Exercise Capacity After Acute Aminophylline Administration in Angina Pectoris Eugenio Picano, MD, Mauro Pogliani, MD, Fabio Lattanzi, MD, Alessandro Distante, MD, and Antonio L’Abbate, MD Exercise-induced ischemia is generally attributed to an increase in myocardial demand in the presence of coronary stenosis limiting flow supply. An addi- tional mechanism-the occurrence of coronary steal due to excessive endogenous adenosine release-has also been hypothesized. The effect of adenosine receptor blocking by aminophylline in ef- fort ischemia was tested in 8 patients with stable effort-induced angina pectoris, reproducible posi- tive exercise stress tests and angiographically as- sessed coronary artery disease. Following double- blind, randomized intravenous infusion of amino- phylline (3 mg/kg over 3 minutes) or placebo (20 ml of saline over 3 minutes), the patients under- went upright bicycle exercise stress tests on 2 con- secutive days. After aminophylline, there was an increase in work tolerance (aminophylline 7.5 f 1.8 minutes of exercise vs placebo 5.4 f 1.5 minutes; p ~0.05). There was a parallel increase in the is- chemic threshold, evaluated with the rate-pressure product (mm Hg X beats/min X loo-*) at 0.1 mV of ST-segment depression (221 -f 35 vs 184 f 20; p CO.01). Thus, at a dosage that should effectively inhibit adenosine receptors, aminophylline infusion exerts a beneficial effect on exercise-induced ische- mia, possibly through the prevention of myocardial flow maldistribution elicited by excessive adenosine release during effort. (Am1 Cardiol 1989;63:14-16) From the CNR Institute of Clinical Physiology and Istituto di Patologia Medica, the University of Pisa, and the Cardiological Division, Lucca Hospital, Pisa, Italy. Manuscript received May 24,198s; revised manu- script received and accepted September 12, 1988. Address for reprints: Eugenio Picano, MD, Istituto di Fisiologia Clinica de1 CNR, Via P. Savi, 8, 56100 Pisa, Italy. 14 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 63 T he arteriolar dilation induced by dipyridamole is elicited through accumulation of adenosine. Through blocking of adenosine receptors, ami- nophylline is the antidote of dipyridamole.1,2 Frequent- ly, dipyridamole infusion (and thus myocardial adeno- sine accumulation not mediated by increased metabolic demand) induces the same symptomatic, electrocardio- graphic and mechanical signs of &hernia as exercise does in patients with effort angina pectoris and angio- graphically documented coronary artery disease.3-5 We consideredwhether a pathogenetic similarity exists be- tween dipyridamole and effort-induced ischemia.Could the physiologic vasodilation occurring during effort re- produce the flow maldistribution induced by dipyrida- mole? The link between these 2 conditions might be adenosine, the physiologic modulator of arteriolar vaso- motion.6 Both experimental7and clinica18*g evidence has recently outlined a role for primary reduction in supply occurring through flow maldistribution (triggered by endogenousadenosine release) as a mechanism of ef- fort-induced angina.7,8 The aim of this study was to test the hypothesis that aminophylline-at a dosage inhibit- ing adenosine receptors-might increase exercise capac- ity in patients with stable effort angina pectoris. METHODS Patients: Eight men (50 f 8 years) with chronic sta- ble angina and an abnormal exercise test limited by an- gina with clear-cut horizontal or downsloping ST-seg- ment depression (10.15 mV) were selected. All patients had coronary artery disease proved by angiography with >75% luminal diameter narrowing in at least 1 major artery. Three patients had l-vessel, 3 had 2-vessel and 2 had 3-vessel disease; none had significant left main nar- rowing. As an inclusion criterion, all patients had to have a positive dipyridamole-echocardiography test result with angina1 pain and electrocardiographic changes similar in quality and degreeto those observed during exercise stress testing. In all thesepatients, the administration of aminophylline (3 mg/kg over 3 minutes) fully and promptly resolvedall symptomsand signs (both electro- cardiographic and echocardiographic) of dipyridamole- induced ischemia. An additional inclusion criterion required all pa- tients to be in pharmacologic washout and have at least 2 reproducible positive exercisestress tests in the previ- ous week. Patients were excluded if they had myocardial in- farction within 3 months, unstable angina, chronic left