Differentiation of myocardial ischemia and necrosis by technetium 99m glucaric acid kinetics

Background. Current clinical approaches may not always be helpful in the early differentiation of necrotic tissue from ischemic viable myocardium in patients with acute myocardial infarction, Tc-99m-glucaric acid is a carbohydrate ligand that may permit differentiation of necrosis from ischemia, However, the myocardial kinetics of Tc-99m-glucaric acid have not been well defined early after myocardial injury, The aim of this study was to evaluate the effect of necrosis in comparison to postischemic injury alone on the kinetics of Tc-99m-glucaric acid with the use of an isolated perfused rat heart model. Methods and Results. Three groups of hearts were studied: group I: control (n = 6); group II: postischemia (15 minutes of no flow with complete reperfusion, n = 6); and group III: necrosis (90 minutes of no flow to induce necrosis with complete reperfusion, n = 6). Tc-99m-glucaric acid (1.3 +/- 0.6 mCi/L of buffer) was perfused for 30 minutes to evaluate tracer accumulation. Then tracer-free buffer was perfused for 45 minutes to evaluate clearance, The peak accumulation relative to the control group mean was significantly increased (p < 0.01) in group III (necrosis) (254% +/- 75%) compared with control (100% +/- 10%) and compared with postischemia (108% +/- 26%), On kinetic data analysis, the monoexponential clearance rate constant (k(c)) was significantly reduced with necrosis (control: k(c) = 20.2 +/- 14.0 x 10(-4) sec(-1); postischemia: k(c) = 22.3 +/- 15.2 x 10(-4) sec(-1); and necrosis: k(c) = 1.2 +/- 0.3 x 10(-4) sec(-1); p < 0.05), A retention fraction was calculated from the activity after 45 minutes of clearance corrected for the peak activity for each group, The necrotic group had significant myocardial retention in comparison to control and postischemia (control: 12% +/- 8%; postischemia: 14% +/- 16%; necrosis: 64% +/- 10%;p < 0.01). Conclusions. The accumulation and retention of Tc-99m-glucaric acid is markedly increased in the presence of myocardial necrosis in comparison to control and postischemic myocardial injury, In this model, Tc-99m-glucaric acid is capable of defining the presence of necrotic myocardial injury in comparison to postischemic injury alone, This agent may have potential application for the early differentiation of ischemic from necrotic myocardium in acute myocardial infarction.