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Biomedical subjects

H Schiffl

Publications and source records attributed to H Schiffl.

At least 109 records · Page 6Linked to original sources
PubMed1983

Acute effects of combined vasodilation and beta-adrenoceptor blockade with prizidilol on renal function.

1 The effects of a single oral dose of 600 mg of prizidilol on renal function were studied 5 to 6 h after dosing in six normal subjects and eight patients with essential hypertension. 2 Mean arterial blood pressure was reduced to 92% of the control value in normal subjects and to 75% in hypertensive patients. Heart rate increased slightly. 3 In normal subjects, effective renal plasma flow was increased to 107% of control values while glomerular filtration rate (83%), filtration fraction (79%), sodium (84%) and potassium (50%) clearances were significantly decreased. 4 In hypertensive subjects, effective renal plasma flow was increased to 120% of control values, while glomerular filtration rate (67%), filtration fraction (57%), sodium (27%) and potassium (72%) clearances were significantly decreased. 5 Plasma noradrenaline increased significantly in normal subjects (150%) and in patients (173%). Plasma renin activity, aldosterone and epinephrine levels did not change consistently. 6 The results indicate that the acute effects of prizidilol on blood pressure and renal function are more marked in hypertensive than in normotensive subjects. Prizidilol increases renal plasma flow like hydralazine and depresses glomerular filtration rate and fractional sodium excretion like endralazine. In addition to the fall in arterial pressure, efferent vasodilation and/or a specific effect on the glomerular ultrafiltration coefficient Kf may account for the striking decrease in filtration fraction.

Adrenergic beta-Antagonists↗
PubMed1982

Serum lipoproteins in patients with mild renal disease treated with the diuretic muzolimine.

Patients with renal functional impairment are prone to develop hypertension and hyperlipidemia, and both abnormalities tend to occur already at an early stage of kidney disease. In 18 patients with mild renal disease (glomerular filtration rate 65 +/- 5 ml/min) and hypertension (mean blood pressure 126 +/- 4 mm Hg), the effect of six weeks of treatment with the loop-diuretic muzolimine on serum lipoproteins was assessed. Compared to placebo values, the diuretic significantly increased serum low-density lipoprotein cholesterol (LDL-C) and apoprotein B (+ 18 and 11%, respectively, P less than 0.005) in 13 men or postmenopausal women, but not in 5 premenopausal women. Serum high-density lipoprotein cholesterol (HDL-C), and total triglycerides or lipoprotein triglyceride fractions were not consistently changed in both subgroups. Thus, the ratio LDL-C/HDL-C was increased from 3.2 +/- 0.3 to 3.9 +/- 0.3 (P less than 0.05) in the men or postmenopausal women, while no such tendency occurred in the premenopausal women (4.1 +/- 0.6 to 3.7 +/- 0.6). Changes in serum LDL-C were not associated with hemoconcentration or alterations in carbohydrate metabolism and were not related to variations in serum potassium or blood pressure. Increased serum levels of the atherogenic LDL-C fraction during diuretic treatment in men or postmenopausal women with renal disease may represent a potentially undesirable effect, particularly since such patients may tend to have hyperlipidemia in the untreated state.

Female↗
PubMed1982

Antihypertensive mechanism of the diuretic muzolimine in mild renal failure. Roles of sodium and cardiovascular norepinephrine responsiveness.

Eighteen patients with mild impairment of renal function (glomerular filtration rate 65 +/- 5 ml/min:m +/- SEM) and hypertension (168/105 +/- 6/3 mmHg) were shown on average to have abnormally increased cardiovascular pressor responsiveness to infused norepinephrine (NE; p less than 0.05), whereas plasma and urinary NE, exchangeable body sodium and blood-volume did not differ significantly from normal. A slightly increased pressor responsiveness to angiotensin II was associated with a tendency to low plasma renin activity (PRA). Compared to placebo conditions, treatment with the loop-diuretic muzolimine in a mean dose of 35 +/- 2 mg/day for six weeks decreased blood-pressure and exchangeable sodium (p less than 0.05), and NE pressor responsiveness was restored to normal values, whilst plasma and urinary NE were not significantly changed. This was consistent with improvement of the initially abnormal relationship between NE levels and NE responsiveness factors. In contrast, the pressor dose of angiotensin II and PRA were increased to an approximatively similar extent during muzolimine treatment. These observations suggest that removal of body sodium and a decrease in NE reactivity without an equivalent increase in sympathetic nervous activity may be important complementary factors in the antihypertensive mechanisms of diuretic treatment in patients with mild renal functional impairment.

