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Biomedical subjects

A Hedman

Publications and source records attributed to A Hedman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Renal elimination of ceftazidime during pregnancy.

OBJECTIVE: Our purpose was to study the pharmacokinetics of ceftazidime at different stages of pregnancy and in the nonpregnant state to determine whether glomerular filtration rate is altered and whether tubular secretions occurs. STUDY DESIGN: Twelve pregnant women with asymptomatic bacteruria were given a bolus dose of 400 mg of ceftazidime followed by a constant infusion for 4 hours. Inulin was infused simultaneously to determine glomerular filtration rate. Blood samples were drawn every 30 minutes. Urine was collected immediately after the bolus dose and then every hour. The same study procedure was then repeated twice: 2 weeks before the expected delivery and after termination of breast-feeding. RESULTS: At term clearance values were raised by 50% to 100% compared with the values found in the postpartum period. At all observation points a close correlation between inulin and ceftazidime clearance values were found. CONCLUSION: The results strongly indicate that ceftazidime is excreted exclusively by glomerular filtration with no tubular reabsorption. During pregnancy the excretion pattern is unaltered, but renal elimination is increased.

Bacteriuria↗
PubMed1993

Dose proportional absorption of 25-150 mg atenolol.

We investigated the dose proportionality after the intake of oral atenolol 25, 50, 100 and 150 mg. Standard tablets were taken by 8 healthy volunteers in randomised order of doses. The area under the curve divided by dose did not differ between the doses, indicating that the absorption of this hydrophilic compound, with known incomplete bioavailability, was constant over the range tested.

Administration, Oral↗
PubMed1992

Inhibition by basic drugs of digoxin secretion into human bile.

Bile samples from previous interaction studies in man were re-analysed by a combined HPLC/radioimmunoassay method. Quinidine, quinine and verapamil but not probenecid or spironolactone were found to inhibit the biliary secretion of unchanged digoxin.

Bile↗
PubMed1992

Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance.

The possibility of an inhibitory effect of spironolactone on the biliary clearance of digoxin has been investigated in 6 healthy subjects. Plasma clearance and the renal and biliary clearance of digoxin were determined twice at steady state (digoxin 0.5 to 1 mg.d-1 p.o. for 6 days), alone or in combination with spironolactone 200 mg daily, after an intravenous dose of digoxin (0.7 x oral dose) on Day 7. Plasma and urine were collected for 48 h. Biliary clearance of digoxin was determined on Day 8 by a duodenal perfusion technique. During spironolactone treatment plasma digoxin clearance tended to be lower (255 vs 224 ml/min; P = 0.057) and renal clearance significantly lower (166 vs 144 ml/min), while the biliary clearance of digoxin remained unchanged (106 vs 103 ml/min). Thus, spironolactone reduced the renal clearance of digoxin by an average of 13%, without affecting its biliary clearance.

Adult↗
PubMed1991

Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans.

The interaction between digoxin and verapamil was studied in six patients (mean age +/- SD, 61 +/- 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 +/- 0.24 to 1.15 +/- 0.40 nmol/L (p less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 +/- 31 versus 173 +/- 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route.

Bile↗
PubMed1991

No effect of probenecid on the renal and biliary clearances of digoxin in man.

1. The cardiac glycoside digoxin is subject to a number of pharmacokinetic interactions. This study concerns the influence of the anionic transport inhibitor probenecid on the steady-state kinetics of digoxin. 2. Six healthy young men were enrolled in the study. After an administration period of 6 days with digoxin only (0.5 to 1 mg p.o. day-1) or digoxin in combination with probenecid (2 g p.o. day-1; 8 days), digoxin was administered intravenously (0.7 oral dose) on day 7. Plasma and urine samples were taken over 48 h. The biliary clearance of digoxin was measured during day 8 by a duodenal perfusion technique. 3. Probenecid did not affect the plasma clearance (mean +/- s.d.: 255 +/- 80 vs 266 +/- 40 ml min-1), renal clearance (166 +/- 17 vs 155 +/- 10 ml min-1), biliary clearance (106 +/- 40 vs 111 +/- 50 ml min-1), elimination half-life (34.4 vs 35.2 h) or volume of distribution (538 +/- 241 vs 566 +/- 60 l) of digoxin. 4. Our results suggest that different systems exist in man for the renal and biliary secretion of probenecid and digoxin.

