TY - JOUR T1 - Apolipoprotein A-I<sub>Milano</sub> and 1-Palmitoyl-2-oleoyl Phosphatidylcholine Complex (ETC-216) Protects the in Vivo Rabbit Heart from Regional Ischemia-Reperfusion Injury JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1023 LP - 1031 DO - 10.1124/jpet.104.070789 VL - 311 IS - 3 AU - Marta Marchesi AU - Erin A. Booth AU - Treasa Davis AU - Charles L. Bisgaier AU - Benedict R. Lucchesi Y1 - 2004/12/01 UR - http://jpet.aspetjournals.org/content/311/3/1023.abstract N2 - Ex vivo studies demonstrated that a synthetic high-density lipoprotein (HDL) comprised of a complex of recombinant apolipoprotein A-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine protects the isolated rabbit heart from reperfusion injury. Therefore, we sought to determine whether a pharmaceutical preparation of this complex, ETC-216, was cardioprotective in an in vivo model of left anterior descending artery (LAD) occlusion and reperfusion. Initially, ETC-216 (100 mg/kg) was tested in acute (one-treatment) and chronic (two-treatment) i.v. administrations. ETC-216-treated rabbits developed smaller infarcts expressed as percentage of area at risk (p &lt; 0.01) compared with vehicle treatments. No differences were noted between chronic and acute administration. Therefore, ETC-216 (10, 3, or 1 mg/kg) or equivalent vehicle volumes were acutely infused. Compared with vehicle, ETC-216 reduced infarct size as a percentage of the area at risk at 10 (p &lt; 0.0005) and 3 mg/kg (p &lt; 0.05). No significant differences occurred at 1 mg/kg. To determine whether ETC-216 could protect the heart after initiation of ischemia, the synthetic HDL (10 mg/kg) was infused intravenously beginning 5 min before the end of 30 min of LAD occlusion. Infarct size as percentage of the area at risk was 31.6 ± 3.0 (ETC-216) versus 49.5 ± 2.5 (vehicle) (p &lt; 0.001), and as percentage of left ventricle was 19.7 ± 1.6 (ETC-216) versus 34.1 ± 2.3 (vehicle) (p &lt; 0.0005). Electron microscopy demonstrated that ETC-216 prevented irreversible cardiac damage as assessed by mitochondrial granulation and sarcomere contraction band formation. These findings suggest ETC-216 reduces reperfusion injury and may have utility for coronary artery revascularization procedures. The American Society for Pharmacology and Experimental Therapeutics ER -