Oxidative stress during myocardial ischaemia and heart failure.
Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. The heart needs oxygen but it is also susceptible to oxidative stress, which occurs during post-ischaemic reperfusion, for example. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals. At the same time, production of oxygen free radicals increases. In man, there is evidence of oxidative stress during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. At present, there are few data on oxidative stress in the failing heart. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Importantly, tumour necrosis factor causes a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but also occurs at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. The immunological response to heart failure may result in endothelial and myocyte dysfunction through oxidative stress-mediated apoptosis. A better understanding of these mechanisms may lead to novel therapeutic strategies.
Ferrari
R
R
University of Brescia, Chair of Cardiology, Spedali Civili, Italy.
Agnoletti
L
L
Comini
L
L
Gaia
G
G
Bachetti
T
T
Cargnoni
A
A
Ceconi
C
C
Curello
S
S
Visioli
O
O
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D017682:Myocardial Stunning / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000502:physiology
D010088:Oxidoreductases; D010100:Oxygen