Potassium substitution via the oral route: does its efficacy depend on the anion of the potassium salt?

In an open, randomized study, we investigated the effect of oral potassium chloride (KCl) and of potassium citrate/bicarbonate (K-cit/bic) in 42 patients with hypokalemia (less than or equal to 3.5 mmol/l). In both groups 80 mmol K+ were administered daily. The parameters examined were serum potassium concentration, acid-base status, and urinary electrolyte excretion. Parameters were evaluated on days 0, 2, 4, and 6. With KCl, [K+] increased from 3.2 +/- 0.2 (mean +/- SD) on day 0 to 3.8 +/- 0.4 mmol/l on day 2 (p less than 0.005) and 4.0 +/- 0.5 mmol/l on day 4 (p less than 0.005). On day 6 [K+] was also 4.0 +/- 0.4 mmol/l (p less than 0.005 vs day 0). With K-cit/bic, [K+] increased from 3.2 +/- 0.2 to 3.7 +/- 0.4 on day 2, 3.9 +/- 0.5 on day 4, and 4.1 +/- 0.6 mmol/l on day 6 (all p less than 0.005 vs day 0). The increase of [K+] was not different between the two groups. Blood pH on day 0 was in the normal range in both groups and did not change significantly during the study. There was a decrease of carbon dioxide partial pressure (pCO2) with KCl from 38.7 +/- 4.9 on day 0 to 36.4 +/- 3.6 on day 2 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and long term effects of loop diuretics in heart failure.

Diuretics, together with digitalis glycosides and vasodilators are of prime importance in the medical treatment of patients with congestive heart failure (CHF). Diuretics provide quick symptomatic relief in these patients. Their beneficial effect is related to the promotion of sodium and water excretion via the kidney, thus reducing extracellular fluid volume expansion and mitigating the increase in preload and afterload caused by sodium and water retention. Loop diuretics administered intravenously are indispensable in the management of pulmonary oedema; thiazides and loop diuretics in low doses are effectively used in the oral treatment of mild to moderate heart failure. Torasemide is a new loop diuretic which differs from furosemide (frusemide) and related loop diuretics by virtue of its longer elimination half-life and longer duration of action, with almost complete bioavailability. The efficacy and tolerability of torasemide have been compared with furosemide in several studies. Once daily oral administration of torasemide (starting with 5mg) or furosemide 40mg reduce bodyweight, oedema and symptoms of heart failure to a similar extent. Mean New York Heart Association class is consistently reduced by 0.5 to 0.7. Intravenous administration attenuates the increase in intracardiac pressures during exercise in patients with CHF, and produces acute improvements in cardiac haemodynamics in patients with high grade left heart failure. A beneficial effect on both pulmonary and cardiac haemodynamics has been demonstrated during chronic oral treatment of patients with previously untreated CHF. Torasemide was well tolerated with only mild and transient adverse effects reported in a small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Severe periodic hypokalemic paralysis. Prevention using beta-receptor blockade]. / Schwere periodische hypokaliämische Lähmung. Prophylaxe durch beta-Rezeptorenblockade.

For ten years, severe physical exercise in a 24 year old male patient had been an almost constant trigger of frequent attacks of pareses which were mostly accompanied by complete tetraplegia and once by the occurrence of cardiac arrest with atrial fibrillation. During the attack, the serum potassium concentration fell to 1.2 mmol/l, whereas the intraleukocytic potassium concentration rose from 136 mmol/l to 149 mmol/l. The catecholamine excretion in the urine was raised during the first 24 hours after admission as an emergency (189 micrograms noradrenalin and 54 micrograms adrenalin). After intravenous adrenalin infusion (0.01-0.1 microgram/kg X min) during the symptom-free interval, there was a major fall of the serum potassium concentration from 3.9 mmol/l to 3.1 mmol/l. This was not accompanied by a raised insulin excretion and could be prevented by prior administration of the nonselective beta blocker propranolol. On the basis of these results, the patient was treated prophylactically with three times 40 mg/d p.o. propranolol. Pareses requiring treatment no longer occurred under this therapy.

Cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion: a new variant of Cushing's syndrome.

A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy. Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF. The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.

Induction of puberty in a patient with hypogonadotropic hypogonadism: effect of sequentially applied hCG and pulsatile GnRH administration.

Pulsatile substitution with GnRH appears to be the therapy of choice in patients with Kallmann's syndrome, a well defined type of hypogonadotropic hypogonadism. We tried to simplify the treatment and to limit the subcutaneous GnRH therapy to the period absolutely necessary to induce spermatogenesis. Therefore we applied in sequence first hCG to stimulate testicular growth and second pulsatile GnRH application to induce spermatogenesis. We herein report that with this mode of therapy testicular growth from infantile to adult size and normal spermatogenesis could be achieved. We conclude that pulsatile GnRH application is a new effective therapy of hypogonadotropic hypogonadism which can be simplified considerably by pretreatment with hCG.

Hemodynamic, renal, and hormonal responses to changes in dietary potassium in normotensive and hypertensive man: long-term antihypertensive effect of potassium supplementation in essential hypertension.

The hemodynamic, hormonal, and renal responses to alterations in dietary potassium were studied in normotensive and hypertensive subjects. In a short-term study, nine normotensive and nine hypertensive young men received a normal diet and low potassium, high potassium, and high potassium/low sodium diets for 1 week, each. The long-term effect of potassium supplementation (normal diet plus 96 mmol KC1/d for 8 weeks) was evaluated in 17 patients with essential hypertension. Blood pressure did not change significantly during short-term alterations of potassium intake but decreased during long-term supplementation (from 152.2 +/- 3.5/99.6 +/- 1.9 mm Hg to 137.4 +/- 2.9/89.1 +/- 1.4 mm Hg). High dietary potassium induced a significant but transient natriuresis. Plasma potassium concentration was increased during long- but not during short-term high potassium intake. In contrast to plasma renin activity (PRA) and aldosterone, urinary kallikrein was consistently stimulated during long-term potassium supplementation. The plasma concentrations of adrenaline and noradrenaline were significantly higher in hypertensive than in normotensive subjects and were not markedly altered by the dietary changes. It is concluded that long- but not short-term potassium supplementation lowers blood pressure in patients with essential hypertension. The antihypertensive effect may be mediated by potassium-induced natriuresis, by a stimulation of Na-K-ATPase secondary to increased plasma potassium levels, and/or by a modulation of the renin-angiotensin-aldosterone, kallikrein-kinin, and sympathetic nervous systems.

Studies on the role of sodium- and potassium-activated adenosine triphosphatase inhibition in the pathogenesis of human hypertension. Changes in vascular and cardiac function following inhibition of the sodium pump in normotensive subjects and effects of calcium entry blockade.

An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 micrograms ouabain/kg body weight inhibited red blood cell (RBC) - Na-K-ATPase by 49% which was accompanied by a significant increase in RBC - ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vasoconstriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase - in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion - may play a role in the pathogenesis of human arterial hypertension.

Relation of endogenous digoxin-like immunoreacting activities to salt balance and renal function in man.

