Aminophylline for angina: the "Robin Hood" effect?

In normally perfused myocardium, coronary blood flow is greater within the endocardium than in the epicardium because of greater metabolic activity and oxygen requirements. Adequate perfusion is maintained by local autoregulation with greater vasodilation of endocardial arterioles compared with the more constricted epicardial arteriolar bed (l), with alpha-adrenergic tone probably contributing to maintaining an arteriolar resistance gradient from epicardium to endocardium (2). In coronary artery disease, decreased perfusion pressure distal to an obstructive atherosclerotic plaque in epicardial coronary arteries necessitates even greater endocardial arteriolar vasodilation to maintain appropriate endocardial oxygen delivery at the cost of further compromising vasodilator capacity. Any intervention that increases myocardial oxygen consumption further dilates the arterioles; the resulting increase in flow creates increased viscous and turbulent energy losses across the obstruction, which lead to a further drop in distal coronary perfusion pressure. This pressure drop compromises perfusion of the maximally vasodilated endocardium because of a redistribution of blood from endocardium to epicardium (transmural “steal”) (3-7). Mediators for arteriolar vasodilation probably include adenosine, withdrawal of alphaadrenergic tone, tissue hypoxia, increased local partial pressure of carbon dioxide (Pco,) and tissue acidosis among other possibilities and may differ for ischemic as opposed to nonischemic myocardium (1). Aminophylline and coronary artery flow. For many years, adenosine has been known to be a potent coronary arteriolar vasodilator (8), similar in potency to reactive hyperemia after brief coronary occlusion. More recently, antagonism of adenosine-mediated coronary vasodilation by aminophylline has been demonstrated (9). Thus, at first glance, aminophylline would seem to be an unlikely choice as a useful drug in coronary artery disease, where the coronary flow response