Gross and Histologic Changes in the Developing Rabbit Subglottis in Response to a Controlled Depth of Injury

Abstract

OBJECTIVE: Our goal was to determine the effects of both perichondrial and intracartilaginous injury in the developing rabbit subglottis versus normal development. DESIGN: We conducted a descriptive, pilot study of changes in the shape and histology of the subglottis after a controlled depth of injury in 27 New Zealand White rabbits, ages 4 weeks, 8 weeks, and 1 1/2 years. INTERVENTION: Within each age group, 3 animals underwent no surgery, 3 underwent perichondrial injury, and 3 underwent intracartilaginous injury. RESULTS: Perichondrially injured animals in the 4-week age group developed a marked abnormality in the shape of the cricoid cartilage in the injured region. Cartilage of the perichondriallly injured animals in the 8-week and 1 1/2-year groups became histologically consistent with fibrous tissue. The cartilage of all animals that underwent intracartilaginous injury was replaced with fibrous tissue. CONCLUSION: In this observational study, we identified 3 relevant findings. First, the responses of the cartilage to a perichondrial injury suggest that the luminal soft tissues may exert some morphologic control in developmentally young animals. Second, only the 4-week-old group's cartilage was tolerant of a perichondrial injury with continued growth of the ring. Third, no animal's cartilage could withstand an intracartilaginous injury regardless of age. Acquired or congenital cricoid cartilage abnormalities are a frequent source of airway distress in both pediatric and adult populations. Narrowing of the cricoid cartilage, as seen in subglottic stenosis (SGS), creates a significant increase in morbidity and mortality rates 1 with an array of surgical interventions described extensively in the otolaryngology literature. The acquired form of SGS usually is iatrogenic, resulting from prolonged intubation or surgical intervention. Few published reports exist describing the histologic changes associated with SGS. Of the published studies, the source of SGS appears to be both cartilage ring abnormalities and concomitant mucosal fibrosis. 2–5 Histologic examination of injured cricoid samples suggests that the abnormal cricoid growth and development may be due to a combination of (1) inflammation within the cartilage leading to loss of chondrocytes, (2) replacement of the cartilage with fibrosis leading to decreased cartilage extracellular matrix and loss of structural support, and/or (3) alterations in the shape of the ring. It is generally accepted that intubation is better tolerated in younger patients than in older patients. Premature infants can be intubated for up to 4 to 5 months, but adults can be intubated for a maximum of 2 to 3 weeks before an alternate airway is sought. However, no exact guidelines exist for the duration of intubation as a function of age. Even physicians who care for intubated patients disagree about when to consider tracheotomy. We began our series of experiments attempting to understand the biochemical changes that would explain the difference in tolerance to intubation and the mechanisms behind loss of the structural support of the cricoid ring. In preparing the experimental substrate for these studies, we identified an interesting age-dependent and depth of injury-dependent morphologic change in the rabbit subglottis that was not expected. Biochemical changes in the rabbit subglottis will follow in future reports; however, herein we report on the observed morphologic changes. Due to the limited number of animals in this study, the data presented represent a pilot study.