[Misleading analyses of digoxin without standardized rest prior to sampling].
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Digoxin↗
Biomedical subjects
T Jogestrand
Publications and source records attributed to T Jogestrand.
Effect of salbutamol on digoxin pharmacokinetics.
A single dose of the beta 2-adrenoceptor agonist salbutamol has previously been shown to decrease serum digoxin concentration in healthy volunteers. A possible explanation of the phenomenon is a beta 2-adrenoceptor-mediated increase in the specific binding of digoxin to skeletal muscle. The present study was undertaken to further elucidate the effect of salbutamol on the pharmacokinetics of digoxin in man. Nine volunteers were studied on two occasions during salbutamol or placebo treatment. On test days salbutamol, 4 micrograms.kg-1.h-1 or saline was infused for 10 h, preceded and followed by four and three days, respectively, of oral administration. A single i.v. injection of digoxin 15 micrograms.kg-1, was given 20 min after starting the infusion. At the end of the infusion a muscle biopsy was taken from the vastus lateralis. Blood samples for the analysis of serum digoxin and potassium were repeatedly taken over 72 h. Urine was collected over a period of 24 h for determination of the renal excretion of digoxin and potassium. The serum digoxin concentration, expressed as the AUC 0-6 h was 15% lower during salbutamol infusion than during saline infusion. Salbutamol caused significantly faster elimination of digoxin from the central volume of distribution to deeper compartments. Salbutamol had no effect on the renal clearance of digoxin. The skeletal muscle digoxin concentration tended to be higher (48%) during salbutamol compared to placebo treatment. The serum potassium concentration was significantly lower after salbutamol compared to placebo, as was the rate of renal excretion of potassium.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Platelet activation and prostacyclin release in essential hypertension.
To evaluate platelet activation thromboxane A2 (TxA2) and beta-thromboglobulin (beta TG) were used as markers and in addition we studied the biosynthesis of prostacyclin. Synthesis of TxA2 and prostacyclin was assessed by measurement of urinary metabolites. Fifteen untreated hypertensive patients (HT) and 15 age-matched normotensive controls (NT) were investigated at rest, during and after exercise. HT patients were re-examined after 3 months on enalapril. During basal conditions there was no difference in the excretion of Tx-M, PGI-M or beta TG between the groups. During strenuous exercise HT exhibit a significantly higher increase in prostacyclin synthesis (162%) compared to NT (76%). The levels of beta TG increased with 82% in the HT and 24% in the NT group, Tx-M increased with 27% and 23% respectively. Treatment with the ACE-inhibitor enalapril did not significantly alter these findings. These results indicate that there is no evidence of basal platelet activation in early essential hypertension. Strenuous exercise leads to some increase in Tx-M in both groups, with no pronounced differences between the groups. Hypertensive patients exhibit a significantly increased prostacyclin response to exercise which could be due to differences in vessel-wall reactivity. Enalapril seems to exert no effect on platelet activation or on prostacyclin biosynthesis.
Adult↗
Non-invasive assessment of vessel-wall changes in hypertensives and normotensive controls.
The aim of this study was to evaluate the feasibility of non-invasive assessment of vessel wall changes in early, untreated hypertension. Measurement of intimal+medial (I-M) thickness in the common carotid artery (CCA) using B-mode ultrasound imaging showed no differences between 12 patients with untreated, newly diagnosed hypertension and 9 age-matched controls (0.63 mm vs 0.63 mm just proximal to the carotid bulb). Echocardiography showed that the hypertensive group had thicker left ventricular walls (LVW) than the normotensive group. Correlation analyses disclosed that I-M thickness was significantly associated with age (r = 0.63; P less than 0.05) for the whole material but not with blood pressure levels, serum lipids, or LVW thickness. These results imply that the arterial I-M layers of the CCA are less responsive to pressure overload than the left ventricle. The feasibility of using I-M thickness as an early marker of structural vessel wall changes in hypertensive patients must await results from large scale prospective studies. In view of the present results, age homogenous materials should be selected for such studies.
Adult↗
Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients.
Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients. We examined the effects of erythropoietin (EPO) treatment in 12 predialytic uremic patients (EPO group: mean age 46 +/- 12 years; 6 men, 6 women) with a mean glomerular filtration rate (GFR) of 10 +/- 4 ml/min x 1.73 m2. These patients were compared to a control group of 8 patients (5 men, 3 women). The observation period was 3 months. The EPO group received 300 U/kg body weight i.v. once a week. The EPO group increased their total hemoglobin (THb) from 323 +/- 89 to 466 +/- 128 g (p less than 0.001) and their hemoglobin concentration from 86 +/- 8 to 117 +/- 11 milligrams (p less than 0.001). Their exercise capacity, measured by a standardized exercise test on a bicycle ergometer, increased from 128 +/- 45 to 147 +/- 57 W (p less than 0.01). The control group did not change their THb (349 +/- 124 and 357 +/- 131 g), hemoglobin (93 +/- 8 and 94 +/- 10 milligrams) or exercise capacity (98 +/- 49 and 101 +/- 50 W) during the observation period. There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group (r = 0.81, p less than 0.005). The GFR was unchanged in both groups (EPO group: 10 +/- 4 and 10 +/- 6 ml/min x 1.73 m2; control group: 8 +/- 3 and 8 +/- 3 ml/min x 1.73 m2).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of adrenaline and mental stress on serum digoxin concentration.
Physical activity and pharmacological stimulation of beta 2-adrenoceptors by salbutamol increase skeletal muscle digoxin binding with a secondary decrease in serum digoxin, possibly due to increased Na-K-ATPase activity. The present study was undertaken to examine if adrenaline (ADR) infusion and sympathoadrenal stimulation by mental stress affect the serum concentrations of digoxin and potassium. After 10 days on 0.50 mg digoxin orally, 35 healthy volunteers were investigated following 2 h of supine rest. They were divided into four groups: intravenous saline (placebo, n = 10). ADR infusion at the rates of 0.1 nmol kg-1 min-1 (ADR-L, n = 8), 0.4 nmol kg-1 min-1 (ADR-H, n = 7), or subjected to a mental stress [a color-word conflict test (CWT), n = 10]. Arterial blood samples were taken before and during the active period (50 min) and during the following 60 min (at rest) to analyze serum digoxin and potassium and plasma ADR and noradrenaline (NA). All variables were stable during placebo infusion. ADR infusions caused significant and dose-dependent decreases in serum digoxin (p less than 0.05 during ADR-L and p less than 0.001 during ADR-H) and serum potassium (p less than 0.05 and p less than 0.001, respectively). CWT, on the other hand, did not reduce serum digoxin and caused a slight decrease in serum potassium only in the poststress period. Thus, ADR caused dose-dependent shifts of digoxin and potassium, whereas mental stress failed to do so, possibly due to a modest ADR response and small increases in sympathetic nerve activity in skeletal muscle.
Administration, Oral↗
Effects of exercise training in predialytic uremic patients.
We examined the effects of physical training in 10 predialytic uremic patients (7 men, 3 women, mean age 47 +/- 8 years) with an average glomerular filtration (GFR) of 15 +/- 7 ml/min x 1.73 m2. All 10 patients participated in an exercise programme 3 times/week for 3 months and were compared to a control group of 9 patients with comparable baseline variables. The exercise group increased its maximal exercise capacity measured by standardized exercise test on a bicycle ergometer, from an average 159 +/- 49 to 174 +/- 57 W (p less than 0.01). They also showed a decrease in heart rate at equal load (138 +/- 29-123 +/- 18 beats/min, p less than 0.05). The control group did not change its exercise capacity (171 +/- 60 and 171 +/- 65 W, respectively, NS), nor its heart rate at equal load (124 +/- 24 and 123 +/- 24 beats/min, respectively, NS). Thigh muscular function assessed by static endurance increased from a median 77 s (range 27-197) to 113 s (range 66-201), p less than 0.002. Dynamic muscular endurance increased from a median number of 41 movements (range 28-105) to 93 movements (range 45-139), p less than 0.001. The corresponding figures for the controls were: static endurance 60 (range 20-209) and 47 s (range 9-203), respectively, NS; dynamic endurance 53 (range 19-190) and 43 movements (range 10-126), respectively, NS. Total hemoglobin, blood volume, GFR, blood pressure and echocardiographic variables remained unchanged during the observation period. We conclude that in predialytic uremic patients, physical training improves exercise capacity mainly due to an improved muscular function.
Adult↗
Oral salbutamol decreases serum digoxin concentration.
The effect of a therapeutic dose of oral salbutamol on serum and skeletal muscle digoxin concentrations has been studied in volunteers digitalised with digoxin. On one occasion a biopsy was taken from the quadriceps after 2 h of supine rest and then 3-4 mg salbutamol was given orally. Blood samples were taken before and after that dose and another muscle biopsy specimen was taken from the same thigh 180 min after the medication. On another occasion control blood sampling, ECG and blood pressure recordings were made but without muscle biopsies or salbutamol administration. Compared to the control measurements, salbutamol decreased the serum digoxin concentration (0.30 nmol.l-1). It also reduced the serum potassium concentration (0.58 mmol.l-1). The digoxin concentration in skeletal muscle did not change significantly after the intake of salbutamol. Thus, even a therapeutic oral dose of salbutamol reduces the serum digoxin concentration in man.
