Amiloride impairs lung water clearance in newborn guinea pigs.
To determine whether epithelial ion transport is physiologically important for lung water clearance after birth, the sodium transport inhibitor amiloride or its vehicle saline was given intratracheally to newborn full-term guinea pigs before the first breath. Guinea pigs given saline intratracheally breathed normally and had arterial O2 saturations (SaO2) greater than 94%. In contrast, guinea pigs that had an estimated 10(-4) M intra-alveolar concentration of amiloride had chest wall retractions and 88 +/- 3.6% (SD) SaO2 (P less than 0.01). Extravascular lung water (EVLW) per gram of dry lung weight 4 h after birth was significantly greater in newborns that received amiloride (8.3 +/- 1.1, n = 5) than in those that received saline (5.6 +/- 0.9, n = 7, P less than 0.01). The degree of perivascular fluid cuffing at 25 cmH2O inflation was quantitatively similar in amiloride- and saline-treated animals. The effect of amiloride was dose dependent. Intratracheal amiloride did not affect EVLW in 9-day-old guinea pigs. This study demonstrates that intratracheal amiloride before the first breath results in respiratory distress, hypoxemia, and an abnormally high EVLW. Epithelial sodium transport contributes normal lung liquid clearance after birth.
O'Brodovich
H
H
Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Hannam
V
V
Seear
M
M
Mullen
J B
JB
D000584:Amiloride / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D015633:Extravascular Lung Water / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced; D007231:Infant, Newborn; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D011654:Pulmonary Edema / Q000139:chemically induced; D012127:Respiratory Distress Syndrome, Newborn / Q000139:chemically induced; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels; D000584:Amiloride