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Hemospan: Design Principles for a New Class of Oxygen Therapeutic
Author(s) -
Vandegriff Kim D.,
Winslow Robert M.
Publication year - 2009
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/j.1525-1594.2008.00697.x
Subject(s) - hemoglobin , oxygen transport , oxygen delivery , oxygen , vasoconstriction , chemistry , medicine , anesthesia , biochemistry , organic chemistry
Hemoglobin‐based oxygen carriers have been under development for decades, but safety concerns have prevented commercial approval. Early designs for modified hemoglobins by polymerization or intramolecular cross‐linking reactions increased molecular size and decreased oxygen affinity, but all exhibited side effects of vasoconstriction and reduced blood flow. A new strategy has been established by applying principles of oxygen transport to cell‐free hemoglobin. Sangart has developed a new oxygen therapeutic, Hemospan, using site‐specific, poly(ethylene) glycol conjugation chemistry designed on two principles: (i) increased macromolecular size to prolong intravascular retention time, and (ii) increased oxygen affinity to prevent premature oxygen offloading in arterioles. In contrast to early‐generation products, Hemospan infusion maintains normal arteriolar vascular tone and capillary flow. Phase I and Phase II clinical trials have been completed, showing that Hemospan is well‐tolerated in humans, with evidence of efficacy to impart hemodynamic stability in surgical patients under anesthesia. Phase III trials in orthopedic surgery have recently completed enrollment in Europe.