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Biomedical subjects

L Storstein

Publications and source records attributed to L Storstein.

At least 19 recordsLinked to original sources
PubMed1992

Diuretics, arrhythmias and silent myocardial ischaemia in hypertensive patients.

Patients with high blood pressure have an increased risk of sudden death compared to the normotensive population. In the highest quintile of patients with systolic blood pressure above 155 mmHg, the risk of sudden death is 3.2 greater than those in the lowest quintile. Ventricular premature contractions without known coronary artery disease also increase the risk of sudden death. Other known risk factors in this regard are age, smoking, obesity and left ventricular hypertrophy. Hypertensive patients have an increased prevalence of ventricular arrhythmias which is most pronounced in those with left ventricular hypertrophy. However, a causal relationship between ventricular arrhythmias and sudden death is uncertain. Existing data do not allow any firm conclusion as to the effects of antihypertensive treatment on such arrhythmias or on the risk of sudden death. Silent ischaemia is not uncommon in patients with hypertension but, so far, no consistent relation with coronary artery disease, left ventricular hypertrophy or neurohormonal abnormalities has been demonstrated. Silent ischaemia is an independent predictor for the development of cardiac events in patients with hypertension and may be a predictor for sudden death in these patients. Ninety-two percent of patients with ventricular tachycardia (VT) and silent myocardial ischaemia can be expected to develop morbid cardiac events compared with only 37% of those who have neither VT or silent ischaemia. At present, there is no information on the influence of diuretics on silent ischaemia in hypertensive patients. It can be concluded that both ventricular arrhythmias and silent ischaemia are important and independent risk factors for cardiac events in hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1991

Arrhythmias in heart failure--therapeutic challenges.

Electrophysiologic disorders are common at all stages of heart failure due to myocardial mechanical factors, neuroendocrine disturbances, electrolyte abnormalities, or ischemia, and also because of cardiovascular drugs. The prevalence of various forms of heart block, bradycardias, and arrhythmias in heart failure is largely unknown, as is their relationship to the etiology of the syndrome. Complex and multiform ventricular premature beats and nonsustained ventricular tachycardia are common, and their frequency is broadly related to the severity of heart failure. Supraventricular arrhythmias are also common features of the syndrome. The heart failure syndrome has an ominous prognosis. Approximately half the patients die suddenly, but the causal relationship between preexisting arrhythmias and sudden death is not known. Equally vital is knowledge of the influence of drug therapy on the arrhythmias of heart failure, but at present this is scarce and needs further study.

Arrhythmias, Cardiac↗
PubMed1991

Electrocardiographic findings according to sex in athletes and controls.

We have previously compared the electrocardiogram of 1,299 male and female students of physical education and sports with 151 age- and sex-matched sedentary controls and found that the former had lower heart rate, longer conduction times and increased voltages. The same material of 1,450 young adult subjects was split according to sex into 617 females and 833 males in order to analyze the influence of gender on the resting 12-lead electrocardiogram. We found that females had a significant higher heart rate, shortened conduction times (PQ, Q, ventricular activation time and QRS) and a prolonged repolarization time (QTc), decreased P, Q and T amplitudes as well as indices of right, septal and left hypertrophy, and ST elevation in precordial leads were lower in females than in males. These differences were highly significant with p values less than 0.0001 for almost all parameters. Sinus bradycardia was more common in men and sinus tachycardia in women. The prevalence of other rhythms and supraventricular and ventricular premature beats was low in both sexes. AV block grade I was found in 1% of females and 3% of males (p less than 0.02). Notching of R/S in V1-V2 and incomplete right bundle branch block were less common in females (p less than 0.0001). The differences in ECG parameters between the two sexes in the total material persisted also when the athletic and control groups were investigated separately. Gender seems to be highly important for most ECG parameters in the resting ECG. This points to the necessity of discussing different upper normal limits for ECG parameters according to gender.

Adult↗
PubMed1991

Electrocardiographic findings in athletic students and sedentary controls.

