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Biomedical subjects

S Waldorff

Publications and source records attributed to S Waldorff.

36 records · Page 2Linked to original sources
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

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

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

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↗
PubMed1980

Reduction of digoxin-induced inotropism during quinidine administration.

A kinetic and dynamic study of digoxin was performed in 6 healthy subjects, and repeated in the same subjects after administration of quinidine for 1 wk. Myocardial performance evaluated by systolic time intervals increased in parallel with plasma digoxin concentration, whereas left ventricular end-diastolic diameter on echocardiography and arterial blood pressure remained constant. The positive inotropic effect of digoxin was abolished during concomitant treatment with quinidine. Quinidine has been reported to increase the risk of digitoxicity, and therefore the treatment with digoxin and quinidine in combination should be reconsidered.

Adult↗
PubMed1980

Correlation between changes in systolic time intervals and left ventricular end-diastolic diameter after preload reduction. Non-invasive monitoring of pharmacological intervention.

In order to measure the effect of a decrease in preload on systolic time intervals and left ventricular end-diastolic diameter (LVEDD) measured by echocardiography, eight healthy young subjects were given 40 mg frusemide intravenously. The pre-ejection period index (PEPI) increased and the left ventricular end-diastolic diameter decreased. A correlation between delta PEPI and delta LVEDD was shown. Using changes in systolic time intervals in the evaluation of changes in contractility it is important to correct for changes in preload. For normal subjects it is suggested that the relation between delta PEPI and delta LVEDD as a percentage of the mean values should be used for this correction. A method is suggested for estimating the changes in pre-ejection period index induced by changes in left ventricular end-diastolic diameter.

Adult↗
PubMed1979

Kinetics of propylthiouracil in the elderly.

The pharmakokinetics of propylthiouracil was evaluated in 9 elderly patients and compared to previous results from 6 younger subjects. By giving the drug both by the intravenous and oral route of administration it was possible to estimate the rate and extent of bioavailability. The various kinetic parameters were calculated according to a two-compartment model by use of two different methods: a graphical hand drawn one and by a special developed computer program based on a least squares minimalisation. While no significant differences could be demonstrated between the two age groups concerning volumes of distribution, clearance and extent of absorption, a large difference was found with regard to the absorption rate constant ka, which was about 3 times higher in the younger than in the elderly subjects, presumably due a reduced gastric emptying time. Considering the comparison between the two methods of calculations all the kinetics parameters were similar except ka and the slow disposition rate constant betw which were underestimated by the graphical method. It is concluded that no-age dependent changes exist concerning the kinetics of propylthiouracil except for a decreased rate of absorption. Graphical methods in pharmacokinetics are useful in obtaining distribution and elimination data but seem often biased for the evaluation of absorption rate constants.

Age Factors↗
PubMed1979

Canrenoate--a spironolactone metabolite. Acute cardiac effects in digitalized patients.

Canrenoate (Soldactone)--a spironolactone metabolite for intravenous use--has recently been suggested as a specific antidote in patients suffering from digitalis intoxication. Theoretically, this would imply that canrenoate could counteract the effect of digoxin. The influence of canrenoate on inotropy in 12 digitalized patients was investigated by measurement of sytolic time intervals. Canrenoate improved the left ventricular contractility, since both preejection period (PEP) and the ratio between PEP and left ventricular ejection time (PEP/LVET) decreased significantly. The maximal changes in controlled atrial fibrillation, canrenoate had no effect on ventricular rate, whereas atropine increased the ventricular rate significantly.

Aged↗
PubMed1978

Serum digoxin and empiric methods in identification of digitoxicity.

A prospective study of consecutive patients admitted to a medical service was undertaken to evaluate the prevalence of cardiac digitalis toxicity and the relative diagnostic values of serum digoxin versus an empiric method, based on calculations of digoxin dose in relation to kidney function and body weight. Of 711 patients admitted, 109 were treated with digitalis on admission. Sixteen of the patients developed cardiac arrhythmias consistent with digitalis intoxication. Five of these, none with serum digoxin above 1.6 ng/ml, were not toxic. The remaining eleven patients, all with serum digoxin levels above 1.6 ng/ml, were either definitely or possibly toxic. A similar borderline between intoxicated and nonintoxicated patients could not be established on the basis of calculations based on body weight and renal function. In all cases in which suspicion of digitalis intoxication was raised, serum digoxin measurements could discriminate between the toxic and the nontoxic patients.

Aged↗
PubMed1978

Spironolactone-induced changes in digoxin kinetics.

Plasma clearance, volumes of distribution, and renal and extrarenal clearances of digoxin were calculated from plasma digoxin concentrations and urinary excretion of digoxin after intravenous injection of digoxin in 8 subjects. The investigation was repeated in the same subjects during long-term treatment with spironolactone. Increased plasma concentration of digoxin was detected during spironolactone treatment. Calculated plasma and renal clearances of digoxin and the volumes of distribution decreased statistically significant. Near maximal capacity for the tubular secretion of digoxin was found when normal digoxin dosage was used. It is suggested that unless spironolactone decreases the myocardial sensitivity for digoxin, the loading dose as well as the maintenance dose of digoxin should be reduced during treatment with spironolactone.

Adult↗
PubMed1975

Continuous estimation of adipose tissue blood flow in rats by 133Xe elimination.

A method is described which permits continuous estimation of adipose tissue blood flow (ATBF) in anesthetized female rats. The method is basesd on continuous monitoring of the elimination of 133Xe after labeling of the animal by intraperitoneal injection. From 2 to 6 h after the beginning of the elimination period close to 100% of the measured activity is shown to be located in adipose tissue, mainly in the parametrial fat. About 18% of the elimination is by way of intertissue diffusion, 82% of the perfusing blood. Changes in ATBF can readily be detected. The coefficient of variation for ATBF determinations is 9-11%. Changes in ATBF can be determined with great accuracy. Average ATBF per g tissue for fed and 48-h fasted rats were 0.105 and 0.122 ml-g-1-min-1, respectively. Total ATBF was lower in fasted than in fed rats (1.05 vs. 1.43 ml-min-1 for parametrial plus retroperitoneal fat). Intravenous administration of glucose (250 mg/h) decreased ATBF significantly in fed but not in fasted rats.

Adipose Tissue↗