Effect of inhaled prostacyclin in combination with almitrine on ventilation-perfusion distributions in experimental lung injury

Background: Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion ((V) overdot/(Q) overdot)) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone. Methods: Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 mug.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 mug.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and (V) over dot/(Q) over dot distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences. Results: All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and (V) over dot A/(Q) over dot distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (Pao,) increased, whereas intrapulmonary shunt ((Q) over dot (S)/(Q) over dot (T)) decreased (P < 0.05). Combined prostacyclin and almitrine also increased Pao, and decreased (Q) over dot (S)/(Q) over dot (T) (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or (V) over dot A/(Q) over dot distribution. Conclusions: The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 mug.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or (V) over dot/(Q) over dot distribution when compared with prostacyclin or almitrine alone.