The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits

Background:Recent phase-contrast X-ray imaging studies suggest that inspiration primarily drives lung aeration and airway liquid clearance at birth, which questions the role of adrenaline-induced activation of epithelial sodium channels (ENaCs). We hypothesized that pressures generated by inspiration have a greater role in airway liquid clearance than do ENaCs after birth.Methods:Rabbit pups (30 d of gestation) were delivered and sedated, and 0.1 ml of saline (S) or amiloride (Am; an ENaC inhibitor) was instilled into the lungs before mechanical ventilation. Two other groups (30 d of gestation) were treated similarly but were also given adrenaline (S/Ad and Am/Ad) before mechanical ventilation.Results:Amiloride and adrenaline did not affect functional residual capacity (FRC) recruitment (P > 0.05). Amiloride increased the rate of FRC loss between inflations (Am: −5.2 ± 0.6 ml/kg/s), whereas adrenaline reduced the rate of FRC loss (S/Ad: −1.9 ± 0.3 ml/kg/s) as compared with saline-treated controls (S: −3.5 ± −0.6 ml/kg/s; P < 0.05).Conclusion:These data indicate that inspiration is a major determinant of airway liquid clearance and FRC development during positive pressure ventilation. Although ENaC inhibition and adrenaline administration had no detectable effect on FRC development, ENaC may help to prevent liquid from re-entering the airways during expiration.

[1]  Kentaro Uesugi,et al.  Surfactant Increases the Uniformity of Lung Aeration at Birth in Ventilated Preterm Rabbits , 2011, Pediatric Research.

[2]  G. Enhorning,et al.  Radiologic evaluation of the premature newborn rabbit after pharyngeal deposition of surfactant. , 1975, American Journal of Obstetrics and Gynecology.

[3]  A. Collett,et al.  Beta-adrenoceptor-mediated control of apical membrane conductive properties in fetal distal lung epithelia. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[4]  P. Davis,et al.  Positive end-expiratory pressure enhances development of a functional residual capacity in preterm rabbits ventilated from birth. , 2009, Journal of applied physiology.

[5]  S. Hooper,et al.  Regulation of lung liquid secretion by arginine vasopressin in fetal sheep. , 1990, The American journal of physiology.

[6]  R. Harding,et al.  FETAL LUNG LIQUID: A MAJOR DETERMINANT OF THE GROWTH AND FUNCTIONAL DEVELOPMENT OF THE FETAL LUNG , 1995, Clinical and experimental pharmacology & physiology.

[7]  L. Jain,et al.  Physiology of fetal lung fluid clearance and the effect of labor. , 2006, Seminars in perinatology.

[8]  D. Mcmillan,et al.  Clearance of liquid from lungs of newborn rabbits. , 1980, Journal of applied physiology: respiratory, environmental and exercise physiology.

[9]  J. Raj,et al.  Lung luminal liquid clearance in newborn lambs. Effect of pulmonary microvascular pressure elevation. , 1986, The American review of respiratory disease.

[10]  O. Helve,et al.  Improvement of lung compliance during postnatal adaptation correlates with airway sodium transport. , 2006, American journal of respiratory and critical care medicine.

[11]  D. Walters,et al.  The Role of Catecholamines in Lung Liquid Absorption at Birth , 1978, Pediatric Research.

[12]  D. Walters,et al.  The role of amiloride‐blockable sodium transport in adrenaline‐induced lung liquid reabsorption in the fetal lamb. , 1986, The Journal of physiology.

[13]  H. O'brodovich,et al.  Amiloride impairs lung water clearance in newborn guinea pigs. , 1990, Journal of applied physiology.

[14]  K K W Siu,et al.  Dynamic imaging of the lungs using x-ray phase contrast , 2005, Physics in medicine and biology.

[15]  Kentaro Uesugi,et al.  Imaging lung aeration and lung liquid clearance at birth , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[16]  P. Davis,et al.  Establishing Functional Residual Capacity at Birth: The Effect of Sustained Inflation and Positive End-Expiratory Pressure in a Preterm Rabbit Model , 2009, Pediatric Research.

[17]  L. Strang Fetal lung liquid: secretion and reabsorption. , 1991, Physiological reviews.

[18]  S. Hooper,et al.  A new design for high stability pressure-controlled ventilation for small animal lung imaging , 2010 .

[19]  R. Bland,et al.  Labor decreases the lung water content of newborn rabbits. , 1979, American journal of obstetrics and gynecology.

[20]  S. Hooper,et al.  Amiloride blocks the inhibition of fetal lung liquid secretion caused by AVP but not by asphyxia. , 1993, Journal of applied physiology.

[21]  G. Miserocchi,et al.  Pulmonary interstitial pressure in anesthetized paralyzed newborn rabbits. , 1994, Journal of applied physiology.

[22]  H. O'brodovich,et al.  Pulmonary oedema fluid induces non‐α‐ENaC‐dependent Na+ transport and fluid absorption in the distal lung , 2002, The Journal of physiology.

[23]  S. Hooper,et al.  Inspiration regulates the rate and temporal pattern of lung liquid clearance and lung aeration at birth. , 2009, Journal of applied physiology.

[24]  H. O'brodovich,et al.  Low expression of human epithelial sodium channel in airway epithelium of preterm infants with respiratory distress. , 2004, Pediatrics.

[25]  E. Schneeberger,et al.  Epithelial solute permeability, ion transport and tight junction morphology in the developing lung of the fetal lamb , 1981, The Journal of physiology.

[26]  Y. Kohmura,et al.  Refraction-enhanced x-ray imaging of mouse lung using synchrotron radiation source. , 1999, Medical physics.

[27]  P. Davis,et al.  From liquid to air: breathing after birth. , 2008, The Journal of pediatrics.

[28]  E. Egan,et al.  Changes in non‐electrolyte permeability of alveoli and the absorption of lung liquid at the start of breathing in the lamb. , 1975, The Journal of physiology.

[29]  Colin J. Morley,et al.  Establishing Functional Residual Capacity at Birth , 2010 .

[30]  D. Paganin,et al.  On the origin of speckle in x-ray phase contrast images of lung tissue. , 2004, Physics in medicine and biology.

[31]  B. Robertson,et al.  Effect of amiloride and surfactant on lung liquid clearance in newborn rabbits. , 1992, Respiration physiology.

[32]  G. Gabella,et al.  Liquid flow across the epithelium of the artificially perfused lung of fetal and postnatal sheep. , 1992, The Journal of physiology.

[33]  D. Walters,et al.  Developmental regulation of lung liquid transport. , 2004, Annual review of physiology.

[34]  K K W Siu,et al.  Dynamic measures of regional lung air volume using phase contrast x-ray imaging , 2008, Physics in medicine and biology.

[35]  S. Hooper,et al.  Effects of elevated fetal cortisol concentrations on the volume, secretion, and reabsorption of lung liquid. , 1995, The American journal of physiology.

[36]  J. Gatzy,et al.  Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice. , 1996, Nature genetics.

[37]  M. Brown,et al.  Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb. , 1983, The Journal of physiology.

[38]  S. Hooper,et al.  Role of Aeration in the Physiological Adaptation of the Lung to Air- Breathing at Birth , 2005 .