A review of carboxymyoglobin formation: a major mechanism of carbon monoxide toxicity.

Clinical data suggest, and experimental studies indicate direct cardiotoxic effects of carbon monoxide, apart from carboxyhemoglobin formation. Carbon monoxide interactions with cytochrome oxidase and myoglobin are suspect. Of these, myoglobin is the favored tissue target for carbon monoxide binding. On what evidence? Examination of the literature reveals the following: A 16% greater "volume of distribution" (Vd) for carbon monoxide, versus other blood volume indicators, concentrating in skeletal and cardiac muscle; A high myoglobin content in these tissues corresponding to this "excess" Vd for carbon monoxide; Evidence from animals of significant carboxymyoglobin concentrations; Hemeprotein independent changes produced by carbon monoxide which promote carbon monoxide-myoglobin interactions; A high ratio of deoxymyoglobin (carbon monoxide binding form) to oxymyoglobin intracellularly; Direct intercellular measurements of oxymyoglobin saturations and "cycling" in vivo illustrating favorable conditions for carbon monoxide binding; Data indicating decrements in cardiac performance with loss of functional myoglobin; Evidence that myoglobin is important to the proper functioning of cardio-adaptive mechanisms in stress. The total picture of carbon monoxide poisoning must take into account pathogenic effects due to carboxymyoglobin formation.