Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning

作者：Péter Ferdinandy, Ioanna Andreadou, Gary F. Baxter, Hans Erik Bøtker, Sean M. Davidson, Dobromir Dobrev, Bernard J. Gersh, Gerd Heusch, Sandrine Lecour, Marisol Ruiz‐Meana, Coert J. Zuurbier, Derek J. Hausenloy, Rainer Schulz · 发表于：Pharmacological Reviews · 年份：2022 · DOI：10.1124/pharmrev.121.000348 · 被引用次数：154 · 研究领域：Cardiac Ischemia and Reperfusion、Anesthesia and Neurotoxicity Research、Cardiac Arrest and Resuscitation

Preconditioning, postconditioning, and remote conditioning of the myocardium enhance the ability of the heart to withstand a prolonged ischemia/reperfusion insult and the potential to provide novel therapeutic paradigms for cardioprotection. While many signaling pathways leading to endogenous cardioprotection have been elucidated in experimental studies over the past 30 years, no cardioprotective drug is on the market yet for that indication. One likely major reason for this failure to translate cardioprotection into patient benefit is the lack of rigorous and systematic preclinical evaluation of promising cardioprotective therapies prior to their clinical evaluation, since ischemic heart disease in humans is a complex disorder caused by or associated with cardiovascular risk factors and comorbidities. These risk factors and comorbidities induce fundamental alterations in cellular signaling cascades that affect the development of ischemia/reperfusion injury and responses to cardioprotective interventions. Moreover, some of the medications used to treat these comorbidities may impact on cardioprotection by again modifying cellular signaling pathways. The aim of this article is to review the recent evidence that cardiovascular risk factors as well as comorbidities and their medications may modify the response to cardioprotective interventions. We emphasize the critical need for taking into account the presence of cardiovascular risk factors as well as comorbidities and their co...