PATTERNS OF MOBILIZATION OF COPPER AND IRON FOLLOWING MYOCARDIAL-ISCHEMIA - POSSIBLE PREDICTIVE CRITERIA FOR TISSUE-INJURY

Direct evidence for substantial iron and copper mobilization into the coronary now immediately following prolonged, but not short, cardiac i schemia is presented. When small volumes of coronary now fractions (CF Fs) were serially collected upon reperfusion, after 25-60 min of ische mia, the copper and iron levels in the first CFF were 50-fold and 12- to 15-fold higher, respectively, than corresponding pre- ischemic valu es. The copper and iron levels after shorter periods (15-21 min) of is chemia were only about five-fold higher than the pre-ischemic values. This demonstrates that the resumption of coronary now is accompanied b y a burst of both metal ions. The levels of Cu/Fe in the CFFs correlat ed well with the loss of cardiac function following global ischemia of varying duration, After 18 min of ischemia, the residual cardiac func tion was less than 50%, and the damage was essentially reversible, Aft er 25 min of ischemia, it exceeded 50% and was only partially reversib le, while after 35 min, the damage exceeded 80%, and was mostly irreve rsible. The results are in accord with the hypothesis that copper and iron play causative roles in myocardial injury through mediation of hy droxyl radical production. Thus, the pattern of Cu/Fe mobilization fro m the tissue into the CFF can be used for the prediction of the severi ty of myocardial damage following ischemia, and could be developed int o useful modalities for intervention in tissue injury. (C) 1997 Academ ic Press Limited.