Adult↗
PubMed1982

Acute effects of prizidilol on blood pressure, heart rate, catecholamines, renin and aldosterone in essential hypertension.

Prizidilol is a new antihypertensive agent reported to possess combined precapillary vasodilator and betareceptor-blocking properties. To clarify the profile of the acute effects of prizidilol in man, a variable dose study was performed in 8 patients with benign essential hypertension. Blood pressure, heart rate, plasma renin activity, aldosterone, plasma and urinary catecholamines and electrolytes were determined at short intervals before and up to 23 h after oral administration of placebo and prizidilol 150, 300 and 600 mg. The 4 studies were performed at weekly intervals according to a Latin square design. Prizidilol produced dose-dependent decreases in supine and upright blood pressure, with an initial change after about 2 h and maximal effects from 4 to 8 h after drug ingestion. Following a high dose of prizidilol, supine mean blood pressure (average 128 mmHg prior to treatment) was normalised (less than 107 mmHg) from 3 to 7 h and was still below predose level 23 h after ingestion. The only reported side effects were postural dizziness in 2 cases (corresponding to a fall in systolic upright blood pressure to less than 95 mmHg) and headache in one case. A biphasic variation in heart rate and plasma renin activity, with an early drop and a subsequent tendency to a slight rise, was observed after an intermediate or high dose of prizidilol. Plasma norepinephrine levels were increased by a high dose of prizidilol, while plasma epinephrine, aldosterone and plasma and urinary electrolytes were not consistently changed. Prizidilol in a a single oral dose appeared to be a potent antihypertensive agent. The profile of heart rate and plasma renin point to early dominance of beta-blockade followed by appearance of the concomitant vasodilator properties of prizidiol.

Adrenergic beta-Antagonists↗
PubMed1982

Comparative evaluation of the new vasodilator carprazidil and minoxidil in the treatment of moderate to severe hypertension.

The efficacy and side effects of the new vasodilator carprazidil and the established vasodilator minoxidil were compared in 18 hypertensive patients inadequately controlled by 2 to 4 conventional drugs; the latter included diuretics, beta-blockers and/or sympatholytics and, in half the cases, vasodilators, such as hydralazine, diazoxide or the postsynaptic alpha-blocker prazosin. The vasodilators were withdrawn and, using a crossover design all patients received carprazidil (mean final dose 88 mg) and minoxidil (20 mg) for an average period of 5 to 6 months. The effects of the 2 agents appeared to be qualitatively and quantitatively similar. Both tended to cause sodium retention and an increase in heart rate, which required an increased dose of diuretic in one third of the cases or of a beta-blocker in a quarter. With this approach mean body weight and blood volume were not altered in the established phase of carprazidil or minoxidil treatment; heart rate and plasma norepinephrine tended to be only minimally increased, plasma renin was slightly increased, and plasma aldosterone and epinephrine were largely unchanged. Supine and upright blood pressure were reduced from initial values of 189/113 and 167/ 113 mm Hg, to 149/95 and 138/95 mm Hg (-18 and - 17%), respectively, during carprazidil, and to 154/95 and 141/96 mm Hg (-17 and - 15%) during minoxidil therapy. Hypertrichosis occurred with both agents in almost all patients, and limits their more prolonged use in females. No adverse side effects on haematological parameters, liver or renal function were observed, nor was antinuclear antibody detected. It is concluded that carprazidil and minoxidil are equivalent vasodilator agents in the treatment of severe hypertension, particularly in males.

Adult↗
PubMed1982

Reversal of diuretic-induced increases in serum low-density-lipoprotein cholesterol by the betablocker pindolol.

Seventeen patients with mild to moderate essential hypertension received during three consecutive 4 wk periods a matched placebo, the thiazide-like diuretic, clopamide in a low dosage of 5 mg/day, or this diuretic combined with the betablocker, pindolol in a low dosage of 10 mg/day. Compared to placebo conditions, clopamide monotherapy significantly increased serum low-density lipoprotein cholesterol (LDL-C) by 13% (p less than 0.025). Following addition of pindolol, serum LDL-C was restored to control values. These variations in serum LDL-C were unrelated to concomitant changes in blood pressure, plasma potassium, renin activity or aldosterone levels. Blood pressure in the supine position was reduced from 152/99 +/- 13/9 mm Hg (+ SD) to 141/93 +/- 15/7 mm Hg following diuretic-monotherapy and to 139/90 +/- 12/9 mm Hg following diuretic-betablocker combination treatment. These findings suggest that antihypertensive combination treatment with low doses of clopamide and pindolol is not only effective and well tolerated, but may also avoid the increase in serum LDL-C levels occurring when the thiazide-like diuretic is given alone.

