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Biomedical subjects

A M Abrahamsen

Publications and source records attributed to A M Abrahamsen.

At least 19 recordsLinked to original sources

Comparison of the side-effects of pindolol and atenolol in the treatment of hypertension.

A double-blind multicentre study of 349 hypertensive patients was performed to compare the side-effects of the two beta-blockers atenolol (selective beta 1-blocker) and pindolol (beta 1- and beta 2-blocker with Intrinsic sympathomimetic activity (ISA] in equipotential doses (100 mg atenolol vs. 15 mg pindolol). Male and female patients aged 20-65 years with essential hypertension WHO stages I and II were included. Patients were examined 1 and 6 months after the start of treatment, and side-effects were recorded. The antihypertensive effect was similar for the two drugs. After 1 month there was significantly less bradycardia (P less than 0.01), cold hands and feet (P less than 0.05) and tiredness (P less than 0.02) in the pindolol group, and less sleep disturbance (P less than 0.02) in the atenolol group. After 6 months there was no significant difference in sleep disturbance, but the differences in the other side-effects remained significant.

Adult

Effect of metoprolol on early exercise-induced ST-segment changes and ventricular arrhythmias in patients with suspected acute myocardial infarction.

One-hundred and ninety-seven consecutive patients admitted for suspected acute myocardial infarction were randomized to double-blind treatment with intravenous followed by oral metoprolol or matching placebo within 24 hours (mean 6.9 hours) after onset of symptoms. A symptom-limited exercise test was performed 15 days after admission in 132 patients (70 patients receiving metoprolol; 62 placebo). Patients treated with metoprolol had a lower observed frequency of exercise-induced ST-segment elevation (11.4% vs. 22.6%; P less than 0.05) and less ventricular arrhythmias (7.1% vs. 19.4%; P less than 0.05) on the predischarge exercise test compared to placebo-treated patients; however, ST-segment depressions were equally distributed to the two treatment groups. Mean exercise capacity was the same in the two groups. Early administration of metoprolol to patients with suspected acute myocardial infarction reduces early exercise-induced parameters related to a bad prognosis and may therefore improve the long-term prognosis without reducing physical performance.

Arrhythmias, Cardiac

The pharmacokinetics of enalapril in hospitalized patients with congestive heart failure.

The pharmacokinetics of the converting enzyme inhibitor, enalapril, were studied in an open, randomized, balanced crossover design in 12 hospitalized patients with stable, chronic congestive heart failure (CHF). Enalapril maleate is a prodrug requiring in vivo hepatic esterolysis to yield the active diacid inhibitor enalaprilat. CHF results in changes in regional blood flow that may affect the gastrointestinal absorption, hepatic hydrolysis and renal excretion of enalapril and enalaprilat. In order to evaluate the pharmacokinetics of enalapril in CHF, the following treatments were given: enalapril maleate 10 mg orally, enalapril maleate 5 mg intravenously and enalaprilat 5 mg intravenously. Each dose was followed by a 72 h period with frequent blood sampling and fractionated urine collection for the radioimmunoassay of enalaprilat, before and after sample hydrolysis. Mean absorption for the oral dose was 69%, hydrolysis 55%, bioavailability 38%, urinary recovery 77% and estimated first-pass effect 10%. The results were compared with available data in normal subjects. After oral administration of 10 mg enalapril maleate, the extent of absorption, the degree of hydrolysis and the bioavailability in CHF patients appear to be similar to those in normals with differences less than 10%. The rate of absorption and hydrolysis appear to be slightly slower in CHF. The serum concentrations of enalaprilat were consistently greater in CHF and maximal concentrations were reached at 6 h in CHF as compared to 4 h in normal subjects. We conclude that the presence of CHF does not appreciably alter the pharmacokinetic behaviour of enalapril. The observed differences may be associated with age as well as the disease state.

Administration, Oral

Tolerability and antiarrhythmic efficacy of disopyramide compared to lignocaine in selected patients with suspected acute myocardial infarction.

In a randomized open study with intravenous lignocaine and disopyramide in patients with suspected acute myocardial infarction and ventricular premature contractions the occurrence of cardiac events, adverse reactions, withdrawals and arrhythmias were compared. Of the total 68 patients included in the study, 33 were randomized to disopyramide and 35 to lignocaine treatment. The treatment was given for 24 hours or until withdrawal due to occurrence of serious cardiac events or side-effects possibly related to the drugs. Sustained ventricular tachycardia occurred in one patient in each treatment group. 15 per cent of the patients treated with disopyramide and 14 per cent of the patients treated with lignocaine were withdrawn because of adverse reactions. Withdrawals due to depressed left ventricular function and sinoatrial and atrioventricular conduction disturbances were not different in the two treatment groups. However, more patients treated with lignocaine had supraventricular arrhythmias compared to disopyramide. Significantly more patients treated with disopyramide obtained complete abolition of premature ventricular contractions on Holter recordings compared to lignocaine treatment (P less than 0.001). The results indicate that disopyramide and lignocaine can be used alternatively in the treatment of ventricular arrhythmias in patients with suspected acute myocardial infarction.

