Biomedical subjects

F Waagstein

Publications and source records attributed to F Waagstein.

At least 109 records · Page 6Linked to original sources

PubMed1984

Göteborg Metoprolol Trial: design, patient characteristics and conduct.

The Göteborg Metoprolol Trial was a double-blind, placebo-controlled, stratified trial aimed at evaluating the effect of the beta 1-selective blocker, metoprolol, in suspected acute myocardial infarction and during 2 years of follow-up. The primary end-point was 3-month mortality (blind treatment period). Secondary end-points were 2-year mortality, indirect signs of infarct size, chest pain, arrhythmias and tolerability. The entry criteria were fulfilled in 2,802 patients, 1,395 of whom were included in the trial. Treatment started as soon as possible after arrival in hospital with intravenous administration followed by oral treatment for 3 months. All patients were randomized 48 hours or less after estimated onset of infarction and 69% were randomized at 12 hours or less. The blind treatment had to be withdrawn in 19% of all randomized patients before the end of the 3-month follow-up.

Aged↗

PubMed1984

Göteborg Metoprolol Trial: effects on chest pain.

The effect of metoprolol on chest pain was compared with that of placebo in all randomized patients. The pain score before and 15 minutes after the injection of trial medication was registered and a reduction in chest pain was observed in the metoprolol group. Increasing chest pain after blind injection was observed in only 16 and 9 patients from the placebo and metoprolol groups, respectively. Comparison with the placebo as well as detailed analysis of clinical data revealed that in these patients the increasing pain could not be explained by coronary spasm evoked by beta-blockade. Similarly, metoprolol did not exhibit any unfavorable effect on the 14 patients who were withdrawn (together with the 28 patients given placebo) from blind treatment due to angina pectoris. Either metoprolol does not induce coronary vasospasm or spasm does not play a role in these patients with definite and suspected acute myocardial infarction as well as unstable angina pectoris. Metoprolol reduced the need for analgesics during the first 4 days and shortened the duration of pain. The effects were similar in patients with early and late treatment, but may depend on initial heart rate, blood pressure and site of infarction.

Administration, Oral↗

PubMed1984

Göteborg Metoprolol Trial: clinical observations.

Heart rate, systolic blood pressure and rate-pressure product were analyzed during the first 18 hours and 4 days after intravenous metoprolol or placebo. On injection of metoprolol there was an immediate decrease in mean heart rate from 72.9 +/- 0.6 to 62.7 +/- 0.4 beats/min, but no change was found in the placebo group. The difference in heart rate remained during the first 4 days. Systolic blood pressure was reduced from 144.1 +/- 0.9 to 134.6 +/- 0.9 mm Hg after intravenous metoprolol and was lower than that in the placebo group during 4 days of follow-up. Indirect signs of congestive heart failure tended to be less severe in patients given metoprolol within 12 hours of the onset of symptoms than in those given placebo. The duration of hospitalization also tended to be shorter in patients given early metoprolol treatment than in those given placebo early.

Blood Pressure↗

PubMed1984

Göteborg Metoprolol Trial: mortality and causes of death.

During the 3-month blind treatment period there were 40 deaths in the metoprolol group compared with 62 deaths in the placebo group (p = 0.024). During the first year (after 3 months the 2 groups were treated similarly) there were 64 deaths in the metoprolol group vs 93 in the placebo group (p = 0.017) and during 2 years 92 patients died in the metoprolol group vs 120 in the placebo group (p = 0.043). The relative incidence of different causes of death did not differ significantly between the 2 treatment groups, indicating that metoprolol reduced all causes of death to the same extent as its effect on overall mortality.

Aged↗

PubMed1984

Hemodynamic and clinical findings after combined therapy with metoprolol and nifedipine in acute myocardial infarction.

In a double-blind trial, 30 patients with suspected acute myocardial infarction with onset of symptoms within the previous 24 h were randomized to treatment with 10 mg nifedipine/placebo orally 4 times a day during hospitalization. All patients were given 15 mg metoprolol intravenously 20 min after the initial administration of nifedipine/placebo, and thereafter, 50 mg 4 times a day. The combined therapy resulted only in moderate changes in systolic blood pressure and heart rate compared with metoprolol alone. Three of the 15 patients in the nifedipine group versus 2 of the 15 in the placebo group were withdrawn because of hypotension and/or bradycardia. None was withdrawn because of congestive heart failure or A-V block. It is concluded that the combination of nifedipine and metoprolol seems to be a relatively well-tolerated combination in acute myocardial infarction.

