Physicochemical Characteristics of OxyVita Hemoglobin, a Zero-Linked Polymer: Liquid and Powder Preparations
OxyVita-zero-link polymerized hemoglobin (OxyVita Hb) is a novel generation hemoglobin based oxygen carrier (HBOC). Our focus in this paper is to address the question of "Why is OxyVita Hemoglobin different than the previous generation of HBOCs?" Several critical related topics will be discussed: 1) OxyVita's unique chemistry; 2) the introduction of a viable powder form of OxyVita hemoglobin for dissolution in IV water or other IV fluids; 3) the physiochemical characteristics of OxyVita hemoglobin preparations; 4) the ability to formulate different products based upon specific applications; and 5) the important storage properties essential for use in a wide range of geographical locations.
[Show abstract] [Hide abstract] ABSTRACT: The use of hemoglobin-based oxygen carriers (HBOC) as oxygen delivering therapies during hypoxic states has been hindered by vasoconstrictive side effects caused by depletion of nitric oxide (NO). OxyVita C is a promising oxygen-carrying solution that consists of a zero-linked hemoglobin polymer with a high molecular weight (~17 MDa). The large molecular weight is believed to prevent extravasation and limit NO scavenging and vasoconstriction. The aim of this study was to assess vasoactive effects of OxyVita C on systemic blood pressures and cerebral pial arteriole diameters. Anesthetized healthy rats received four intravenous (IV) infusions of an increasing dose of OxyVita C (2, 25, 50, 100 mg/kg) and hemodynamic parameters and pial arteriolar diameters were measured pre- and post-infusion. Normal saline was used as a volume-matched control. Systemic blood pressures increased (P ≤ 0.05) with increasing doses of OxyVita C, but not with saline. There was no vasoconstriction in small (<50 µm) and medium-sized (50-100 µm) pial arterioles in the OxyVita C group. In contrast, small and medium-sized pial arterioles vasoconstricted in the control group. Compared to saline, OxyVita C showed no cerebral vasoconstriction after any of the four doses evaluated in this rat model despite increases in blood pressure.0Comments 0Citations
- "It has an oxygen affinity (P50) of 6 mm Hg  and retention time of about 3 hours in the rat . The OxyVita hemoglobin can be stored at a wide range of temperatures (−80 to −45 °C) without changing its physiochemical properties and can be formulated in preparations using various physiological fluids (Lactated Ringer's or saline ). This versatility makes this oxygen-carrier amenable for use in different situations including austere non-hospital military environments. "
[Show abstract] [Hide abstract] ABSTRACT: OxyVita Hb is a new generation hemoglobin based oxygen carrier (HBOC) produced through modification of a zero-linked polymerization mechanism using activators which incorporate cross-linked bovine tetramer hemoglobin into "super-polymeric" macromolecules (Average molecular weight = 17 MDa) for the purpose of oxygen delivery when whole blood or packed red cells are not available. This molecular design approach was generated in order to address several fundamental biochemical and physiological weaknesses of previous generations of HBOCs. Observation during pre-clinical and clinical studies provided evidence that these early generation acellular HBOCs were directly associated with loss of retention within the circulatory system, extravasation across endothelial tissue membranes due to their small molecular size leading to arterial and venous vasoconstriction with coupled increases in mean arterial pressure (MAP). The inherent increase in molecular size and structural stability of the OxyVita Hb is a direct response to addressing these serious weaknesses that have occurred during the evolution of HBOC development within the past two decades. The nature of the zero-linked synthetic route eliminates any chemical linkers remaining in the product, eliminating side reaction concerns, such as reversibility and decomposition due to weak chemical bonds, dependency on temperature and pressure, and residual toxicity.0Comments 1Citation
- "Less than 5% methemoglobin is present in the final product. Further studies [15,25] using a wide range of physical and chemical methods over the last several years have clearly shown that the polymeric hemoglobin constituting the OxyVita Hb solution, the OxyVita Hb powder form and the Small Volume Resuscitation Fluid (SVRF) are equivalent in all their properties as evident inTable 2. The SVRF is composed of OxyVita Hb (9 g%) and NaCl (7.5 g%). The uniqueness of the chemical methods of synthesis of OxyVita Hb and its resultant molecular size have had profound impacts on some of the most important issues in the field of HBOC development. "
- [Show abstract] [Hide abstract] ABSTRACT: Hemoglobin-based oxygen carriers (HBOC) are being developed to provide the oxygen necessary in clinical situations when whole blood is not available. The safety and effectiveness of each HBOC must be determined before clinical approval. In the past several years animal studies have been conducted with zero-linked polymers to evaluate their effectiveness at delivering oxygen in vivo. Studies have addressed issues associated with interstitial extravasation, cerebral ischemia and blood flow, resuscitation, and coagulation interactions. Several of the investigations reviewed are based on early preparations of zero-linked polymerized bovine hemoglobins (ZL-HbBv), which contained a wide range of high-molecular-weight polymers. Recent studies using the Oxyvita product OxyVita Hb, which contains a more homogenous population (97%) of large-molecular-weight species (~17 MDa), are also included in this review.0Comments 13Citations