The Development of a Second-Generation, Designer, Recombinant Hemoglobin

摘要

The first-generation hemoglobin therapeutics, most of which were created more than 10 years ago, were designed to make a solution that looked identical to hemoglobin contained within a red blood cell. Numerous issues have been raised with their experimental use such as pulmonary and systemic vasoactivity, extravasation of hemoglobin, serum enzyme increases, adverse effects on gastrointestinal motility, generation of myocardial lesions, and potential interactions between hemoglobin and endotoxin. In retrospect, these physiologic effects are not unexpected, since it is now known that an inherent property of all natural (wild-type) hemoglobins is their ability to interact with nitric oxide (NO), secondary to extravasation of the hemoglobin into parenchymal tissue.