Huge Compact Soluble Molecules: A New Old Concept to Develop an Oxygen Carrying Blood Substitute

Abstract

Some primitive animals have compact huge soluble oxygen binding molecules in extracellular solution for oxygen transport. As this old principle of nature works without complication it is tried to transfer it to man using native human hemoglobin. There are a lot of strong indications that human hemoglobin associates in high concentration (> 20 g/dl). So, a procedure was elaborated to covalently fixate the associates. A molecular weight higher than 6 ± 106 dalton is achieved in a 97% yield as evidenced by chromatography. Performing ultrafiltration a cut-off retentat at 300,000 dalton has a yield of 80%. Starting with outdated blood the oxygen pressure at half saturation of this polymer is 9.5 mmHg (in vivo conditions) without manipulating the oxygen affinity of the binding sites. The cooperativity of the polymer is decreased. Presumably known complications with extracellular hemoglobin solution (e.g. high viscosity, low residence time, oncotic interference) are avoided by applying the “new” principle.