Long-term inhibition of myocardial infarction by postconditioning during reperfusion

Abstract

Cardioprotection with postconditioning has been well demonstrated after a short period of reperfusion. This study tested the hypothesis that postconditioning reduces infarct size, vascular dysfunction, and neutrophil accumulation after a long-term reperfusion. Canines undergoing 60 min left anterior descending artery (LAD) occlusion were divided into two control groups of either 3 h or 24 h of full reperfusion and two postconditioning groups with three 30 s cycles of reperfusion and re-occlusion applied at the onset of either 3 h or 24 h of reperfusion. Size of the area at risk (AAR) and collateral blood flow during ischemia were similar among groups. In controls, infarct size as percentage of the AAR (30 +/- 3 vs. 39 +/- 2* %) by TTC staining, superoxide anion generation from the post-ischemic coronary arteries by lucigenin-enhanced chemiluminescence [(89 +/- 5 vs. 236 +/- 27* relative light units (RLU/mg)], and neutrophil (PMN) accumulation by immunohistochemical staining in the AAR (52 +/- 11 vs. 84 +/- 14* cells/mm(2) myocardium) significantly increased between 3 and 24 h of reperfusion. Postconditioning reduced infarct size (15 +/- 4 and 27 +/- 3.6 %), superoxide anion generation (24 +/- 4 and 43 +/- 11 RLU/mg), and PMN accumulation (19 +/- 6 and 45 +/- 8 cells/mm(2) myocardium) in the 3 and 24 h reperfusion groups relative to time-matched controls. These data suggest that myocardial injury increases with duration of reperfusion; reduction in infarct size and attenuation in inflammatory responses with postconditioning persist after a prolonged reperfusion. * p < 0.05 24 vs. 3 h control; p < 0.05 postconditioning vs. time-matched control.

Neuroprotective antioxidant STAZN protects against myocardial ischemia/reperfusion injury

“…By understanding the mechanisms of postconditioning, it is possible that pharmacological agents may be discovered that are able to mimic or enhance postconditioning. This would be advantageous as the mechanical implementation of postconditioning is not always feasible and its efficacy is known to decline with the duration of reperfusion [30].…”

Clinical effect of postconditioning in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials

“…Unlike ischemic preconditioning, postconditioning can be easily performed during primary PCI. Although its cardioprotective effect has been well studied in different animal models (Argaud et al, 2005;Tang et al, 2006;Lim et al, 2007;Mykytenko et al, 2007), the clinical effect of postconditioning is still unclear from divergent results from clinical trials and small sample sizes. The current meta-analysis involving 1346 patients from 10 randomized trials reveals that postconditioning is associated with a significant decrease of heart failure and a slight increase of non-fatal reinfarction, as compared with the usual care.…”

Local Ischemic Postconditioning during Primary Percutaneous Coronary Intervention: A Meta-Analysis

“…The underlying mechanism of cardioprotection was initially attributed to the reduction of oxidative stress, decreasing intracellular calcium overload, improving endothelial function and depressing inflammation like ischemic preconditioning [4]. Further observations underlying the cardioprotective effects of IPC have been well studied in different animal models [27,28,29,30,31] and reviewed in multiple reviews [32,33,34]. …”