tection by postconditioning in conscious rats is limited to coronary occlusions Ͻ45 min. Am J Physiol Heart Circ Physiol 291: H2308-H2317, 2006. First published June 30, 2006 doi:10.1152 doi:10. /ajpheart.00479.2006 Brief episodes of ischemia and reperfusion after a lethal ischemic insult confer cardioprotection, a phenomenon termed "ischemic postconditioning." However, all studies reported to date have been conducted in open-chest animal models. We sought to determine whether postconditioning occurs in conscious animals and whether it protects against severe myocardial injury. Methods: Chronically instrumented rats were assigned to a 30-(Subset 1), 45-(Subset 2), or 60-min (Subset 3) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control), were preconditioned with 12 cycles of 2-min occlusion/2-min reperfusion immediately (early preconditioning; EPC) or 24 h (late preconditioning; LPC) before myocardial infarction, or were postconditioned with 20 cycles of 10-s occlusion/10-s reperfusion immediately after myocardial infarction (20-10 PostC). Results: With a 30-min occlusion, infarct size (54.4 Ϯ 2.3% of risk region in control-30) was significantly reduced in EPC-30, LPC-30, and 20-10 PostC-30 groups (by 72, 70, and 47%, respectively; all P Ͻ 0.05 vs. control-30). With a 45-min occlusion, infarct size (62.2 Ϯ 2.4% in control-45) was reduced in EPC-45 and LPC-45 groups (by 47 and 41%, respectively; all P Ͻ 0.05 vs. control-45) but not in the 20-10 PostC-45 group [55.4 Ϯ 2.3%, P ϭ not significant (NS) vs. control-45]. With a 60-min occlusion, infarct size (72.7 Ϯ 2.2% in control-60) was reduced in the EPC-60 (by 20%, P Ͻ 0.05) but not in the LPC-60 (63.6 Ϯ 2.5%, P ϭ NS) or in the 20-20 PostC group (71.5 Ϯ 3.4%, P ϭ NS). Conclusions: Both early and late ischemic preconditioning as well as ischemic postconditioning confer protection in conscious rats; however, unlike early preconditioning, postconditioning protects only against coronary occlusions Ͻ45 min. In the conscious rat, the cardioprotection afforded by postconditioning is limited to mild to moderate myocardial injury. myocardium; ischemia; infarct size; preconditioning ISCHEMIC PRECONDITIONING, a powerful endogenous protective phenomenon (17), is manifest in all species tested and is associated with two distinct phases of cardioprotection (early and late) (3,5). In addition, a recent study by Zhao et al. (32) in open-chest dogs has shown that brief episodes of ischemia and reperfusion after a lethal ischemic insult confer cardioprotection, a phenomenon termed ischemic postconditioning. This phenomenon has subsequently been confirmed in vivo in dogs (11), rabbits (1, 4, 13, 30), rats (14, 15, 31), and humans (22) and in vitro in rabbits (7, 29), rats (14, 26), and mice (12, 14), although a study in pigs (21) failed to detect myocardial protection with ischemic postconditioning. The cardioprotection conferred by postconditioning appears to vary greatly with species, experimental settings, and proto...