Because of the striking similarity between papain-induced emphysema and human panlobular emphysema both morphologically and physiologically and the further similarity between normal canine and human lungs in the disposition of interstitial septal gaps, alveolar macrophages and type 2 cells which we have demonstrated, it would seem prudent to study this convenient model further. The complexities of the pathogenesis of emphysema need to be probed more extensively in the hope that such efforts may lead to rational preventive pharmacotherapy. Understanding each step in the complicated progression from injury to full-blown emphysema would increase the possibility of developing an agent, such as an enzyme inhibitor or one capable of enhancing antiprotease activity or stimulating repair, that might have a positive influence on the prevention of the disease or in slowing or altering its damaging effects.
We have previously reported evidence favoring the hypothesis that interalveolar pores resulted from the subepithelial degradation of interstitial extracellular matrix. Boren, Pump, Parra et al and Sanderson et al have hypothesized that interalveolar pores were the likely precursors of larger openings, or fenestrae, which have been taken to represent the earliest microscopic findings of pulmonary emphysema. One might therefore expect to find an increase in the prevalence of pores and fenestrae following exposure to papain. That we did not observe this could be accounted for by alveolar collapse and coalescence of alveolar septa, resulting in thickening of the alveolar septum, thus masking the true prevalence of interalveolar pores. Nevertheless, the degree of lung remodeling which might result from pore formation and septal fenestration occurring at septal junctions is theoretically considerably greater than that occurring along the wall between junctions, as shown in Figure 5. buy ortho tri-cyclen
Figure 5. Two-dimensional diagramatic representation of alveolar airspaces as hexagons delineated by alveolar septa. A, hypothesized normal condition. Possible sites of alveolar septal fenestration are shown at S (septum between septal junctions) and J (septal junction). Fenestration at S with retraction of edges of fenestra would theoretically produce coalescence of two airspaces, as shown in B. Fenestration of the septal junction w’ith retraction of the edges of the fenestra would produce coalescence of three airspaces, and hence more rapid lung remodeling, as shown in C.