Adrenergic beta-Antagonists

Acute hemodynamic and hormonal effects of lisinopril (MK-521) in congestive heart failure.

The acute hemodynamic and hormonal effects of the oral angiotensin-converting enzyme (ACE) inhibitor lisinopril (MK-521) were assessed over a period of 96 hours in 12 patients with heart failure. This compound is the lysine analogue of enalaprilat (MK-422), is biologically active following absorption, and is cleared via the urine without any known metabolic transformation. Single doses of lisinopril, ranging from 1.25 mg to 10 mg, were administered on days 1 and 3, each followed by 48 hours of intensive hemodynamic observation. Across all doses, maximal reductions in mean arterial pressure (17.2%), mean pulmonary capillary wedge pressure (28%), and systemic vascular resistance (25.6%) were observed compared to baseline values. No significant changes in heart rate were recorded. Arterial blood was sampled at frequent intervals for angiotensin II, ACE activity, plasma renin activity, renin substrate, plasma aldosterone, and serum drug levels. Right atrial blood was sampled simultaneously for angiotensin I, thus permitting assessment of the degree of pulmonary conversion to angiotensin II. The results indicate potent inhibition of the renin-angiotensin-aldosterone system along with hemodynamic efficacy over a period exceeding 24 hours. Frequent clinical follow-up on long-term chronic therapy has revealed no adverse experience.

Adult

Effect of smoking habits and timolol treatment on mortality and reinfarction in patients surviving acute myocardial infarction.

The Norwegian Multicenter Group Study noted the effect of smoking habits before and after myocardial infarction and their relation to mortality and reinfarction rate after treatment with timolol in patients surviving acute myocardial infarction. The mean follow up period was 17.3 (range 12-33) months. No relation was found between initial smoking habits and risk category after infarction or between initial smoking habits and later outcome. At the time of their first infarct smokers were seven years younger than non-smokers. One moth after infarction nearly 60% of the smokers had stopped smoking completely. A significantly lower incidence of early cardiac death and lower total mortality was found in patients treated with timolol in both those who continued smoking and in the combined non-smoking groups and a significantly lower reinfarction rate among non-smokers. Cessation of smoking alone was associated with a reduced reinfarction rate by 45% but a non-significant reduction in mortality by 26%. It is concluded that treatment with timolol and cessation of smoking have an additive effect in reducing mortality and reinfarction rate after myocardial infarction.

Aged

Acute and chronic hemodynamic effects of enalapril (MK-421) in congestive heart failure.

Enalapril, a new long-acting angiotensin-converting enzyme inhibitor, was administered orally to 12 patients with stable congestive cardiac failure, NYHA function class III-IV. Acute and chronic hemodynamic effects were evaluated in addition to clinical response. The results of this open pilot study indicated marked reduction of pulmonary capillary wedge pressure from 21.8 +/- 5.9 mm Hg (mean +/- 1 SD) to 13.3 +/- 4.5 mm Hg (P less than 0.01) and peripheral resistance from 1837 +/- 860 dynes X sec-1 X cm-5 to 1063 +/- 584 dynes X sec-1 X cm-5 at 6 hr (P less than 0.01). Well-tolerated hypotension with mean arterial pressure from 88.0 +/- 11.6 mm Hg to 73.1 +/- 11.7 mm Hg at 6 hr (P less than 0.01) was recorded. No significant increase in cardiac output was observed. Angiotensin-converting enzyme activity was powerfully inhibited at the time of peak hemodynamic effect from 25.3 +/- 9.8 U/ml to 4.9 +/- 3.4 U/ml (P less than 0.01) and sustained, but attenuated reduction at 24 hr (8.7 +/- 4.7 U/ml) was observed. All patients reported subjective improvement and this clinical improvement has been sustained during follow-up from 19 to 21 months although baseline hemodynamic parameters at chronic re-catheterization did not demonstrate significant improvement. The pharmacodynamics and toxicity of enalapril as compared to captopril are discussed. The long half-life, low toxicity and gradual onset of action are seen as representing a clinical advantage with regard to patient therapy.

Aged

Changes in heart size during long-term timolol treatment after myocardial infarction.

The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.

Adult

Acute and long-term response to enalapril in congestive failure.

Enalapril, a novel long acting angiotensin converting enzyme (ACE) inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and IV) and cardiomegaly. The optimal dose averaged 17 mg given once-daily. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. Eleven patients were recatheterised 3 months later. After stabilisation of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 20 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at 3 months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. ACE activity was inhibited at the time of peak haemodynamic effect from 25.3 +/- 9.8 to 4.9 +/- 3.4 U/ml (P less than 0.01). Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.

Aged

Acute hemodynamic and hormonal effects of MK-521 in congestive heart failure.

