Propranolol in the Treatment of Acute Myocardial Infarction

Abstract

Improvement of myocardial oxygenation is a major goal in the treatment of ischemic heart disease. Propranolol, 0.1 mg/kg intravenously, was administered to 20 patients in the acute state of myocardial infarction without clinical evidence of left ventricular failure. The most important hemodynamic response was a substantial decrease in myocardial contractility. This was reflected by a fall i cardiac index (average of 0.6 L/min/M2, P < 0.001) and of arterial mean pressure (average of 16 mm Hg, P < 0.001) with little change in systemic vascular resistance. Decrease in cardiac index was due mainly to decrease in stroke volume. Heart rate, not strikingly increased at the control state in the majority of patients, decreased an average of 7 beats/min (P < 0.001). Pulmonary wedge pressure rose an average of 2 mm Hg (P < 0.05). It remained unchanged or decreased in three patients. These varying but small changes in wedge pressure in the presence of decreased contractility may be related to improved left ventricular compliance, produced by propranolol. Propranolol markedly improved myocardial metabolism. Arterialcoronary sinus oxygen difference decreased an average of 0.72 ml/100 ml (P < 0.001); coronary sinus oxygen tension increased an average of 2 mm Hg. Myocardial lactate production shifted to extraction (average of -8% to 14%) or the rate of lactate extraction increased (average of 20% to 29%). Coronary blood flow decreased an average of 13 ml/100 g/min (P < 0.001). Both decrease in mean aortic pressure and decrease in myocardial oxygen requirements probably contributed to the fall in coronary blood flow. The finding, that myocardial metabolism improved, suggests that reduction in myocardial oxygen demand outweighed the decrease in coronary blood flow. None of the 20 patients developed left ventricular failure or other complications related to beta-adrenergic blockade. Severe chest pain, unresponsive to conventional therapy in four patients, was relieved by propranolol.These findings demonstrate that acutely administered propranolol improves myocardial oxygenation in patients with uncomplicated acute infarction without endangering perfusion of other vital organs.

Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease.

“…A reduction of coronary blood flow after propranolol associated with a widening of the arterial-coronary sinus oxygen difference has suggested a vasoconstrictor effect,34 3 while narrowing of transcoronary oxygen difference after,8 blockade is consistent with reduction of myocardial metabolism. 23 The increase in myocardial oxygen consumption due to the elevated rate-pressure product during CPT was associated with an inappropriate increase in coronary vascular resistance in patients with CAD. 4 The potentiation of coronary vascular resistance during CPT after ,3-adrenergic blockade occurred with identical CPT-induced changes in the ratepressure product, suggesting that enhanced a-adrenergic tone, rather than diminished myocardial metabolic demand, was responsible for the further increase in coronary vasoconstrictor tone.…”

Plasma Propranolol Concentration in Patients With Angina and Acute Myocardial Infarction

“…In animals, specific blockade of /3-adrenoceptor stimulation has been found to reduce the severity of initial ischaemic injury (Maroko et al, 1971) following coronary ligation and to minimize the extent of subsequent necrosis (Reiner, Rasmussen & Jennings, 1973). A favourable action on the metabolism of ischaemic myocardium in animals (Haneda et al, 1973) as well as man (Mueller et al, 1974) has also been noted, a finding significant in relation to the claimed beneficial effect of p-adrenoceptor blockade on long-term prognosis of patients following acute myocardial infarction (Wilhelmsson et a/., 1974). These observations are thus at variance with the results of studies (Balcon et al, 1966;Clausen et al, 1966;Norris et al, 1968), which showed that /I-adrenoceptor blockade had no effect on early hospital mortality in patients with acute myocardial infarction.…”

“…In the case of propranolol, it is possible that relatively large initial oral doses may ensure high plasma drug levels early by rapid saturation of hepatic binding capacity of the drug. Alternatively, the loading doses may be administered intravenously since Mueller and her colleagues (Mueller et a/., 1974) have recently shown that 0.1 mg/kg propranolol by this route improves myocardial oxygenation in patients with uncomplicated infarction without producing serious adverse effects. It may also be necessary to undertake a variable rather than a fixed dose trial, so that the dose used can be appropriately adjusted individually to produce a defined degree of sympathetic blockade as indicated by alterations in heart rate and plasma drug concentrations.…”

The use of dobutamine in myocardial infarction for reversal of the cardiodepressive effect of metoprolol.

“…Since fi-adrenoceptor blockade is widely used in cardiovascular disease and there is a growing interest in the use offi-adrenoceptor blockade for reduction of myocardial ischemia (Waagstein, Hjalmarson & Wasir, 1974;Mueller et aL, 1974;Waagstein & Hjalmarson, 1975a, b), patients arriving in coronary care units will frequently be under such medication.…”