A Critical Appraisal of Carbon Monoxide Uptake Measurements for the Follow-up of Experimental Respiratory Diseases in the Laboratory Mouse

Adaptation of double-chamber plethysmography to the laboratory mouse was recently proven to yield stable and reliable pulmonary function values. This approach to investigation of the respiratory function in mice owes its success to its decisive advantages in terms of non-invasiveness, practical implementation and generation of quantitative flow/volume measurements and nondisputed airway resistance calculation. When implemented to screen the resistance/susceptibility patterns to pathogens displayed by a panel of mouse inbred strains, the resistance value obtained was indeed able to detect tracheobronchic inflammation and to scale its severity. However, extension of the pathological process to most distal parts of the respiratory system did not translate in further alteration of resistance, suggesting that its value rather reflects constraints acting on airflow in the airways than pathologic processes located in the more distal parts of the lungs. In this context, we hypothesized that a more exhaustive functional picture could be obtained, still noninvasively, by combining double-chamber plethysmography with carbon monoxide (CO) uptake measurements. The feasibility of CO-uptake measurements in mice was demonstrated and the conditions under which reproducibility can be maximized were defined. Differences linked to strain, somatic growth, and sex were examined and discussed, and reference values in growing male and female conscious and healthy BALB/cBy, SJL/J, C57BL/6, C3H/HeN, DBA/2 and 129/Sv mice were given. Finally, double-chamber plethysmography and CO-uptake values were proven to be exquisitely complementary in assessing and dissecting the functional impact of Sendai virus pneumonia in the laboratory mouse.