Apoptosis and oxygen free radicals after interventional reperfusion in acute myocardial infarction: diagnostic value and prognostic implications

Reperfusion of the infarct related artery is mandatory to salvage the myocardium, and the best way nowadays to achieve this goal is percutaneous transluminal coronary angioplasty (PTCA). Although important to preserve the myocardium, reperfusion leads to what is called reperfusion injury which decreases the benefits of reperfusion. The process of reperfusion is known to generate oxygen free radicals and activation of apoptosis (programmed cell death) through different mechanisms, both may participate in the pathophysiology of reperfusion injury.

Methodology

This study was intended to evaluate the effects of reperfusion done by PTCA of the infarct related artery, on both the generation of oxygen free radicals (assessed indirectly by measuring oxygen free radicals scavenger Glutathione Peroxidase 'GPx') as well as the induction of apoptosis (assessed by measuring Soluble Fas using APO-1/Fas), in correlation with the clinical outcome. This study comprised 32 pts admitted with acute MI, including 28 males and 4 females (mean age 52.09 ± 9.6 years) to Critical Care Department of Cairo University from December 98 to June 2000. Peripheral & coronary arterial samples were withdrawn before and after inteventional restoration of coronary arterial patency as well as 24 hours later.

Results

Our study, has shown that following interventional restoration of coronary arterial patency, there was significantly decreased GPx levels in the coronary vessels (expressed as mean rank 16.1 vs 15.8, P < 0.05), possibly due to the liberation of excessive amounts of oxygen free radicals after reperfusion, consuming the GPx scavengers. There was a further significant decrease in the GPx scavenger levels after 24 hours following reperfusion (expressed as mean rank 16.44 vs 15.1, P < 0.05), probably due to a reactionary increase in oxygen free radicals levels. A 15% increase in sFas levels in coronary arteries and peripheral circulation after reperfusion (4.83-5.58 ng/ ml) points to increased apoptosis after reperfusion. Stratified into 27 survivors and 5 non-survivors, non-survivors exhibited a significant decrease in GPx levels in coronary samples after reperfusion (66%) compared to an insignificant increase in survivors (7%). Suggesting that the high levels of oxygen free radicals produced after reperfusion may directly affect patients mortality, together with a significant increase in coronary arterial sFas levels after reperfusion (44%) in non-survivors versus an insignificant increase in survivors (12%)

Conclusion

Increased levels of oxygen free radicals 'indirectly assesed by peripheral and coronary arterrial levels of GPx scavenger' and increased apoptosis 'indirectly assesed by the apoptotic marker sFas' charecterise the reperfusion phase of ischemic myocardium following interventional PTCA. Non-survivors were found to have higher levels of oxygen free radicals and higher incidence of apoptosis, than survivors, indicating a direct relationship between their levels and the ultimate pts prognosis. Modern technology of molecular markers thus permits elucidation of the potential mechanisms of reperfusion injury.