Administration, Oral↗
PubMed1991

Decreased renal clearance of sodium in cystic fibrosis.

In 10 patients with cystic fibrosis (CF) and 10 controls of similar age quantitative segmental handling of sodium was estimated by lithium clearance. In the CF group, there was a tendency for an increased glomerular filtration rate (GFR) and increased absolute proximal sodium reabsorption. The fractional distal sodium reabsorption was significantly (p = 0.015) increased and sodium clearance was significantly (p less than 0.01) decreased in CF.

Adult↗
PubMed1991

Hemodynamics and exercise capacity during pacemaker stimulation.

This review summarizes the present knowledge concerning the hemodynamic and myocardial effects of various pacing modalities with special reference to the importance of heart rate variability and atrioventricular synchronization. An adequate increase in heart rate, irrespective of atrioventricular synchronization, seems to be the most important denominator for cardiac output and exercise tolerance. Atrioventricular synchronization will add some hemodynamic benefit, which is most pronounced at rest. The importance of a rate-adaptive atrioventricular delay and a normalized ventricular activation sequence remains, however, to be fully established. Myocardial oxygen consumption does not differ during fixed rate ventricular pacing, atrial synchronous or non-synchronous rate-adaptive ventricular pacing, neither at rest nor during exercise, despite a higher cardiac output during the rate-adaptive modes. This indicates a more "economic" cardiac work with rate-adaptive pacing. Fixed rate ventricular pacing, on the other hand, may have negative long-term effects on myocardial function due to an increased cardiac sympathetic activity compared with rate-adaptive ventricular pacing, in particular during exercise. It is concluded that the majority of pacemaker-dependent patients will benefit from restored rate variability, with the atrial electrogram still being the most appropriate trigger for rate-adaptive ventricular pacing. When the atrial signal cannot be used or when it is unreliable, however, other rate-triggering signals can be used with comparable results regarding hemodynamics and exercise tolerance.

Arrhythmias, Cardiac↗
PubMed1990

Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine.

The interactions between digoxin and quinine and quinidine that affect the renal and biliary clearances of digoxin were investigated in eight healthy subjects. Digoxin (0.5 to 0.75 mg/day) was given alone and with concomitant administration of quinine (750 mg/day) to reach a steady-state level. In four of the subjects, the study was repeated by administration of equimolar doses of the diastereoisomer quinidine together with digoxin, enabling a within-subject comparison of the effects of the two isomers on digoxin clearance. The biliary excretion of digoxin was studied by use of a modified duodenal marker perfusion technique. A marked reduction was found in the steady-state biliary clearance of digoxin from control value 134 +/- 57 ml/min (mean +/- SD) to 87 +/- 39 ml/min during treatment with quinine (p less than 0.05) and from 95 +/- 24 to 55 +/- 27 ml/min during treatment with quinidine (p less than 0.01; n = 4). Quinidine reduced the renal clearance of digoxin (155 +/- 26 versus 110 +/- 21 ml/min) (p less than 0.05; n = 4), whereas quinine had no such effect (177 +/- 40 versus 185 +/- 53 ml/min; not significant). These findings explain the difference in magnitude between quinidine and quinine in regard to the interaction with digoxin and imply a different degree of stereoselectivity for these isomers in the renal and biliary secretory systems of digoxin.

Adult↗
PubMed1990

Effects of mental and physical stress on central haemodynamics and cardiac sympathetic nerve activity during QT interval-sensing rate-responsive and fixed rate ventricular inhibited pacing.

