Effects of erythromycin on the rabbit pleura: its potential role as a pleural sclerosant.

Tetracycline (TCN) has been considered the agent of choice for pleurodesis in patients with symptomatic malignant pleural effusions and recurrent pneumothoraces. However, the intravenous form of TCN used for pleurodesis is no longer available. Erythromycin, like TCN, often produces irritation when administered intravenously. In view of these irritant properties, we tested the effect of erythromycin as a pleural sclerosant in rabbits as compared with TCN. Normal saline was used as a control. Adult rabbits weighing 2.5 to 3.0 kg underwent sterile placement of a silastic pleural tube in the right pleural space. Erythromycin (n = 17) or TCN (n = 6), each in doses of 35 mg/kg in 2 ml saline, was administered via the tube. Control animals (n = 6) received 2 ml saline. The chest tubes were left in place for removal of pleural fluid and to maintain lung expansion. Animals were killed 8 d after receiving the various treatments, and their pleural surfaces were examined grossly and histologically. Numerous adhesions were present between the visceral and parietal pleurae in all animals receiving erythromycin and TCN, but not in those receiving saline. On light microscopy, pleurae treated with erythromycin or TCN were histologically identical, showing inflammation, edema, and fibroblast proliferation in the submesothelial tissues. The saline-treated animals had a normal pleura. Because erythromycin produced pleural inflammation and adhesions within 8 d of treatment, we propose that it may have a potential role as a pleural sclerosant.

Independent lung ventilation with a single ventilator using a variable resistance valve.

Independent lung ventilation using two ventilators has been attempted in the treatment of acute respiratory failure due to unilateral lung disease. However, this method has been found to be cumbersome and difficult to use. We reasoned that a bifurcated endotracheal tube with a variable resistance valve may enable us to change the inspiratory airway pressures and, hence, the inspired tidal volume to one lung using a single ventilator. We tested this hypothesis in eight anesthetized sheep and created a bronchopleural fistula in one lung as a model of unilateral lung disease. A bifurcated endotracheal tube was placed to separate the ventilation to each lung and, through a "Y" connector, both right and left lungs were ventilated simultaneously with a single ventilator. A variable resistance valve was placed between the "Y" connector and the tube ventilating the experimental lung with bronchopleural fistula. With a ventilator-generated peak inspiratory pressure of 31 +/- 2 cm H2O, the airway pressure distal to the valve was randomly changed from 31 cm H2O to 23 +/- 2, 15 +/- 1, 8 +/- 1, and 0 cm H2O. This resulted in progressive diversion of tidal volume from the experimental lung to the control lung and an increase in exhaled tidal volume due to a decrease in air leak from the bronchopleural fistula. These data suggest that a variable resistance valve may be used for independent lung ventilation using a single ventilator.

Streptococcus pneumoniae-induced pulmonary hypertension and systemic hypotension in anesthetized sheep.

Because some patients with Streptococcus pneumoniae bacteremia may present with shock, we reasoned that this organism may produce substances that cause shock. To test this hypothesis, type III pneumococcus supernatant, suspended in 10 ml of sterile water, was infused over 1 min in 8 adult anesthetized sheep. Normal saline was used as a control and had no effect on any of the hemodynamic parameters. Infusion of supernatant resulted in a precipitous fall in cardiac output from a control value of 4.25 +/- 0.54 to 2.80 +/- 0.43 (SE) l/min, a fall in mean systemic arterial pressure from 70 +/- 4 to 49 +/- 8 mmHg, and an increase in the mean pulmonary arterial pressure from 13 +/- 2 to 23 +/- 4 mmHg within 1 min after the infusion was completed. The peak hemodynamic effects were observed at approximately 3 min and returned to normal within 10 min after the infusion was completed. The thromboxane B2 level increased from a control value of 10 +/- 5 to 156 +/- 43 pg/ml at 3 min after the infusion was completed and decreased to 63 +/- 34 pg/ml at 20 min. A second identical dose of pneumococcal supernatant, repeated within 2 h of the first dose, had no effect on hemodynamic variables. Pretreatment with indomethacin, 5 mg/kg body wt, completely blocked the hemodynamic effects of pneumococcal supernatant (n = 3 sheep). Thus, we conclude that S. pneumoniae supernatant contains substances that cause septic shock syndrome through the synthesis of arachidonic acid metabolites and that a sublethal dose of the supernatant causes rapid tachyphylaxis.