Medicine of the Future in America

Histologic Changes of Doxycycline Pleurodesis in Rabbits: Effect of Concentration of Doxycycline (Group 2 vs Group 4)

Marked histologic changes were evident in both the visceral and the parietal pleura (Table 1). The thickness of the visceral pleura was 0.50 ±0.18 (mean±SEM) in the TCN and 0.56 ±0.14 in the DOXY group (Fig 2). These values are significantly greater than the normal values of 0.01 mm but are not significantly different from one another. Visceral pleural thickness was greatest at the interlobar fissures, although this may reflect the changes of two juxtaposed pleural surfaces.

Inflammatory changes, characterized by infiltration with fibroblasts and to a lesser degree with macrophages and lymphocytes, were similar in both the visceral and the parietal pleura. Although loose connective tissue was seen in a few of the animals, most showed a dense infiltration with cells, fibrin, and collagen. Neovascularization was a prominent finding in both pleura. Although it was difficult to quantify the number or size of these capillary spaces, we found no gross differences in neovascularity between the TCN and the DOXY groups. Mesothelial cells were absent from the visceral pleura in all five of the DOXY-treated rabbits but in only two of five TCN-treated rabbits further.

Fibrous bands between the visceral and parietal pleura were extensive in all but two rabbits. These adhesions contained fibrous connective tissue in various stages of maturity. Early stages of fibrosis in these adhesions were typified by a predominance of fibrin with minimal cellularity or collagen deposition. Later stages of fibrosis consisted of dense collagen fibers and an abundance of fibroblasts.
The two rabbits in the TCN group without intrapleural adhesions also had an intact mesothelial surface on the visceral pleura. To compare the effect of concentration of DOXY on the extent of pleurodesis, five rabbits received a high concentration (35 mg/kg) and five rabbits received a moderate concentration (10 mg/kg); in both groups, the pH of the injected solution was acidic (pH 2.0). All animals had bloody fluid in the left pleural space.

Table 1—Histologic Changes in Visceral Pleura

Groups Studied Thickness,mm Cellularity,0-3 Neovascularity,0-3 Adhesions,0-3 MesotheliumIntact
TCN, 35 mg/kg; pH 2.0 0.50 ±0.18 1.2 ±0.2 1.4±0.4 2.6 ±0.4 3/5
DOXY, 35 mg/kg; pH 2.0 0.56 ±0.14 1.0 ±0.3 1.8±0.4 2.8 ±0.2 0/51
DOXY, 35 mg/kg; pH 7.6 0.66 ±0.17 1.4 ±0.2 1.2±0.4 3.0 ±0.0 0/51
DOXY, 10 mg/kg; pH 2.0 0.95 ±0.07 1.2±0.2 1.6±0.4 2.8 ±0.2 1/5
DOXY, 10 mg/kg; pH 7.6 0.59 ±0.24 1.6±0.2 2.2 ±0.2 2.6 ±0.4 3/5


Figure 2. Microscopic section of left lung and visceral pleural surface of rabbit exposed to intrapleural doxycycline 14 days earlier. The visceral pleural width has increased to 0.6 mm (normal value, 0.01 mm) and the mesothelium has been denuded. A portion of intrapleural adhesion is extending from the visceral pleural surface. Using Masson’s trichrome stain, collagen and fibroblasts are stained blue whereas fibrin is pink.

This entry was posted in Pulmonary function and tagged doxycycline, fibrin collagen, pleural space, pleurodesis.
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