Search PubMed⌕ Search

Biomedical subjects

L Storstein

Publications and source records attributed to L Storstein.

At least 37 records · Page 2Linked to original sources
PubMed1989

Electrophysiological alterations in heart failure.

Electrophysiological defects are common and diverse features of heart failure. Cardiac arrhythmias may be precipitated by mechanical factors, catecholamine release, ischaemia drug therapy or drug-induced hypokalaemia. There is a high prevalence of ventricular and supraventricular arrhythmias, and chronic atrial fibrillation is also common. Ventricular arrhythmias are characterized by multiform, bigeminal and paired beats. There is also a high incidence of non-sustained ventricular tachycardia. These abnormalities are particularly prevalent amongst patients in New York Heart Association (NYHA) functional class IV. Although the presence of complex ventricular arrhythmias and non-sustained ventricular tachycardia are regarded as prognostic markers, their role in the initiation of sudden death has yet to be proven. The results of a recent placebo-controlled clinical trial have indicated that combined therapy with isosorbide dinitrate and hydralazine can reduce mortality due to sudden death or pump failure, and is superior in this respect to prazosin. In another key study, enalapril was superior to placebo at lowering mortality caused by pump failure, but did not reduce the incidence of sudden death. These findings point to new directions of investigation which might clarify the importance of arrhythmias in heart failure, and reveal improved ways of controlling cardiac rhythm and improving prognosis.

Arrhythmias, Cardiac↗
PubMed1989

Digitoxin in patients with hepatorenal insufficiency after repeated oral administration.

Following chronic oral administration of digitoxin 0.1 mg day-1 the pharmacokinetics of this glycoside were studied in seven patients with hepatorenal insufficiency and were compared with those of seven healthy volunteers. Liver cirrhosis of the patients was confirmed by liver biopsy. Mean creatinine clearance of the healthy subjects was 129.7 +/- 3.3 ml min-1 (mean +/- SEM), that of the patients was 25.6 +/- 20.4 ml min-1. Mean antipyrine clearance (parameter of oxidative liver function) was 49.7 +/- 6.0 ml min-1 in the volunteers and 22.0 +/- 2.9 ml min-1 in the patients. Plasma protein binding of digitoxin (PPB) was 95.0 +/- 1.1% in the patients and 96.7 +/- 0.6% in the healthy subjects (n.s.). Total body clearance of digitoxin (Cltot) was 0.0728 +/- 0.0120 ml min-1 kg-1 in the patients and 0.0615 +/- 0.0027 ml min-1 kg-1 in normals (n.s.]. Mean steady state plasma levels (Css) of the patients were 18.3 +/- 4.7 ng ml-1 and 15.8 +/- 1.3 ng ml-1 in the normals (n.s.). Our data obtained from chronic oral administration do not indicate a reduced total body clearance of digitoxin in patients with hepatorenal insufficiency.

Administration, Oral↗
PubMed1988

Benzodiazepine-receptor antagonist, a clinical double blind study.

In a double blind study including 18 patients in whom a benzodiazepine intoxication was suspected, the first specific benzodiazepine antagonist was compared to placebo. There was a highly significant effect on consciousness, all patients given antagonist awaked, usually within minutes. No adverse effects were observed. In 2 patients the clinical condition deteriorated 1 to 2 hrs after the antagonist was given. This might endanger intoxicated patients withdrawing from medical attention.

Adult↗
PubMed1988

Non-receptor-mediated inotropic drugs.

There has been an active search recently for non-glycoside, non-sympathomimetic positive inotropic agents. Phosphodiesterase inhibitors inhibit the breakdown of cyclic AMP, leading to an increase in intracellular cAMP concentration, and can be expected to enhance the force of myocardial contraction. The methylxanthines exert such an action in vitro; the situation in vivo is more complex, due to their manyfold actions. Phosphodiesterase F-III is relatively specific for cAMP degradation; the new phosphodiesterase inhibitors may act specifically by inhibiting this enzyme. Phosphodiesterase inhibitors with combined inotropic and vasodilatory action include amrinone, which is no longer in widespread use due to its pronounced side-effects, milrinone, which is much better tolerated and has shown promising results in recent large-scale trials, and sulmazole which has been withdrawn due to toxic effects in rodents. Other drugs are still under investigation. Of importance is the relative role of the inotropic versus dilatory action of these drugs. A salutory effect on resting haemodynamics, does not necessarily imply improved exercise haemodynamics. The pharmacokinetic profile of these drugs is also of interest. The clinical benefits should be sustained and the side-effects should not outweigh the beneficial actions of these drugs.

Calcium Channel Agonists↗
PubMed1987

How should changes in life-style be measured in cardiovascular disease?

