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

Abstract

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 undisputed 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 quantify its severity. However, extension of the pathological process to the most distal parts of the  respiratory system did not result in further alteration of resistance, suggesting that its value reflects constraints  acting on airflow in the airways rather 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  non-invasively, 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.