Dose-dependent effects of almitrine on hemodynamics and gas exchange in an animal model of acute lung injury

Abstract

Objective: To determine the dose-response relationship of almitrine (Alm) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). Design: Prospective, randomized, controlled study. Methods: Twenty anesthetized, tracheotomized and mechanically ventilated (FIO2 1.0) pigs underwent induction of ALI by repeated saline washout of surfactant. Animals were randomly assigned to either receive cumulating doses of Alm intravenously (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 μg/kg-1/min-1) for 30 min each (treatment; n = 10) or to receive the solvent malic acid (controls; n = 10). Measurements and results: Measurements of pulmonary gas exchange and hemodynamics were performed at the end of each infusion period. Alm < 4.0 μg/kg-1/min-1 improved arterial oxygen pressure (PaO2) (105 ± 9 mmHg for Alm 1.0 vs 59 ± 5 mmHg) and decreased intra-pulmonary shunt (Q(s)/Q(t)) (32 ± 4% for Alm 1.0 vs 46 ± 4%) (P < 0.05). Alm ≥ 8.0 μg/kg-1/min-1 did not improve pulmonary gas exchange compared to controls. When compared to low doses of Alm < 4.0 μg/kg-1/min-1, high doses ≥ 8.0 μg/kg-1/min-1 decreased PaO2 (58 ± 11 mmHg for Alm 16.0) and increased Q(s)/Q(t) (67 ± 10% for Alm 16.0) (P < 0.05). Conclusions: In experimental ALI, effects of almitrine on oxygenation are dose-dependent. Almitrine is most effective when used at low doses known to mimic hypoxic pulmonary vasoconstriction.