We have investigated resting electrocardiograms from 1,299 athletic students taken in the same laboratory during the years 1973-1982 and compared them with electrocardiograms recorded in 151 age- and sex-matched sedentary controls. Fifty-two parameters were recorded for each electrocardiogram and computerized. We found that athletic students had a significant lower heart rate, longer PQ time and a prolonged QTc compared to control subjects. Athletes had higher maximal Q amplitudes in precordial leads, higher R in V1, and higher indices of right ventricular hypertrophy (RV1 + SV5) and left ventricular hypertrophy (Sokolow-Lyon and Grant indices). Furthermore, the athletes had higher maximal ST elevation and higher maximal T wave amplitudes in precordial leads. Sinus bradycardia was more frequent in athletes. All control subjects were in sinus rhythm whereas 0.9% of the athletes had other rhythms (nodal, coronary sinus or wandering pacemaker). Athletes and control subjects did not differ significantly with regard to premature beats, atrioventricular block, bundle branch block or the Wolff-Parkinson-White pattern. We conclude that training induces significant changes in heart rate, conduction times, ST elevation. QRS and T voltage, slow rhythm disturbances and atrioventricular and sinoatrial block were infrequent in the resting electrocardiogram taken in the supine position and disappeared immediately on sitting and during exercise. Training-induced electrocardiographic changes may partly be due to alterations in autonomic tone and partly to structural changes in the myocardium. Different normal criteria for left ventricular hypertrophy may be warranted in athletes.

Adolescent↗
PubMed1991

Cardiac arrhythmias in patients with small cell lung cancer and cardiac disease before, during and after doxorubicin administration. An evaluation of acute cardiotoxicity by continuous 24-hour Holter monitoring.

Cardiac arrhythmias have been reported during doxorubicin infusion. The aim of the present study was to investigate the prevalence of arrhythmias and elucidate whether previous cardiac disease might increase the probability of treatment-related ectopic activity. In 18 patients with small cell lung cancer, 11 with concomitant heart disease, electrocardiogram (ECG) was continuously registered by a portable tape recorder 24 h before, during and 24 h after doxorubicin infusion (Holter monitoring). The only significant finding was an increased number of bigeminal ventricular extrasystoles after doxorubicin infusion. A trend of increased number of ventricular extrasystoles was also observed. The study suggests that pretreatment arrhythmias do not dispose for increased cardiac irritability and that bolus injections of doxorubicin do not seriously influence the ectopic activity in patients with and without heart disease.

Adult↗
PubMed1990

Effect of ibopamine, a dopamine congener, on arrhythmias in heart failure.

Patients with heart failure exhibit a high prevalence of both ventricular and supraventricular arrhythmias, and the ventricular arrhythmias are characterized by multiform, bigeminal and paired beats as well as nonsustained ventricular tachycardia. The prognosis of heart failure is severe and approximately half of the patients die suddenly. In view of the high prevalence of arrhythmias in heart failure and the complex ventricular arrhythmias, it is important to consider the effect of antifailure treatment on such arrhythmias. Dopaminergic drugs represent one interesting therapeutic alternative. Ibopamine is an orally active dopaminergic substance and acts mainly as a vasodilator in patients with heart failure. According to published investigations on ibopamine in heart failure, this drug does not seem to have a proarrhythmic effect.

Animals↗
PubMed1990

Comparison between theophylline and an adenosine non-blocking xanthine in acute asthma.

Enprofylline, a drug without adenosine antagonism and theophylline, a potent adenosine antagonist, were compared, double-blind, randomized, in acute asthma (n = 33). The drugs were given intravenously as loading over 10 min followed by maintenance infusion for 24 h. Mean final plasma levels were very high with enprofylline (14 mg.l), and larger than calculated with theophylline (16 mg.l). Seven patients had maximum levels of enprofylline ranging between 16 and 42 mg.l. Extreme plasma levels of enprofylline were not associated with any theophylline-like central nervous system excitatory effects related to seizure-inducing ability. Some irregularities in the heart rhythm did not raise clinical problems and no significant difference between enprofylline and theophylline was recorded. At 1 h patients on enprofylline (mean plasma level: 5.7 mg.l) and theophylline (12.2 mg.l) had improved their peak expiratory flow rates by 31% and 15% (p less than 0.05), respectively. The improvement in lung function after 24 hours did not differ between treatments suggesting that the high levels of enprofylline were supramaximal for its anti-asthma effects in this situation. In conclusion, with enprofylline it is demonstrated that an adenosine non-blocking xanthine derivative may lack CNS-excitatory effects, but be more potent than theophylline in the treatment of acute asthma.

