Central haemodynamics in acute myocardial infarction. Natural history, relation to enzyme release and effects of metoprolol.

Abstract

The aim of this investigation was to study central haemodynamics in initially uncomplicated acute myocardial infarction (AMI) with respect to natural history, relation to enzyme estimated infarct size, mortality and effects of metoprolol. A total of 212 patients with AMI but without clinical signs of serious heart failure or hypotension and with a mean delay from onset of pain to study entry of about 7 hours were studied. They were randomised to placebo or metoprolol (15 mg i.v. + 50 mg orally q.i.d.) treatment. Central pressures and cardiac output were evaluated by repeated measurements over 24 hours by means of pulmonary artery catheters. The pharmacokinetics of metoprolol were studied in further 20 patients with AMI. The natural history, as reflected by the placebo group, was observed to be a gradual significant fall in systemic artery pressures, pulmonary capillary wedge pressure (PCWP; 13.6-10.5 mmHg) and stroke volume, while heart rate increased, leaving cardiac output unchanged. The decrease in PCWP was confined to the group with baseline pressure above the median of 13 mmHg and was of equal magnitude in the group given concomitant medication to that of those who required no such therapy. Significant but weak correlations between the peak serum aspartate aminotransferase level and the baseline PCWP (r = 0.28) and stroke volume (r = 0.22) were found. Non-survivors had a significant baseline depression of cardiac output and stroke volume, while PCWP was increased. However, the overlap with survivors was large. The dosage of metoprolol used resulted in mean plasma levels of about 200 nmol/l, which should induce a rapid and sustained degree of beta-blockade. The patients randomised to placebo or metoprolol were assessed according to initial heart rate. The haemodynamic changes induced by metoprolol were similar but were more pronounced in patients with high heart rate compared to those with low rate. In patients with heart rate greater than 65 beats/min, the metoprolol treated group, in comparison to the placebo group, was characterised by a decrease of 10-20% in systolic artery pressure and heart rate, suggesting a decreased myocardial oxygen consumption. Cardiac index (2.9-2.2 l/min/m2) and stroke volume index (36-32 ml/beat/m2) decreased to a minimum after 30 minutes and gradually rose thereafter. The PCWP increased from 13.7 to 15.4 mmHg, 30 minutes after the injection of metoprolol. This increase was confined to the group with baseline low pressure and the difference compared to the placebo group disappeared after 8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)