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Visualization of Myocardial Phosphoinositide Turnover with 1-[1-¹¹C]-Butyryl-2-Palmitoyl-rac-Glycerol in Rats with Myocardial Infarction

Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai; Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto; Cyclotron Unit, Nishijin Hospital, Kyoto; Department of Pathology, National Sendai Hospital, Sendai; and Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan

Phosphoinositide turnover mediates the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). We tested the hypothesis that phosphoinositide turnover can be visualized by 1-[1-¹¹C]butyryl-2-palmitoyl-rac-glycerol (¹¹C-DAG) in both infarcted and noninfarcted myocardium after MI in rats. Methods: Rats received an injection of ¹¹C-DAG 7 d after left coronary artery ligation, and myocardial lipids were extracted from both infarcted and noninfarcted areas of myocardium (n = 3). Metabolites of ¹¹C-DAG were determined by thin-layer chromatography. Quantitative autoradiography of hearts was performed to visualize myocardial phosphoinositide turnover in rats that received an injection of ¹¹C-DAG 1 d (n = 3) and 7 d (n = 5) after MI and 7 d after a sham operation (n = 3). Quantitative autoradiography with ²⁰¹TlCl was also performed 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 phosphoinositide turnover was predominant in both the infarcted (67.1% ± 5.2% of the total activity) and the noninfarcted (57.4% ± 3.2%) myocardium. ¹¹C-DAG radioactivity in the infarcted region normalized to that in the noninfarcted region was 1.09 ± 0.04 in rats 7 d after MI, which was significantly higher than that in rats 1 d after MI (0.38 ± 0.03, P < 0.001). ²⁰¹Tl radioactivity in the infarcted region normalized to that in the noninfarcted region was only 0.19 ± 0.01 7 d after MI. ¹¹C-DAG radioactivity in the noninfarcted region normalized to that in the right ventricular free wall tended to be increased in rats 1 and 7 d after MI compared with the sham-operated rats; the differences, however, were not statistically significant (1.30 ± 0.15, 1.20 ± 0.07, and 1.13 ± 0.02, respectively). Immunohistochemistry revealed that abundant fibroblasts, myofibroblasts, and macrophages occupied the infarcted myocardium 7 d after MI, but the cellularity was low during the first day after MI. Conclusion: These data suggest that ¹¹C-DAG may be useful for visualizing regions with activated phosphoinositide turnover after MI. Because wound healing and fibrogenic processes are important factors of ventricular remodeling, ¹¹C-DAG and PET may offer new information benefiting patient management after MI.

Key Words: myocardial infarction • ventricular remodeling • phosphoinositide turnover

Received Jan. 10, 2000; revision accepted May 16, 2000.

For correspondence or reprints contact: Kunio Shirato, MD, PhD, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan.

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