Acute Disease↗
PubMed1979

Pharmacokinetics of quinidine related to plasma protein binding in man.

The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134--0.303 (mean 0.221). Elimination rate constant (beta) varied from 0.071 to 0.146 h-1 (mean 0.113), and apparent volume of distribution (Vbeta) varied from 1.39--3.20 1 . kg-1 beta (mean 2.27). Total body clearance was 2.32--6.49 ml min-1 . kg-1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both V beta (r = 0.885, p less than 0.01) and total body clearance (r = 0.668, p less than 0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compound and its elimination rate will remain unaffected.

Blood Proteins↗
PubMed1979

Absorption of quinidine from an enteric-coated preparation.

The absorption of quinidine from single and multiple doses of an enteric-coated preparation (Systodin) was studied in seven healthy subjects, and was compared with the pharmacokinetics of intravenously administered quinidine and the results of in vitro dissolution tests of the tablets. Absorption of quinidine began after a variable delay, 2-8 h (mean 4.8) after fasting and 3-10 h (mean 6.1) after food. The rate of absorption varied both in and between individuals. It appeared to be lower when the drug was administered after food. Multiple doses after food gave a pattern of plasma concentration-time curves similar to that found on administration of single doses after food. The delay prior to absorption was prolonged at night. The ratio between the maximum and minimum concentration of quinidine during a dose interval varied from 1.3 to 3.2 (mean 2.0). Bioavailability of quinidine in fasting subjects ranged from 69 to 95% (mean 83); variation was greater when doses were administered after food. The release of quinidine from the enteric-coated preparation was pH dependent and was sustained at low pHs as may be found in the intestines. The results indicate that the absorption of quinidine from the enteric-coated formulation was dependent on the highly variable rate of gastric emptying and the pH of intestinal fluid, and it varied greatly both within and between individuals.

Adult↗
PubMed1979

Absolute bioavailability of quinidine in two sustained release preparations.

The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median values 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.

Administration, Oral↗
PubMed1979

Response to bicycle exercise testing in long-standing juvenile diabetes.

Submaximal bicycle ergometry was used in the evaluation of cardiac function in 22 patients with juvenile diabetes and 21 age-matched control subjects. Six patients had moderate to severe retinopathy and 2 had peripheral neuropathy. Half of the patients, but only 3 of the controls, were smokers. No differences were found in BP, serum cholesterol, triglycerides and serum creatinine levels between diabetics and controls. None had proteinuria. Patients with juvenile diabetes had higher heart rates (HR) at rest as well as during and after exercise than the healthy controls. Diabetics also had a reduced HR response to postural changes compared with the controls. Five diabetics and one control had a pathological exercise ECG (0.05 less than P less than 0.1) that may indicate early non-symptomatic coronary heart disease. The observed changes in HR may be due to autonomic neuropathy.

Adolescent↗
PubMed1979

Disopyramide plasma levels in cardiac patients on maintenance therapy.

The antiarrhythmic agent disopyramide, in a dosage of 200 mg/8 h, was given to 7 cardiac patients. The drug was fairly rapidly absorbed, and the mean peak plasma concentration (3.5 microgram/ml) was measured 1 h after administration of the first dose. The mean biological half-life (7.8 h) was slightly prolonged compared to that reported in normal volunteer subjects. Mean steady state plasma concentrations within the therapeutic range were attained 24--32 h after the start of medication. The fluctuations in the plasma levels were in the order or 30 percent; however, a wide spread of the values was observed. The drug was well tolerated.

