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

Objective: To determine the dose-response relationship of almitrine (Alm) o n 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 (F IO2 1.0) pigs underwent induction of ALI by repeated saline washout of surf actant. Animals were randomly assigned to either receive cumulating doses o f Alm intravenously (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 mu g . kg(-1) . min(- 1)) for 30 min each (treatment; n = 10) or to receive the solvent malic aci d (controls; n = 10). Measurements and results: Measurements of pulmonary gas exchange and hemody namics were performed at the end of each infusion period. Alm < 4.0 mu g . kg(-1) . min(-1) improved arterial oxygen pressure (PaO2) (105 +/- 9 mmHg f or Alm 1.0 vs 59 +/- 5 mmHg) and decreased intrapulmonary shunt (Q(s)/Q(t)) (32 +/- 4% for Alm 1.0 vs 46 +/- 4%) (P < 0.05). Alm greater than or equal to 8.0 mu g . kg(-1) . min(-1) did not improve pulmonary gas exchange comp ared to controls. When compared to low doses of Alm < 4.0 mu g kg(-1) . min (-1), high doses greater than or equal to 8.0 mu g kg(-1) . min(-1) decreas ed PaO2 (58 +/- 11 mmHg for Alm 16.0) and increased Q(s)/Q(t) (67 +/- 10% f or Alm 16.0) (P < 0.05). Conclusions: In experimental ALI, effects of almitrine on oxygenation are d ose-dependent. Almitrine is most effective when used at low doses known to mimic hypoxic pulmonary vasoconstriction.