Hemodilution with liposome-encapsulated low-oxygen-affinity hemoglobin facilitates rapid recovery from ischemic acidosis after cerebral ischemia in rats.

Liposome-encapsulated hemoglobin (LipoHb) with low oxygen affinity (P50 = 40–50 mmHg) has been developed. The purpose of this study was to evaluate the effects of the LipoHb on incomplete cerebral ischemia. Wistar rats were randomly assigned to one of the following three groups: (A) exchange transfusion with LipoHb solution (Hb = 6 g/dl) (LipoHb, n = 7), (B) exchange transfusion with rat red blood cell (RBC) solution (Hb = 6 g/dl) (RBC, n = 7), (C) no exchange transfusion (control, n = 7). Forebrain ischemia was induced for 9 min by bilateral carotid artery occlusion combined with a decrease in the mean arterial pressure (MAP) to 40 mmHg. 31P-magnetic resonance spectroscopy was performed during ischemia and 60 min of reperfusion. After exchange transfusion, the MAP increased in the LipoHb group and decreased in the RBC group (LipoHb versus RBC; P = 0.0028). During ischemia, intracellular pH (pHi) rapidly decreased in all groups; after reperfusion, the pHi recovery to preischemic levels was more rapid in the LipoHb group than in the RBC group (P < 0.05). Phosphocreatine and β-adenosine triphosphate decreased during ischemia and returned to the preischemic level in all groups following reperfusion. Inorganic phosphate (Pi) increased during ischemia and decreased to the normal value after reperfusion. The LipoHb group had a smaller production of Pi than the other two groups and demonstrated a rapid normalization, although the differences were not significant. Hemodilution with liposome-encapsulated low-oxygen-affinity hemoglobin facilitates rapid pHi recovery from incomplete forebrain ischemia in the rat.