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Early reperfusion with hemoglobin vesicles into tracheal subepithelial capillaries in a mouse tracheal transplant model.

Hiroto Onozawa, Mitsutomo Kohno, Kana Oiwa, Ryo Hashimoto, Masatoshi Yamaguchi, Tai Hato, Masazumi Watanabe, Hirohisa Horinouchi, Hiromi Sakai, Koichi Kobayashi, Masayuki Iwazaki

Introduction: Hemoglobin Vesicles (HbVs) have been developed as artificial oxygen carriers in the form of liposomes containing concentrated hemoglobin extracted from outdated human Red Blood Cells (RBC). Because HbVs have a small particle size of 250 nm in diamete, rthey can efficiently perfuse capillaries.

Objectives: To evaluate the reperfusion of capillaries with HbVs in a tracheal transplant model and compare it with that of RBC.

Methods: Isogenic mice were used as both donors and recipients in a parallel trachea transplant model, which realizes simultaneous histological observation of the recipient and the grafted tracheas. Both ends of the donor trachea were anastomosed end-laterally to the recipient trachea to form in parallel. After transplantation, 0.3 ml of HbV solution (Hb concentration, 10 g/dl) was administered via the tail vein. The recipients were sacrificed 1, 4, 6, and 8 h after surgery. The tracheas were harvested, and the reperfusion of tracheal Subepithelial Capillaries (SEC) was histologically evaluated.

Results: A significant number of particles defined as HbV by electron microscopy were observed in the SEC of the grafted tracheas 4 h after the transplant surgery and HbV administration when no RBC were found in the SECs. The number increased 6 h later, and HbVs were observed in the SEC 8 h later.

Discussion: Our experiment with a tracheal transplantation model suggests that HbVs, which are smaller than RBC, can reperfuse the capillaries of grafts earlier than RBC after transplantation and contribute to the oxygenation of transplanted tissues.