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. Using open-chested dogs under anesthesia, we created a syste...

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Veröffentlicht in:The Journal of nuclear medicine (1978) 1996-11, Vol.37 (11), p.1836-1840
Hauptverfasser: Hosokawa, Ryohei, Nohara, Ryuji, Fujibayashi, Yasuhisa, Okuda, Kazumi, Ogino, Motonari, Hata, Tatsuhiko, Fujita, Masatoshi, Tamaki, Nagara, Konishi, Junji, Sasayama, Shigetake
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container_end_page 1840
container_issue 11
container_start_page 1836
container_title The Journal of nuclear medicine (1978)
container_volume 37
creator Hosokawa, Ryohei
Nohara, Ryuji
Fujibayashi, Yasuhisa
Okuda, Kazumi
Ogino, Motonari
Hata, Tatsuhiko
Fujita, Masatoshi
Tamaki, Nagara
Konishi, Junji
Sasayama, Shigetake
description 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. 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. 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. 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.
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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. 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%--&gt;70.5% +/- 10.7%, p &lt; 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%--&gt;5.5% +/- 3.5%, p &lt; 0.01). In addition, back diffusion of BMIPP increased (25.1% +/- 8.0%--&gt;41.9% +/- 12.0%, p &lt; 0.05) in the etomoxir-treated animals without affecting the levels of alpha-oxidation metabolite and the intermediate metabolites. BMIPP is very sensitive to etomoxir and is suitable for assessing mitochondrial dysfunction. 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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. 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%--&gt;70.5% +/- 10.7%, p &lt; 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%--&gt;5.5% +/- 3.5%, p &lt; 0.01). 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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. 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%--&gt;70.5% +/- 10.7%, p &lt; 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%--&gt;5.5% +/- 3.5%, p &lt; 0.01). In addition, back diffusion of BMIPP increased (25.1% +/- 8.0%--&gt;41.9% +/- 12.0%, p &lt; 0.05) in the etomoxir-treated animals without affecting the levels of alpha-oxidation metabolite and the intermediate metabolites. 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.</abstract><cop>Reston, VA</cop><pub>Soc Nuclear Med</pub><pmid>8917188</pmid><tpages>5</tpages></addata></record>
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source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Animals
Biological and medical sciences
Cardiovascular system
Chromatography, High Pressure Liquid
Coronary Circulation - drug effects
Dogs
Epoxy Compounds - pharmacology
Fatty Acids - metabolism
Heart - diagnostic imaging
Heart - drug effects
Investigative techniques, diagnostic techniques (general aspects)
Iodine Radioisotopes
Iodobenzenes - metabolism
Medical sciences
Myocardial Ischemia - diagnostic imaging
Myocardium - metabolism
Radionuclide Imaging
Radionuclide investigations
title Metabolic Fate of Iodine-123-BMIPP in Canine Myocardium after Administration of Etomoxir
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