THE ACTION OF AMINOPHYLLINE ON THE ACUTELY TRANSPLANTED DOG HEART: EFFECT OF α‐ AND β‐ADRENOCEPTOR BLOCKADE

Abstract

1 Aminophylline inhibits the coronary vasodilator actions of adenosine. Our previous studies suggested that low dose infusions of aminophylline reduce coronary blood flow in the isolated heart. In the present study we investigated the actions of aminophylline on coronary blood flow and myocardial contractility in a transplanted heart model. Drugs were given by close coronary arterial infusion. 2 Aminophylline in low doses (200 μg/min) reduced coronary blood flow by 21 ± 2% (mean ± s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000 μg/min) increased coronary blood flow and myocardial contractility without changing heart rate. 3 α-Adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 μg/min). 4 Propranolol in doses of 10 and 30 μg/min blocked β-adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility. 5 The effects of a high dose of aminophylline (1000 μg/min) on coronary blood flow were not changed by either α- or β-adrenoceptor blockade, although propranolol (30 μg/min) reduced the augmentation in myocardial contractility. 6 The results show that when given in doses which do not alter myocardial contractility, aminophylline reduces coronary blood flow in the isolated heart and that this is not mediated through an α-adrenoceptor mechanism, They also show that the increases in coronary blood flow and positive inotropic effects obtained with higher doses of aminophylline are not mediated through catecholamines and suggest that higher doses of aminophylline have a small direct coronary vasodilator action. The low dose vasoconstrictor response may be produced by inhibition of the coronary vasodilator action of locally produced adenosine.