Fetal airway wound repair: a new frontier.

PURPOSE: Fetal dermal repair is regenerative and scarless until middle to late gestation, when there is a transition to fibrotic repair. Fetal skeletal muscle and tendon undergo repair with fibrosis similar to the process in adults. This study addresses whether fetal mucosal healing is regenerative and scarless. METHODS: Anesthetized pregnant rabbits underwent laparotomy and controlled hysterotomy at 21 to 23 days' gestation (term is 31 days). A midline thyrotomy was made, followed by cricoidotomy and circumferential cauterization of the subglottic mucosa. A similar insult was applied to weanlings. The data were collected in 2 groups. One group was followed to term and killed at 4 weeks. A second group was killed after 6 days (30 days' gestation). The weanlings were killed at similar points. The larynges were harvested and processed for histological and morphometric analysis. RESULTS: Three litters were followed to term. Of these, 1 was not recovered; in the other two, 7 of 8 manipulated fetuses were found and 3 of 8 were viable. The fourth litter was harvested after 6 days; all 4 injured fetuses were recovered and viable. All animals in the fetal injury groups healed with complete regeneration of the airway mucosa. In contrast, weanlings injured post partum had mucosal inflammation, necrosis, and ulceration; squamous metaplasia and basal cell hyperplasia were also found. There were fibrosis, granulation tissue, and inflammation in the lamina propria; chondritis, cartilaginous necrosis, chondrolysis, and perichondritis were also found. CONCLUSIONS: Fetal airway mucosal healing is regenerative and, thus, scarless. This study provides further support for the thesis that skin and mucosa respond to injury similarly in both the developmental and postpartum stages, and that subglottic stenosis is reasonably thought of as the "hyperplastic scar" of the airway. These results have potential therapeutic applications for mucosal wound management.

Acquired subglottic stenosis--depth and not extent of the insult is key.

In contrast to skin, mucosal wound healing has not been extensively studied. Subglottic stenosis (SGS) is an excellent model for such investigation. The main objective of this pilot study was to develop a chronic model of SGS in a small animal (i.e. rabbit). In so doing, a serendipitous observation was made that the development of SGS is directly related to depth of the injury and is independent of circumferential extent. Animals with deep injury (i.e. deep to the lamina propria, reaching the perichondrium), independent of age and circumferential extent, experienced respiratory obstruction resulting from edema and granulation tissue formation and died or had to be sacrificed in the acute period. This was in contrast to no risk of mortality in the more superficially injured group. Histology was used to characterize this model of SGS. In the mucosal epithelium, or mucosa, changes of inflammation, squamous metaplasia, basal cell hyperplasia, necrosis and ulceration were only seen acutely and total regeneration of the epithelium was achieved by the end of the study period. In contrast, changes within the lamina propria, including chronic inflammatory cellular infiltrates and fibroplasia, were lasting and resulted in fibrotic repair, not regeneration. These findings are quite similar to the healing events in skin and suggest that SGS is the mucosal equivalent of a 'keloid' or, perhaps more appropriately, a 'hypertrophic scar.' Likewise, cartilage degeneration and deformation were persistent markers of the chronic phase of healing. Like the lamina propria, the response to injury was reparative. Therefore, injury to the connective tissue is a critical component of development of SGS.

Anomalies of centriolar derivatives manifest in spermatic flagella and respiratory cilia of the stallion.

Anomalies of centriolar derivatives were identified in ejaculates and testicular and tracheal biopsies of a sterile stallion, using light, scanning, and transmission electron microscopy. LM revealed that over half the sperm population had only a vestigial or no tail, while the rest had tails of variable length and shape. The vestigial tail was represented by its anlage, which was implanted on the nucleus and differentiated up to capitulum and collum stage. The stunted tail had an axoneme and its derivatives, but was short in all tail segments. Regardless of the tail length or shape, virtually all axonemes were devoid of the central tubular complex ("9 + 0" defect). Abnormal tail segmentation was associated with missing or defective flagellar sheaths and a profusion of extraneous dense fibers, which contributed to the knobby, bulbous, or lobuliform tail configurations. The gradient of flagellar anomalies seems associated with the inability of the distal centriole to implant on the plasmalemma, to produce the axoneme, or maintain its growth, and to induce the normal differentiation of periaxonemal structures. In contrast to sperm, the tracheal epithelium displayed moderate changes, which are manifest in circumscribed rarefaction of cilia, increased incidence of compound cilia, and disturbed orientation of cilia regarding the plane of central tubular complex. The tracheal cilia were free of "9 + 0" defect.