Effect of histamine on lung mechanics in sheep. Comparison of aerosol and parenteral administration

The purpose of this study was to examine the effects of parenteral and aerosol histamine on lung mechanics in sheep. Eleven sheep were chronically prepared with pulmonary arterial (PA) and left atrial (LA) catheters, a tracheostomy, and a silastic envelope in the pleural space. Unanesthetized sheep were studied in a pressure-compensated integrated-flow whole-body plethysmograph, and measurements of dynamic lung compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC) were made. Histamine was infused through PA or LA catheters or given as an aerosol at increasing concentrations until Cdyn decreased by 35%, RL doubled, or FRC increased by 25%. Parenteral histamine caused a reproducible decrease in Cdyn, a variable increase in RL, and no change in FRC. There were no significant differences between the LA and PA infusions. Aerosol histamine had similar effects to parenteral histamine, except some sheep did show an increase in FRC. Repeat studies in 3 animals showed PA histamine infusions to be highly reproducible, whereas changes associated with aerosol histamine were slightly less reproducible. Among sheep there was a several hundredfold range in responsiveness to either aerosol or parenteral histamine. There was a significant correlation (r = 0.98, p less than 0.001) between the parenteral histamine dose required for a response and the aerosol dose. These data were interpreted as suggesting that airway responsiveness to histamine is an inherent physiologic property.