Adult↗

PubMed1984

Relationship between infarct size and incidence of severe ventricular arrhythmias in a double-blind trial with metoprolol in acute myocardial infarction.

In 585 patients having an acute myocardial infarction for the first time the relationship was investigated between estimated infarct size and the incidence of ventricular fibrillation and treated ventricular tachycardia during hospitalization. The size of the infarct was estimated from analyses of heat stable lactate dehydrogenase (LD) (EC 1.1.1.27.) in serum collected every 12 hr for 48-108 hr. All patients participated in a double-blind comparison of the beta 1-selective blocker metoprolol with placebo in suspected acute myocardial infarction. A correlation was observed between the enzymatically estimated infarct size and the incidence of ventricular fibrillation and treated ventricular tachycardia in patients on placebo (P less than 0.001), while this could not be demonstrated in patients on the beta-blocker (P greater than 0.2). In placebo treated patients there was a correlation between the maximum heat stable LD activity and early ventricular fibrillation (P = 0.034), late ventricular fibrillation (P less than 0.001), primary ventricular fibrillation (P = 0.002) as well as secondary ventricular fibrillation (P = 0.034). It is concluded that there seems to be a relatively strong correlation between the final size of the infarction and the occurrence of severe ventricular arrhythmias. Treatment with beta-blockade appeared to disturb this correlation.

Adult↗

PubMed1984

Comparison of atrial pacing and the cold pressor test in patients with angina pectoris.

A haemodynamic and myocardial metabolic study was performed to compare effects of maximal atrial pacing and the cold pressor test (CPT) in patients with angina pectoris. Twelve patients (group I) had angiographically severe coronary artery disease, while 16 patients (group II) had normal coronary angiograms. At maximal pacing, angina developed in all patients in group I, and myocardial lactate production was found in eight of 12 patients. In group II, 12 out of 16 patients experienced chest pain, but only two patients had myocardial lactate production. Neither angina nor myocardial lactate production was present in any patient in either group during CPT. Coronary sinus flow increased and coronary vascular resistance decreased significantly in both groups at maximal pacing (P less than 0.001). At CPT, coronary flow decreased (P less than 0.05) and coronary resistance increased (P less than 0.001) in group I, while individual response was more variable in group II. In conclusion, maximal pacing was a more effective method of provocation of angina pectoris than CPT. The reactions of coronary sinus flow and coronary vascular resistance were different in group I than in group II. However, because of the variability of response in patients with normal coronary arteries, CPT cannot be used to distinguish patients with coronary artery disease from patients with no such disease.

Adult↗

PubMed1984

Effects of felodipine on systemic and coronary haemodynamics in patients with angina pectoris.

In order to study the systemic and coronary haemodynamic effects of felodipine, a new dihydropyridine derivative, 10 patients with coronary artery disease were studied during cardiac catheterization. Measurements were performed at rest and during pacing-induced angina pectoris. At rest, the heart rate rose from 70 +/- 20 to 78 +/- 20 (P less than 0.05), the systemic arterial pressure decreased by about 20% (P less than 0.01) and the cardiac index rose from 2.9 +/- 1.2 to 4.0 +/- 1.0 (P less than 0.05). The coronary sinus flow (CSF) increased about 50% (P less than 0.01). During pacing to the same heart rate as in the control measurements, felodipine induced similar changes in systemic haemodynamic values as in the resting position. Myocardial lactate extraction and ST segment depression were not significantly altered. After felodipine, the pacing rate could be further increased in 7 patients as compared with the control value. Both systemic and coronary effects were then very similar compared with those during the lower pacing rate. In conclusion, felodipine is a very potent systemic and coronary vasodilator with potential value in the treatment of hypertension and cardiac failure. The drug may also be of value in the treatment of ischaemic heart disease, but further studies with titration of optimal doses are needed in that respect.

Adult↗

PubMed1984

Effect of metoprolol on chest pain in acute myocardial infarction.

A total of 1395 patients aged 40 to 74 years were included in a double blind trial with the beta 1 selective blocker metoprolol in suspected acute myocardial infarction. Metoprolol was given intravenously (15 mg) as soon as possible after admission to hospital followed by 200 mg daily for three months. A placebo was given in the same manner. The severity of chest pain in the acute phase was calculated by recording the number of injections of analgesics given and the time from the start of blind treatment to the time when the last analgesic was given (duration of pain). The patients receiving metoprolol were given a lower mean number of injections of analgesics during the first four days and after randomisation than those receiving a placebo. The estimated duration of pain was shorter in the metoprolol group than in the placebo group. These effects were related to the initial heart rate, the initial systolic blood pressure, and the final site of the infarct as determined electrocardiographically. Thus metoprolol given in the acute phase of suspected or definite myocardial infarction appears to reduce the severity of chest pain.

