Timing of treatment for myocardial reperfusion injury

Early reperfusion of acute myocardial infarctions halts cell death due to ischemia but causes further injury, probably by oxidant mechanisms. We identified the window of opportunity during which antioxidants must be present in therapeutic concentrations to prevent reperfusion injury during 90 min of ischemia and 48 h of reperfusion in 57 dogs. We examined the effect on myocardial infarct size of intravenous infusion of N-2-mercaptopropionyl glycine (MPG), a diffusible antioxidant with a plasma half-time of 7 min, by using a series of protocols with a range of timing. Whereas infusions of MPG for > or =3 h reduced infarct size by approximately 50%, infusions for 1 h only (the first, second or third hours of reperfusion) caused only small reductions. A statistical analysis that focused on identifying components of group membership responsible for differences revealed that duration of treatment was a major determinant of infarct size. If begun any time within the first hour of reperfusion, infusions of > or =3 h markedly diminished infarct size. Because reperfusion injury proceeds for the first 3 h of reperfusion, but decreases thereafter, adequate protection is needed for > or =3 of the first 4 h of reperfusion, but more prolonged protection is not necessary.