Biological Consequences of Cross-linked Hemoglobin in Animal Models of Surgery and Endotoxemia

Abstract

Cross-linked purified human hemoglobin produced by several companies has been administered successfully to multiple individuals in phase I clinical trials and is now undergoing evaluation in phase II studies. Since hemoglobin will be administered in acute care settings to patients who may have limited cardiovascular reserve or who are septic, its potential biologic activities other than the ability to carry oxygen require consideration. Hemoglobin has an affinity for nitric oxide (NO), a gas with multiple physiologic functions, that is orders of magnitude greater than for oxygen. NO has a dominant role as a vasodilator in regulating blood pressure, as well as in inhibiting adhesion and aggregation of platelets and leukocytes (Moncada and Higgs 1993).