The action of aminophylline on the acutely transplanted dog heart: effect of alpha- and beta-adrenoceptor blockade.

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 mug/min) reduced coronary blood flow by 21 plus or minus 2% (mean plus or minus s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000 mug/min) increased coronary blood flow and myocardial contractility without changing heart rate. 3 Alpha-adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 mug/min). 4 Propranolol in doses of 10 and 30mug/min blocked beta-adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility. 5 The effects of a high dose of aminophylline (1000 mug/min) on coronary blood flow were not changed by either alpha- or beta-adrenoceptor blockade, although propranolol (30 mug/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 alpha-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.