Technetium-99m glucarate uptake in a swine model of limited flow plus increased demand

Background. Glucarate is a 6-carbon dicarboxylic acid shown to be taken up by necrotic myocytes, binding to nuclear histones in animal models of coron ary occlusion, resulting in infarction, This study investigated glucarate u ptake in a model of severe ischemia. Methods and Results. Thirty-five experiments were performed, in which a cat heter-mounted stenosis (reducing lumen dimensions by 80%) was placed in the left anterior descending coronary artery (LAD) of an anesthetized, instrum ented domestic swine and technetium-99m glucarate (GLU) was injected during the last minute of 5 minutes of pacing, Hemodynamic and blood flow measure ments were performed at control, during pacing, and during recovery The ani mals were killed; their hearts were stained with fluorescein dye and triphe nyl tetrazolium chloride (TTC). Electron micography (EM; n = 6) and cell ce ntrifugation (n = 7) were also performed. On the basis of net lactate produ ction and severe blood flow reduction in the risk region (RR), ischemia wit h pacing developed in 25 animals, Fifteen of 25 animals showed tracer uptak e in the RR on in vivo and ex vivo imaging (scan positive), and 10 were sca n negative in the RR, Endocardial blood flow in the RR during pacing was 0. 28 +/- 0.16 ml/g/min for scan-positive and 0.30 +/- 0.17 ml/g/min for scan- negative experiments (P = not significant [NS]). Transmyocardial net lactat e extraction during pacing was -63% +/- 44% for scan-positive and -53% +/- 60% for scan-negative experiments (P = NS), Control and recovery heart rate s were higher in scan-positive experiments (108 +/- 14 vs 92 +/- 17, and 12 5 +/- 24 vs 104 +/- 18, P <.02). Lactate extraction was lower during contro l and recovery in scan-positive animals (2 +/- 29 vs 30 +/- 19, P =.03). Sc an-positive animals had a more proximal stenosis position. Minimal necrosis was documented by means of TTC negative staining in 8 of 15 scan-positive experiments (comprising 10 % +/- 4.3 % of RR area). EM or cell fractionatio n was performed in 5 of the 7 remaining scan-positive and TTC-positive hear ts, and in those 5 experiments, necrosis was documented by means of EM in 2 and by means of cell fractionation in 3. Conclusions. Uptake of Tc-99m glucarate was seen in the RR in a swine model of ischemia severe enough to produce myocyte injury and early cell death.