Report on the Relative Affinity Constant (M) of Hemoglobin for Carbon Monoxide in the Animal World: A Comparative Review with a Meta-Analysis Based on a Systematic Review

Delvau, Nicolas [UCL] Penaloza-Baeza, Andrea [UCL] Liistro, Giuseppe [UCL] Thys, Frédéric Mégarbane, Bruno Hantson, Philippe [UCL] Roy, Pierre-Marie

The Haldane M-value is the ratio of half-saturation pressures for O2 and CO (PO2/PCO) and is a key value of physiological and pathological models exploring CO metabolism or exposure to CO. Nevertheless, the M-values obtained from different studies and different species appear to be inconsistent. A better estimation of M-values and a consideration of interspecies variation will ensure the accuracy of CO study results and allow reliable models to be constructed. We performed a systematic review and meta-analysis in order to determine and compare M-values according to species and experimental conditions. We used electronic libraries (PubMed/Embase/JSTORE) from 1895 to January 2016. For each article, we collected the following parameters: species, age, temperature, pH, atmospheric pressure, concentration of 2,3-diphosphoglycerate (2,3-DPG) or methemoglobin, and type of hemoglobin. The systematic review found 25 articles addressing the M constant, including 135 with individual data and 51 with mean values concerning mammals, laboratory animals, fish, fetal hemoglobin and invertebrates. M-values at a physiological temperature and pH were assessed only for adult (137 [119–153]) and fetal (135 [112–168]) sheep, dogs (215 [193–218]), mice (194 [118–278]) and rats (191 [177–200]). A correlation between M-values and temperature was confirmed for sheep and horses. A correlation between M-values and pH could not be inferred because there was a lack of data. M-values varied according to species. Only the influence of temperature was confirmed. A formal measurement of the M constant in the given experimental conditions should be performed for each animal model study of CO. Further homogeneous studies are necessary to compare the M-values of different animals.