Adult↗

PubMed1984

Development of congestive heart failure after treatment with metoprolol in acute myocardial infarction.

In a double blind study of metoprolol in the treatment of suspected acute myocardial infarction 698 patients (study group) received metoprolol and 697 a placebo (control group). Metoprolol was given in an intravenous dose of 15 mg as soon as possible after admission to hospital followed by 50 g by mouth four times a day for two days and thereafter 100 mg twice a day for three months. A placebo was similarly given. Congestive heart failure occurred in a similar percentage of patients in both the study (27%) and the control groups (30%). Its severity was estimated by calculating the total dose of frusemide given during the first four days in hospital. Less frusemide was given to patients treated with metoprolol compared with those given a placebo in the total series. An appreciably lower total dose of frusemide was given to patients included in the trial less than or equal to 12 hours after the onset of pain and treated with metoprolol compared with a placebo, while no difference was seen among patients treated later. The initial heart rate, systolic blood pressure, and infarct site affected the results.

Adult↗

PubMed1984

Enzymatically and electrocardiographically estimated infarct size in relation to pain in acute myocardial infarction.

In 563 patients with acute myocardial infarction and no previous myocardial infarction, the estimated infarct size was related to the estimated duration of pain and the amount of analgesics given. The size of infarction estimated from analyses of heat-stable lactate dehydrogenase (EC 1.1.1.27) at 12-hour intervals for 48-108 h and from Q- and R-wave changes in the ECG correlated positively, although weakly with duration of the pain and the amount of analgesics given. These data support the hypothesis that larger infarcts, as a group, evolve over a longer time period than smaller infarcts and that the duration of pain in many patients might be an indicator of the infarct size. In the individual patient, however, one cannot predict the size of the infarction from the severity of pain.

Adult↗

PubMed1983

Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction.

In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta 1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 +/- 0.5 mukat X liter-1) when the patient was treated within 12 hours of the onset of pain (13.3 +/- 0.6 mukat X liter-1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol less than or equal to 12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started less than or equal to 12 hours and greater than 12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve long-term prognosis.

Aged↗

PubMed1983

A double-blind trial of metoprolol in acute myocardial infarction. Effects on ventricular tachyarrhythmias.

During a double-blind trial in which patients with suspected myocardial infarction received metoprolol or placebo, we analyzed the occurrence of ventricular tachyarrhythmias. Metoprolol (15 mg intravenously) was given as soon as possible after admission, and thereafter 200 mg was given daily for three months. Antiarrhythmic drugs were given only for ventricular fibrillation and sustained ventricular tachycardia (greater than 60 beats per second). Definite acute myocardial infarction developed in 809 of the 1395 participants, and probable infarction in 162. Metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia. However, there were 17 cases of ventricular fibrillation in the placebo group (697 patients) and only 6 in the metoprolol group (698 patients, P less than 0.05). During the hospital stay significantly fewer patients receiving metoprolol (16) than placebo (38) (P less than 0.01) required lidocaine. In a separate analysis of 145 patients, metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia during the first 24 hours of treatment. Despite a lack of effect on less serious ventricular tachyarrhythmias, metoprolol had a prophylactic effect against ventricular fibrillation in acute myocardial infarction.

Double-Blind Method↗

PubMed1983

The time course in acute myocardial infarction evaluated with precordial mapping and standard ECG.

Fifty-six patients with acute transmural anterior wall myocardial infarction (MI) were investigated with a 24-electrode grid and 34 patients with an acute transmural inferior wall MI were investigated with standard ECG leads II, III, and aVF in order to study the length of time after the onset of pain during which the development of Q waves and reduction of R waves progress. These ECG changes continued for 18-26 h after onset of pain but the majority appeared during the first 12 h.

Adult↗

PubMed1983

Beta-blockers in dilated cardiomyopathies: they work.

