bq-123 and Meconium-Aspiration-Syndrome

Acute neonatal pulmonary hypertension is associated with increased activation of the endogenous endothelin pathway. We investigated the role of selective endothelin-A receptor blockade using i.v. BQ-123 in a piglet model of meconium aspiration syndrome. Meconium aspiration was induced in 18 anesthetized piglets. Six controls received no further intervention. Six piglets received 1 mg/kg BQ-123 at 120 min, with the addition of 20 ppm inhaled nitric oxide at 240 min. Six commenced nitric oxide therapy at 120 min, and were given i.v. BQ-123 at 240 min. The total study duration was 360 min. Meconium aspiration resulted in acute pulmonary hypertension and elevated endothelin-1 levels in all animals. There were no changes in pulmonary hemodynamics or endothelin-1 levels beyond 120 min in controls. In the group receiving BQ-123 first, this agent alone reduced the pulmonary artery pressure and pulmonary vascular resistance, and the subsequent addition of inhaled nitric oxide further reduced pulmonary artery pressure. In the group first receiving nitric oxide alone, this reduced the pulmonary artery pressure, and the addition of BQ-123 resulted in a fall in pulmonary vascular resistance. Endothelin-1 levels increased with both agents. BQ-123 was found to be a highly effective pulmonary vasodilator and augmented the effects of nitric oxide in this model of acute pulmonary hypertension.

Topics: Administration, Inhalation; Animals; Antihypertensive Agents; Endothelin A Receptor Antagonists; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Meconium Aspiration Syndrome; Nitric Oxide; Peptides, Cyclic; Receptor, Endothelin A; Swine; Syndrome

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.

Topics: Animals; Animals, Newborn; Endothelin Receptor Antagonists; Endothelin-1; Hemodynamics; Humans; Hypertension, Pulmonary; Infant, Newborn; Meconium Aspiration Syndrome; Peptides, Cyclic; Swine