Purpose: Ventilator-associated lung injury (VALI) decreases active Na+ transport and lung edema clearance. It has been shown that dopamine (DA) increases lung edema clearance by stimulating Na,K-ATPase activity in normal lungs. We set out to study whether and by which mechanisms DA increases lung edema clearance in rats ventilated with high tidal volume (HVT). Methods: We studied whether lung edema clearance could be stimulated by DA (10-4 M) in rats ventilated with HVT for 40 min (up to peak airway pressure of 35 cm H2O) and compared to control rat lungs. Also, we evaluated whether cell microtubular transport system disruption by colchicine is involved in intracellular Na,K-ATPase trafficking after DA stimulation of active Na+ transport. Results: Active Na+ transport and lung liquid clearance decreased ∼50% in HVT ventilated rats (0.25±0.03 vs 0.50±0.03). DA increased lung edema clearance in control rat lungs and rats exposed to HVT ventilation (0.76±0.06 and 0.79±0.06, respectively). The stimulatory effects of DA was blocked by colchicine in control and VALI exposed rats (0.40±0.04 and 0.32±0.06, respectively). Whereas the isomer β-lumicolchicine, which does not affect cell microtubular transport, did not inhibit active Na+ transport and lung edema clearance. Conclusions: DA restored the lung ability to clear edema in rats exposed to VALI, probably by stimulating the recruitment and translocation of Na,K-ATPase pumps from inner pools to the basolateral membranes in alveolar epithelial cells. Clinical Implications: Modulation of lung edema clearance by DA may contribute to the improvement of patients with acute respiratory failure due to pulmonary edema.
|Original language||English (US)|
|Issue number||4 SUPPL.|
|State||Published - Oct 1 1998|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine