The histopathologic findings were compared from 20 mg/kg intrapleural tetracycline hydrochloride (TCN) and three doses of intrapleural minocycline hydrochloride (5 10 and 20 mg/kg) (MCN) in just discovered Zealand white rabbits.

The histopathologic findings were compared from 20 mg/kg intrapleural tetracycline hydrochloride (TCN) and three doses of intrapleural minocycline hydrochloride (5 10 and 20 mg/kg) (MCN) in just discovered Zealand white rabbits. Both TCN and MCN produc an early neutrophilic predominant pleural effusion that became mononuclear athwart 48 h. There was no difference in pleural fluid accumulation, number of adhesions, or histologically measured visceral and parietal pleural thickness between TCN and MCN (all p = ns) The TCN 20 mg/kg produc more visceral pleural plaque than MCN 5 mg/kg (p<005) Increasing MCN doses conclusioned in greater pleural fluid neutrophil accumulation. With higher dose MCN greater mesothelial small cavity desquamation and fibroblast proliferation was evident compared to the 5 mg/kg dose. The MCN and TCN show similar histopathologic condition in the rabbit pleura which glance ats that MCN should cause a similar clinical replication in humans.

MCN = minocycline hydrochloride; TCN = tetracycline hydrochloride

Symptomatic pleural effusions fall out frequently in patients with malignancy.[1] Because patients with malignant pleural disease can survive for several month to years, palliative treatment with subdued morbidity and cost are important in their management. Although thoracentesis or tube thoracostomy can transiently relieve dyspnea, chemical-induced pleural inflammation is commonly used to originate pleurodesis and prevent fluid reaccumulation.[2,3]

Tetracycline hydrochloride (TCN) has proven to be an effective, inexpensive pleurodesis agent with minimal morbidity[4-6] The novel pharmaceutical decision to withdraw tetracycline has created a question in the medical community to find cost-effective alternative therapies. While various agents have been utilized, including bleomycin,[7] quinacrine,[8] talc,[9] 5-fluorouracil,[10] thiotepa,[11] and radioisotopes,[1] TCN compares favorably to these in times of efficacy, cost, safety, and ease of administration.

fresh studies have suggested that other tetracyclines, including minocycline (MCN) may be efficacious in the treatment of malignant pleural effusion.[12-14] Preliminary work give an inkling ofs that intrapleural MCN and TCN bring forward a similar degree of pleural symphysis in a rabbit model[15] Using that type we compared the pleural histologic condition and cellular replication after intrapleural instillation of 20 mg/kg TCN and 5 10 and 20 mg/kg MCN

Methods

Forty-eight novel Zealand white rabbits weighing 2 to 3 kg were lightly anesthetized vath 80 to 100 mg of ketamine hydrochloride (Ketalar, Parke-Davis, Morris Plains, NJ) and 025 mg/kg acepromazine (PromAce, Aveco, Fort Dodge, Iowa) via the lateral ear vein. The right chest wall was shaved, and a 10-cm skin incision was made midway between the spine and scapular tip. With aseptic technique, an 18-gauge plastic catheter (Cathlon IV Striped, Critikon, Tampa, Fla) was placed percutaneously into the right pleural space.

Rabbits received intrapleural injection of 20 mg/kg TCN or 5 10 or 20 mg/kg of MCN in 3-ml 09 percent NaCl (Lederle Laboratories, Pearl River, NY) Immediately after instillation, the catheter was remov Postoperative administration of a single dose of 004 mg/kg subcutaneous buprenorphine (Norwich Eaton, Norwich, NY) provided narcotic analgesia for an additional 12 h

Three milliliters of pleural fluid was obtained by the agency of thoracentesis at 24, 48, and 72 h via the fourth to fifth intercostal space ventrolaterally. Total small cavity count was determined by hemocytometry, and differential reckons were performed after cytospin preparation and Leukostat staining (Fisher Diagnostics, Fisher Scientific, Orangeburg, NY)

After 96 h the rabbits were killed with intravenous pentobarbital. Using a ventral midline approach, the rabbits underwent autopsy and the thorax was resect en toto. All visualized pleural fluid was aspirated by the agency of a diaphragmatic incision. The right thorax was go intoed and pleural adhesions were computeed before transection at the midline. The right hemithorax was bisected in the midaxillary plane to permit imaging in a planar view. Photographs were taken of the ventral and dorsal surfaces of the lung and the chest wall surface. The plaque area was planimetrically calculated from the parietal and visceral pleura as a percentage of total parietal and visceral pleural area, respectively upon the Zeiss IBAS 2000 grid image analyzer (Zeiss Inc, Germany).

The lung and hemithoraces were fixed in formalin, and histologic sections were prepared from the parietal pleura at the fourth intercostal space. A transverse circumferential section from the right lower lobe was obtained 1 cm from the lung base. Specimens were embedded in parafin, chop and stained with hematoxylin-eosin and Masson's trichrome stains. Pleural thickness was determined according to the distance from the internal elastica to the liberated pleural space at five random high power fields and averaged for each animal. Mesothelial small room morphology and the extent of mesothelial desquamation were compared between groups

...