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

The importance of environmental variables for submerged macrophyte community assemblage and coverage in shallow lakes: differences between northern and southern Europe

Much information is available on community composition and abundance of submerged macrophytes in North temperate lakes, including their response to variation in environmental variables. Less is known about macrophytes in other climate regions. We studied 98 shallow lakes distributed in three different European latitudinal regions. The lakes were selected along mutually independent gradients of macrophyte coverage and total phosphorus and were sampled monthly from May to October for water chemistry and physical variables. We tested for changes in the impact of selected environmental variables on the macrophyte assemblage, coverage and richness in the three regions. Coverage was measured along transects during July/August and June in the northern/central and southern European lakes, respectively. Correspondence Discriminant Analysis was used to detect for differences in macrophyte composition among different regions, and univariate regression trees were used to detect relationships between environmental variables and macrophyte coverage and richness. In the northern lakes, the coverage was mainly related to chlorophyll a followed by pH, and richness was related to Secchi depth and chlorophyll a. In the southern lakes, pH was the key environmental variable for both coverage and richness. North–south differences may be of relevance for determining management strategies related to global climate change