Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia.

Abstract

The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4 +/- 2.0% versus 39.0 +/- 3.7%, respectively [p < 0.01]; and for the delayed occlusion, 18.8 +/- 3.4% versus 35.1 +/- 4.6%, respectively [p < 0.05]); however, when the infarction was induced 3 hours (31.2 +/- 3.7% versus 37.5 +/- 4.2%, respectively) or 12 hours (25.4 +/- 4.8% versus 35.0 +/- 5.3%, respectively) after repetitive ischemia, the infarct size did not differ. No differences were seen in regional myocardial blood flow or rate-pressure products between the two groups. These results indicate that an infarct-limiting effect of brief repeated ischemia can be observed 24 hours after sublethal preconditioning.

The late phase of preconditioning and its natural clinical application—gene therapy

“…After the initial description of PC in 1986 [1], the next major discovery was in 1993, when it was found that this phenomenon is not monolithic but rather consist of two chronologically and pathophysiologically distinct phases: an early phase, which develops very quickly (within few minutes from the exposure to the stimulus) but is rather ephemeral, lasting only 1-2 h (this is the phenomenon originally described by Murry et al [1]), and a late phase, which develops more slowly (requiring 6-12 h) but lasts much longer (3-4 days) [6,7]. The mechanism for these two phases is completely different.…”

Efeitos da N-acetilcisteína no precondicionamento isquêmico: estudo em corações isolados de ratos

“…In 1993, Kuzuya et al [21] reported a late phase of myocardial protection, less intense but more prolonged that lasted 72 hours. The authors attributed this effect to increasing of antioxidant enzymes such as MnSOD.…”

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

“…An early phase of protection that develops within minutes after the preconditioning stimulus lasts for 2-3 h, whereas a late phase of protection that occurs 12-24 h later lasts for 3-4 days (8,21,23). A number of chemical signals that trigger the development of the late phase of preconditioning, including adenosine, NO, reactive oxygen species, and opioid receptor agonists, have been identified (8,23).…”

“…Activation of protein kinase C (4), protein tyrosine kinases (16), and mitogen-activated protein kinases (33) by these triggers leads to increased expression of the mediators of the late phase of preconditioning. Myocardial protein synthesis of several mediators (or effectors), including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), aldose reductase, antioxidant enzymes, and heat shock proteins (HSPs), and activation of ATP-sensitive K ϩ (K ATP ) channels play a critical role in late-phase preconditioning (8,15,21,23,24,29). It has been proposed that activator protein 1 (AP-1) and nuclear factor-B (NF-B) may mediate the transcriptional activation of iNOS, COX-2, aldose reductase, and other genes (22,36).…”