Traditionally, assessment of therapy has been judged by the ability of treatment to alleviate symptoms with tolerable side effects or toxicity. In recent years, it has become obvious that more subtle and patient-oriented approaches are urgently needed to evaluate progression of cardiovascular disease and to monitor the efficacy of medical and surgical therapy. Aspects of well-being include physical, emotional, and social status in cardiovascular diseases. While several major assessment methods are available within the social sciences, experiences with the use of comprehensive questionnaires in cardiovascular diseases remains relatively limited. Self-administered questionnaires have been shown to be more reliable than those given by a trained interviewer. Two forms of questionnaires--the visual analogue scale and the one in which patients check off boxes--can be used to quantify symptoms, but the former necessitates more time spent on patient information. Measurements of quality of life can be characterized by the test's validity, reproducibility, and sensitivity. Our information on the sensitivity of life-quality tests is so far scarce, but it has recently been shown that it is possible to discern the effect of various drug treatments in hypertension. The methodology of this assessment needs to be further optimized, and the quality of life parameters need to be correlated with hemodynamics, exercise capacity, morbidity, and mortality.

Cardiovascular Diseases↗
PubMed1986

Instant and sustained-release verapamil in the treatment of essential hypertension.

In a series of controlled studies for periods of 4 to 6 weeks comprising 103 patients altogether, and in 1 long-term trial for 1 year, various dosages of instant and sustained-release verapamil were administered in the treatment of mild and moderate essential hypertension. One of these trials was a double-blind comparison with nifedipine, in which the 2 calcium antagonists had an equally good effect on blood pressure. A significant blood pressure reduction was achieved with verapamil both at rest and during isometric work in most patients. About 10% of the patients were nonresponders. Pharmacokinetic studies demonstrated great interindividual variations in plasma concentrations of verapamil and its active metabolite norverapamil. Except for 1 study, no significant correlation was found between drug concentration and blood pressure reduction. All formulations of verapamil were well tolerated by the patients, and adverse effects were generally mild and often transient. No negative metabolic effects were observed during long-term treatment; serum lipids, in particular, were unaffected. PQ intervals on the electrocardiogram were significantly but moderately prolonged. QRS and QT intervals were unchanged. No increase in body weight occurred. It is concluded that verapamil is an efficacious, safe drug and a first-line treatment alternative in mild and moderate essential hypertension. The recently developed sustained formulation of the drug renders a simple dosage regimen possible.

Adult↗
PubMed1986

Bioavailability and elimination of digitoxin in patients with hepatorenal insufficiency.

Following administration of digitoxin, 1 mg intravenously, the pharmacokinetics of this glycoside were studied in eight healthy volunteers and in eight patients with hepatorenal insufficiency (mean creatinine clearance 19.6 +/- 2.9 ml/min; antipyrine clearance 25.6 +/- 3.2 ml/min; means +/- SEM). Liver cirrhosis of the patients was confirmed by liver biopsy. Plasma protein binding of digitoxin (means +/- SEM) was 95.1 +/- 0.7% in the patients and 95.6 +/- 1.2% in the volunteers (NS). Total body clearance of digitoxin was 0.0530 +/- 0.0040 ml/min/kg of body weight in the patients and 0.0547 +/- 0.0043 ml/min/kg of body weight in the healthy subjects (NS). When elimination half-lives of the patients and the volunteers were compared, there was also no significant difference (7.0 +/- 0.77 days in the patient group and 7.8 +/- 0.8 days in the volunteers). Our data concerning digitoxin kinetics in patients with hepatorenal insufficiency do not indicate an accumulation of the drug in these patients.

Adult↗
PubMed1986

Which patients for secondary prevention with calcium-antagonists?

Experimental studies have shown that calcium antagonists are beneficial in reducing myocardial damage following induced infarction and thus substantiate the concept that these drugs may influence reinfarction rate and death following myocardial infarction in man. Multicenter studies with verapamil and nifedipine are in progress but without conclusive results as yet. Which patients--if any--should receive calcium antagonists for secondary prevention after myocardial infarction remains an open question. The answer will depend on whether calcium antagonists are greater, equal or less effective than beta blockers for this purpose. If calcium antagonists should prove more efficacious than beta blockers, it would seem reasonable to give calcium antagonists preference for secondary prevention in those patients where contraindications to these drugs do not exist. If however, beta blockers prove the better alternative, they should be given preference unless beta blockers are contraindicated. The complex question of the future role of drugs in secondary prevention after myocardial infarction is by far not clarified and socioeconomic consequences as well as quality of life will have to be considered in context with drug influence on survival.

Adrenergic beta-Antagonists↗
PubMed1986

Studies on verapamil in the treatment of essential hypertension: a review.

Various doses of verapamil, using the conventional and sustained release formulations, have been administered for the treatment of mild or moderate hypertension in different controlled studies for periods of 4-6 weeks, involving a total of 103 patients, and in one long-term trial for 1 year in 12 patients. A double-blind comparison of verapamil and nifedipine showed that the two calcium antagonists had equal antihypertensive action. A significant blood pressure (BP) reduction was achieved with verapamil both at rest and during isometric exercise in the great majority of patients. No significant correlation was found between age and BP reduction, but pretreatment BP and pressure reduction correlated positively. Heart rate (HR) was moderately but significantly reduced by verapamil. The established wide interindividual differences in verapamil pharmacokinetics were confirmed. There was no significant correlation between plasma drug concentrations and BP reduction, but the dosage regimens with the highest mean plasma drug concentrations were associated with the greatest mean reduction in BP. A moderate, but significant, prolongation of AV-conduction was demonstrated. QRS- and QT-intervals were unaffected. Side-effects, with all formulations of verapamil, were generally mild and often transient. No significant haematological or metabolic effects were observed during long-term treatment. It is concluded that the calcium antagonist verapamil is an effective and safe drug. It can be considered as an alternative drug in mild and moderate essential hypertension.

Delayed-Action Preparations↗
PubMed1986

Verapamil effects on left ventricular performance in patients with congestive heart failure studied with echocardiography before and after cardiac surgery.

Cardiac effects of a single dose of verapamil was studied with digitalization of M-mode echocardiograms in 6 patients before and after surgery, along with pharmacological examinations. Corresponding to the different distribution volume and excretion pre- and postoperatively, the cardiodepressive effect on the contraction of the left ventricle was more pronounced and lasted longer postoperatively. Probably due to initial reduction of peripheral resistance, there was an initial improvement of ventricular contractility indices. Obviously depending on serum concentration, maximal cardiodepression occurred at 35-40 ng/ml, and no effect could longer be found as the values reached 20 ng/ml, pre- as well as postoperatively.

Adult↗
PubMed1985

Pharmacokinetics and pharmacodynamics of muzolimine in chronic heart failure.

The aim of the present study was to investigate muzolimine pharmacokinetics and pharmacodynamics in chronic heart failure. We report preliminary results from 6 patients, aged 64.2 years (range 54-73), in chronic heart failure (NYHA class III). All patients had lowered ejection fraction determined by echocardiography, and increased heart volume determined by cardiac X-ray. They were under treatment with long-term digitoxin with serum digitoxin concentrations within or below the therapeutic range. We investigated muzolimine pharmacokinetics on day 1 of treatment and after 28 days. Heart rate and rhythm were monitored with 24 hours ECG recording and analyzed on an Avionics Arrhythmia Analyzer. Heart rate, cardiac volume, ejection fraction and laboratory findings were not significantly changed between day 1 and day 28 of treatment. The time for peak absorption ranged between 1.5 and 6 hours on day 1 and 1.0 and 3 hours on day 28. The peak concentration was significantly higher on day 28. No significant difference was found in the areas under the concentration curves, serum elimination half-lives and renal clearances after acute and chronic administration. In the first 4 patients studied, we found ventricular and supraventricular arrhythmias before treatment and after 28 days on muzolimine. These preliminary data indicate a change in the pharmacokinetics of muzolimine on chronic dosing with more rapid absorption, higher peak concentrations, and increased area under the other plasma concentration curves.

Aged↗
PubMed1984

A double-blind, crossover comparison of flecainide acetate and disopyramide phosphate in the treatment of ventricular premature complexes.

The efficacy and safety of flecainide, 200 mg twice daily, was compared with disopyramide, 150 mg 4 times daily, in a randomized, double-blind, crossover study in 25 patients (19 men and 6 women, aged 20 to 71 years, mean 52.5) with more than 1,000 ventricular premature complexes (VPCs) in a pretrial 24-hour Holter monitoring screen. Each 14-day active treatment period was preceded and followed by a 7-day placebo period. Ambulatory ECGs were recorded at the end of each study week and analyzed blindly. Average VPCs recorded during each of the 2 active periods were compared with average VPCs in the placebo periods. Twenty-two of 25 patients attained therapeutic plasma levels of both drugs. The occurrence of VPCs was significantly less during flecainide than during disopyramide treatment, 92 and 39%, respectively (p less than 0.01). Complex arrhythmic events were significantly more suppressed with flecainide than with disopyramide. No difference was observed between the 2 drugs in the incidence or severity of reported side effects. PQ, QRS and QT intervals increased beyond normal limits on both drugs in some patients, significantly more with flecainide than with disopyramide. The JT interval did not change or decrease; hence, all changes in the QT interval were attributable to a widening of the QRS complex. Neither drug showed any significant effect on blood pressure or heart rate. Flecainide may be a well-tolerated and valuable alternative to currently available antiarrhythmic agents.

Adult↗
PubMed1984

Chronic paroxysmal hemicrania: heart rate changes and ECG rhythm disturbances. A computerized analysis of 24 h ambulatory ECG recordings.

Ambulatory ECG recordings have been carried out in five patients suffering from CPH. During the study a total of 105 attacks occurred. Contrary to findings in cluster headache, no typical pattern of heart rate change was found in association with attacks of CPH. A striking finding in all patients, however, was that there were often large and rapid variations in heart rate which could be observed "before", "during" or "after" the attacks. One patient developed bradycardia and sino-atrial block and another bundle branch block together with episodes of atrial fibrillation in association with attacks.

Adult↗