Journal
EUROPEAN HEART JOURNAL
Volume 40, Issue 22, Pages 1771-U46Publisher
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehy365
Keywords
Toxicity; Safety; Cardiac; Heart; Ischaemia; Conditioning; Pre-conditioning; Post-conditioning; Comorbidity; Comedication; Remote conditioning
Categories
Funding
- Hungarian National Research, Development, and Innovation Office [OTKA K 109737, OTKA KH_17 125570, NVKP 16-1-2016-0017, VEKOP-2.3.2-16-2016-00002]
- German Research Foundation [CRC 1213]
- Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary
- Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences
- COST action [CA16225]
Ask authors/readers for more resources
Unexpected cardiac adverse effects are the leading causes of discontinuation of clinical trials and withdrawal of drugs from the market. Since the original observations in the mid-90s, it has been well established that cardiovascular risk factors and comorbidities (such as ageing, hyperlipidaemia, and diabetes) and their medications (e.g. nitrate tolerance, adenosine triphosphate-dependent potassium inhibitor antidiabetic drugs, statins, etc.) may interfere with cardiac ischaemic tolerance and endogenous cardioprotective signalling pathways. Indeed drugs may exert unwanted effects on the diseased and treated heart that is hidden in the healthy myocardium. Hidden cardiotoxic effects may be due to (i) drug-induced enhancement of deleterious signalling due to ischaemia/reperfusion injury and/or the presence of risk factors and/or (ii) inhibition of cardioprotective survival signalling pathways, both of which may lead to ischaemia-related cell death and/or pro-arrhythmic effects. This led to a novel concept of 'hidden cardiotoxicity', defined as cardiotoxity of a drug that manifests only in the diseased heart with e.g. ischaemia/reperfusion injury and/or in the presence of its major comorbidities. Little is known on the mechanism of hidden cardiotoxocity, moreover, hidden cardiotoxicity cannot be revealed by the routinely used non-clinical cardiac safety testing methods on healthy animals or tissues. Therefore, here, we emphasize the need for development of novel cardiac safety testing platform involving combined experimental models of cardiac diseases (especially myocardial ischaemia/reperfusion and ischaemic conditioning) in the presence and absence of major cardiovascular comorbidities and/or cotreatments.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available