Prognosis in congestive cardiomyopathy (COCM) with marked dilatation and heart failure is poor. A low rate of spontaneous recovery was observed. A high level of circulating catecholamines is often found, which may explain the common finding of resting tachycardia. An early series of COCM patients with tachycardia responded surprisingly well when chronic beta-blockade was added to the conventional treatment of failure. Later, even patients without tachycardia were included with a period of placebo preceding beta-blocker treatment in order to exclude patients with spontaneous recovery. Acute beta-blockade was surprisingly well tolerated, possibly because the reduction in contractility was compensated for by an increase in myocardial compliance. After long-term beta-blockade, improvement was observed after 6 months and further improvement was seen after 24 months. In patients improving functionally, there was reduction in heart size and left ventricular end diastolic diameter and increase in working performance. For the whole group, there was a decrease in rapid filling wave in apex cardiogram, reduction in third heart sound and increase in ejection fraction. Changes in the reverse way were seen in these three variables after beta-blocker withdrawal and relapse into heart failure occurred in 6/15 patients. Changes in diastolic function may be an early important effect of beta-blockade in COCM. Increase in survival was seen when beta-blocker-treated patients with COCM were compared to well matched COCM controls. It is suggested that increased sensitivity to sympathetic stimulation contributes to the pathogenesis in some patients with COCM and that improvement in myocardial function explains prolonged survival.

Administration, Oral↗

PubMed1983

Possible adrenergic effects on heart protein metabolism.

It is known that the heart will adapt to actual demand by increasing or decreasing its size through different mechanisms. In this presentation, the possible role of catecholamines in regulating heart protein synthesis and developing cardiac hypertrophy and cardiomyopathy is discussed. Injecting animals with catecholamines has been found to induce cardiac hypertrophy. In vitro perfusion of rat heart in the presence of catecholamines has been found to induce a time-dependent and dose-dependent stimulation of amino acid transport and incorporation into proteins. Acute haemodynamic effects of catecholamines increase cardiac performance while long-term treatment seems to cause depression of cardiac function, especially during ischaemic conditions. Chronic beta-blockade in patients with primary congestive cardiomyopathy improved both cardiac function and clinical condition in more than half the patients. Furthermore, a beneficial effect on survival was also found, when compared with a matched control group. It is hypothesised that catecholamines may play a role in developing cardiac hypertrophy as well as congestive cardiomyopathy.

Adrenergic beta-Antagonists↗

PubMed1983

Correlation between enzymatic estimation of infarct size and early mortality rate.

In 585 patients with a first acute myocardial infarction the maximum activity of heat stable lactate dehydrogenase (EC 1.1.1.27) was correlated with mortality at three months. The patients participated in a double blind trial with metoprolol in acute myocardial infarction. In all patients not taking a beta blocker a highly significant correlation was found, but this was not evident in those who were. When patients with anterior or inferior infarctions treated with a placebo were analysed separately the correlation remained, as it did when the patients who were alive on the fourth day after the onset of pain were analysed separately. No correlation was observed between enzyme activity and three month mortality in these subgroups if only patients treated with metoprolol were included. In a subsample of only 171 patients it was found that the maximum activity of creatine kinase (EC 2.7.3.2) and creatine kinase subunit B did not correlate with three month mortality regardless of treatment. Thus it is concluded that when a sufficiently large number of patients are investigated there is a highly significant correlation between the enzymatic estimation of infarct size and early mortality in acute myocardial infarction. This relation did not persist when patients treated with beta blockade were analysed.

Adult↗

PubMed1983

The Göteborg metoprolol trial. Effects on mortality and morbidity in acute myocardial infarction.

In the Göteborg Metoprolol Trial, 1395 patients with suspected acute myocardial infarction were, on admission, randomly allocated to double-blind treatment, 697 to placebo and 698 to metoprolol (15 mg i.v. + 200 mg/day) for 90 days. During this period, there were 62 deaths in the placebo group (8.9%) and 40 in the metoprolol group (5.7%), a mortality reduction of 36% (p less than 0.03). This effect persisted regardless of age, previous infarction or previous chronic beta blockade. All deaths were classified as cardiovascular. After 3 months, all patients were recommended open treatment with metoprolol, and the difference in mortality between the two groups was maintained after 1 year. Early institution of metoprolol (within 12 hours) influenced infarct development during the first 3 days (infarct diagnosis and indirect measures of infarct size). Metoprolol also reduced the incidence on fatal and nonfatal infarction during the next 4-90 days by 35%. Furthermore, fewer episodes of ventricular fibrillation were recorded in the metoprolol than in the placebo group (six vs 17 patients). The tolerance was judged to be very good. The same percentage of patients (19%) was withdrawn from the blind treatment in the two groups. Fewer patients in the metoprolol group used lidocaine, furosemide and analgesics. We conclude that metoprolol therapy instituted on admission in patients with suspected acute myocardial infarction reduced 3-month mortality and exerted beneficial clinical effects.

Adult↗