Assessment of Dextran 10-Benzene-Tetracarboxylate-Hemoglobin, An Oxygen Carrier, Using Guinea Pig Isolated Bowel Model

Abstract

With the aim of assessing of dextran-benzene-tetracarboxylate hemoglobin as an oxygen carrier, we studied histological changes in the intestinal loop in anesthetized guinea pig. The intestinal tissue being very sensitive to hypoxia, an innervated loop was vascularly perfused with open-flow during one hour at zero hematocrit. To estimate the capacity of hemoglobin solution to oxygenate this tissue, we observed the mechanical and histological changes in the organ and the arterio-venous difference in PO₂, oxyhemoglobin, deoxyhemoglobin and we compared them with human albumin, Tyrode and non-modified hemoglobin. The PO₂ arteriovenous differences were 51.9±7.1 torr (mßM) for Tyrode, 40.2±6.4 torr for albumin solution, 113.7 ± 6.5 torr for non-modified hemoglobin and 132.7 ± 6.8 torr for dex-BTC-Hb. Compared to albumin and Tyrode solutions, hemoglobin solutions transferred more oxygen to tissues. The desaturation of dex-BTC-Hb was significantly superior (p<0,05) to the one non-modified hemoglobin. With Hb solutions, this desaturation increased with time and it depended on the perfusion flow. The structure of jejunal villi when perfused with a hemoglobin solution, remained almost normal and the loop was still active. Nevertheless, non-modified hemoglobin leaked from the vessels to the lumen and caused edema and a rupture of overlapping epithelium at the tip of the villi. With dex-BTC-Hb, such histological modifications were less significant. With albumin and Tyrode, all villi were totally necrosed and the loop was completely inert.

We have demonstrated that dextran-benzene-tetracarboxylate hemoglobin had the ability to maintain the tissue alive thank to its good capacity to release oxygen and its satisfactory vascular persistence. Dex-BTC-Hb solution can answer to needs of tissue.