Background. Liposome-Encapsulated Hemoglobin (NRC, Terumo Co, Ltd) has been modified to have a high O2-affinity (P50=10 mmHg, hNRC) to increase O2, delivery to hypoxic tissues such as ischemic myocardium. We hypothesize that targeted O2 delivery by hNRC may suppress arrhythmogenicity and improve reversibility in caine myocardium under ischemia. Methods. Empty liposome or hNRC (0.5% of body weight) was infused 5 minutes after occlusion of the left anterior descending artery (LAD) in open chest dogs. Ten minutes after LAD occlusion, programmed electric stimuli on the left ventricle were started to titrate vulnerability for ventricular fibrillation (VF). Once VF is induced, LAD occlusion is released and defibrillated by direct current cardioversion using 1, 3, 5, 7 and 101. Ten minutes after reperfusion, the same VF inductionheversal study was repeated using the alternate solution, empty liposome or hNRC. Results. While hNRC increased VF threshold and decreased energy for defibrillation in each animal (n=3), empty liposome failed to change vulnerability or reversibility of VF in any of the animals (n=3) regardless of order of administration, empty liposome or hNRC. Conclusion. Liposome-Encapsulated Hemoglobin with a high O2-affinity appears to be effective to suppress vulnerability, and improve reversibility of VF in ischemic canine myocardium. Optimal dose, timing and O2-affinity need to he defined.