Ischemic postconditioning: experimental models and protocol algorithms

Abstract

Ischemic postconditioning, a simple mechanical maneuver at the onset of reperfusion, reduces infarct size after ischemia/reperfusion. After its first description in 2003 by Zhao et al. numerous experimental studies have investigated this protective phenomenon. Whereas the underlying mechanisms and signal transduction are not yet understood in detail, infarct size reduction by ischemic postconditioning was confirmed in all species tested so far, including man. We have now reviewed the literature with focus on experimental models and protocols to better understand the determinants of protection by ischemic postconditioning or lack of it. Only studies with infarct size as unequivocal endpoint were considered. In all species and models, the duration of index ischemia and the protective protocol algorithm impact on the outcome of ischemic postconditioning, and gender, age, and myocardial temperature contribute.

Cardioprotective Pathways During Reperfusion: Focus on Redox Signaling and Other Modalities of Cell Signaling

“…Cross-talk between different modalities of signaling may occur and may be the basis of controversial observations. Therefore a better understanding of this crosstalk may contribute to solve the conundrum relative to the role of RISK and=or SAFE pathway in cardioprotection deriving from conflicting results obtained with different models of pre-and postconditioning (14,70,131,174,190). It will be important to understand how posttransitional modifications of different proteins are regulated in the context of cardioprotection.…”

“…Notably in humans, PostC has long-term protective effects (86). The infarct size reduction by ischemic PostC depends on duration of the index-ischemia, on the number and duration of the brief re-occlusions, and=or on the presence of comorbidities (81,148,174). Further studies should resolve the difference in efficacy of PostC between experimental models and human subjects with comorbidities and=or aging (40,149,155,190).…”

Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways

“…Infarct size is a key determinant of major clinical outcomes (mortality and morbidity of consequent heart failure) (Gibbons et al, 2004); therefore, development of procedures that effectively decrease infarct size along with reperfusion therapy is in the focus of preclinical and clinical studies (Ovize et al, 2010). IPost is a widely studied approach, and the infarct size-reducing effect of this procedure was confirmed in various mice, rat, rabbit, dog and swine animal models (Skyschally et al, 2009b) as well as in clinical trials (Ovize et al, 2010). However, some studies reported the ineffectiveness of IPost in animal models (Dow and Kloner, 2007;Skyschally et al, 2009b) and in clinical trials (Hahn et al, 2013).…”

“…IPost is a widely studied approach, and the infarct size-reducing effect of this procedure was confirmed in various mice, rat, rabbit, dog and swine animal models (Skyschally et al, 2009b) as well as in clinical trials (Ovize et al, 2010). However, some studies reported the ineffectiveness of IPost in animal models (Dow and Kloner, 2007;Skyschally et al, 2009b) and in clinical trials (Hahn et al, 2013). A possible explanation for the controversial results could be that the cardioprotective effect of IPost depends upon several factors such as (i) species, strain, gender and age of research animal; (ii) experimental model and set-up; (iii) the duration of index ischaemia before reperfusion; (iv) number and duration of brief I/R cycles; (v) technical difficulty to achieve complete reperfusion; (vi) temperature; and (vii) presence of co-morbidities.…”

“…Nevertheless, some studies have reported the ineffectiveness of IPost both in animals and in humans (Dow and Kloner, 2007;Hahn et al, 2013). A possible explanation for the controversial results could be that the outcome of postconditioning may depend on several factors, such as failure to achieve complete reperfusion during application of brief I/R cycles, the duration of index ischaemia, the algorithm of postconditioning manoeuvre, gender, age and temperature (Skyschally et al, 2009b). In addition, co-morbidities, such as hyperlipidaemia (Kupai et al, 2009) and diabetes (Miki et al, 2012), may interfere with the infarct size-limiting effect of postconditioning.…”