The acute hemodynamic and hormonal effects of the oral angiotensin converting enzyme (ACE) inhibitor MK-521 were assessed over a period of 96 hours in 6 patients with heart failure. This compound is the lysine analogue of enalapril diacid (MK-422) and is biologically active following absorption. Dosages ranging from 1.25 mg to 5.0 mg were administered on days 1 and 3, followed by 48 hours intensive hemodynamic observation. Marked reduction in mean arterial pressure (25.2%), pulmonary capillary wedge pressure (47.3%), and systemic vascular resistance (34.5%) was observed. Arterial blood was sampled at frequent intervals for angiotensin I (AI), angiotensin II (AII), plasma renin activity, renin substrate, plasma aldosterone, urinary aldosterone, ACE activity, and serum drug levels. Right atrial blood was sampled simultaneously for AI and AII thus permitting reliable assessment of the degree of pulmonary conversion to angiotensin II. Prolonged inhibition of the renin-angiotensin-aldosterone system was confirmed and corresponded to drug concentration. The results indicate hemodynamic efficacy and potent ACE inhibition over a period exceeding 24 hours.

Adult

Long-term effect of beta-blockade with timolol on maximal work capacity following myocardial infarction.

In a double-blind, randomized, placebo controlled trial 74 patients surviving a myocardial infarction (MI) were stress tested three and twelve months following MI. Thirty-eight patients received the beta blocking agent timolol and 36 patients received placebo. There was no significant difference in the mean total exercise capacity of the two groups. Most of the patients treated with timolol discontinued the exercise test because of exhaustion, but the placebo treated patients usually stopped the test because of chest pain, exhaustion or a fall in blood pressure. Patients treated with timolol had significantly less increase in heart rate, systolic blood pressure and rate-pressure product during exercise compared to placebo. We conclude that beta-blockade with timolol after MI does not affect work capacity, but timolol-treated patients perform the same work with a lower rate-pressure product.

Adult

Sustained haemodynamic effects of enalapril in left ventricular failure.

Enalapril, a novel angiotensin converting enzyme inhibitor, was given orally to 12 patients with chronic heart failure (NYHA functional class III and VI) and cardiomegaly. Heart rate, systemic arterial blood pressure, pulmonary arterial pressure, right and left ventricular filling pressures and cardiac index were monitored during dose efficacy titration. The optimal dose averaged 17 mg given once-daily. All patients were recatheterized three months later. After stabilization of cardiac filling pressures, all patients had left ventricular filling pressures in excess of 18 mmHg. Enalapril increased cardiac index acutely by 34% but at 12 weeks follow-up, cardiac index was not different from control levels. Left ventricular filling pressure was reduced acutely by 36% and by 41% at three months. Heart rate, systemic arterial and right atrial pressures and plasma concentrations of aldosterone were reduced during the observation period. Renin was markedly elevated. These changes were accompanied by marked and sustained clinical improvement and subjective well-being.

Aged

Transvenous pacemaker implantation via a unilateral left superior vena cava.

A 72-year-old man with a unilateral left superior vena cava and anomalous drainage of the inferior vena cava required permanent pacing. The anomalies were verified by venography and cardiac catheterization. Difficulties in implantation of a temporary and permanent pacemaker are described. A transvenous endocardial lead was placed in a stable position in the right ventricle. The pacemaker system has now functioned normally for 32 months.

Aged

Timolol-related reduction in mortality and reinfarction in patients ages 65-75 years surviving acute myocardial infarction. Prepared for the Norwegian Multicentre Study Group.

Long-term treatment with timolol in patients ages 65--75 years who survived myocardial infarction was related to a significant reduction, compared with placebo, in overall mortality (p less than 0.05), total cardiac death (p less than 0.01), sudden death (p less than 0.05) and reinfarction (p less than 0.01). The analyses were based on 732 patients (384 taking placebo and 348 timolol) from a cohort of 1884 patients in the Norwegian multicenter timolol study. The dosage of timolol was 10 mg twice daily and the patients were followed for 12--33 months (mean 17 months). There were 83 deaths in the placebo group and 52 deaths in the timolol group, a reduction of 35.5%. There were 69 initial reinfarctions in the placebo group and 38 in the timolol group, a reduction of 39.2%. There was no difference in the reduction of mortality and reinfarction between patients 65--75 years of age and patients less than 65 years of age. The incidence of side effects, the number of withdrawals and the reasons for withdrawal were similar in older and younger patients. We conclude that age should not be a decision-making factor concerning timolol therapy in postinfarct patients.

Adrenergic beta-Antagonists

Temperature dependent pulse generator dysfunction.

Malfunction of a lithium-powered R-wave inhibited unipolar pulse generator (CPI Model 0505) necessitated removal 15 months after implantation. Examination of the pulse generator in a water bath revealed abnormal function at temperatures above 31.5 degrees C and normal function at temperatures below 31.5 degrees C. CPI suggested that the failure was caused by the 10 kHz timing crystal in the generator.

Aged