Effects of inhaled nitric oxide and intravenous almitrine in an animal model of acute lung injury

Objective: To determine dose-dependent effects of intravenous almitrine dur ing inhaled nitric oxide (iNO) in an animal model of acute lung injury (ALI ). Design: Prospective, randomised, controlled study. Setting: Animal laboratory of a university hospital. Methods: 25 anaesthetised, tracheotomized and mechanically ventilated (FIO2 1.0) pigs (25 +/- 5 kg) underwent induction of ALI by repeated saline wash out of surfactant. Animals were randomly assigned to either receive iNO (20 ppm) continuously (NO; n=8) or to receive iNO (20 ppm), followed by cumula ting doses of intravenous almitrine (0.5, 1.0, 2.0, 4.0, and 8.0 mu g.kg(-1 ).min(-1)) each dose for 30 min (NO-ALM; n=8). A third group of animals rec eived no further treatment and served as controls (CTR; n=9). Measurements of pulmonary gas exchange and hemodynamics were performed at the end of eac h treatment period. Statistical analysis was performed using Kruskal-Wallis -ANOVA followed by post-hoc comparisons using Mann-Whitney-U test with Bonf erroni's correction (p < 0.05). Measurements and results: Induction of ALI decreased PaO2 from 528 +/- 17 t o 65 +/- 5 mmHg (mean +/- SEM) in all animals. Inhalation of NO Induced an increase in PaO2 to 104 +/- 11 mmHg that remained stable throughout the exp eriment (p < 0.05 compared to CTR). In the NO-ALM group, PaO2 was increased to 90 +/- 5 and 83 +/- 5 mmHg during additional infusion of 0.5 and 1 mu g .kg(-1).min(-1) almitrine (p < 0.05 compared to CTR). Higher doses of almit rine (> 1 mu g.kg(-1).min(-1)) impaired PaO2 when compared to NO alone (p < 0.05). Inhalation of NO alone induced a significant and sustained reductio n in mean pulmonary artery pressure (MPAP) (-11 +/- 3% compared to CTR, p < 0.05). In the NO-ALM group, doses of almitrine > 2 mu g.kg(-1) min induced an increase in MPAP (n.s.). Cardiac output and mean arterial pressure rema ined stable in all study groups. Conclusion: In this animal model of ALI, iNO significantly increased arteri al oxygenation. Inhaled NO in combination with incremental doses of almitri ne was not effective in additionally improving pulmonary gas exchange. More over, during iNO, higher doses of almitrine significantly impaired PaO2.