Human Meconium Has a Pulmonary Vascular and Airway Smooth Muscle Relaxant Effect

Abstract

Meconium aspiration is believed to cause persistent pulmonary hypertension syndrome of the newborn (PPHN) via vasoconstriction, whereas meconium has a relaxant effect on rat tracheal muscle. We evaluated the meconium effect on lung vascular and airway muscle. Three-days old and adult rat 3rd-4th generation arteries and adjacent bronchi were studied in vitro. Fresh homogenized meconium did not induce arterial or airway muscle contraction. In precontracted arteries, meconium induced muscle relaxation that was greater (p < 0.01) in the newborn (53 +/- 5%), when compared with adult vessels (34 +/- 3%). This relaxant response was partially abrogated (p < 0.01) by L-NAME (28 +/- 4%) and enhanced by a superoxide scavenger (55 +/- 4%). Precontracted bronchial muscle relaxed to meconium in vitro and the magnitude of response was greater in the adult when compared with the newborn (p < 0.01). In vitro incubation with meconium (3 h) reduced agonist-stimulated force and enhanced endothelium-dependent relaxation (p < 0.01). Airway meconium instillation followed by mechanical ventilation enhanced thromboxane-induced newborn rat pulmonary arterial muscle contraction in vitro (p < 0.01). We conclude that meconium is a pulmonary vasodilator in vitro Meconium is first noted to be present at 12 wk gestation in humans. It is the by-product of fetal amniotic fluid, lanugo, skin cells, and vernix caseosa swallowing, as well it contains cells derived from the gastrointestinal tract (). Meconium composition also includes four different biliary acids (cholic, chenodeoxycholic, deoxycholic, and lithocholic) and minerals of which copper, zinc, magnesium, calcium iron, and phosphorus are the most common (). In addition, it contains plasmatic proteins such as alpha1-antitripsin and phospholipase A2 (4,5).