IngentaConnect Coronary Vascular Bed Perfusion with a Polyethylene Glycol-Modifi...

Authors: Nakai, Kunihiko¹; Usuba, Akira²; Ohta, Toshio³; Kuwabara, Mikinori⁴; Nakazato, Yoshikazu³; Motoki, Ryoichi²; Takahash, Tsuneo A.¹

Source: Artificial Organs, Volume 22, Number 4, April 1998 , pp. 320-325(6)

Publisher: Blackwell Publishing

Abstract:

Whether hemoglobin (Hb) encapsulated liposomes have vasoconstrictive activity remains controversial. We therefore examined the vascular activity 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), however, induced an immediate and abnormal increase in perfusion pressure. Histological examinations revealed that embolisms were the likely cause of this disturbance. Inorganic crystals formed by the mixing of NRC with the perfusate were a possible source of the embolisms. We found that the addition of bovine serum albumin to the perfusate was effective in avoiding embolic events. This protocol was used to compare the vasoconstrictive properties of unmodified bovine Hb and NRC. Unmodified 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 results provide the first information regarding perfusion of the circulatory vascular bed by NRC and further evidence that the encapsulation of Hb into liposomes is an effective approach to modulate Hb-related vasoconstrictive activity.

Keywords: Embolism; Hemoglobin; Langendorff perfusion; Liposomes; Neo red cell; Oxygen carrier; Vasoconstriction

Document Type: Original article

DOI: 10.1046/j.1525-1594.1998.05092.x

Affiliations: 1: Department of Cell Processing, Institute of Medical Science, University of Tokyo, Tokyo; 2: First Department of Surgery, Fukushima Prefecture Medical University, Fukushima; 3: Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan 4: Laboratory of Radiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan

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Coronary Vascular Bed Perfusion with a Polyethylene Glycol-Modified Hemoglobin-Encapsulated Liposome, Neo Red Cell, in Rats