Alveolar distribution of nebulized solution in health and lung injury assessed by confocal microscopy

Abstract

Abstract Parenchymal distribution of nebulized drug in healthy and diseased lungs has not, as evident from a literature review, been well characterized. We use a vibrating mesh nebulizer to deliver fluorescein solution in vivo to healthy or intratracheal‐lipopolysaccharide (LPS)‐instilled anesthetized rats in dorsal recumbency, or ex vivo to the lungs of LPS‐instilled rats. Following in vivo nebulization (healthy/LPS‐instilled), we quantify fluorescein intensity distribution by confocal microscopy in standard locations on the surface of freshly isolated lungs. Following LPS instillation (in vivo/ex vivo nebulization), we quantify fluorescein intensity in visibly injured locations. In standard locations, there is uniform, low‐intensity basal fluorescein deposition. Focal regions receive high deposition that is, in upper (cranial), middle, and lower (caudal) locations, 6.4 ± 4.9, 3.3 ± 3.0, and 2.3 ± 2.8 times greater, respectively, than average basal intensity. Following LPS instillation, deposition in moderately injured regions can be high or low; deposition in severely injured regions is low. Further, actively phagocytic cells are observed in healthy and LPS‐instilled lungs. And LPS particularly impairs mechanics and activates phagocytic cells in the male sex. We conclude that a low level of nebulized drug can be distributed across the parenchyma excepting to severely injured regions.

Keywords

• confocal microscopy
• lung injury
• nebulization
• parenchymal distribution