Adult↗
PubMed1982

Enhanced cardiovascular pressor reactivity to norepinephrine in mild renal parenchymal disease.

The cardiovascular pressor responsiveness to infused norepinephrine (NE) or angiotensin II (AII) as related to endogenous plasma NE or renin levels was assessed in 20 patients with mild parenchymal kidney disease (plasma creatinine 2.20 +/- 0.58 mg/dl, +/- SEM) and in 20 normal subjects approximately matched for sex and age. The two groups did not differ significantly in mean body weight, heart rate, blood volume, plasma electrolytes, exchangeable or urinary sodium, plasma aldosterone, epinephrine and renin levels, or AII threshold or pressor doses. Basal (including pre-infusion) plasma NE levels, the relationship between plasma NE measured during NE infusion and the corresponding NE infusion rate, as well as the total plasma clearance of NE (5.0 +/- 0.8 vs. 5.5 +/- 0.5 liter/min) also did not differ significantly between the two groups. In contrast, the threshold or pressor doses of infused NE decreased significantly in the patients with kidney disease (94 +/- 11 vs. 134 +/- 14 ng/kg/min and 21 +/- 3 vs. 40 +/- 7 ng/kg/min; P less than 0.05). Moreover, based on analysis of covariance, the individual pressor doses as related to basal plasma NE levels were distributed differently (P less than 0.01) between the patients and normal subjects. These findings suggest that the kinetics of plasma NE are unaltered largely in early stage kidney disease. However, such patients tend to develop an exaggerated pressor responsiveness to NE in the presence of normal plasma NE levels. This disturbance may favor the development of hypertension.

Adult↗
PubMed1982

Menopause-dependent plasma lipoprotein alterations in diuretic-treated women.

The effects of chlorthalidone, 100 mg/d given for 6 weeks, on serum lipids and lipoproteins were assessed in 22 premenopausal and 18 postmenopausal women. In the latter, chlorthalidone significantly increased total serum cholesterol (13%, p less than 0.001), low-density-lipoprotein (LDL) cholesterol (21%, p less than 0.001) and apoprotein B (16%, p less than 0.05). In contrast, these values were not altered in the premenopausal group. Levels of LDL cholesterol, high-density-lipoprotein cholesterol, total and very-low-density triglycerides, apoproteins A1 and A2, and plasma volume, plasma glucose, insulin, epinephrine, estradiol, and free fatty acids were unchanged in both groups. Chlorthalidone-induced changes in levels of LDL cholesterol did not correlate significantly with variations in blood pressure, plasma potassium, uric acid, renin, aldosterone, or norepinephrine levels. These findings indicate that the thiazide-like diuretic chlorthalidone increases serum LDL cholesterol in postmenopausal but not in premenopausal women.

Adult↗
PubMed1982

Catecholamines, sodium and renin in unilateral renal hypertension in man.

The relative roles of plasma or urinary norepinephrine (NE) and epinephrine (E), exchangeable sodium, blood volume, and plasma renin (PRA) or aldosterone in the pathogenesis of unilateral renal hypertension was evaluated. 99 normal subjects and 33 age-matched untreated hypertensive patients with unilateral renal parenchymal disease (RPD) (n = 18) or unilateral renal artery stenosis (RAS) (n = 15) were compared. Measurements were repeated following operative treatment in 23 patients. Plasma and urinary NE or E, exchangeable sodium and blood volume did not differ significantly between normal and untreated subjects with RPD or RAS. Both patient subgroups had increased blood pressure and supine PRA (p less than 0.001); these abnormalities were milder with RPD. Plasma aldosterone and upright PRA were significantly elevated (p less than 0.05) in RAS only. Operative treatment of RPD and RAS caused decreases in blood pressure (-18 and -28%) and PRA; they correlated in RPD (r = 0.56; p less than 0.05). In RPD and RAS, exchangeable sodium, blood volume, and NE or E values were not significantly changed following operation, except for mildly increased upright PNE in RAS. These observations suggest that the sympathetic system plays no major role in the maintenance of unilateral renal hypertension in man. However, the 'normal' body sodium-volume state in RPD or RAS may be inappropriate relative to coexisting hypertension. In addition to its established role in RAS, mild activation of the renin-angiotensin system may also be important for the pathogenesis of hypertension caused by unilateral RPD.

