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Biomedical subjects

E Steiness

Publications and source records attributed to E Steiness.

At least 37 records · Page 2Linked to original sources
PubMed1986

Tubular sites of furosemide natriuresis in volume-replaced and volume-depleted conscious rats.

There is accumulating evidence that the renal Li clearance reflects the delivery of Na and volume out of the proximal tubules. In the present study we used the Li clearance technique to evaluate the effects of submaximal furosemide (Fur) infusion (7.5 mg/kg/hr) on proximal and distal Na reabsorption in conscious rats with and without volume replacement with saline. Li was given as an p.o. test dose (0.5 mmol/kg) and [3H]inulin was infused in saline to measure the glomerular filtration rate (GFR). In control rats not infused with F, fractional Na excretion was about 1% and fractional Li excretion was about 30 to 35%. Infusion of F with constant rate and volume replacement increased fractional Na excretion to 22% and fractional Li excretion to 57% associated with a small decrease of the GFR. Without volume replacement F infusion caused a smaller and temporary diuretic and natriuretic response (maximum fractional Na excretion = 7.5%) followed by a decrease of urine flow and Na excretion almost to control levels, despite continued high excretion rates of F. The GFR decreased by 25% and fractional Li excretion showed an initial increase followed by return to baseline levels. The results suggest that in conscious rats submaximal doses of F cause major inhibition of proximal tubular Na reabsorption, which effect contributes substantially to the initial natriuresis. Along with diuretic-induced volume contraction, the natriuretic response is abolished due to a fall in GFR and particularly due to a secondary increase in fractional Na reabsorption, which occurs both in proximal distal tubular nephron segments.

Animals↗
PubMed1985

Similar changes in cardiac morphology and DNA synthesis induced by doxorubicin and 4'-epi-doxorubicin.

Doxorubicin is an antineoplastic agent whose clinical administration is limited by dose-dependent irreversible cardiomyopathy. Doxorubicin inhibits the rate of DNA synthesis in cultured rat myocardial cells after 1 h incubation with 16 microM, as is demonstrated by a decreased incorporation of [methyl-3H]thymidine. An analogue of doxorubicin, 4'-epi-doxorubicin, also inhibits the rate of DNA synthesis within 1 h after treatment with 16 microM, to the same extent as doxorubicin-treatment of myocardial cells. Furthermore, similarity between doxorubicin and 4'-epi-doxorubicin in their effect on the myocardial thymidylate pool was also demonstrated by a significantly decreased incorporation of total [methyl-3H]thymidine. The effect of doxorubicin on the rate of DNA synthesis in cultured rat skeletal muscle cells treated for 1 h with 16 microM was quantitatively the same as in myocardial cells. Light microscopy of doxorubicin- and 4'-epi-doxorubicin-treated myocardial cells and doxorubicin-treated skeletal muscle cells showed distinct nucleolar fragmentation and revealed no differences between the two drugs in their effect on either myocardial or skeletal muscle cells. Electron microscopy of myocardial cells following doxorubicin treatment showed increased nuclear pleomorphism and invaginations, along with a striking and distinctive clumping of nuclear chromatin. Furthermore, an apparent high density of the mitochondria due to an increased matrix volume and a concomitant decrease in the intermembrane compartment were observed. The results of this study indicate that doxorubicin-induced inhibition of cardiac DNA synthesis in cultured myocardial cells is nonpredictive of cardiotoxicity. The mechanism is at least bimodal, and the apparent minor toxicity of 4'-epi-doxorubicin compared with that of doxorubicin in clinical trials cannot be distinguished by a difference in the inhibition of DNA synthesis in the rat heart.

Animals↗
PubMed1984

Thiazide-induced potassium loss not prevented by beta blockade.

Potassium balance was followed in 12 subjects with hypertension during treatment either with timolol and hydrochlorothiazide or with timolol, hydrochlorothiazide, and amiloride. Subjects treated with the beta-blocker and thiazide developed potassium depletion, which was prevented by concomitant treatment with amiloride. Thiazide augments timolol-induced potassium loss and it is suggested that the renal handling of potassium is changed by other mechanisms. The decrement in potassium loss during concomitant amiloride treatment cannot be explained.

Aldosterone↗
PubMed1984

Influence of atenolol and nifedipine on digoxin-induced inotropism in humans.

Short term effect of digoxin on left ventricular performance was studied in six healthy volunteers before and during atenolol or nifedipine administration. Left ventricular function was evaluated by systolic time intervals and echocardiography. No changes in left ventricular end diastolic or systolic dimensions occurred throughout the study, indicating unchanged ventricular pre- and afterload. Thus, changes in the systolic time intervals must be attributed to changes in cardiac contractility. Changes in the pre-ejection period index (PEPI) obtained from the systolic time intervals were used as a measure of digoxin-induced inotropism. A concentration-response relationship between plasma digoxin level and changes in PEPI was revealed when digoxin was given alone. Atenolol did not influence the digoxin-induced inotropism at a given serum digoxin level. During nifedipine administration no inotropic effect of digoxin could be demonstrated. Thus, it is concluded that nifedipine attenuates digoxin-induced inotropism, while atenolol seems without this effect. These results are in accordance with previous experiments and reflect the different pharmacological sites of action of beta-adrenoceptor antagonists and calcium channel blocking agents. Plasma digoxin concentration, renal digoxin clearance and creatinine clearance did not change during atenolol or nifedipine.

