Effects of inhaled nitric oxide and intravenous almitrine in an animal model of acute lung injury
Armin Sommerer, Thilo Busch, Steffen Wolf, Hansjörg Lohbrunner, Maria Deja, Udo Kaisers

Objective: To determine dose-dependent effects of intravenous almitrine during 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 washout of surfactant. Animals were randomly assigned to either receive iNO (20 ppm) continuously (NO; n=8) or to receive iNO (20 ppm), followed by cumulating doses of intravenous almitrine (0.5, 1.0, 2.0, 4.0, and 8.0 µg·kg-1·min-1) each dose for 30 min (NO-ALM; n=8). A third group of animals received no further treatment and served as controls (CTR; n=9). Measurements of pulmonary gas exchange and hemodynamics were performed at the end of each treatment period. Statistical analysis was performed using Kruskal-Wallis-ANOVA followed by post-hoc comparisons using Mann-Whitney-U test with Bonferroni’s correction (p < 0.05).

Measurements and results: Induction of ALI decreased PaO2 from 528 ± 17 to 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 experiment (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 µg·kg1·min-1 almitrine (p < 0.05 compared to CTR). Higher doses of almitrine (> 1 µg·kg1·min-1) impaired PaO2 when compared to NO alone (p < 0.05).

Inhalation of NO alone induced a significant and sustained reduction in mean pulmonary artery pressure (MPAP) (-11 ± 3% compared to CTR, p < 0.05). In the NO-ALM group, doses of almitrine > 2 µg·kg1·min-1 induced an increase in MPAP (n.s.). Cardiac output and mean arterial pressure remained stable in all study groups.

Conclusion: In this animal model of ALI, iNO significantly increased arterial oxygenation. Inhaled NO in combination with incremental doses of almitrine was not effective in additionally improving pulmonary gas exchange. Moreover, during iNO, higher doses of almitrine significantly impaired PaO2.

Keywords: Acute lung injury, ARDS, nitric oxide, almitrine, gas exchange, hemodynamics

Applied Cardiopulmonary Pathophysiology 8: 21-27, 1999

Autorenanschrift:

PD Dr. Udo Kaisers
Klinik für Anästhesiologie und operative Intensivmedizin
Charité, Campus Virchow-Klinikum
Med. Fakultät der Humboldt Universität zu Berlin
Augustenburger Platz 1
D-13353 Berlin
Germany
Phone: ++49 (0) 30-4505-1001
Fax: ++ 49 (0) 30-4505-1900
E-mail: udo.kaisers@charite.de