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

• Park H
• Kim HS
• Hong YJ
• Min JJ
• Kim HB
• Kim MC
• Sim DS
• Kim JH
• Kim DY
• Lee JS
• Ahn Y
• Jeong MH

• KMID: 2447213
• DOI: http://doi.org/10.4068/cmj.2019.55.2.109

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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