Chonnam Med J.  2019 May;55(2):109-115. 10.4068/cmj.2019.55.2.109.

Therapeutic Effect of Fimasartan in a Rat Model of Myocardial Infarction Evaluated by Cardiac Positron Emission Tomography with [¹⁸F]FPTP

Affiliations
  • 1Division of Cardiology, Chonnam National University Hospital, Gwangju, Korea. hyj200@hanmail.net jjmin@jnu.ac.kr
  • 2Institute for Biomedical Science, Chonnam National University Hwasun Hospital, Hwasun, Korea.
  • 3Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea. hyj200@hanmail.net jjmin@jnu.ac.kr
  • 4Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.

Abstract

We evaluated the efficacy of fimasartan on perfusion defects and infarction size in an animal model of myocardial infarction (MI), with echocardiography and positron emission tomography (PET) using a ¹â¸F-labeled phosphonium cation (5-[¹â¸F]-fluoropentyl-triphenylphosphonium salt, [¹â¸F]FPTP) as a mitochondrial voltage sensor for myocardial imaging. We induced MI in 33 rats by ligation of the left coronary artery, and checked their cardiac PET image using [¹â¸F]FPTP for evaluation of myocardial perfusion. Rats were grouped into 3 groups according to their administered drugs: no drug (n=11), fimasartan 3 mg/kg (n=10), and fimasartan 10 mg/kg (n=12). Each designated drug was administered for 4 weeks, and follow-up PET and histologic examinations were done. In the PET analysis, a perfusion defect size was markedly improved in fimasartan 10 mg/kg group (35.9±7.0% to 28.4±6.9%, p<0.001), whereas treatment with fimasartan 3 mg/kg induced only an insignificant reduction of perfusion defect size (35.9±7.9% to 33.9±7.3%, p=0.095). Using 2, 3, 5-triphenyltetrazolium chloride staining, infarction size was the largest in the control group (36.5±8.3%), and was insignificantly lower in the fimasartan 3 mg/kg group (31.5±6.5%, p for the difference between the control group=0.146) and was significantly lower in the fimasartan 10 mg/kg group (26.3±7.6%, p for the difference between the control group=0.011). PET imaging using a ¹â¸F-labeled mitochondrial voltage sensor, [¹â¸F]FPTP, is useful in evaluation and monitoring of myocardial perfusion states, and treatment with fimasartan decreases the infarction size in animal MI model.

Keyword

Myocardial Infarction; Positron Emission Tomography; Angiotensin Receptor Antagonists

MeSH Terms

Angiotensin Receptor Antagonists
Animals
Coronary Vessels
Echocardiography
Electrons*
Follow-Up Studies
Infarction
Ligation
Models, Animal*
Myocardial Infarction*
Perfusion
Positron-Emission Tomography*
Rats*
Angiotensin Receptor Antagonists

Figure

  • FIG. 1 Study protocol. MI: myocardial infarction, PET: positron emission tomography.

  • FIG. 2 Representative PET images in polar map 1 week after myocardial infarction induction (left) and after 4 weeks of fimasartan treatment (right). Short axis section of the extracted heart is illustrated in right lower side.

  • FIG. 3 (A) ΔLVEF [(LVEF in follow-up echocardiography - LVEF in baseline echocardiography)/LVEF in baseline echocardiography] in 3 groups. (B) Mean perfusion defect size in baseline and follow-up cardiac PET. (C) Mean infarction size in TTC stain. Asterisks between groups mean statistically significant difference between them (p<0.05).

  • FIG. 4 Relation between infarction size in TTC stain (%) and perfusion defect size in PET (%). Partial correlation coefficient (r)=0.89.


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