To prevent, protect and save the ischemic heart: antioxidants revisited.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) formation increases in the post-ischemic myocardium and represents a mechanism of post ischemic injury. ROS, which are formed during reperfusion, trigger lipid peroxidation, oxidize proteins and cause DNA strand breaks, all interfering with and potentially damaging normal cellular function. Oxidative stress is associated with poor recovery of left ventricular function after a sustained period of ischemia and, according to several studies, it contributes significantly to the acceleration of necrosis and thus extension of infarction, apoptosis, arrhythmiogenesis and endothelial dysfunction. Accordingly, targeting the generation of ROS with various antioxidants has been shown to improve left ventricular function after the restoration of flow. Apart from mechanical or pharmacological interventions that open the occluded artery, the heart has endogenous mechanisms of protection, called ischemic pre-conditioning and ischemic post-conditioning. Opening of the mitochondrial ATP-sensitive potassium channels and subsequent generation of ROS is considered to be a pivotal step in the mechanisms of pre- and post-conditioning. Notably, ROS play an ambiguous role in the protection of myocardium and can be both effective and harmful. Thus, the role of antioxidants in the attenuation of the effects of pre-and post-conditioning in vivo remains controversial.
Andreadou
Ioanna
I
University of Athens Medical School, Attikon University Hospital, Second University Department of Cardiology, Athens, Greece. jandread@pharm.uoa.gr
Iliodromitis
Efstathios K
EK
Farmakis
Dimitrios
D
Kremastinos
Dimitrios Th
DT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species