Role of catecholamine oxidation in sudden cardiac death.
Although sudden cardiac death is a leading cause of mortality, the mechanisms for its pathogenesis are poorly understood. Because overactivation of sympathetic nervous system is invariably seen in subjects with high risk for sudden cardiac death, elevated levels of circulating catecholamine levels are considered to result in lethal ventricular arrhythmias and subsequent sudden cardiac death. Such arrhythmogenic effects of catecholamines are generally believed to occur by their actions on α-adrenoceptors in coronary arteries for inducing coronary spasm and subsequent myocardial ischemia as well as on β-adrenoceptors in cardiomyocytes for increasing the concentration of cyclic AMP excessively and producing defects in intracellular Ca2+ handling. Experimental evidence from our laboratory has revealed that excessive amounts of circulating catecholamines are oxidized to aminochromes, which are highly reactive quinine compounds. The oxidation products of catecholamines have been demonstrated to produce subcellular alterations, intracellular Ca2+ overload, coronary spasm, myocardial cell damage, depletion of high energy stores, and ventricular arrhythmias. In addition, oxyradicals, which are known to generate oxidative stress and produce cardiotoxic effects, including arrhythmias, are formed during the oxidation of catecholamines. Accordingly, it is proposed that oxidation of catecholamines and the generation of oxidative stress under stressful conditions may play a critical role in the genesis of ventricular arrhythmias that may result in sudden cardiac death.
Dhalla
Naranjan S
NS
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology and Department of Family Medicine, Faculty of Medicine, University of Manitoba, 351 Tache Avenue, Winnipeg, MB R2H2A6, Canada. nsdhalla@sbrc.ca
Adameova
Adriana
A
Kaur
Meera
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000473:pathology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D002395:Catecholamines; D002118:Calcium