The effects of mental stress and dynamic exercise on central haemodynamic variables and cardiac sympathetic nerve activity were studied in 15 patients during both fixed rate ventricular-inhibited (VVI) and QT interval-sensing rate-responsive (TX) pacing. Haemodynamic measurements were made at rest, during a mental stress test and during supine exercise at 30 W. Cardiac sympathetic nerve activity was assessed by measuring the arterial and coronary sinus plasma concentrations of noradrenaline (NA) and adrenaline (ADR), the NA kinetics in arterial plasma (radiotracer infusion) and the overflow of NA into the coronary sinus. During exercise the paced ventricular rate increased by 47% with TX. TX provided a higher cardiac output than VVI despite a similar myocardial oxygen consumption and a lower level of cardiac sympathetic activity. Cardiac NA overflow based on 3H-NA extraction over the heart increased from 182 to 1046 pmol min-1 in the VVI mode (P less than 0.01) and from 178 to 793 pmol min-1 in the TX mode (P less than 0.001). The difference in cardiac NA overflow in response to exercise (P less than 0.05 by ANOVA) was not reflected in similar differences in arterial NA concentrations or spill over rates. During mental stress the ventricular rate increased in 12/14 patients. Noradrenaline overflow increased similarly in the two modes. Changes in cardiac NA overflow during mental stress and exercise were correlated with increases in TX pacing rate. This study confirms that both mental and physical stress cause significant changes in cardiac sympathetic nerve activity and central haemodynamic variables, and that the TX pacemaker responds by increasing its pacing rate in a physiological manner.

Aged↗
PubMed1990

Increased renal clearance of cefsulodin due to higher glomerular filtration rate in cystic fibrosis.

The steady-state renal clearance of cefsulodin was studied in 6 patients with cystic fibrosis and 8 healthy controls. The drug was administered by constant rate infusion to obtain 2 values of plasma concentration, 2 and 30 mg/L. As an estimate of the glomerular filtration rate, the renal clearance of inulin was measured simultaneously. The results showed the figures for inulin clearance to be approximately 30% higher in cystic fibrosis patients than in healthy controls at both concentrations, and a corresponding increase in the renal clearance of cefsulodin was seen in patients over controls. The ratio between the renal clearances of the 2 substances was on average 0.9 in both groups. The correlation found between the 2 renal clearances (r = 0.75; p less than 0.001) indicates that glomerular filtration rate has considerable influence on the renal elimination of cefsulodin. This finding emphasises the importance of glomerular filtration rate for the renal clearance of drugs in cystic fibrosis.

Adolescent↗
PubMed1990

Plasma and renal clearance of iohexol--a study on the reproducibility of a method for the glomerular filtration rate.

The reproducibility of iohexol clearance as a determination of the glomerular filtration rate was assessed in 12 healthy subjects during triplicate constant-rate infusions. Renal and plasma clearance of iohexol demonstrated a total within-subject variation (CV) ranging between 0% and 16%. The inter-individual variation in renal clearance was about 10%, the clearance values being (mean +/- SD) 116 +/- 10, 117 +/- 9 and 110 +/- 12 ml/min 1.73 m2 in the three experiments and corresponding figures for the plasma clearance were 120 +/- 17, 118 +/- 12 and 112 +/- 14 ml/min 1.73 m2. The renal clearance (CLR) and the plasma clearance (CL) showed good correlation (regression equation CL = 11.80 + 0.93 CLR, rs = 0.67). The method is simple and reproducible; thus, it is suitable for both clinical examinations and research.

Adult↗
PubMed1989

Long-term follow-up of patients treated with the QT interval sensing rate-responsive pacemaker.

Thirty-seven patients (mean age 70 years) with QT-interval sensing (TX) rate-responsive pacemakers were followed for a mean of 27 months. This pacemaker measures the QT interval of the paced beat and, if the QT shortens, the pacing rate increases according to a programmed relationship, the 'slope'. With TX pacing the heart rate was 56% and the exercise tolerance 15% higher than with fixed-rate ventricular-inhibited (VVI) pacing during exercise. Holter ECG monitoring showed a physiological rate variability. Six patients (16%) have died during follow-up, and programming to the VVI mode was necessary in six patients (16%). The remaining patients were alive with a subjectively adequate TX function at the end of follow-up. Including the five patients who were on TX pacing at the time of death, satisfactory TX pacing was obtained in 84% of the patients. Although the TX pacemaker has been reliable and provides an adequate rate response during exercise, complaints of worsening angina pectoris and the somewhat complicated programming of the device are problems with the current models.

