INHIBITION OF POSTCARDIAC ARREST BRAIN PROTEIN OXIDATION BY ACETYL-L-CARNITINE

Free radical mediated, site-specific protein oxidation has been implic ated in the pathophysiology of ischemia/reperfusion brain injury. The purpose of this study was to determine whether this form of molecular damage could be detected in a clinically relevant model employing 10-m in cardiac arrest in dogs followed by restoration of spontaneous circu lation for up to 24 h. The effects of postischemic acetyl-L-carnitine administration on protein oxidation were also tested due to its previo usly reported improvement of brain energy metabolism and neurological outcome in this model. Following the experimental period, soluble prot eins were extracted from a sample of frontal cortex and reacted with d initrophenylhydrazine for spectrophotometric measurement of protein ca rbonyl groups. The most important results of this study were that brai n protein carbonyl groups were significantly elevated following 2 and 24 h of reperfusion compared to nonischemic controls, and that postisc hemic IV administration of acetyl-L-carnitine eliminated the increase in carbonyl groups observed at the 24-h period. These results indicate that brain protein oxidation does occur in a clinically relevant mode l of complete global cerebral ischemia and reperfusion, and that oxida tion is inhibited under treatment conditions that improve neurological outcome.