Adult↗
PubMed1984

Flow dependence of propranolol elimination in perfused rat liver.

The effect of experimental variations of the blood flow rate on hepatic elimination of propranolol was studied in livers from 200 g rats perfused in a recirculating system given a constant infusion of propranolol into the reservoir throughout each experiment. This design ensures that, at steady state, the elimination rate of propranolol is the same as the infusion rate of propranolol, and equal to the hepatic blood flow rate multiplied by the hepatic inlet to outlet propranolol concentration difference. Thus, when flow is increased, the concentration difference will decrease, and vice versa. It is currently a matter of debate whether or not this change in concentration difference will influence the outlet substrate concentration. The venous equilibration model (Rowland et al., J. Pharmacokinet. Biopharm. 1: 123-136, 1973) predicts that at a given elimination rate, the outlet concentration is flow-independent, whereas the sinusoidal perfusion model (Bass et al., J. Theor. Biol. 61: 393-410, 1976) predicts that both inlet and outlet concentrations will change. In 13 of 14 experiments, increasing the flow rate (from an average 9 to 14 ml/min) resulted in a decrease of the inlet concentration and elevation of the outlet concentration (each P less than .005). Thus, the data reject the venous equilibration model but are consistent with the sinusoidal perfusion model under the experimental conditions investigated.

Animals↗
PubMed1983

Interactions between digoxin and potassium-sparing diuretics.

A kinetic and hemodynamic study of digoxin was performed in six healthy subjects and similar studies were performed during digoxin with spironolactone and with triamterene. Spironolactone reduced renal tubular secretion of digoxin and attenuated its positive inotropic effect (evaluated by systolic time intervals and echocardiography) and triamterene reduced the extrarenal elimination of digoxin, but induced no changes in digoxin-elicited inotrophy. It is suggested that the renal handling of digoxin is influenced by the intracellular potassium concentration in the renal tubular cell. The results indicate a drug-receptor interaction between spironolactone metabolites and digoxin at the hypothetical inotropic digitalis receptor. Amiloride has been reported to suppress digoxin inotropism, whereas spironolactone induces minor inhibition and triamterene does not affect digoxin inotropism.

Adult↗
PubMed1982

Renal digoxin clearance: dependence on plasma digoxin and diuresis.

The renal handling of digoxin in animals involves glomerular filtration, tubular secretion and tubular reabsorption, while only glomerular filtration and tubular secretion have been described in humans. The influence of plasma digoxin and urine flow on the renal handling of digoxin was investigated in 6 healthy volunteers. Non-glomerular renal excretion of digoxin (tubular secretion minus tubular reabsorption) was inversely correlated with plasma digoxin concentration and directly with urine flow. Hence, the present study demonstrated the occurrence of tubular reabsorption in addition to glomerular filtration and tubular secretion of digoxin. The results suggest that renal clearance of digoxin should be increased by increased urine flow, which might be of importance during digoxin toxicity.

Adult↗
PubMed1982

Systolic time intervals during spironolactone treatment of digitalized and non-digitalized patients with ischaemic heart disease.

The effect of spironolactone on cardiac contractility indices was studied by externally recording systolic time intervals in four digitalized and four non-digitalized patients with ischaemic heart disease. A negative inotropic effect was found after spironolactone 100mg b.i.d. in all eight patients, as measured by an increase in pre-ejection period index PEPI (p less than 0.01), and the ratio between pre-ejection period and left ventricular ejection time PEP/LVET (p less than 0.001), while pre- and afterload remained constant. As expected, digoxin exerted a positive inotropic effect, as a decrease was observed in PEPI (p less than 0.01), and PEP/LVET (p less than 0.001). It was not possible to ascertain whether the observed effect was caused by a pharmacological interaction at receptor level between spironolactone and digoxin, or indirectly to changes in endogenous substances e.g. aldosterone. The results suggest that spironolactone may have unintended side effects in patients with severe heart failure and that its use be reevaluated.

Aged↗
PubMed1982

Negative potassium balance during beta-blocker treatment of hypertension.

Potassium balance was followed in seven hypertensive patients during treatment with timolol. The patients developed a mean 150 mmol total potassium loss. Serum potassium and body weight were not changed. It is suggested that the changes in total body potassium during timolol treatment may be due to mobilization of potassium from the intracellular space, but, since serum potassium did not rise, timolol may also influence renal handling of potassium.

Adrenergic beta-Antagonists↗
PubMed1982

Effects of propranolol and pindolol on plasma lignocaine clearance in man.

