Intravenous immunoglobulin g attenuates pulmonary hypertension but induces local neutrophil influx in meconium aspiration in piglets.
BACKGROUND
Pulmonary hypertension and inflammation are well-identified pathogenetic features in meconium aspiration syndrome of newborns, but current approaches to their treatment or prevention are still often unsatisfactory.


OBJECTIVE
To investigate the possible protective effects of human intravenous immunoglobulin G (IVIG) on the hypertensive and inflammatory lung injury in severe neonatal meconium aspiration.


METHODS
Eleven newborn (10-12 days old) ventilated and catheterized piglets that received an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture of human meconium were studied for 6 h. IVIG was infused in 5 piglets 30 min before meconium administration, and 6 piglets served as controls and received the vehicle only.


RESULTS
Meconium instillation induced a biphasic pulmonary hypertensive response, which was significantly diminished by IVIG pretreatment. Similarly, IVIG improved the oxygenation of the piglets, but the intrapulmonary shunt fraction or systemic hemodynamic parameters did not differ between the study groups, except of a minor decrease in the mean arterial blood pressure caused by IVIG. The blood leukocyte count was comparable in the 2 groups. The lung tissue ultrastructural and histological changes, number of apoptotic cells and phospholipase A2 activity were similar in the 2 groups. The amount of neutrophil accumulation, assessed by myeloperoxidase activity, was however significantly increased in macroscopically damaged lung tissue after IVIG administration.


CONCLUSIONS
Our results thus indicate that IVIG treatment of newborns with severe meconium aspiration significantly diminishes the pulmonary hypertensive response and improves oxygenation, but the effects do not extend to protection of lung cellular injury.
Holopainen
R
R
Research Centre of Applied and Preventive Cardiovascular Medicine (CAPC), Department of Pediatrics, University of Turku, Turku, Finland.
Soukka
H
H
Halkola
L
L
Kääpä
P
P
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology; D001784:Blood Gas Analysis; D001794:Blood Pressure; D006651:Histocytochemistry; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D007958:Leukocyte Count; D008168:Lung / Q000201:enzymology / Q000276:immunology; D008471:Meconium Aspiration Syndrome / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D008854:Microscopy, Electron; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D013552:Swine
D016756:Immunoglobulins, Intravenous; D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2