Therapeutic role of terbutaline in a rat whole-lung lavage model

Abstract

ABSTRACTWhole-lung lavage (WLL) is the preferred therapy for patients with pulmonary alveolar proteinosis (PAP). However, WLL can cause fluid retention, surfactant lost, and hypoxia. Terbutaline has been shown to accelerate the rate of alveolar fluid clearance and augment surfactant secretion. The present study aimed at investigating effects of terbutaline and oxygen ventilation in rats with WLL. Forty rats were randomly divided into control, ventilation, NS (normal saline) + ventilation, LT (terbutaline in low concentration, 10−4 M) + ventilation, and HT (terbutaline in high concentration, 10−3 M) + ventilation groups. The left thoracic cavity was opened and a cannula was inserted into the left bronchus. The left lung was ventilated, while the right lung was lavaged. Arterial blood gas, electrocardiogram, histological changes, and wet/dry ratio of lung tissues were examined. The concentrations of total protein (TP), total phospholipids (TPL), and disaturated phosphatidylcholine (DSPC) in recovery fluid were measured. For the in vitro study, alveolar type II (ATII) cells were isolated from healthy male rats, incubated for 24 hours, and divided into control, LT, and HT groups and exposed to different concentration of terbutaline (10−4 and 10−3 M) for 2 hours, followed by measuring sodium-potassium adenosine triphosphatase (Na+,K+-ATPase) activity. Oxygen ventilation significantly increased Pao2/Fio2 after lavage in the ventilation group, as compared to control group (249.4 ± 7.9 vs 210.6 ± 9.4; P = .001). Compared with NS + venlitation group, a higher concentration of terbutaline decreased the wet/dry ratio of lung tissues (5.0 ± 0.1 vs 5.6 ± 0.1; P = .007), increased the concentrations of TPL (175.9 ± 14.0 vs 162.0 ± 6.8 mg/L; P = .031) and DSPC (93.2 ± 6.9 vs 70.9 ± 6.2 mg/L, P = .0001) in the recovery fluid, and alleviated hypoxia significantly. Terbutaline in both low and high doses increased Na+,K+-ATPase activity in ATII cells (62.5 ± 2.4 and 62.6 ± 2.8 vs 32.2 ± 2.1 mmol/h/mg protein; P < .01). Theses results show that the administration of terbutaline facilitates alveolar fluid absorption and increases surfactant secretion during lung lavage, the former is partly driven by increasing Na+,K+-ATPase activity. The modified lavage method, with the use of terbutaline and oxygen ventilation, is one of potential therapies for patients with PAP.