The effects of diaspirin crosslinked hemoglobin (DCLHb) on oxygenation, perfusion and resuscitation: preclinical experience

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Preclinical studies of DCLHb, a highly solution of stabilized human hemoglobin tetramers, in animals with normovolemic hemorrhagic shock have demonstrated its ability to quickly restore mean arterial blood pressure, base deficit, and subcutaneous and mucosal pO₂ to baseline levels or higher. In addition, DCLHb has been shown to be capable of preserving normal gut architecture, decreasing bacterial translocation, increasing blood flow to key tissues and organs, and decreasing mortality in some models.

Administration of DCLHb to hemorrhaged animals may serve to create a small shift in blood flow from the muscle, resulting in a large increase in flow to vital organs. This shift may have a significant beneficial effect in certain indications, such as shock, and result in maintenance of vital organ perfusion. A further study of DCLHb as a low-volume resuscitation agent in severe hypovolemic, hemorrhagic shock in pigs demonstrated the agent's ability to improve gut microvascular oxygenation. In this study, palladium porphyrine phosphorescence was used as a marker of microvascular pO₂, the results indicated that DCLHb restores microvascular oxygenation to pre-hemorrhagic levels.

The studies outlined above and others have shown the ability of DCLHb to maintain vital organ perfusion consistently. This property of DCLHb may be explained in part by examining its pharmacological characteristics. For example, DCLHb has a pressor effect, involving a number of different autocrine systems in the body, including interactions with nitric oxide, endothelin, and the α-adrenergic system. DCLHb appears to work through multiple endogenous systems and mechanisms, each of which probably interact.

In summary, studies in animal models of hemorrhagic shock indicate the DCLHb has oxygen-carrying capabilities similar to fresh blood and has the potential to treat blood loss and ischemic situations, such as hemorrhagic shock, in humans. Trials are underway to investigate the safety and efficacy of DCLHb in such patient populations.