Metabolic fate of iodine-123-BMIPP in canine myocardium after administration of etomoxir.
To clarify the metabolic fate of 123I-(-p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in dysfunctional myocardium, a comparison between normal dogs and those with etomoxir administration was studied using an open-chest canine model.


METHODS
Using open-chested dogs under anesthesia, we created a system to release all the blood in the great cardiac vein outside without recirculation, if necessary. Iodine-123-BMIPP was directly injected into the left anterior descending artery, its extraction, retention and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using a high-performance liquid chromatography. Moreover, these factors were compared between normal dogs and those pretreated with etomoxir, that creates a condition similar to ischemia.


RESULTS
Although rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, early washout (8 min) of radioactivity significantly increased (49.6% +/- 13.3%-->70.5% +/- 10.7%, p < 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%-->5.5% +/- 3.5%, p < 0.01). In addition, back diffusion of BMIPP increased (25.1% +/- 8.0%-->41.9% +/- 12.0%, p < 0.05) in the etomoxir-treated animals without affecting the levels of alpha-oxidation metabolite and the intermediate metabolites.


CONCLUSIONS
BMIPP is very sensitive to etomoxir and is suitable for assessing mitochondrial dysfunction. Iodine-123-BMIPP might be a promising radiopharmaceutical for the evaluation of ischemic heart disease, cardiomyopathy and mitochondrial encephalomyopathy.
Department of Internal Medicine, Kyoto University Hospital, Japan.
R
R
Hosokawa
R
R
Nohara
Y
Y
Fujibayashi
K
K
Okuda
M
M
Ogino
T
T
Hata
M
M
Fujita
N
N
Tamaki
J
J
Konishi
S
S
Sasayama
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004852:Epoxy Compounds / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging; D009206:Myocardium / Q000378:metabolism*; D011877:Radionuclide Imaging
D004852:Epoxy Compounds; D005227:Fatty Acids; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; C049338:iodofiltic acid; C054207:etomoxir