European Resuscitation Council Guidelines for Resuscitation.

話題 「Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care--International Consensus on Science」の日本における普及と取り組み

Background:Metformin toxicity, a challenging clinical entity, is associated with a mortality of 30%. The role of extracorporeal treatments such as hemodialysis is poorly defined at present. Here, the Extracorporeal Treatments In Poisoning workgroup, comprising international experts representing dive

Extracorporeal Treatment for Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workgroup.

https://scielo.isciii.es/pdf/medinte/v34n8/especial.pdf

Ética de las decisiones en resucitación cardiopulmonar

Background and Purpose
In the pharmaceutical industry risk assessments of chronic cardiac safety liabilities are mostly performed during late stages of preclinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity.

Experimental Approach
Video microscopy-based motion field imaging was applied to evaluate the chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs. In parallel, the release of cardiac troponin I (cTnI), heart fatty acid binding protein (FABP3) and N-terminal pro-brain natriuretic peptide (NT-proBNP) was analysed from cell medium, and transcriptional profiling of hiPS-CMs was done at the end of the experiment.

Key Results
Different cardiotoxic drugs altered the contractile motion properties of hiPS-CMs together with increasing the release of cardiac biomarkers. FABP3 and cTnI were shown to be potential surrogates to predict cardiotoxicity in hiPS-CMs, whereas NT-proBNP seemed to be a less valuable biomarker. Furthermore, drug-induced cardiotoxicity produced by chronic exposure of hiPS-CMs to arsenic trioxide, doxorubicin or panobinostat was associated with different profiles of changes in contractile parameters, biomarker release and transcriptional expression.

Conclusion and Implications
We have shown that a parallel assessment of motion field imaging-derived contractile properties, release of biomarkers and transcriptional changes can detect diverse mechanisms of chronic drug-induced cardiac liabilities in hiPS-CMs. Hence, hiPS-CMs could potentially improve and accelerate cardiovascular de-risking of compounds at earlier stages of drug discovery.

Linked Articles
This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.13713

J. Ortega Carnicer

Papers

La desfibrilaciÓn temprana: conclusiones y recomendaciones del I Foro de Expertos en DesfibrilaciÓn Semiautomática

La resucitación cardiopulmonar en el hospital: recomendaciones 2005

Sobredosis de metformina secundaria a insuficiencia renal aguda. A propósito de 6 observaciones

Taquicardias ventriculares polimorfas inducidas por marcapasos temporales transvenosos

Gangrena gaseosa espontánea del páncreas y neumoperitoneo sin perforación visceral por Clostridium perfringens