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.
SUMMARYThe haemodynamic effects of a new pl-receptor agonist, 1-(4 hydroxyphenoxy) 3-isopropylamino-2-propanol, were studied in 25 patients after acute myocardial infarction using non-invasive methods. The drug caused an increase in systolic blood pressure and pulse pressure, without change in diastolic blood pressure, and a slight increase in heart rate and reduction in the pre-ejection period. These changes were greater in patients without a history of left heart failure. It is suggested that this cardioselective drug possesses positive inotropic activity but only slight positive chronotropic activity. The substance has been further investigated as a possible antidote to unwanted cardiac side effects of the cardioselective p-blocker, metoprolol. The changes in the cardiovascular dynamics caused by metoprolol in patients with acute myocardial infarction were promptly reversed by this new PA-agonist.With its positive inotropic properties and its efficacy in reversing the effects of a cardioselective p-blocker, the drug is a potentially useful pharmacological agent to support an acutely depressed myocardium in patients on p-blocking agents.Myocardial failure is an important if not a major cause of mortality in acute myocardial infarction, and is related to the size of the infarct (Bolooki et al., 1971) and to the severity of the coronary artery disease (Wackers et al., 1976). Until a definitive form of treatment becomes available, pharmacological support of the failing myocardium is necessary. Beregovich and co-workers (1972) reported that short-term administration of catecholamines improved myocardial contractility after myocardial infarction. The substance racemic 1-(4 hydroxyphenoxy)-3-isopropylamino-2 propanol3 and its laevo form4, new compounds with (l-selective agonist activity, were investigated in animals by Carlsson et al. (1977) and in healthy volunteers by Johnsson et al. (1979) and Knaus et al. (1978). Preliminary investigations of their haemodynamic effects, using non-invasive methods in healthy subjects (Johnsson et al., 1979), showed a significant shortening of the pre-ejection period (PEP), left ventricular ejection time (LVET), and electromechanical systole, and a rise in the systolic blood pressure. There were no great changes in heart rate or diastolic blood pressure when the racemic form was given as an intravenous infusion in doses up to 20 ,ug per kg body weight or in oral doses of 2-5 to 20 mg. These findings indicate a selective inotropic action, making the substance a useful pharmacological agent to support a myocardium whose function has been depressed 'H 80/62, AB Hassle
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