CORONARY VASCULAR BED PERFUSION WITH A POLYETHYLENE GLYCOL-MODIFIED HEMOGLOBIN-ENCAPSULATED LIPOSOME, NEO RED-CELL, IN RATS

Whether hemoglobin (Hb) encapsulated liposomes have vasoconstrictive a ctivity remains controversial. We therefore examined the vascular acti vity of a liposome Hb. Neo red cell (NRC), in a simple in vitro model of Langendorff perfusion of the rat heart using Krebs-Henseleit. (KH) solution as the perfusate. In the KH solution, NRC (Hb at 1 mg/ml), ho wever, induced an immediate and abnormal increase in perfusion pressur e. Histological examinations revealed that embolisms were the likely c ause of this disturbance, Inorganic crystals formed by the mixing of N RC with the perfusate were a possible source of the embolisms. We foun d that the addition of bovine serum albumin to the perfusate was effec tive in avoiding embolic events. This protocol was used to compare the vasoconstrictive properties of unmodified bovine Hb and NRC. Unmodifi ed bovine Hb (1 mg/ml) caused an increase in perfusion pressure and a decrease in the duration of bradykinin-induced relaxation. In contrast , NRC (Hb at 1 mg/ml) had no such vasoconstrictive effects. These resu lts provide the first information regarding perfusion of the circulato ry vascular bed by NRC and further evidence that the encapsulation of Hb into liposomes is an effective approach to modulate Hb-related vaso constrictive activity.