In March 2006, a workshop sponsored by the National Heart, Lung, and Blood Institute was convened to identify the role of basic science research in clarifying issues that are impeding progress in the development of hemoglobin-based oxygen carrying (HBOC) solutions. These discussions resulted in a consensus that, although HBOCs have shown clinical promise, various side effects have inhibited further development and regulatory approval, with cardiovascular events being of particular concern. As a consequence, workshop participants focused on formulating research recommendations to better understand and mitigate these side effects. In addition, several important corollary issues were identified, including better understanding of the impact of HBOC infusion on human physiology; the need for rapid, noninvasive methods for the measurement of tissue oxygenation in human patients to better inform transfusion decisions; further investigation of routes and consequences of hemoglobin metabolism; optimization of clinical protocols for HBOC use; and assessment of the impact of HBOC formulation excipients. Also discussed was the possibility and desirability of developing new HBOCs with improved characteristics, such as prolonged functional intravascular persistence, greater stability, and a decreased propensity to generate reactive oxygen species. One practical limitation in this area is the consistent availability of pure, well-characterized HBOC solutions for the research community. This communication summarizes the opinion of workshop participants on these issues and concludes with a list of specific recommended areas of research that could positively impact the development of blood substitutes.
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