Myocardial stunning in exercise-induced ischemia in dogs: lack of late preconditioning

Late preconditioning (PC) against myocardial stunning develops after corona ry artery occlusion (CAO) at rest and subsequent reperfusion. We investigat ed whether late PC occurs after exercise-induced ischemia (high-flow ischem ia) in dogs. A circumflex coronary artery stenosis (by using occluders) was set up before the onset of treadmill exercise in nine chronically instrume nted dogs to suppress exercise-induced increase in mean coronary blood flow velocity (CBFV, Doppler) without simultaneously affecting left ventricular (LV) wall thickening (Wth) at rest. Two similar exercises were performed 2 4 h apart. On day 1, LV Wth was reduced by 84 +/- 5% (P< 0.01), and exercis e-induced increases in transmural myocardial blood flow (MBF, fluorescent m icrospheres) in the ischemic zone were blunted. LV Wth was depressed throug hout the first 10 h and returned to its baseline value after 24 h. On day 2 , changes in LV Wth and MBF were similar as was the time course for LV Wth recovery, indicating lack of late PC. Also, CBFV responses to acetylcholine , nitroglycerin, and reactive hyperemia (20-s CAO) were not significantly d ifferent on days 1 and 2. Similar results were obtained in a subgroup of fo ur additional dogs with more severe stenosis during exercise. Late PC again st myocardial stunning was confirmed to occur in a model of 10-min CAO foll owed by coronary artery reperfusion (CAR) in another four dogs. Thus in con trast with CAO at rest followed by CAR, severe myocardial ischemia in coron ary flow-limited exercising dogs does not induce late PC against myocardial stunning.