
Cardioprotective Effects of Angiotensin II Type 1 Receptor Blockade with Olmesartan on Reperfusion Injury in a Rat Myocardial Ischemia‐Reperfusion Model
Author(s) -
Dai Wangde,
Hale Sharon L.,
Kay Gregory L.,
Jyrala Aarne J.,
Kloner Robert A.
Publication year - 2010
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/j.1755-5922.2009.00108.x
Subject(s) - olmesartan , medicine , myocardial infarction , cardiology , reperfusion injury , ischemia , angiotensin ii , anesthesia , infarction , ischemic preconditioning , blood pressure
We determined the effects of olmesartan on infarct size and cardiac function in a rat ischemia/reperfusion model. Rats underwent 30 min of left coronary artery (CA) occlusion followed by 2 h of reperfusion. In protocol 1, the rats received (by i.v.) 1 mL of vehicle at 10 min after CA occlusion (Group 1, n = 15); olmesartan (0.3 mg/kg) at 10 min after CA occlusion (Group 2, n = 15); 1 mL of vehicle at 5 min before CA reperfusion (Group 3, n = 15); or olmesartan (0.3 mg/kg) 5 min before CA reperfusion (Group 4, n = 15). In protocol 2, the rats received (by i.v.) 1 mL of vehicle at 5 min before CA reperfusion (Group 5, n = 21); or olmesartan (3 mg/kg) at 5 min before CA reperfusion (Group 6, n = 21). Systemic hemodynamics, left ventricular (LV) function, LV ischemic risk zone, no‐reflow zone, and infarct size were determined. In protocol 1, olmesartan (0.3 mg/kg) did not affect blood pressure (BP), heart rate, LV ± dp/dt or LV fractional shortening during the experimental procedure, and did not alter no‐reflow or infarct size. In protocol 2, olmesartan (3 mg/kg) significantly reduced infarct size to 21.7 ± 4.1% from 34.3 ± 4.1% of risk zone in the vehicle group ( P = 0.035), but did not alter the no‐reflow size. Prior to CA reperfusion, olmesartan (3 mg/kg) significantly reduced mean BP by 22% and LV ±dp/dt, but did not affect heart rate. At 2 h after reperfusion, olmesartan significantly decreased heart rate by 21%, mean BP by 14%, and significantly increased LV fractional shortening from 54.1 ± 1.4% to 61.3 ± 1.6% ( P = 0.0018). Olmesartan significantly reduced myocardial infarct size and improved LV contractility at a dose (3 mg/kg) with systemic vasodilating effects but not at a lower dose (0.3 mg/kg) without hemodynamic effects.