Clinical Potential of Nonhemoglobin Oxygen Therapeutics in Cardiac and General Surgery

Abstract

Significant efforts have been made over the past 70 years to find a solution that could substitute for blood. Over the years, the focus has shifted to developing a solution capable of delivering oxygen to the tissues. Fluorocarbons (FC) are highly inert solutions with a high solubility for all gases, making them a prime candidate to become such an oxygen delivery agent. Although clinical research efforts into the use of these agents as substitutes for blood transfusions continue at present, the rapid disappearance of emulsified FCs from the vascular space and accumulation in the liver and spleen may well limit their usefulness as transfusion substitutes. Because of their ability to dissolve significant quantities of oxygen and carbon dioxide, these agents may be more attractive as oxygen delivery agents during periods of local or global organ ischemia, including preservation of organs for transplantation. FCs have also been tested in animal models of cardiopulmonary bypass, and may be efficacious in adsorbing the gases present in air emboli. Recently a second class of oxygen therapeutics (allosteric modifiers) has been developed, and these agents enhance oxygen delivery by shifting the oxygen dissociation curve to the right, thus increasing tissue PO(2). Allosteric modifiers have been shown to effectively shift the p50 of hemoglobin 10mm Hg at clinically relevant dosages, and have been shown (in animal models) to reduce cerebral infarct size following carotid ligation and to improve myocardial performance following myocardial ischemia. Despite significant research efforts, however, none of the solutions under development are currently approved for clinical use by the Food and Drug Administration, with the exception of myocardial contrast imaging agents.