Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

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

La possessione e i suoi aspetti teatrali

Leiris torna alla grande spedizione Dakar Gibuti per raccontare i rapporti tra rito e teatro per come li ha vissuti studiando il culto degli za

Fish oil and heart health.

Invited Review ArticleInternational audienceLarge controlled trials have shown that intake of fish oil (marine n-3 fatty acids, eicosapentaenoic acid, and docosahexaenoic acid), whether from dietary sources or fish oil supplements, may exhibit beneficial effects on total and cardiovascular disease mortality. Stabilization of cell membranes and suppression of cardiac arrhythmias have been identified as possible mechanisms. Moreover, n-3 fatty acids have anti-inflammatory effects, reduce blood pressure, and may also be antiatherogenic. Finally, high doses of n-3 fatty acids can lower elevated serum triglyceride levels. The n-3 index (erythrocyte eicosapentaenoic acid plus docosahexaenoic acid) may be considered as a potential risk marker for coronary heart disease mortality, especially sudden cardiac death. The balance of n-6 to n-3 fatty acids is an important determinant in decreasing the risk for coronary heart disease, both in the primary and in the secondary prevention of coronary heart disease. Patients with known coronary heart disease should be recommended to consume n-3 fatty acid supplements at 1 g per day, without raising concerns for interactions with other medications or side effects. On the other hand, fish in the diet (preferably oily fish, 1-2 meals/week) should be considered as part of a healthy diet low in saturated fat