Bøtker, HE;
Hausenloy, D;
Andreadou, I;
Antonucci, S;
Boengler, K;
Davidson, SM;
Deshwal, S;
... Heusch, G; + view all
(2018)
Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection.
Basic Research in Cardiology
, 113
(5)
, Article 39. 10.1007/s00395-018-0696-8.
Preview |
Text
Hausenloy_Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection_VoR.pdf - Published Version Download (2MB) | Preview |
Abstract
The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment.
| Type: | Article |
|---|---|
| Title: | Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00395-018-0696-8 |
| Publisher version: | https://doi.org/10.1007/s00395-018-0696-8 |
| Language: | English |
| Additional information: | © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Adenosine diphosphate, Analysis of variance, Adenosine triphosphate, Creatine kinase, Creatine kinase-muscle/brain, Cardiac magnetic resonance imaging, Cyclosporine A, Electrocardiogram, Ethylene glycol-bis(β-aminoethyl ether)-N,N,N’,N’-tetraacetic acid, Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone, Fetal calf serum, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, International conference on harmonization, Interfibrillar mitochondria, Tetraethyl-benzimidazolyl-carbocyanine iodide, Krebs–Henseleit buffer, Lactate dehydrogenase, Late gadolinium enhancement, Last observation carried forward, Major adverse cardiac and cerebral events, 3-(N-morpholino)propanesulfonic acid, Mitochondrial permeability transition pore, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium, Primary percutaneous coronary intervention, Ribonucleic acid, Reactive oxygen species, Single-photon emission computed tomography, Subsarcolemmal mitochondria, ST segment elevation myocardial infarction, T2-weighted cardiac magnetic resonance imaging, Ethyl ester of tetramethylrhodamine, Methyl ester of tetramethylrhodamine, 2,3,5-triphenyl tetrazolium chloride, Animal research: reporting of in vivo experiments, Consortium for preclinical assessment of cardioprotective therapies, Effect of remote ischemic conditioning on clinical outcomes in STEMI patients undergoing pPCI, Effect of remote ischemic conditioning on clinical outcomes in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, European system for cardiac operative risk evaluation, Thrombolysis in myocardial infarction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10054730 |
Archive Staff Only
 |
View Item |
