pharmacokinetic study. After administration of a dose of 200 mg by the oral route to hypertensive subjects, one may observe a maximal plasma concentration 3 hours after the dose average value 3.91 +/- 0.71 mumol/l (1.04 +/- 0.19 mg/l). The apparent half life of elimination of phase beta is 14.1 +/- 4.9 h, values comparable with those calculated from urinary data 14.6 +/- 2.0 h. The renal clearance was 140 +/- 32 ml/min; 54 +/- 14% of the administered dose are excreted in the urine. After administration by the venous route, urinary excretion represents 96% of the dose administered.

[Anuria caused by tight stenosis of the renal arteries. 2 cases]. / Anurie par sténose serrée des artères rénales. Deux observations.

Two patients developed anuria associated with tight stenosis, though not complete obstruction, of the renal arteries. This rare and little known accident is found in atheromatous patients with severe arterial hypertension of renovascular origin. It usually occurs when blood pressure falls under the influence of a precipitating factor. Diagnosis rests on angiography. Diuresis is resumed immediately after surgical revascularization. The operation must be performed in every case, even after a long delay, since the kidneys remain viable for a long time due to the development of an extensive collateral circulation. Such anurias are particularly severe in patients with poor underlying condition and when vascular lesions are diffuse.

Effects of perindopril on renal haemodynamics and natriuresis in essential hypertension.

Renal haemodynamics and natriuresis were studied before and 6 h after oral intake of perindopril (8 mg) in eight hypertensive patients without renal failure. The patients were then treated with perindopril (8 mg per day) and renal haemodynamics were measured on the fifth day, 6 h after the morning intake. Sodium intake was controlled during the study (100 mmol sodium per day). Renal blood flow and the glomerular filtration rate were measured by the clearance method using 131I-hippuran and 125I-iothalamate, respectively. Mean blood pressure decreased from 135 to 110 after 6 h, and was 118 mmHg on the fifth day (P less than 0.001, respectively). Renal vascular resistance decreased significantly after acute drug intake from 0.19 to 0.15 arbitrary units (P less than 0.001) and on the fifth day to 0.16 arbitrary units (P less than 0.001). Renal blood flow rose from 708 to 723 after 6 h, and to 750 ml/min per 1.73 m2 on the fifth day but the change was no significant. There was no alteration in the glomerular filtration rate so that the filtration fraction decreased from 0.27 to 0.26 (after 6 h), and to 0.25 on the fifth day (P less than 0.02). Natriuresis increased after the first intake between the first and tenth hours. On the fifth day, maximum natriuresis was observed between the fourth and sixth hours. Perindopril caused strong renal vasodilation after the first intake and during the following days, with no change in the glomerular filtration rate. There was a significant decrease in the filtration fraction, indicating efferent, as well as afferent, arteriolar vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)