The major goal of this article was to quantify relationships of the carboxyhemoglobin % saturation, a calculated tissue PCO and tissue hypoxia to the binding of carbon monoxide (CO) to canine skeletal and heart ventricular muscle extravascular (EV) tissue under normal conditions and during CO poisoning scenarios. These data are relevant to CO poisoning because CO bound to EV cellular hemoproteins evoke metabolic changes that produce toxic effects. Skeletal and heart muscle EV CO contents were calculated from data obtained from biopsies performed on living anesthetized dogs reported in previous publications (4, 6). Results include normal values of EV CO contents of resting skeletal muscle and heart ventricular muscle, effects of increasing COHb% saturation and a calculated mean tissue PCO on skeletal muscle EV CO binding, and effects of tissue hypoxia evoked by arterial hypoxemia on EV CO binding in both of these tissues. This study is the first that shows that tissue hypoxia-induced CO shifts out of blood resulting in increased EV CO binding are a mechanism that causes CO toxicity. Projections of results to tissue PCO levels occurring during different severe CO toxicity scenarios predict that skeletal muscle EV CO contents could increase as much as 100 to 300 fold.
Carbon Monoxide Binding to the Iron–Molybdenum Cofactor of Nitrogenase: a Detailed Quantum Mechanics/Molecular Mechanics Investigation