We have previously shown that a natriuretic factor which is present in a small molecular weight fraction (IV) of serum and urine from salt loaded animals and healthy subjects, respectively, inhibits the Na-K-ATPase enzyme in vitro and also binds to a specific digoxin antibody. In the present study digoxin-like immunoreacting activity (DLIA) was therefore determined in the serum of healthy volunteers during low (35 nmol/day) and high (greater than 400 mmol/day) sodium intake and of patients with chronic renal failure and serum creatinine concentrations ranging from 127 to 757 mumol/l. DLIA was determined with a radioimmunoassay for digoxin in native serum and in the salt (III) and post-salt (IV) serum fractions eluted from a Sephadex G-25 column. DLIA in native serum of healthy subjects was less than 0.125 ng/ml. After gel filtration DLIA eluted exclusively in the small molecular weight salt (F III) and post-salt (F IV) fractions. Whereas DLIA increased in F III and decreased in F IV, total DLIA in F III + IV slightly increased from 0.37 +/- 0.03 to 0.49 +/- 0.05 ng/ml (p less than 0.01) with the change from low to high sodium intake. DLIA in native serum of uremic patients ranged from 0 to 1.70 ng/ml and was detectable consistently only in patients with serum creatinine concentrations above 250 mumol/l. DLIA in F III which averaged 0.22 +/- 0.04 ng/ml and total activity which ranged from 0.11 to 0.88 ng/ml closely correlated with the degree of renal impairment (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of 8-arginine-vasopressin by radioimmunoassay. Development and application to urine and plasma samples using one extraction method.

This paper describes the production and evaluation of an antiserum with high affinity (Ka = 1.9 X 10(11) l/mol) and specifity to 8-arginine-vasopressin (AVP). The antiserum binds only to the intact and unchanged ring and tail of the AVP-molecule. AVP was labelled with 125I by a modification of the chloramin T method and purified by gel-filtration. We describe the development and validation of a radioimmunoassay for AVP in human plasma and urine, using only one extraction method (octa-decasilyl-treated silica microcolumns) for both biological fluids. The overall sensitivity of the assay method is 0.3 pg/ml plasma and 0.6 pg/ml urine. Mean (+/- SD) plasma AVP-concentration in normally hydrated females was 1.2 +/- 0.6 pg/ml (median 1.2 pg/ml) and 1.7 +/- 0.7 pg/ml (median 1.8 pg/ml) in males. Mean urinary AVP excretion was 73 +/- 43 ng/day with ad libitum water intake and normal activity. Sex differences were not statistically significant. We also assessed the response of plasma AVP and urinary AVP-excretion to waterload and dehydration.

[Pulsed Doppler echocardiography in aortic valve disease]. / Gepulste Doppler-Echokardiographie bei Aortenvitien.

The diagnostic value of pulsed Doppler echocardiography (PDE) had not been sufficiently assessed up until now. Invasive catheter velocitometric measurements in the central vessels give quantitative information on the blood movement across the aortic and pulmonary valves. It is particularly useful in the quantification of aortic regurgitation. We successfully investigated 52 patients by means of PDE (ATL 500 A); 20 were suffering pure aortic incompetence, 11 pure stenosis and 21 had combined stenosis and regurgitation. Fifteen patients without aortic valvular disease served as controls. Our findings were compared with the results of cardiac catheterization and angiography in each case. In addition, 14 patients with aortic regurgitation were studied invasively by catheter velocitometry. The obtained regurgitation values were compared to the PDE method. In the PDE the underlying criteria for the assessment of the recordings were as follows: formal analysis of the analog signal and of the turbulence content during systole and diastole; in the flow velocity tracings aortic incompetence showed a steep increase with high peak to peak aortic velocities and scant turbulence formation; the reverse flow during regurgitation was accompanied by a high grade turbulent velocity pattern. The area under the diastolic (regurgitant) flow velocity curve (the time-amplitude integral) corresponded significantly with the angiographic severity of aortic insufficiency (r = 0.87). In aortic stenosis, turbulence formation leads to an approximately flat velocity profile across the ascending aorta, if the region in the vicinity of the valve is omitted. The flow velocity analog signals are considerably disturbed. However, the turbulence content which can be qualitatively estimated from the recordings, correlates well with the calculated valve area. In combined aortic valve stenosis and incompetence, the prevailing turbulent pattern does not always permit one to assess sufficiently the severity of the stenotic component, whereas the grade of incompetence can be, in general, evaluated. PDE complements the existing non-invasive techniques and probably essentially enriches non-invasive diagnostics.

