Combined Exposures to Hydrogen Cyanide and Carbon Monoxide in Army Operations: Final Report (2008)

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Appendix C Proposed Experiments to Study Effects of Rapid Changes in Inspired Carbon Monoxide Concentrations and Effects of Rapid Changes in Pulmonary Ventilation The committee recommends that these studies be performed in a pulmonary function laboratory. Inspired and mixed expired gas carbon monoxide (CO) concentrations and venous blood carboxyhemo- globin (COHb) should be monitored. Gas CO levels can be measured using infrared- or gas- chromatographic methods. Blood COHb should be measured using gas chromatography. Subjects should be nonsmokers, male, ages 20-30 years, and in good physical condition. About 10 subjects should be studied. EXPERIMENT 1. EFFECTS OF RAPID CHANGES IN INSPIRED CO CONCENTRATION AT A CONSTANT RATE OF VENTILATION In the first part of Experiment 1 (Exp.1A), pulmonary CO uptake will be directly measured under conditions where inspired CO contours duplicate those present in the armored-vehicle cabin at constant ventilation. These results should allow determination of relevant inspired CO values that can be used in second part of Experiment 1 (Exp.1B) to evaluate the Coburn-Forster-Kane (CFK) equation. Exp. 1A: The Relationship of Inspired CO Concentrations to CO Uptake Subjects will be studied at rest; minute ventilation will be monitored using standard methods, and inspired and mixed expired gas CO concentrations and volumes will be measured. CO uptake will be cal- culated from differences in inspired and mixed expired gas CO concentrations multiplied by the ventila- tion rate (minute ventilation). Thus, it will be possible to access effects of rapid changes in inspired CO concentration on uptake of CO. This experiment requires technology that can rapidly change inspired CO concentrations, mimicking CO spikes and varying inspired CO concentrations for different time dura- tions. Inspired CO contours and concentrations that mimic those in the armored-vehicle cabin, using ei- ther a single firing or multiple firing sequences, will be studied. These data will allow determination if rapid increases in CO concentrations during spikes are taken up via the lungs, and effects of slower inter- spike CO increases on CO uptake. It is anticipated that an equation can be developed that can be used in determining errors inherent in the use of the CFK equation by converting rapid changes in inspired CO concentrations into an “average” or buffered alveolar gas CO concentration that drives pulmonary CO uptake. 35 

Combined Exposures to HCG and CO in Army Operations: Final Report Exp. 1B: Evaluation of the CFK Equation The same experiments will be performed as described in Exp. 1A, but, in addition, in these ex- periments venous blood will be sampled each minute before, during, and after CO exposures. Relevant “normalized” inspired CO concentrations to be plugged into the CFK equation will be determined using approaches obtained in Exp. 1A. Other terms—lung diffusing capacity, alveolar partial pressure of O2, and mean pulmonary capillary O2Hb% saturation—can be assumed. A normal pulmonary dead space can be assumed to allow calculation of alveolar ventilation from total ventilation measurements. In these short time-duration experiments, venous blood COHb levels reflect uptake and time-dependent mixing in body stores, including blood and muscle myoglobin stores. Because the CFK equation assumes complete mix- ing in body stores, measured blood COHb levels used in comparing values calculated using the CFK equation should be obtained at least 5 minutes after cessation of CO uptake. COHb values calculated us- ing the CFK equation will be plotted versus measured venous blood COHb. EXPERIMENT 2: EFFECTS OF RAPID CHANGES IN VENTILATION AT A CONSTANT INSPIRED CO CONCENTRATION These experiments will be similar to those described above except that inspired CO will be kept constant after a step increase and effects of changes in ventilation on CO uptake and increases in blood COHb will be determined. These experiments will be performed with the subject standing or running on a treadmill. After a control rest period, subjects will start exercising using estimates of work performed by armored-vehicle personnel. After increased ventilation has become constant, CO will be added to inspired air giving concentrations of 50 to 200 parts per million (ppm). This will be followed by reducing the workload to resting level and removal of CO from inspired gas. Venous blood will be taken every minute for COHb analysis. CO uptake will be determined as above from measurements of inspired and mixed expired gas CO concentration. Repeats of these experiments at different workloads and time durations, will allow determination of effects of rapid changes in ventilation on CO uptake and on blood COHb lev- els. To evaluate the CFK equation, the same approach as above will be used. Inspired CO is the con- stant value used in each run, and alveolar ventilation is the measured value minus the assumed dead space. COHb calculated using the CFK equation will be compared with measured venous blood COHb obtained 5 minutes after removal of CO from inspired gas. EXPERIMENT 3: EFFECTS OF SIMULTANEOUS INCREASES IN INSPIRED CO CONCENTRATION AND VENTILATION ON CO UPTAKE, VENOUS BLOOD COHb, AND COHb PREDICTED BY THE CFK EQUATION The goal of these experiments is to duplicate experiments described in Experiments 1 and 2 but under conditions of simultaneous rapid changes in ventilation and inspired CO. After control data are ob- tained, the subjects will start exercising, and inspired CO will be increased. CO increases in different ex- periments will be in the same range as found during and following canon firing. This will be followed by cessation of both exercise and CO exposure. The approaches used to compare venous COHb increases with those predicted by the CFK equations will be identical to those described above. 36