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

An erupting macrospicule: characteristics derived from SOHO-CDS spectroscopic observations

We report results from the analysis of a sequence of SOHO/CDS observations obtained off-limb in the south polar coronal hole on 6 March 1998. Three successive data sets were obtained with the Normal Incidence Spectrometer (NIS), the first of which showed a jet-like feature visible in the chromospheric and low transition region lines. The morphological characteristics of this feature suggested it was a macrospicule. The two remaining observations of the same region indicated a quiet coronal hole with a density of 108 cm-3 and a temperature rising from $0.95 \times 10^6$ K near the limb to $1.2 \times 10^6$ K at about $4.7 \times 10^4$ km above the limb. These data were averaged and used as “background” for the macrospicule observation. The resulting subtracted spectra showed more details of the feature. In particular, a cloud of plasma was detected at about $3 \times 10^4$ km above the limb. The macrospicule was found to have a density of the order of 1010 cm-3 and a temperature of about $2{-}3 \times 10^5$ K. The initial outflow velocity near the limb was over 80 km s-1. This decreased to a terminal value of 26 km s-1 above about $6 \times 10^4$ km