1 Steady state concentrations and clearance of lignocaine were determine in eight healthy volunteers during 360 min continuous lignocaine infusion (2 mg/min). Before the infusion propranolol (0.18 mg/kg i.v.), pindolol (0.023 mg/kg i.v.) or placebo were administered in a random double-blind, cross over design. 2 During the infusion of lignocaine heart rate, cardiac output and arterial blood pressure were measured every 60 min. 3 Propranolol decreased heart rate and cardiac output significantly by 10--20%, while pindolol or lignocaine did not change cardiac output or heart rate significantly. None of the drugs changed the arterial blood pressure. 4 Propranolol pretreatment decreased lignocaine significantly by 14.7% and the steady state concentration was increased by 22.5%. Pindolol produced no significant change in steady state concentration or clearance of lignocaine.

Adult↗
PubMed1981

Essential tremor treated with propranolol: lack of correlation between clinical effect and plasma propranolol levels.

Five patients with essential tremor were treated with increasing daily doses of propranolol. Tremor intensity was assessed after each propranolol dose had been given daily for a period of at least seven days. The evaluation was made 12 to 15 hours after the last propranolol ingestion. It included a semiquantitative clinical tremor evaluation and quantitative registration with an accelerometer. Electronic integration of the accelerometer curves gave an arbitrary measure of tremor intensity. Plasma propranolol concentration was determined at each tremor measurement. The reduction in tremor correlated with increasing propranolol doses, whereas plasma propranolol concentrations varied widely among individuals and could not be correlated with tremor reduction. Most of the patients had considerable diminution in tremor at low propranolol doses, often with an unmeasurable plasma propranolol concentration. Determination of plasma concentrations has little value in long-term treatment of essential tremor with propranolol. The dosage can be sufficiently guided by clinical evaluation of effect.

Adult↗
PubMed1981

Amiloride-induced changes in digoxin dynamics and kinetics: abolition of digoxin-induced inotropism with amiloride.

Digoxin dynamics and kinetics were studied in six healthy subjects with and without amiloride. Amiloride increased mean renal digoxin clearance from 1.3 to 2.4 ml . kg-1 . min-1 (p less than 0.001) due to increased tubular secretion of digoxin, while the glomerular filtration rate was unchanged. This might be caused by an increase in intracellular potassium concentration in the tubular cells provoked by amiloride. In contrast, the extrarenal clearance of digoxin was almost blocked by amiloride; it fell from a mean of 2.1 to 0.2 ml . kg-1 . min-1 (p less than 0.025). Total body clearance tended to fall, but the decrease was not statistically significant. EValuation of myocardial contractility by systolic time intervals revealed a concentration-response relationship between digoxin and changes in preejection period index when digoxin was given alone (rs = 0.750, p less than 0.001). Pretreatment with amiloride abolished this relationship (rs = 0.307, p = NS). Blood pressure and echocardiographically determined left ventricular end-diastolic diameter measurements indicated no changes in the left ventricular post- and preload. It is concluded that amiloride suppressed digoxin-induced inotropism.

Adult↗
PubMed1981

Diuretics, digitalis and arrhythmias.

Arrhythmias induced by digitalis are believed to be secondary to changes in ion concentrations in the myocardial cells or changes in the transcellular ion gradient. Both diuretic induced hypokalemia and digitalis inhibit the membrane-Na+K+ ATPase activity which cause a decrease of the intracellular potassium concentration. This may explain the risk of cardiac arrhythmias during digitalis treatment and during severe hypokalemia, and may further explain the increase for myocardial sensitivity for digitalis when hypokalemia is present. The myocardial uptake of digitalis however is markedly increased at low extracellular potassium concentration and this may be the explanation of the interaction between digitalis and hypokalemia. Not only the myocardial digoxin kinetic is changed during hypokalemia but the renal excretion rate of digoxin is markedly reduced during hypokalemia leading to increased serum digoxin concentration and thereby the risk of digitalis intoxication.

Animals↗
PubMed1981

Time course of ouabain uptake in isolated myocardial cells: dependence on extracellular potassium and calcium concentration.

1 Spontaneously beating myocardial cells isolated from newborn rats have been used to evaluate the time course of cellular ouabain uptake. 2 The rate of cellular uptake and the amount of ouabain bound at equilibrium were computed by fitting the experimental data to the conventional exponential equation for receptor binding of drugs. 3 At normal extracellular potassium and calcium concentrations a biexponential equation was the best fit to the experimental data, indicating two receptor sites of ouabain with different rates of uptake. 4 Increasing extracellular potassium or calcium concentrations decreased the amounts of ouabain bound at equilibrium. 5 High and low extracellular concentrations of potassium or calcium decreased the rate of ouabain uptake. 6 It is well known that ouabain changes ionic fluxes. Changes in the extracellular potassium and calcium concentrations also influence the amount of ouabain taken up by myocardial cells, as demonstrated in the present study.

Animals↗