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

2015 
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. Graphical Abstract Keywords: Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, Myocardial Infarction INTRODUCTION The role of angiotensin receptor blockers (ARBs) in attenuating ischemia-reperfusion injury is not fully elucidated. It has been suggested that the myocardial protective effects of ARB against ischemia-reperfusion injury is mediated by activation of angiotensin II type 2 (AT2) receptors by angiotensin II, while the deleterious effects of AT1 receptors are blocked by the ARB (1, 2), leading to release of bradykinin with downstream activation of protein kinase C, nitric oxide synthase and eicosanoid release (2, 3, 4). Fimasartan (BR-A-657-K, KANARB®, Boryung Pharmaceutical Co., Ltd, Seoul, Republic of Korea) is a new ARB developed for the first time in Korea. It is a selective blocker of AT1 receptor subtype and has shown rapid and potent antihypertensive effect in a number of clinical trials (5, 6, 7, 8). Furthermore, anti-atherosclerotic effects of fimasartan were demonstrated in animal studies (9, 10). However, the efficacy of fimarsartan in acute MI is not elucidated. The goal of the present study is, therefore, to evaluate the effect of fimasartan in a porcine model of acute myocardial infarction (MI).
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