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  3. Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure

Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure

  • PLoS One. 2015 Jan 16;10(1):e0117091. doi: 10.1371/journal.pone.0117091.
Akira Kawamoto 1,  Takao Kato 2,  Tetsuo Shioi 1,  Junji Okuda 1,  Tsuneaki Kawashima 1,  Yodo Tamaki 1,  Shinichiro Niizuma 1,  Yohei Tanada 1,  Genzou Takemura 3,  Michiko Narazaki 4,  Tetsuya Matsuda 4,  Takeshi Kimura 1
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 2 Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Cardiovascular Center, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan.
  • 3 Division of Cardiology, Gifu University, Graduate School of Medicine, Gifu, Japan.
  • 4 Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan.
PMID: 25594546 DOI: 10.1371/journal.pone.0117091
Abstract

Background: Many methods have been used to assess mitochondrial function. Technetium-99m sestamibi ((99m)Tc-MIBI), a lipophilic cation, is rapidly incorporated into myocardial cells by diffusion and mainly localizes to the mitochondria. The purpose of this study was to investigate whether measurement of (99m)Tc-MIBI signals in animal models could be used as a tool to quantify mitochondrial membrane potential at the organ level.

Methods and results: We analyzed (99m)Tc-MIBI signals in Sprague-Dawley (SD) rat hearts perfused with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler known to reduce the mitochondrial membrane potential. (99m)Tc-MIBI signals could be used to detect changes in the mitochondrial membrane potential with sensitivity comparable to that obtained by two-photon laser microscopy with the cationic probe tetramethylrhodamine ethyl ester (TMRE). We also measured (99m)Tc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle. (99m)Tc-MIBI signals decreased in rat hearts administered CCCP, and the ATP content, as measured by (31)P magnetic resonance spectroscopy, decreased simultaneously. Next, we administered (99m)Tc-MIBI to Dahl salt-sensitive rats fed a high-salt diet, which leads to hypertension and heart failure. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with heart weight, cardiac function, and the expression of atrial natriuretic factor, a marker of heart failure, and positively correlated with the accumulation of labeled fatty acid analog. The (99m)Tc-MIBI signal per liver tissue weight was lower than that per heart tissue weight.

Conclusion: Measurement of (99m)Tc-MIBI signals can be an effective tool for semiquantitative investigation of cardiac mitochondrial membrane potential in the SD rat model by using a chemical to decrease the mitochondrial membrane potential. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with the severity of heart failure in the Dahl rat model.

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