Randomized, Double-Blind Crossover Study to Investigate the Effects of Amlodipine and Isosorbide Mononitrate on the Time Course and Severity of Exercise-Induced Myocardial Stunning

Abstract

Background —Myocardial stunning may cause prolonged left ventricular dysfunction after exercise-induced ischemia that can be attenuated by calcium antagonists in animal models. To assess their effects in humans, we performed a randomized, double-blind crossover study comparing the calcium antagonist amlodipine (10 mg once daily) versus isosorbide mononitrate (ISMN, 50 mg once daily) on postexercise stunning. Methods and Results —Twenty-four men with chronic stable angina and normal left ventricular function underwent serial quantitative exercise stress echocardiography after 3 weeks on each treatment to assess the degree of postexercise stunning with simultaneous sestamibi single-photon emission computed tomography perfusion scans at peak stress to quantify the ischemic burden. Exercise time ( P =1), maximum ST depression ( P =0.48), and sestamibi single-photon emission computed tomography scores ( P =0.17) were unchanged between treatments. Stunning occurred more often with ISMN than amlodipine (82% versus 48%). The global and segmental stress echocardiography parameters of stunning were attenuated in patients while taking amlodipine compared with ISMN. Shortening fractions and ejection fractions were less impaired 30 minutes after exercise in patients receiving amlodipine (3.5±1.4% versus 2.5±1.4%, P =0.014, and 59.7±5.4% versus 54.5±8%, P <0.001); similarly, the isovolumic relaxation period was less prolonged with amlodipine (93±15.5 versus 106.3±14.9 ms, P =0.018). Conclusions —Despite comparable levels of ischemia, amlodipine attenuated stunning when compared with ISMN. This beneficial effect may relate to a prevention of the calcium overload implicated in the pathogenesis of stunning.