Myocardial metabolism of 123I-BMIPP under low-dose dobutamine infusion: implications for clinical SPECT imaging of ischemic heart disease.
OBJECTIVE
123I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of 123I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake.


METHODS
Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6).


RESULTS
Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48+/-19% vs 66+/-14%, p<0.05) and its subsequent retention (73+/-13% vs 85+/-8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0+/-20.0% to 15.8+/-9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3+/-21.9% to 71.3+/-10.1%, p<0.05).


CONCLUSIONS
These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight into the pathophysiology of stunned myocardium.
Hosokawa
Ryohei
R
Department of Cardiovascular Medicine, and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nohara
Ryuji
R
Hirai
Taku
T
Fujibayashi
Yasuhisa
Y
Fujita
Masatoshi
M
Kambara
Naoshige
N
Ohba
Muneo
M
Tadamura
Eiji
E
Kimura
Takeshi
T
Kita
Toru
T
D000818:Animals; D004280:Dobutamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D005227:Fatty Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods; D007261:Infusions, Intra-Arterial; D007462:Iodobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D017202:Myocardial Ischemia / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D017682:Myocardial Stunning / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D004338:Drug Combinations; D005227:Fatty Acids; D007462:Iodobenzenes; D019275:Radiopharmaceuticals; C049338:iodofiltic acid; D004280:Dobutamine