Carbon Dioxide Accumulation during Small Animal, Whole Body Plethysmography: Effects on Ventilation, Indices of Airway Function, and Aerosol Deposition

Abstract

Barometric (whole body) plethysmography is used to examine changes in ventilation and breathing pattern in unrestrained animals during exposure to therapeutic or toxic aerosols. Whole body plethysmographs (WBP) may be operated with a bias flow in order to maintain an adequate supply of oxygen and remove expired CO(2). However, some aerosol generation and delivery methods may require operation of the WBP without bias flow, which would artificially deplete aerosol concentration. Under these conditions, expired CO(2) accumulates in the plethysmograph and stimulates ventilation, increasing total aerosol deposition, shifting regional deposition, and significantly altering some airway function indices. We characterized these effects in guinea pigs using a commercially available 4.5-L WBP, with and without a 1 L/min bias flow. CO(2)-induced changes in breathing frequency (f), tidal volume (Vt), minute ventilation (Ve), and indices of airway function -- including enhanced pause (penh), flow derived parameter (FDP), and respiratory duty cycle -- were measured. Without bias flow, CO(2) in the plethysmograph increased steadily to 5.4% after 30 min compared to a steady state 0.9% with bias flow. This resulted in a moderate suppression of f, and significant increases in Vt and Ve by factors of 1.5 and 1.4, respectively. Changes in regional deposition were stimulated for 300 mg/m(3) polydisperse aerosols with mass median aerodynamic diameters of 0.3, 1, 3, or 7 microm and geometric standard deviations of 1.7. Percent increase in aerosol deposition from CO(2) inhalation ranged from 24% to 90%, by mass, depending on aerosol size distribution and respiratory tract region. In addition, fractional deposition shifted toward the pulmonary region. Empirical indices of airway constriction, penh and FDP, also were increased significantly to 1.7 and 1.3 times their respective baseline values. The study quantifies the effect of inadvertent coexposure to CO(2) on ventilation, aerosol deposition, and airway function in WBP evaluation of aerosol effects in airway function.

Methods, Measurements, and Interpretation of Animal Lung Function in Health and Disease

“…This observation is in apparent agreement with the findings of Mautz et al (1985a) who demonstrated increased histopathology in the bronchoalveolar duct region of O 3 exposed rats that were exercised. Increased aerosol deposition has also been reported in animals rebreathing CO 2 (Kimmel et al, 2002). In contrast, however, studies in exercised hamsters exposed to a sulfur-colloid aerosol showed no difference in the particle deposition pattern compared to hamsters that were not active during exposure (Harbison and Brain, 1983).…”

Respiration in Sprague-Dawley Rats During Pregnancy

“…The changes in pressure are due to gas compression from breathing mechanics of the animal and gas conditioning from heating and humidification of inspired air, with the gas conditioning being the predominate source for the pressure change (Lundblad et al, 2002;Mitzner & Tankersley, 1998). This method has been used by previous researchers (Kimmel et al, 2002;Mortola & Seifert, 2002;Seifert & Mortola, 2002a, 2002b, 2002cStrohl et al, 1997;Tankersley et al, 1997;Weideman et al, 1996) to measure respiratory parameters in small animals. The technique is advantageous because it is noninvasive and nonstressful, thus allowing repetitive monitoring of the same rats over the entire period of gestation.…”

Airway reactivity response to aged carbon–graphite/epoxy composite material smoke

“…2% in 10 min from expiration (guinea pig) but does not alter significantly the baseline respiratory parameters. 10 With the contribution of CO 2 from the smoke (up to 0.56%), CO 2 levels high enough to alter ventilation may be achieved, particularly near the end of a 10-minute interval between smoke replenishment. However, temporal variations in the observed breathing pattern changes did not appear to coincide with purging the plethysmograph.…”

“…Previous experiments showed that in 10 min the accumulation of CO 2 in the plethysmographs did not significantly change baseline respiratory parameters in guinea pigs. 10 After 30 min of exposure, each plethysmograph was flushed at a rate of 9 l min −1 for 3 min with fresh air to clear the smoke. Breathing parameters were recorded for an additional 30 min.…”

“…Regardless, accumulation of CO 2 in the plethysmograph may have affected some of the parameters being measured. 10 Because the pneumotachographs remained open, pressure build in the plethysmograph was not a confounding factor in the measurement of respiratory parameters. Likewise, depletion of O 2 was not sufficient to cause hypoxic changes in ventilation.…”