OXIDATIVE STRESS DURING MYOCARDIAL-ISCHEMIA AND HEART-FAILURE

Oxidative stress is a condition in which oxidant metabolites exert tox ic effects because of their increased production or an altered cellula r mechanism of protection. The heart needs oxygen but it is also susce ptible to oxidative stress, which occurs during post-ischaemic reperfu sion, for example. Ischaemia causes alterations in the defence mechani sms against oxygen free radicals. At the same time, production of oxyg en free radicals increases. In man, there is evidence of oxidative str ess during surgical reperfusion of the whole heart? or after thromboly sis, and it is related to transient left ventricular dysfunction or st unning. At present, there are few data on oxidative stress in the fail ing heart. It is not clear whether the defence mechanisms of the myocy te are altered or whether the production of oxygen free radicals is in creased, or both. Recent data have shown a close link between oxidativ e stress and apoptosis. Importantly, tumour necrosis factor causes a r apid rise in intracellular reactive oxygen intermediates and apoptosis . This series of events is not confined to the myocytes, but also occu rs at the level of endothelium, where tumour necrosis factor causes ex pression of inducible nitric oxide synthase, production of the reactiv e radical nitric oxide, oxidative stress and apoptosis. The immunologi cal response to heart failure may result in endothelial and myocyte dy sfunction through oxidative stress-mediated apoptosis. A better unders tanding of these mechanisms may lead to novel therapeutic strategies.