Adult↗
PubMed1982

Dialysis treatment of acute chromium intoxication and comparative efficacy of peritoneal versus hemodialysis in chromium removal.

External burns with chromic acid have been fatal even in cases with corrosions covering less than 10% of the body surface area. We observed a 19-year-old man with third-degree burns and chromium intoxication following accidental contact of both legs with chromium acid solution. The initial course was characterized by serum chromium levels known to be usually lethal (220 micrograms/100 ml), complete anuria, hepatic damage and progressive anemia. Aggressive peritoneal dialysis with a total duration of 252 h between the 4th and 22nd day after exposure caused a progressive decrease in serum chromium levels and resulted in a complete recovery after 35 days. The comparative efficacy of peritoneal versus hemodialysis in chromium removal was evaluated in 5 patients with acute renal failure who were treated with peritoneal dialysis and in 6 patients with end-stage renal failure who underwent hemodialysis. Following intravenous injection of 500 muCi51CrCl3 chromium clearance averaged 0.8 +/- 0.3 ml/min and 2.5 +/- 0.8 ml/min during peritoneal dialysis (n = 50) or hemodialysis (n = 24), respectively. It is concluded that hemodialysis is about 3 times as effective as peritoneal dialysis in chromium removal per unit of time. However, the possibility of applying uninterrupted peritoneal dialysis during the first few days suggests that this method is at least equivalent to hemodialysis for treatment in the initial stage of chromium intoxication.

Acute Disease↗
PubMed1981

Relationship between plasma catecholamines and urinary catecholamine excretion rates in normal subjects and certain diseased states.

Relationships between plasma norepinephrine (PNE) or epinephrine (PE) and urinary norepinephrine (UNE) or epinephrine (UE) excretion rates were studied in 37 normal subjects, 39 patients with benign essential hypertension, 23 with unilateral renal hypertension, and 20 with bilateral renal disease (serum creatinine 2.3 +/- 2.6 mg/100 ml). measurements were also performed after 6 weeks of diuretic treatment in 27 normal subjects and all patients with essential hypertension. In the untreated state, PNE and UNE values were generally normal in essential or unilateral renal hypertension; PNE tended to be decreased in diabetics and increased in bilateral renal disease. Diuretic treatment caused a tendency for slightly increased PNE and UNE. UNE correlated significantly with supine PNE or upright PNE or their mean value, and this relationship appeared to be comparable between untreated normal subjects and the various patients groups, except for a tendency for slightly higher PNE at given UNE values in bilateral renal disease. No significant correlations between UE and PE were apparent in the normal subjects or patient groups. These data demonstrate a dissociation of UE from PE levels. In contrast, UNE is an approximative index of PNE, and this relationship appeared to be generally unaltered in essential or unilateral renal hypertension. In patients with bilateral renal disease the slight shift of this relationship indicates that consideration of renal function is necessary for interpretation of NE levels.

Adult↗
PubMed1981

Chronic treatment with the new potent vasodilator Ro 12-4713 in moderate to severe hypertension: effects on blood pressure, endocrine function, sodium and plasma volume.

The antihypertensive efficacy and endocrine profile of the new antihypertensive agent, Ro 12-4713, were evaluated in 23 patients (17 men and 6 women) with moderate to severe arterial hypertension. Following addition of Ro 12-4713 to pre-existing therapy with diuretics and beta-blockers or sympatholytics, blood pressure in most of the patients was normalized within one month by a daily dose of 60 to 120 mg. Heart rate was only slightly increased. Orthostatic hypotension was not observed. Weight gain or oedema formation occurred in 14 patients within the first four weeks, but could be controlled satisfactorily by intensified diuretic therapy. Increased hair growth occurred in most of the patients. After a mean duration of treatment of 2.8 months, plasma volume and plasma and urine sodium were unaltered, and plasma potassium was slightly decreased. Plasma renin activity was doubled, whereas plasma aldosterone concentrations were unaltered. Plasma norepinephrine levels were high before and increased only slightly during chronic Ro 12-4713 treatment, whereas urinary norepinephrine excretion was unchanged. Plasma and urinary epinephrine were unaltered by Ro 12-4713. Ro 12-4713 appears to be a potent vasodilator for the combination treatment of hypertension in men.

