Potential role of isoketals formed via the isoprostane pathway of lipid peroxidation in ischemic arrhythmias.
Unabated reactive oxygen species (ROS) are potentiated by an ischemia-induced shift in anaerobic metabolism, which generates superoxide anion upon reperfusion and reintroduction of oxygen. ROS can modify protein structure and function in fundamental ways, one of which is by forming reactive lipid species from the oxidation of lipids. In this review, we discuss these pathways and discuss the literature that shows that these species can produce dramatic effects on cardiac ion channel function (eg, Na+ channel function). Furthermore, we review what is known about the generation of such in the highly remodeled post myocardial infarction substrate. We suggest prevention of adduction of these highly reactive compounds would be antiarrhythmic.
Boyden
Penelope A
PA
Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. pab4@columbia.edu
Davies
Sean S
SS
Viswanathan
Prakash C
PC
Amarnath
Venkataraman
V
Balser
Jeffrey R
JR
Roberts
L Jackson
LJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D028441:F2-Isoprostanes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D015394:Molecular Structure; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D011733:Pyridoxamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use
D028441:F2-Isoprostanes; D014803:Vitamin B Complex; D011733:Pyridoxamine