Investigating the Vasodilatory Effects of Tgpolyhb: A Potential Hemoglobin-Based Oxygen Carrier for Sickle Cell Disease and Thalassemia

Abstract

Background: Hemoglobin-based oxygen carriers (HBOC) hold promise in improving oxygen delivery to organs and tissues, potentially reducing the need for transfusions and associated complications, thus presenting an alternative approach to managing anemia. Methods: We created a polymerized human hemoglobin called TgPolyHb, using transglutaminase, which has demonstrated effective oxygen transport and blood flow maintenance in animal studies. Our hypothesis suggests that TgPolyHb will not induce vasoconstriction or hypertension, side effects observed in previous generations of HBOC, such as HBOC-201. In the present study, we assessed the potential of TgPolyHb to reduce the side effects previously seen with HBOC-201, comparing it to stroma-free acellular hemoglobin (hHb - negative control) in Golden Syrian Hamsters. The animals were instrumented with a metallic frame with a small cover slip placed over the dorsal skin fold to observe and quantify microcirculatory health following a toapload infusion (arterial injection of 10% of their blood volume). Results: The innovative HBOC, TgPolyHb, exhibited vasodilation effects in comparison to HBOC-201 and hHb, both exhibited a 10% reduction in diameter compared to baseline. Furthermore, TgPolyHb demonstrated a 10% increase in functional capillaries compared to HBOC-201 and hHb. Functional capillary density is an important marker of tissue health. Conclusions: Our study provides preliminary data that could lead future investigations of HBOC such as TgPolyHb in decreasing transfusion burden in severe anemias.