Aged↗
PubMed1989

QT sensing rate responsive pacing compared to fixed rate ventricular inhibited pacing: a controlled clinical study.

Eighteen patients, five women and 13 men, (mean age 70 +/- S.E.M. 2 years) treated with QT sensing rate responsive pacemakers due to symptomatic high degree AV block took part in a double-blind study, comparing the rate responsive (TX) mode with fixed rate ventricular inhibited (VVI) pacing. The pacemaker was blindly programmed to either mode in a cross-over design. During the 1 month period a daily diary of symptoms (chest pain, vertigo, dyspnea, and palpitations) was kept. At the end of each period, a mental stress test and an exercise test were performed. The patient rated the general well-being and stated a preference for one of the modes. In the TX mode the heart rate was significantly higher at the end of exercise compared with VVI (107 +/- 4 vs 73 +/- 3 bpm; P less than 0.001) and the exercise tolerance was improved by 9% (104 +/- 8 vs 96 +/- 7 W; P less than 0.01). The patients reported significantly less dyspnea and fatigue at comparable workloads with TX pacing. During the mental stress test the pacing rate increased by 10% in the TX mode (from 73 +/- 2 to 82 +/- 4 bpm; P less than 0.001). There was a physiological rate variability on 24-hour Holter monitoring. Ten patients reported a significant improvement in feeling of general well-being in the TX mode. Eleven patients preferred the TX mode, five patients could not distinguish between the modes and two patients preferred the VVI mode due to worsening of angina pectoris with TX pacing. This preference for the TX mode was significant (P less than 0.05). The results of this controlled study indicate that TX is preferable to VVI in most cases, but the worsening of angina pectoris in two of the patients and the occurrence of rapid rate oscillations in a third patient are factors that warrant some caution in selecting patients.

Aged↗
PubMed1989

QT sensing rate responsive pacing and myocardial infarction: a case report.

A 65-year-old man, treated with the QT sensing rate responsive pacemaker required to manage high degree AV block, sustained a transmural inferior wall myocardial infarction 6 months after the pacemaker implant. The rate response of the pacemaker during the acute phase of the infarction was physiological as evidenced by increased pacing rate during pain and with the gradual decrease in rate during the first postinfarction days. The underlying mechanisms are discussed.

Aged↗
PubMed1988

Changes in QT and Q-aT intervals induced by mental and physical stress with fixed rate and atrial triggered ventricular inhibited cardiac pacing.

We have investigated the influence of mental stress and physical stress, i.e., exercise, on the QT and Q-aT intervals (measured from the pacemaker stimulus to the end or the apex, respectively, of the T wave). The study was made on ten patients with high degree atrioventricular block treated with AV universal (DDD) pacemakers. These were programmed to a fixed rate ventricular (VVI) or an atrial triggered (VDD) function for different parts of the study. An arithmetic mental stress test and a bicycle exercise test were performed with each mode of pacing. In the VVI pacing mode, the atrial rate increased by 11% during mental stress and by 46% during exercise. There was a significant shortening of QT and Q-aT intervals with both types of stress. With VDD pacing, mental stress induced a 12% increase in rate and a significant shortening of QT and Q-aT. The paced rate increased by 50% during the exercise test. This increase in ventricular rate was associated with the most marked changes in QT and Q-aT intervals. Thus, both types of stress cause a significant shortening of the QT and Q-aT interval even in the absence of a simultaneous increase in ventricular rate. When the latter is allowed to increase during VDD pacing, both intervals shorten considerably more. There was a marked inter-individual variability in the response to both types of stress. These findings are of importance with regard to the QT sensing rate responsive pacemaker which can be expected to respond to mental stress in most patients, but that response might be unpredictable in the individual.

Cardiac Pacing, Artificial↗