Cardioprotective efficacy of limb remote ischaemic preconditioning in rats: discrepancy between a meta-analysis and a three-centre in vivo study

Sayour, Viktor Nabil and Brenner, Gábor and Makkos, András and Kiss, Bernadett and Kovácsházi, Csenger and Gergely, Tamás G and Aukrust, Sverre Groever and Tian, Huimin and Zenkl, Viktória and Gömöri, Kamilla and Szabados, Tamara and Bencsik, Péter and Heinen, Andre and Schulz, Rainer and Baxter, Gary F and Zuurbier, Coert J and Vokó, Zoltán and Ferdinandy, Péter and Giricz, Zoltán (2023) Cardioprotective efficacy of limb remote ischaemic preconditioning in rats: discrepancy between a meta-analysis and a three-centre in vivo study. CARDIOVASCULAR RESEARCH, 119 (6). pp. 1336-1351. ISSN 0008-6363

Preview	Text Cardioprotectiveefficacyoflimbremoteischaemicpreconditioninginratsdiscrepancybetweenameta-analysisandathree-centreinvivostudy.pdf - Published Version Available under License Creative Commons Attribution Non-commercial. Download (1MB) | Preview
Preview	Text (graphical abstract) cvad024_ga1.jpeg - Published Version Available under License Creative Commons Attribution Non-commercial. Download (765kB) | Preview

Abstract

Aims Remote ischaemic preconditioning (RIPC) is a robust cardioprotective intervention in preclinical studies. To establish a working and efficacious RIPC protocol in our laboratories, we performed randomized, blinded in vivo studies in three study centres in rats, with various RIPC protocols. To verify that our experimental settings are in good alignment with in vivo rat studies showing cardioprotection by limb RIPC, we performed a systematic review and meta-analysis. In addition, we investigated the importance of different study parameters. Methods and results Male Wistar rats were subjected to 20–45 min cardiac ischaemia followed by 120 min reperfusion with or without preceding RIPC by 3 or 4 × 5−5 min occlusion/reperfusion of one or two femoral vessels by clamping, tourniquet, or pressure cuff. RIPC did not reduce infarct size (IS), microvascular obstruction, or arrhythmias at any study centres. Systematic review and meta-analysis focusing on in vivo rat models of myocardial ischaemia/reperfusion injury with limb RIPC showed that RIPC reduces IS by 21.28% on average. In addition, the systematic review showed methodological heterogeneity and insufficient reporting of study parameters in a high proportion of studies. Conclusion We report for the first time the lack of cardioprotection by RIPC in rats, assessed in individually randomized, blinded in vivo studies, involving three study centres, using different RIPC protocols. These results are in discrepancy with the meta-analysis of similar in vivo rat studies; however, no specific methodological reason could be identified by the systematic review, probably due to the overall insufficient reporting of several study parameters that did not improve over the past two decades. These results urge for publication of more well-designed and well-reported studies, irrespective of the outcome, which are required for preclinical reproducibility, and the development of clinically translatable cardioprotective interventions.

Actions (login required)

Edit Item