Abstract
Original language | English |
---|---|
Pages (from-to) | 1336-1351 |
Number of pages | 16 |
Journal | Cardiovascular research |
Volume | 119 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 May 2023 |
Keywords
- Limb remote ischaemic preconditioning
- Meta-analysis
- Myocardial ischaemia/reperfusion injury
- Systematic review
- Three-centre study
Access to Document
Other files and links
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Cardiovascular research, Vol. 119, No. 6, 01.05.2023, p. 1336-1351.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Cardioprotective efficacy of limb remote ischaemic preconditioning in rats
T2 - discrepancy between a meta-analysis and a three-centre in vivo study
AU - Sayour, Nabil V.
AU - Brenner, G. bor B.
AU - Makkos, András
AU - Kiss, Bernadett
AU - Kovácsházi, Csenger
AU - Gergely, Tamás G.
AU - Aukrust, Sverre Groever
AU - Tian, Huimin
AU - Zenkl, Viktória
AU - Gömöri, Kamilla
AU - Szabados, Tamara
AU - Bencsik, P. ter
AU - Heinen, Andre
AU - Schulz, Rainer
AU - Baxter, Gary F.
AU - Zuurbier, Coert J.
AU - Vokó, Zoltán
AU - Ferdinandy, P. ter
AU - Giricz, Zoltán
N1 - Funding Information: The Ministry for Innovation and Technology in Hungary provided funding to this study under the Thematic Excellence Programme (2020-4.1.1.-TKP2020), the 2020-1.1.5-GYORSITOSAV call programme (2020-1.1.5-GYORSITOSAV-2021-00011), the TKP2021-EGA funding scheme (TKP2021-EGA-23), and the Research Excellence Programme (TKP/ITM/NKFIH). This study was also supported by Project no. RRF-2.3.1-21-2022-00003 National Heart Laboratory, Hungary implemented with the support provided by the European Union. This study was further supported by the National Research, Development and Innovation Office of Hungary (NKFIA; NVKP-16-1-2016-0017 National Heart Program). The research was further funded by the National Research, Development and Innovation Office of Hungary (NKFIA; VEKOP-2.3.2-16-2016-00002 and VEKOP-2.3.3-15-2017-00016). N.V.S., K.C. and T.G.G. were supported by the Semmelweis 250+ Excellence PhD Scholarship (EFOP-3.6.3-VEKOP-16-2017-00009) and by the Gedeon Richter Excellence PhD Scholarship. C.K. was supported by the National Talent Program of the Ministry of Human Capacities (NTP-NFTO-22-B-0200). G.B.B. was supported by EFOP-3.6.3-VEKOP-16-2017-00009 and Richter Gedeon Nyrt. scholarship. A.M. was supported by the UNKP-21-4-I-SE-6 New National Excellence Program of the Ministry of Human Capacities. T.Sz. was supported by the Cooperative Doctoral Programme (KDP-2020) of the Ministry for Innovation and Technology. P.B. was supported by the János Bolyai Research Scholarships of the Hungarian Academy of Sciences, the ÚNKP-22-5-SZTE-542 New National Excellence Program of the Ministry of Human Capacities, and the Hungarian National Scientific Research Fund (OTKA-138223). R.S. was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [Project number 268555672—SFB 1213, Project B05]. Z.G. was supported by a Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences by the UNKP-18-4 New National Excellence Program of the Ministry of Human Capacities and the Hungarian National Scientific Research Fund (K_21-139105) Funding Information: The Ministry for Innovation and Technology in Hungary provided funding to this study under the Thematic Excellence Programme (2020-4.1.1.-TKP2020), the 2020-1.1.5-GYORSÍTÓSÁV call programme (2020-1.1.5-GYORSÍTÓSÁV-2021-00011), the TKP2021-EGA funding scheme (TKP2021-EGA-23), and the Research Excellence Programme (TKP/ITM/NKFIH). This study was also supported by Project no. RRF-2.3.1-21-2022-00003 "National Heart Laboratory, Hungary" implemented with the support provided by the European Union. This study was further supported by the National Research, Development and Innovation Office of Hungary (NKFIA; NVKP-16-1-2016-0017 National Heart Program). The research was further funded by the National Research, Development and Innovation Office of Hungary (NKFIA; VEKOP-2.3.2-16-2016-00002 and VEKOP-2.3.3-15-2017-00016). N.V.S., K.C. and T.G.G. were supported by the Semmelweis 250+ Excellence PhD Scholarship (EFOP-3.6.3-VEKOP-16-2017-00009) and by the Gedeon Richter Excellence PhD Scholarship. C.K. was supported by the National Talent Program of the Ministry of Human Capacities (NTP-NFTÖ-22-B-0200). G.B.B. was supported by EFOP-3.6.3-VEKOP-16-2017-00009 and Richter Gedeon Nyrt. scholarship. A.M. was supported by the ÚNKP-21-4-I-SE-6 New National Excellence Program of the Ministry of Human Capacities. T.Sz. was supported by the Cooperative Doctoral Programme (KDP-2020) of the Ministry for Innovation and Technology. P.B. was supported by the János Bolyai Research Scholarships of the Hungarian Academy of Sciences, the ÚNKP-22-5-SZTE-542 New National Excellence Program of the Ministry of Human Capacities, and the Hungarian National Scientific Research Fund (OTKA-138223). R.S. was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [Project number 268555672—SFB 1213, Project B05]. Z.G. was supported by a János Bolyai Research Scholarship of the Hungarian Academy of Sciences by the ÚNKP-18-4 New National Excellence Program of the Ministry of Human Capacities and the Hungarian National Scientific Research Fund (K_21-139105). Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
KW - Limb remote ischaemic preconditioning
KW - Meta-analysis
KW - Myocardial ischaemia/reperfusion injury
KW - Systematic review
KW - Three-centre study
UR - http://www.scopus.com/inward/record.url?scp=85162232047&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cvr/cvad024
DO - https://doi.org/10.1093/cvr/cvad024
M3 - Article
C2 - 36718529
SN - 0008-6363
VL - 119
SP - 1336
EP - 1351
JO - Cardiovascular research
JF - Cardiovascular research
IS - 6
ER -