Adult↗
Effect of salbutamol on digoxin concentration in serum and skeletal muscle.
Beta 2-receptor stimulation has been reported to increase the concentration of 3H-ouabain in rat skeletal muscle. The present study was undertaken to see if beta 2-adrenoceptor stimulation by i.v. injection of salbutamol had any influence on the pharmacokinetics of digoxin in man. Ten volunteers were digitalized with digoxin and were investigated on two occasions. On each occasion a muscle biopsy was taken from the quadriceps after 2 h of supine rest. An injection of salbutamol 4 micrograms.kg-1 b.wt. or saline was then given intravenously. Blood samples were taken before and after the injection and further muscle biopsy was taken from the same thigh 120 min after the injection. Compared to the injection of saline, salbutamol caused a decrease in the serum digoxin and potassium concentrations. The change in serum potassium was significantly correlated with that in digoxin. The digoxin concentration in skeletal muscle was not significantly changed by either the salbutamol or saline injections.
Adult↗
Clinical value of serum digoxin assays in outpatients: improvement by the standardization of blood sampling.
Everyday physical activity previously has been shown to affect serum digoxin concentrations. Standardized rest in the supine position increases outpatient serum digoxin levels 0% to 75%. The present study comprising 56 outpatients treated with digoxin was undertaken to elucidate the clinical importance of a standardized period of rest before collection of the blood sample. Blood samples were taken about 24 hours after the latest dose, before and after 2 hours of rest in the supine position. A careful clinical examination, including electrocardiogram (ECG) findings, systolic time intervals, and chest x-ray studies, was performed to identify adverse effects/intoxication or failure of digitalis treatment. Signs of failure of digitalis treatment occurred in 12% of the patients, with a serum digoxin concentration of 0.68 +/- 0.15 (mean +/- SD) nmol/L before rest and 0.85 +/- 0.22 nmol/L after rest. Eleven percent showed signs of adverse effects/intoxication, with serum digoxin concentrations of 1.70 +/- 0.70 nmol/L before rest and 2.08 +/- 0.80 nmol/L after rest. The serum digoxin concentrations of the adequately treated patients (77%) were 1.02 +/- 0.35 nmol/L before rest and 1.28 +/- 0.41 nmol/L after rest. The importance of standardized rest before blood sampling is illustrated by the fact that only one third of the patients without signs of adverse effects/intoxication or failure of digitalis treatment had serum digoxin concentrations within the therapeutic range most commonly used (1.2 to 2.6 nmol/L) without supine rest. If allowed to rest in the supine position before blood sampling, approximately 60% of the adequately treated patients had serum digoxin concentrations within this range.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of physical exercise on the pharmacokinetics of digoxin during maintenance treatment.
Blood samples were taken repeatedly and urine was collected for digoxin assays on two occasions from 12 healthy male volunteers after an oral maintenance dose of digoxin. On one occasion the subjects exercised intermittently on a bicycle ergometer for 8 h after the dose. On the other occasion they rested in the supine position during the study period. Thirty and 45 min after the intake of digoxin, the serum digoxin concentration was significantly higher during exercise compared with rest, indicating increased absorption rate during exercise. Two and 4 h after the intake of digoxin, the serum digoxin concentration was significantly lower during exercise than during rest. Furthermore, the intermittent bicycle exercise decreased the renal excretion of digoxin during the study period. It also increased the steady state digoxin concentration measured after a terminating standardized period of rest. The most probable reason for these changes in the pharmacokinetics is a previously described increased binding of digoxin to exercising muscles. According to the results, there is reason to believe that the daily physical activity performed by digoxin-treated patients will determine to some extent the body content of digoxin. Changes in activity from day to day may therefore cause variations in the effect of the drug.
Adult↗
Factors influencing physical working capacity in renal transplant patients.
Clyne N, Jogestrand T, Lins L-E & Pehrsson SK. Division of Nephrology and Cardiology, Department of Medicine and Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden. We have examined uraemic patients' exercise capacity, and the factors influencing this capacity, before and after successful renal transplantation. Eleven uraemic patients (mean age 41 +/- 10 years) with an average glomerular filtration rate (GFR) of 5 +/- 4 ml/min x 1.73 before and 45 +/- 19 ml/min x 1.73 after transplantation participated in the study. The maximal exercise capacity, measured by standardized exercise test on a bicycle ergometer, averaged 106 +/- 25 W before and 126 +/- 35 W (p less than 0.05) after transplantation. The patients interrupted the tests prior to and after transplantation because of general fatigue, leg tiredness or both. No patient experienced angina pectoris. All, but one, had a normal ECG reaction during exercise. Total haemoglobin (THb) was 55 +/- 8% of the expected normal before and 84 +/- 19% after transplantation (p less than 0.01). The increase in working capacity was linearly correlated to the increase in THb (r = 0.84, p less than 0.01), but not to the improvement in GFR nor to the decrease in parathyroid hormone. In conclusion, successful renal transplantation improves working capacity. The results indicate that an increased THb is a major determinant for this increase in working capacity.
