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

Background-Myocardial stunning may cause prolonged left ventricular dy sfunction after exercise-induced ischemia that can be attenuated by ca lcium 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 mo nonitrate (ISMN, 50 mg once daily) on postexercise stunning. Methods a nd Results-Twenty-four men with chronic stable angina and normal left ventricular function underwent serial quantitative exercise stress ech ocardiography after 3 weeks on each treatment to assess the degree of postexercise stunning with simultaneous sestamibi single-photon emissi on 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=0.1 7) were unchanged between treatments. Stunning occurred more often wit h ISMN than amlodipine (82% versus 48%). The global and segmental stre ss 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 pat ients 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 r elaxation period was less prolonged with amlodipine (93+/-15.5 versus 106.3+/-14.9 ms, P=0.018), Conclusions-Despite comparable levels of is chemia, amlodipine attenuated stunning when compared with ISMN, This b eneficial effect may relate to a prevention of the calcium overload im plicated in the pathogenesis of stunning.