Adult↗
PubMed1981

Dependency of proximal tubular fluid transport on the load of glomerular filtrate.

In hydropenic rats, the reabsorption of glomerular filtrate by the proximal convoluted tubules was measured before and after reduction of its intratubular flow rate. Three different protocols were used. (1) In 26 tubules (14 rats), nephron glomerular filtration rate (SNGFR) was varied from 37.2 +/- 7.3 to 20.4 +/- 7.1 nl/min by microperfusing their loops of Henle at 0 to 5 nl/min and 40 nl/min, respectively. This 43% reduction of SNGFR was followed by a 36.0 +/- 23.3% reduction of volume reabsorption rate (P less than 0.001). Between both parameters a linear regression line can be calculated, which is given by y = 0.92 chi + 0.0017. (2) In 17 tubules (14 rats), SNGFR was altered again by feedback from 46.0 +/- 9.7 to 28.8 +/- 9.3 nl/min. The volume resorption from the first half of the proximal convoluted tubule was compared with the reabsorption in its late proximal segments, which were microperfused with proximal tubular fluid at a rate of 20 nl/min. The 36.8% reduction of SNGFR was followed by only a 28.2% reduction of volume reabsorption rate in the first half of the tubule. In the microperfused segments, however, reabsorption remained unaltered. (3) In 29 tubules (21 rats), at the midpoint of proximal convolutions, some of the tubule fluid was removed by a suction pump, and volume reabsorption rate in the late segments was compared with that in the early parts of this tubule, when SNGFR remained stable. The reduction of intratubular flow from 27.7 +/- 8.5 to 14.7 +/- 5.8 nl/min, which is 53% of control, were followed by a reduction of volume reabsorption rate in the late segment to 60.6% control. Between both parameters a regression line was calculated, which is given by y = 0.76 chi +/- 0.01. We conclude that the rate of volume reabsorption by the proximal tubule depends on its intratubular load of glomerular filtrate and, further, that this dependency accounts predominantly for the maintenance of glomerular tubular balance under conditions of hydropenia.

Absorption↗
PubMed1981

Beta-receptor-blocking agents may reverse or prevent diuretic-induced increases in serum low-density lipoprotein cholesterol.

1. The effect of treatment with a thiazide-like diuretic alone or combined with a beta-adrenoceptor blocker on serum lipoproteins was investigated in 35 patients with essential hypertension. 2. In group I (18 patients), serum low-density lipoprotein cholesterol was increased (P less than 0.001) during monotherapy with chlorthalidone (100 mg/day) but not during combined chlorthalidone--beta-blocker therapy. 3. This tendency was similar in subgroups studied with an inverse sequence of drug administration. In subgroup IA (11 men), a 22% increase (P less than 0.01) in low-density lipoprotein cholesterol after 6 weeks of chlorthalidone was reversed after use of a beta-blocker as well as chlorthalidone; in subgroup IB (five men, two post-menopausal women), low-density lipoprotein cholesterol was increased by 41% (P less than 0.05) above placebo values 6 weeks after withdrawal of the beta-blocker from combination therapy. 4. In group II (18 men), low-density lipoprotein cholesterol was increased by 13% (P less than 0.025) after 4 weeks of monotherapy with clopamide (5 mg/day) but restored to control levels 4 weeks after addition of pindolol (10 mg/day). 5. No significant changes occurred during any treatment phase in high-density lipoprotein cholesterol. 6. Certain beta-receptor blocking agents may prevent or reverse diuretic-induced increases in serum low-density lipoprotein cholesterol.

Adolescent↗
PubMed1981

Renal fluoride excretion: experimental evaluation of the role of extracellular volume status during intact and impaired kidney function.

The renal disease of inorganic fluoride was studied in 5/6-nephrectomized and kidney-intact rats in order to evaluate the influence of the extracellular fluid volume status on net tubular fluoride reabsorption. Loss of renal functional mass impaired the ability of the hydropenic uremic rat to excrete fluoride, although tubular reabsorption of fluoride was depressed. Fractional fluoride excretion was closely correlated to urinary flow rate in hydropenic rats; no influence of urinary pH from 5.80 to 6.18 could be demonstrated. Acute, moderate expansion of the extracellular fluid volume by isotonic saline was followed by a significant rise in fractional fluoride excretion in uremic as well as in control rats, indicating that extracellular fluid volume is an important physiological determinant of passive tubular fluoride reabsorption.

Animals↗