Adult↗
Factors limiting physical working capacity in predialytic uraemic patients.
The exercise capacity of 20 predialytic uraemic patients (mean age 43 +/- 12 years) was studied prospectively. Nine of these patients were examined twice in a longitudinal study. The maximal working capacity, measured by standardized exercise test on a bicycle ergometer, averaged 74 +/- 19% of the expected normal. Normal exercise ECG were registered in 16 out of 20 patients. Total hemoglobin/kg body weight (THb) was 67 +/- 16% of the expected normal and serum parathyroid hormone concentration (PTH) was 39 +/- 39 micrograms/l (normal range 0.5-1.5). Partial correlation showed a correlation between exercise capacity and PTH (p less than 0.05). In the longitudinal study the decrease in steady state exercise capacity was correlated to the decrease in THb (p less than 0.05), but not to the increase in PTH. In conclusion, patients with predialytic uraemia have a reduced maximal working capacity, due to several possible factors one of which is a reduced THb. Ischaemic heart disease seems to be of minor importance.
Adult↗
Effects of furosemide and slow-release furosemide on thoracic fluid volumes.
Transthoracic electrical impedance (TEI) was used to assess the relative effectiveness of a 60 mg sustained-release furosemide preparation (FR) and a 40 mg standard furosemide tablet (F), in reducing the fluid content in the thoracic cavity. A double-blind crossover study was performed, in which 12 men with a history of one or more myocardial infarctions and mild left heart failure treated with 40 mg furosemide once daily participated. The trial, lasting 28 days, was divided into two 14-day periods. Each participant received one active drug and one placebo preparation daily, the same regimen being maintained for 14 days, when the active substances were switched. TEI, body weight, serum potassium, sodium, creatinine, and urate were measured immediately prior to the start of the study, after 14 days, and at the end of the study. TEI was measured at frequencies of 1 and 100 kHz with a constant current of 100 microA, during a period of one hour following an intravenous injection of 40 mg furosemide, when the urine volumes were measured also. TEI and urine production after the furosemide injections were similar irrespective of the drug preparation. No evidence of treatment period interaction was seen. No significant differences were demonstrated in body weight and blood chemistry during the trial. These results suggest clinical equipotency of the two preparations in mild left heart failure.
Aged↗
Beta-blockade and binding of digoxin to skeletal muscle.
The effect of beta-blockade and a 1-h bicycle exercise test on the digoxin concentration in skeletal muscle (thigh) and serum was studied in 10 healthy men, who had ingested 0.5 mg digoxin daily for 2 weeks. Each subject performed two exercise tests at 100-140 W during maintenance digoxin treatment and 24 h after the latest dose. They rested in the supine position for 2.5 h before the exercise. Sixty minutes before the start of the exercise 0.25 mg/kg b.w. propranolol or saline (control) were injected (single-blind). At the end of the exercise the mean heart rate was 30% lower with beta-blockade (P less than 0.001). During exercise the mean skeletal muscle digoxin concentration increased by 29% (P less than 0.01) in the control situation and by 12% (NS) with beta-blockade. The results indicate that propranolol partly inhibits the exercise-induced increase in skeletal muscle digoxin binding. This might be due to inhibition of a catecholamine-induced stimulation of Na+-K+ATPase during exercise.
Adult↗
Glucose uptake and binding of digoxin to skeletal muscle.
Physical exercise induces increased uptake of both digoxin and glucose in exercising skeletal muscle. Glucose uptake could be a regulatory factor for the digoxin binding to skeletal muscle, since in dogs, insulin and glucose infusion have been reported to increase the uptake of digoxin in muscle. In the present study on eight healthy digitalized subjects (0.5 mg digoxin daily) the uptake of glucose in skeletal muscle was achieved by infusion of 6 mg/kg body weight/min glucose, 0.004 IE/kg body weight/min insulin and 300 micrograms/h somatostatin. Serum and skeletal muscle digoxin levels were analysed before and during the infusion. We found no changes in the digoxin levels in serum and skeletal muscle in spite of an increased uptake of glucose in the muscle. Thus, glucose uptake in skeletal muscle is probably not an important regulatory factor for the change in muscle digoxin binding induced by exercise.
Adult↗
Digoxin binding in right atrium.
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Adult↗
[Clinical experiences with prostaglandin E1 in severe peripheral artery disease].
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Aged↗