Related Experiment Video
Updated: Jul 10, 2026
Model of Ischemia and Reperfusion Injury in Rabbits
Published on: November 3, 2023
Apolipoprotein A-IMilano/POPC complex attenuates post-ischemic ventricular dysfunction in the isolated rabbit heart
Marta Marchesi1, Erin A Booth, Giuseppe Rossoni
1Department of Pharmacological Sciences, University of Milan, Italy. marta.marchesi@unimi.it
Insights
A synthetic high-density lipoprotein (HDL) preparation protected hearts from reperfusion injury by reducing oxidative stress and preserving cardiac function. This novel HDL therapy shows promise for treating myocardial ischemia.
Area of Science:
- Cardiovascular Science
- Biochemistry
- Pharmacology
Background:
- Myocardial injury can occur after coronary artery revascularization due to reperfusion-induced oxidative damage.
- High-density lipoproteins (HDL) possess antioxidant properties, effectively removing oxidized lipids.
- Recombinant apolipoprotein A-I(Milano) (apoA-I(M)) complexed with phospholipids represents a potential therapeutic HDL mimetic.
Purpose of the Study:
- To investigate the cardioprotective effects of a synthetic HDL preparation, apoA-I(M)/POPC, against myocardial reperfusion injury.
- To evaluate the impact of apoA-I(M)/POPC on cardiac function, oxidative stress markers, and ultrastructural changes during ischemia-reperfusion.
Main Methods:
- An ex vivo rabbit heart model using the Langendorff perfusion system was employed.
- Hearts were pretreated with apoA-I(M)/POPC or vehicle, subjected to global ischemia, and then reperfused.
- Measurements included left ventricular end-diastolic pressure, coronary artery perfusion pressure, creatine kinase release, lipid hydroperoxides, and electron microscopy.
Main Results:
- ApoA-I(M)/POPC significantly prevented left ventricular end-diastolic pressure elevation and maintained coronary artery perfusion pressure during reperfusion.
- The synthetic HDL reduced creatine kinase release and cardiac left ventricle muscle lipid hydroperoxides by 46%.
- Electron microscopy confirmed that apoA-I(M)/POPC prevented mitochondrial damage and sarcomere alterations characteristic of reperfusion injury.
Conclusions:
- The synthetic HDL complex, apoA-I(M)/POPC, effectively reduces myocardial reperfusion injury in an ex vivo setting.
- Its potent antioxidant capacity and ability to preserve cardiac structure suggest therapeutic potential for reducing ischemia-related heart damage.
Abstract:
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<0.001), 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. The apoA-I(M)/POPC complex thus appears to reduce reperfusion injury under global ischemic conditions, and may therefore have therapeutic application in the reduction of myocardial ischemia.
