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

Autor:	Sayour NV; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary., Brenner GB; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary., Makkos A; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary.; MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary., Kiss B; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary.; MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary., Kovácsházi C; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary., Gergely TG; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary., Aukrust SG; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary., Tian H; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary., Zenkl V; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary., Gömöri K; Pharmahungary Group, Szeged, Hungary.; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary., Szabados T; Pharmahungary Group, Szeged, Hungary.; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary., Bencsik P; Pharmahungary Group, Szeged, Hungary.; Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary., Heinen A; Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany., Schulz R; Institute of Physiology, Justus-Liebig University Giessen, Giessen, Germany., Baxter GF; School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK., Zuurbier CJ; Laboratory of Experimental Intensive Care and Anesthesiology, Department of Anesthesiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Vokó Z; Centre for Health Technology Assessment, Semmelweis University, Budapest, Hungary.; Syreon Research Institute, Mexikói út 65/A, 1145 Budapest, Hungary., Ferdinandy P; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary.; MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.; Pharmahungary Group, Szeged, Hungary., Giricz Z; Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary.
Jazyk:	angličtina
Zdroj:	Cardiovascular research [Cardiovasc Res] 2023 Jun 13; Vol. 119 (6), pp. 1336-1351.
DOI:	10.1093/cvr/cvad024
Abstrakt:	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. Competing Interests: Conflict of interest: P.F. is the founder and CEO, Z.G. is involved in the management, and G.F.B is a member of the Advisory Board of Pharmahungary Group. (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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