Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats

Intoduction
Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. ├Ä╦ø-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether ├Ä╦ø-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT).

Methods
This was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation.

Results
In animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 ± 0.27 versus 4.9 ± 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when 11 of the 36 animals in the HVT group had died as compared with only one out of the 36 animals in the HVT plus dopamine group.

References
  1. Zemans RL, Matthay MA: Bench-to-bedside review: the role of the alveolar epithelium in the resolution of pulmonary edema in acute lung injury. Crit Care 2004, 8:469-477.
  2. Morty RE, Eickelberg O, Seeger W: Alveolar fluid clearance in acute lung injury: what have we learned from animal models and clinical studies? Intensive Care Med 2007, 33:1229-1240.
  3. Goodman BE, Fleischer RS, Crandall ED: Evidence for active Na+ transport by cultured monolayers of pulmonary alveolar epithelial cells. Am J Physiol Cell Physiol 1983, 245:C78-C83.
  4. Cott GR, Sugahara K, Mason RJ: Stimulation of net active ion transport across alveolar type II cell monolayers. Am J Physiol Cell Physiol 1986, 250:C222-C227.
  5. Basset G, Crone C, Saumon G: Significance of active ion transport in transalveolar water absorption: a study on isolated rat lung. J Physiol 1987, 384:311-324.
  6. Effros RM, Hacker A, Silverman P, Hukkanen J: Protein concentrations have little effect on reabsorption of fluid from isolated rat lungs. J Appl Physiol 1991, 70:416-422.
  7. Yue G, Russell WJ, Benos DJ, Jackson RM, Olman MA, Matalon S: Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats. Proc Natl Acad Sci USA 1995, 92:8418-8422.
  8. Guidot DM, Folkesson HG, Jain L, Sznajder JI, Pittet JF, Matthay MA: Integrating acute lung injury and regulation of alveolar fluid clearance. Am J Physiol Lung Cell Mol Physiol 2006, 291:L301-L306.
  9. Crandall ED, Heming TA, Palombo RL, Goodman BE: Effects of terbutaline on sodium transport in isolated perfused rat lung. J Appl Physiol 1986, 60:289-294.
  10. Berthiaume Y, Broaddus VC, Gropper MA, Tanita T, Matthay MA: Alveolar liquid and protein clearance from normal dog lungs. J Appl Physiol 1988, 65:585-593.
  11. Jayr C, Garat C, Meignan M, Pittet JF, Zelter M, Matthay MA: Alveolar liquid and protein clearance in anesthetized ventilated rats. J Appl Physiol 1994, 76:2636-2642.
  12. Folkesson HG, Pittet JF, Nitenberg G, Matthay MA: Transforming growth factor-α increases alveolar liquid clearance in anesthetized ventilated rats. Am J Physiol 1996, 271:L236-L244.
  13. SaldĂ­as FJ, Comellas AP, Pesce L, Lecuona E, Sznajder JI: Dopamine increases lung liquid clearance during mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 2002, 283:L136-L143.
  14. Webb HH, Tierney DF: Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures: protection by positive end-expiratory pressure. Am Rev Respir Dis 1974, 110:556-565.
  15. Dreyfuss D, Basset G, Soler P, Saumon G: Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats. Am Rev Respir Dis 1985, 132:880-884.
  16. Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988, 137:1159-1164.
  17. Corbridge TC, Wood LDH, Crawford GP, Chudoba MJ, Yanos J, Sznajder JI: Adverse effects of large tidal volume and low PEEP in canine acid aspiration. Am Rev Respir Dis 1990, 142:311-315.
  18. Dreyfuss D, Soler P, Saumon G: Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation. J Appl Physiol 1992, 72:2081-2089.
  19. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS: Injurious ventilatory strategies increase cytokines and c-fos mRNA expression in an isolated rat lung model. J Clin Invest 1997, 99:944-952.
  20. Sznajder JI, Ridge KM, Saumon G, Dreyfuss D: Lung injury induced by mechanical ventilation. In Pulm Edema. Edited by: Matthay M, Ingbar D. New York: Marcel Dekker; 1998:413-430.
  21. Palmieri TL, Enkbaatar P, Bayliss R, Traber LD, Cox RA, Hawhins HK, Herndon DN, Greenhalgh DG, Traber DL: Continuous nebulized albuterol attenuates acute lung injury in an ovine model of combined burn and smoke inhalation. Crit Care Med 2006, 34:1719-1724.
  22. Perkins GD, McAuley DF, Thickett DR, Gao F: The beta-agonist lung injury trial (BALTI). A randomized placebo-controlled clinical trial. Am J Respir Crit Care Med 2006, 173:281-287.
  23. Lecuona E, Saldias F, Comellas A, Ridge K, Guerrero C, Sznajder JI: Ventilator-associated lung injury decreases lung ability to clear edema in rats. Am J Respir Crit Care Med 1999, 159:603-609.
  24. Frank JA, Wang Y, Osorio O, Matthay MA: ├Ä╦ø-Adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats. J Appl Physiol 2000, 89:1255-1265.
  25. Barnard ML, Olivera WG, Rutschman DM, Bertorello AM, Katz AI, Sznajder JI: Dopamine stimulates sodium transport and liquid clearance in rat lung epithelium. Am J Respir Crit Care Med 1997, 156:709-714.
  26. Saumon G, Basset G: Electrolyte and fluid transport across the mature alveolar epithelium. J Appl Physiol 1993, 74:1-15.
  27. Suzuki S, Zuege D, Berthiaume Y: Sodium-independent modulation of Na, K-ATPase activity by ├Ä╦ø-adrenergic agonist in alveolar type II cells. Am J Physiol 1995, 268:L983-L990.
  28. Pittet JF, Wiener-Kronish JP, McElroy MC, Folkesson HG, Matthay MA: Stimulation of lung epithelial liquid clearance by endogenous release of catecholamines in septic shock in anesthetized rats. J Clin Invest 1994, 94:663-671.
  29. Crandall ED, Heming TA, Palombo RL, Goodman BE: Effects of terbutaline on sodium transport in isolated perfused rat lung. J Appl Physiol 1986, 60:289-294.
  30. Nin N, Penuelas O, De Paula M: Rats surviving after high tidal volume ventilation show marked reversible pulmonary and systemic inflammation and long-term survival. Proc Am Thoracic Soc 2005, 2:A887.
  31. Matthay MA, Landolt CC, Staub NC: Differential liquid and protein clearance from the alveoli of anesthetized sheep. J Appl Physiol 1982, 53:96-104.
  32. Smedira N, Gates L, Hastings R, Jayr C, Sakuma T, Pittet JF, Mathhay MA: Alveolar and lung liquid clearance in anesthetized rabbits. J Appl Physiol 1991, 70:1827-1835.
  33. Manocha S, Gordon AC, Salehifar E, Groshaus H, Walley KR, Russell JA: Inhaled beta-2 agonist salbutamol and acute lung injury: an association with improvement in acute lung injury. Crit Care 2006, 10:R12.