Effects of potassium on blood pressure regulation.

Short-term changes (1 week) of potassium intake had no effect on elevated or normal blood pressure of 18 subjects. Potassium supplementation (100 mmol KCl/day) for 8 weeks caused a fall in blood pressure in 16 patients with mild hypertension. After cessation of potassium supplementation, blood pressure returned to "prepotassium" levels. In healthy volunteers, high potassium intake for 1 week resulted in a marked increase in intraleukocytic concentration of potassium. No change was observed in mean arterial pressure, cardiac index, or total peripheral resistance. The hemodynamic response to an intravenous infusion of ouabain was reduced during high potassium intake. Baroreceptor sensitivity rose during high potassium intake as demonstrated by the infusion of norepinephrine.

Influence of intravenous Mg++ solutions on renal excretion of potassium, sodium, calcium, chloride, intraleukocytic potassium and peripheral vascular resistance: a metabolic and hemodynamic study in normal volunteers.

In an open randomized crossover trial 8 healthy male volunteers received an intravenous infusion of potassium chloride, potassium/magnesium chloride, potassium-(D,L)-aspartate, and potassium/magnesium-(D,L)-aspartate. Equimolar amounts of potassium (27.75 mmol) and magnesium (13.9 mmol) were given in a 500-ml volume during 24 h. During two 9-day periods subjects were maintained on a constant diet with a daily intake of 80 mmol potassium and 60 mmol magnesium. Infusions were administered on day 5 and 7 of each period. Serum and urine electrolyte concentrations as well as intraleukocyte potassium were measured before, during, and after the tests; cardiac output and systemic vascular resistance were determined by impedance cardiography. Potassium and magnesium containing solutions did not influence renal elimination of potassium, and also the circadian rhythm of potassium excretion did not show any change. The elimination of sodium, calcium, potassium, and chloride rose significantly over the corresponding control values during magnesium infusions, but not when potassium salts were given. The increase of calcium excretion after Mg++ is most probably due to suppression of parathyroid hormone. Intraleukocyte potassium was not affected significantly by the various infusions, indicating that intracellular compartments are completely filled. There was no evidence that the anion (D,L-aspartate or chloride) had a significant effect on all measured variables. Mean arterial blood pressure and peripheral vascular resistance were not altered significantly during the infusions.

An improved method for the determination of potassium in leucocytes.

1. In twenty normal subjects and five patients with disturbances of potassium balance, the potassium concentration in leucocytes was measured by a modified technique. 2. The precision of the method was three to four times greater than that of techniques previously described, with a coefficient of variation for duplicate analyses of 2.3%. 3. A comparison between intraleucocyte potassium concentration and total body potassium in five patients with pathological alterations in their potassium balance showed that intracellular potassium concentration may reflect the clinical state better than total body potassium.

Clinical, endocrinological, and cytological characterization of two 46, XX males.

In two 46,XX males, 20 and 21 yr of age, gonadotropins, testosterone, and estradiol were measured in serum and compared to those in a control group of four men. In addition, in one subject, androgen metabolism was measured in biopsied skin and cultured skin fibroblasts. In both XX men, a pulsatile pattern of gonadotropin, testosterone, and estradiol release into serum was observed. The levels of the gonadotropins and estradiol were higher and the levels of testosterone were lower in XX men than in normal men. hCG stimulation resulted in a significant increase in testosterone secretion, and LRH administration caused a more prolonged rise in gonadotropin levels in the XX men. The administration of estradiol caused a positive feedback response in the XX men and resulted in a suppression of gonadotropin secretion in the controls. Finally, the formations of C-19 metabolites from testosterone and estrone from androstenedione were found to be in the same range in skin and skin fibroblasts from the XX men as in those from normal men. It can be concluded that 46,XX men have altered hypothalamic-pituitary and gonadal function compared to normal men.