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 (VA/Q) 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 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q 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 VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (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 VA/Q distribution.


CONCLUSIONS
The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.
Dembinski
R
R
Department of Anesthesiology, Universitaetsklinikum der RWTH Aachen, Germany. Rolf.Dembinski@post.rwth-aachen.de
Max
M
M
López
F
F
Kuhlen
R
R
Kurth
R
R
Rossaint
R
R
D015765:Almitrine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000139:chemically induced*; D019141:Respiratory System Agents / Q000494:pharmacology*; D013552:Swine; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects*
D000959:Antihypertensive Agents; D019141:Respiratory System Agents; D015765:Almitrine; D011464:Epoprostenol