Apolipoprotein A-IMilano/ROPC complex attenuates post-ischemic ventricular dysfunction in the isolated rabbit heart

Irreversible myocardial injury is a potential consequence of coronary artery revascularization. Reperfusion leads to the production of oxidized products that can damage myocardium. High-density lipoproteins (HDL) are effective at removing oxidized lipids. We hypothesized that a synthetic HDL preparation, comprising recombinant apolipoprotein A-I-Milano (apoA-I-M) complexed with 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) (apoA-I-M/POPC) would protect the heart from reperfusion injury. The ex vivo model consisted of rabbit hearts perfused by the Langendorff method. Hearts were equilibrated with Krebs-Henseleit buffer (10 min), pretreated with either apoA-I-M/POPC (0.45 mg/mL) or vehicle (10 min), subjected to global ischemia (30 min) and reperfused for 60 min. ApoA-I-M/POPC (n = 7) prevented the left ventricular end-diastolic pressure elevation observed in the vehicle group (n = 6) at the end of reperfusion (p < 0.05). During reperfusion, coronary artery perfusion pressure increased in the controls (p < 0.00 1), but not with apoA-I-M/POPC. ApoA-I-M/POPC reduced the release of creatine kinase at the end of the ischemic period (p<0.001). It also reduced cardiac left ventricle muscle lipid hydroperoxides by 46% (P < 0.05). Direct comparison of the antioxidant potential indicated that recombinant apoA-I-M was much more potent than apoA-I in attenuating low-density lipoprotein oxidation. Electron microscopy showed that apoA-I-M/POPC prevented mitochondrial granulation, disorganization and sarcomere contraction band formation indicative of reperfusion injury.