Visualization of myocardial phosphoinositide turnover with 1-[1-C-11]-butyryl-2-palmitoyl-rac-glycerol in rats with myocardial infarction

Phosphoinositide turnover mediates the signaling of angiotensin II, which p lays a pivotal role in ventricular remodeling after myocardial infarction ( MI). We tested the hypothesis that phosphoinositide turnover can be visuali zed by 1-[1-C-11]butyryl-2-palmitoyl-rac-glycerol (C-11-DAG) in both infarc ted and noninfarcted myocardium after MI in rats. Methods: Rats received an injection of C-11-DAG 7 d after left coronary artery ligation, and myocard ial lipids were extracted from both infarcted and noninfarcted areas of myo cardium (n = 3). Metabolites of C-11-DAG were determined by thin-layer chro matography. Quantitative autoradiography of hearts was performed to visuali ze myocardial phosphoinositide turnover in rats that received an injection of C-11-DAG 1 d (n = 3) and 7 d (n = 5) after MI and 7 d after a sham opera tion (n = 3). Quantitative autoradiography with (TlCl)-Tl-201 was also perf ormed to evaluate myocardial blood flow in rats 7 d after MI (n = 3). Cells occupying the infarcted myocardium were identified by immunohistochemistry . Results: The radioactivity incorporated into the intermediates of phospho inositide turnover was predominant in both the infarcted (67.1% +/- 5.2% of the total activity) and the noninfarcted (57.4% +/- 3.2%) myocardium. C-11 -DAG radioactivity in the infarcted region normalized to that in the noninf arcted region was 1.09 +/- 0.04 in rats 7 d after MI, which was significant ly higher than that in rats 1 d after MI (0.38 +/- 0.03, P < 0.001). Tl-201 radioactivity in the infarcted region normalized to that in the noninfarct ed region was only 0.19 +/- 0.01 7 d after MI. C-11-DAG radioactivity in th e noninfarcted region normalized to that in the right ventricular free wall tended to be increased in rats I and 7 d after MI compared with the sham-o perated rats; the differences, however, were not statistically significant (1.30 +/- 0.15, 1.20 +/- 0.07, and 1.13 +/- 0.02, respectively). Immunohist ochemistry revealed that abundant fibroblasts, myofibroblasts, and macropha ges occupied the infarcted myocardium 7 d after MI, but the cellularity was low during the first day after MI. Conclusion: These data suggest that C-1 1-DAG may be useful for visualizing regions with activated phosphoinositide turnover after MI. Because wound healing and fibrogenic processes are impo rtant factors of ventricular remodeling, C-11-DAG and PET may offer new inf ormation benefiting patient management after MI.