BAMIPHYLLINE IMPROVES EXERCISE-INDUCED MYOCARDIAL-ISCHEMIA THROUGH A NOVEL MECHANISM OF ACTION

Background. In patients with stable angina pectoris aminophylline, a n onselective antagonist of adenosine receptors, markedly improves exerc ise capacity. To establish the role played by A1 adenosine receptors i n the anti-ischemic action of aminophylline, the effects of bamiphylli ne, a selective A1 antagonist, on exercise-induced ischemia were inves tigated in patients with stable angina pectoris. Methods and Results. In a single-blind, placebo-controlled, randomized cross-over trial in 18 patients, oral administration of 1200 mg bamiphylline increased bot h the time to 1-mm ST segment depression (from 524+/-177 to 664+/-192 seconds, P<.01) and the rate-pressure product at 1-mm ST segment depre ssion (from 159+/-31 to 190+/-34 beats per minute per mm Hg/10(2) (P<. 001). End-diastolic and end-systolic left ventricular volumes, left ve ntricular ejection fraction, and systolic septal and posterior wall th ickening investigated by two-dimensional echocardiography in 12 of the 18 patients were not affected by oral administration of bamiphylline (124+/-22 versus 125+/-20 mL, P=NS; 49+/-12 versus 50+/-13 mL, P=NS; 6 0+/-8% versus 58+/-7%, P=NS; 35+/-6% versus 36+/-70% P=NS; 32+/-6% ver sus 33+/-6%, P=NS, respectively). In 7 of the 18 patients, the intrave nous infusion of bamiphylline (5 mg/kg in 15 minutes) during cardiac c atheterization did not produce any significant change of heart rate (7 6+/-10 versus 75+/-13 beats per minute, P=NS), mean right atrial press ure (3.8+/-1.7 versus 3.7+/-1.7 mm Hg, P=NS), mean aortic pressure (10 2+/-12 versus 99+/-10 mm Hg, P=NS), or left ventricular end-diastolic pressure (14+/-3 versus 14+/-4 mm Hg, P=NS) compared with baseline. Fu rthermore, after intravenous infusion of bamiphylline, the diameter of seven proximal and distal normal segments and of seven stenotic segme nts were similar to those measured at baseline (3.1+/-0.5 versus 3.1+/ -0.5 mm, P=NS; 1.6+/-0.2 versus 1.7+/-0.2 mm, P=NS; 1.6+/-0.5 versus 1 .6+/-0.5 mm, P=NS, respectively). Conclusions. In patients with stable angina pectoris, oral administration of bamiphylline improves exercis e capacity. Its anti-ischemic action does not appear to be mediated by systemic hemodynamic effects or by stenosis dilation. Therefore, the improvement of myocardial ischemia caused by bamiphylline is probably due to redistribution of coronary blood flow toward the underperfused subendocardium. This novel anti-ischemic action would appear to be med iated by antagonism of A1 receptors.