Pharmacological assessment of zebrafish-based cardiotoxicity models.

Cardiotoxicity remains the most common reason for failure during drug development. Recently, the zebrafish (Danio rerio) model has emerged for the evaluation of drug-dependent cardiotoxicity and for the identification of cardioprotective molecules. However, it remains unknown how closely the zebrafish-based results may be translated to humans. To tackle this issue, we established embryonic zebrafish models of doxorubicin-, adrenaline- and terfenadine-induced cardiotoxicity with unified dosing regimen which eventually enabled head-to-head comparison of the drugs. Subsequently, we determined whether human cardioprotective medications - dexrazoxane, metoprolol, carvedilol and valsartan - are able to manage heart dysfunction in zebrafish. Our results indicated that doxorubicin, adrenaline and terfenadine elicited overt signs of cardiotoxicity in fish, and we further showed that the blockade of the renin-angiotensin system and, to a lesser extent, ß-adrenergic system, ameliorated the heart disease in zebrafish. From the drug development standpoint, our work opens the possibility to determine the cardiovascular properties of tested compounds using the rapid and affordable zebrafish model.

Effect of Coronary Artery Disease on COVID-19-Prognosis and Risk Assessment: A Systematic Review and Meta-Analysis.

Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with pre-existing CAD were shown to have a more severe course of COVID-19, but this association has not been clarified. We performed a meta-analysis to determine the association between CAD and COVID-19 outcomes. We searched Scopus, Medline (PubMed), Web of Science, Embase, and Cochrane databases up to 2 November 2021. There were 62 studies with a total population of 49,286 patients included in the meta-analysis. CAD occurrence in survivor vs. non-survivor groups varied and amounted to 9.2% vs. 22.9%, respectively (OR = 0.33; 95%CI: 0.29 to 0.39; I2 = 70%; p < 0.001). CAD was also associated with increased severity of COVID-19 disease and was (10.8% vs. 5.6%, respectively, for severe vs. non-severe groups (OR = 2.28; 95%CI: 1.59 to 3.27; I2 = 72%; p < 0.001). The role of history of CAD in mortality and severe condition in COVID-19 presents itself as prominent-although a risk of bias in retrospective trials needs to be assessed, in case of our meta-analysis the statistically significant results when it comes to higher mortality among patients with CAD compared to non-CAD patients, a more severe condition observed in patients with CAD, and a visibly more frequent admission to intensive care unit in patients with CAD, it seems that an incidence of cardiovascular events plays a role in COVID-19 prognosis.