J Korean Med Sci.  2015 Jan;30(1):34-43. 10.3346/jkms.2015.30.1.34.

Cardioprotective Effect of Fimasartan, a New Angiotensin Receptor Blocker, in a Porcine Model of Acute Myocardial Infarction

• Sim DS
• Jeong MH
• Song HC
• Kim J
• Chong A
• Bom HS
• Jeong IS
• Oh SG
• Kim JM
• Park DS
• Kim JH
• Lim KS
• Kim MS
• Ryu SH
• Kim HK
• Kim SS
• Jang SY
• Cho JY
• Jeong HC
• Lee KH
• Park KH
• Yoon NS
• Yoon HJ
• Kim KH
• Hong YJ
• Park HW
• Kim JH
• Ahn Y
• Cho JG
• Park JC
• Kang JC

• KMID: 2155445
• DOI: http://doi.org/10.3346/jkms.2015.30.1.34

Abstract

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Keyword

Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Blockers; Myocardial Infarction

MeSH Terms

3-Iodobenzylguanidine
Angiotensin II Type 1 Receptor Blockers/therapeutic use
Angiotensin Receptor Antagonists/*therapeutic use
Angiotensin-Converting Enzyme Inhibitors/therapeutic use
Animals
Anterior Wall Myocardial Infarction/*drug therapy/physiopathology
Biphenyl Compounds/*therapeutic use
Cardiotonic Agents/*therapeutic use
Disease Models, Animal
Echocardiography
Fluorodeoxyglucose F18
Perindopril/therapeutic use
Positron-Emission Tomography
Pyrimidines/*therapeutic use
Random Allocation
Swine
Tetrazoles/*therapeutic use
Tomography, Emission-Computed, Single-Photon
Valsartan/therapeutic use
Ventricular Function, Left/*physiology
3-Iodobenzylguanidine
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Biphenyl Compounds
Cardiotonic Agents
Perindopril
Pyrimidines
Tetrazoles
Fluorodeoxyglucose F18
Valsartan

Figure

• 

  Fig. 1 Coronary angiograms during and after induction of anterior wall myocardial infarction. (A) Baseline. (B) Occlusion of the mid-left anterior descending artery just distal to the diagonal branch (black arrowheads) with a 3.0 mm balloon (white arrowheads). (C) 50 min after occlusion. (D) Follow-up angiogram at 6 weeks.

• 

  Fig. 2 Scheme of the study protocol. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; CAG, coronary angiography; 2DE, 2-dimensional echocardiography; MIBG scan, Iodine-123 meta-iodobenzylguanidine cardiac scintigraphy; PET, F-18 fluorodeoxyglucose cardiac positron emission tomography/computed tomography; SPECT, Tc-99m sestamibi myocardial perfusion single photon emission computed tomography; TTC, 2,3,5-triphenyl tetrazolium chloride.

• 

  Fig. 3 SPECT and PET images at 1 week (A) and 4 weeks (B) showing anterior wall myocardial infarction. (A) At 1 week, SPECT shows moderate to severe, large perfusion defect in the apex and anterior wall (arrowhead). PET reveals preserved FDG metabolism in the apex and anterior wall (arrowhead), demonstrating perfusion-metabolism mismatch pattern, which reflects viable myocardium. (B) At 4 weeks, SPECT shows remaining perfusion defect in the apex and anterior wall. PET reveals reduced FDG uptake in the apex and anterior wall, demonstrating perfusion-metabolism match pattern, which reflects nonviable myocardium. PET, F-18 fluorodeoxyglucose cardiac positron emission tomography/computed tomography; SPECT, Tc-99m sestamibi myocardial perfusion single photon emission computed tomography.

• 

  Fig. 4 I-123 MIBG cardiac scintigraphy at 6 weeks. Planar images in the anterior view, acquired at 15 min (A) and 3 hr 50 min (B) after I-123 MIBG injection. Heart-to-mediastinum ratios were 1.64 and 1.51 at early and late phases with washout rate of 29%, indicating reduced cardiac sympathetic nerve activity. I-123 MIBG, Iodine-123 meta-iodobenzylguanidine.

• 

  Fig. 5 2,3,5-triphenyl tetrazolium chloride staining at 6 weeks showing areas of infarcted myocardium in the anterior wall (arrowheads).

• 

  Fig. 6 Infarct size by pathology between groups 2-5. Bonferroni's post hoc test between AMI control (group 2) and AMI with use of perindopril, valsartan, and fimasartan (groups 3-5). AMI, acute myocardial infarction.

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