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


CONCLUSIONS
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.
Chida
M
M
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Kagaya
Y
Y
Imahori
Y
Y
Namiuchi
S
S
Fujii
R
R
Fukuchi
M
M
Takahashi
C
C
Tezuka
F
F
Ido
T
T
Shirato
K
K
D000818:Animals; D001345:Autoradiography; D002855:Chromatography, Thin Layer; D003326:Coronary Circulation; D005989:Glycerides; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D014055:Tomography, Emission-Computed
C121883:1-butyryl-2-palmitoyl-rac-glycerol; D005989:Glycerides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D019275:Radiopharmaceuticals