Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 min

Abstract

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...

Exenatide Reduces Final Infarct Size in Patients With ST-Segment–Elevation Myocardial Infarction and Short-Duration of Ischemia

“…33,34 In addition, the effect of ischemic preconditioning and postconditioning is diminished with longer duration of ischemia, at least in the experimental setting. 6,7 Thus, the association between protection against reperfusion injury and system delay/duration of ischemia may be true with different cardioprotective strategies. The reason for the loss of cardioprotection with a longer duration of ischemia is not fully elucidated but may be related to that interventions generally are most effective in the first 2 to 3 hours after onset of ischemia.…”

“…Experimental studies have shown that the cardioprotective effect diminishes with long duration of ischemia. 6,7 Assessing duration of ischemia in clinical settings is problematic. Traditionally, the duration from symptom onset to balloon dilatation (treatment delay) is used…”

Myocardial Conditioning

“…In addition, these data underscore the important concept that, in the reperfusion era, final myocardial infarct size is the net result of a 2-component insult: the first (well-accepted) related to ischemia and the second (less known) secondary to reperfusion. [17][18][19] In the ensuing years since this first report by Zhao et al, 2 infarct size reduction with postconditioning has been described in most (but not all) experimental studies 20 and, despite the lack of complete consensus, [21][22][23][24] has emerged as a promising cardioprotective intervention. 20,[25][26][27][28] Moreover, the endogenous protection afforded by postconditioning is not limited to heart and can be applied to treat global or regional ischemia-reperfusion injury in other organs or tissues.…”

Cardiac effects of postconditioning depend critically on the duration of index ischemia

“…The present data may also help to understand why, in pigs, postconditioning CAO30 with 3POC30 was not cardioprotective (29), while myocardial postconditioning in this species with the same stimulus after CAO75 was effective (17). Furthermore, it may help to explain why, in rats, in one study, 6POC10 afforded protection against CAO30 (34) but failed to protect against CAO60 (31).…”