A flow- and time-dependent index of ischemic injury after experimental coronary occlusion and reperfusion.

The purpose of the present study was to determine whether an ischemic index--expressed as the product of flow deprivation (FD) and the duration of occlusion (T), FD X T--correlated with biochemical and early morphologic alterations of the subendocardial myocardium and could predict ultimate development of irreversible injury after coronary reperfusion. Myocardial biopsy specimens for measurement of ATP and other purines and for ultrastructure studies were obtained in vivo during coronary occlusion in a canine model and were considered relative to development of necrosis after coronary reperfusion. FD X T correlated negatively with ATP content [ATP, nmol/mg of cardiac protein = 23.6 - 0.24(FD X T) + 0.0007(FD X T)2; r = -0.81] and with a semiquantitative early histologic index of damage (r = 0.70). Values of (FD X T) less than 18 were associated with reversible injury--i.e., complete salvage after coronary reperfusion. (FD X T) greater than 18 was associated with varying degrees of necrosis; necrosis was severe (78 +/- 12% of subendocardial biopsy specimens) when ATP less than 10 nmol/mg of protein and total purine pool was decreased by 50%. FD X T correlated with the eventual percentage of subendocardial necrosis (r = 0.85). Accordingly, as an index of ischemic injury, FD X T may be useful in assessing whether ischemic myocardial tissue will benefit from early restoration of blood flow to the ischemic area.