Endothelin-A receptor antagonist prevents neonatal pulmonary hypertension in meconium aspiration in piglets.
In order to test the hypothesis that endothelin-1 (ET-1) directly contributes to the pathophysiology of pulmonary hypertension induced by meconium aspiration, we randomized 12 anesthetized and paralyzed piglets to receive BQ-123, a selective endothelin-A receptor antagonist (BQ group), or normal saline (NS group) after meconium aspiration. The animals were instilled with meconium mixture (3 mL/kg) via an endotracheal tube, and then given intravenous BQ-123 (2 mg/hr) or normal saline. Plasma ET-1 concentrations, arterial blood gases, and hemodynamics were measured at baseline and at 60, 120, 180, and 240 minutes after instillation. The results showed that plasma ET-1 concentrations were similar in both groups. However, in the BQ group, pulmonary artery pressure was significantly lower after 120 minutes (p < 0.05 at 120 min, p < 0.01 at 180 and 240 min) and pulmonary vascular resistance was significantly lower after 180 minutes (p < 0.01) than in the NS group. No significant difference was found in systemic hemodynamics. These data suggest that ET-1 directly contributes to the pathophysiology of pulmonary hypertension induced by meconium aspiration.
Kuo
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Division of Neonatology, Department of Pediatrics, Chang Gung Children's Hospital, Taiwan.
D000818:Animals; D000831:Animals, Newborn; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007231:Infant, Newborn; D008471:Meconium Aspiration Syndrome / Q000150:complications*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D013552:Swine
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)