Adult↗
PubMed1977

Studies on digitalis. VIII. Digitoxin metabolism on a maintenance regimen and after a single dose.

The metabolic pattern of cardioactive and inactive conjugated metabolites of digitoxin on maintenance (9 patients) and after a single 0.6-mg dose (5 patients) was studied in patients with normal renal and hepatic function. Serum samples were obtained 24 hr after the last dose, and urine was collected over 24 hr. The extent of conjugation to glucuronic and sulfuric acid was 35.0% (SD, 17.4) in whole serum and 31.6% (SD, 19.3) in urine samples. Unchanged digitoxin was the main cardioactive substance found both in serum and in urine (89.7% and 87.0%) in the steady-state group. All known cardioactive metabolites were present; digoxin represented less than 1%. All active metabolites were conjugated to glucuronic/sulfuric acid. Serum and urine patterns of metabolites were quite similar, Hydrolysis and conjugation appeared to be more important pathways than hydroxylation. Unchanged digitoxin was the most important cardioactive substance in serum and urine (80.4% and 56.5%) in the single-dose group. Digoxin was the main cardioactive metabolite (12.5% in serum and 25.5% in urine). All active metabolites were conjugated. Hydroxylation, hydrolysis, and conjugation seemed to be equally important. The most important differences between the steady-state and single-dose groups were that in the steady-state group there was significantly more unchanged digitoxin, far less digoxin, and less hydroxylated metabolities than in the single-dose group. Caution is thus necessary when interpreting single-dose data for a drug that is used for maintenance.

Biotransformation↗
PubMed1977

Studies on digitalis. IX. Some kinetic aspects of digitoxin metabolism.

The metabolic pattern of cardioactive and inactive conjugated metabolites (a maximum of 24 substances) was studied in one female and one male after a single dose of 0.6 mg digitoxin intravenously. Serum samples were obtained after 24 hr, and 24-hr urine was collected after 1, 2, 4, 6, and 8 days. With the methods used, enzymatic cleavage of conjugated bonds, thin-layer chromatography (TLC) separation, and a modified 86Rb method, the products of hydroxylation, hydrolysis, and conjugation could be separated. The Kendall rank correlation coefficient was used to compare the results from Subjects 1 and 2. Conjugation was the most rapid process, followed by hydrolysis and hydroxylation. Metabolism was progressive, leading to an increase in metabolites resulting from several enzymatic processes with time. Unchanged digitoxin reached minimum values on the fourth and sixth days and increased again on the eighth day. This indicated a continuous release of digitoxin from tissue stores and the enterohepatic circulation.

Adult↗
PubMed1977

Studies on digitalis. X. Digitoxin metabolites in human myocardium and relationship between myocardial and serum concentrations of digitoxin in patients on maintenance treatment.

The levels of digitoxin and cardioactive metabolites were measured in 42 atrial biopsies with a 86Rb method modified for analysis of myocardial samples. The mean value was 91.0 ng/gm wet weight (SD 54.4). Myocardial and serum concentrations were compared in 23 patients; there was no significant correlation. The ratio of total drug concentration in myocardium and serum ranged from 1 to 38 with a mean value of 5.4. Calculated from the free drug concentrations, the mean myocardial serum ratio was 200, which reflects the high affinity of digitoxin and cardioactive metabolites to the myocardium. The metabolic pattern of cardioactive and inactive metabolites (conjugates with glucuronic and sulfuric acid) was studied in autopsy samples from left ventricular myocardium from 7 patients. Significant differences between the myocardial and serum patterns of cardioactive and inactive metabolites were demonstrated. The myocardium contained less unchanged digitoxin (25.7%) and more hydrolyzed (55.4%) and conjugated (54.1%) metabolites than serum (57.6%, 31.0%, and 33.1%, respectively). Hydroxylated metabolites in myocardium (15.8%) were not significantly changed compared to serum (10.0%).

Adult↗