Low doses of almitrine compared to inhaled nitric oxide (iNO) in an animal model of acute lung injury (ALI): Effects on pulmonary gas exchange

Introduction: In ALI, iNO is effective in improving pulmonary gas exchange by vasodilating ventilated lung regions and thereby reducing intrapulmonary shunt (Q_s/Q_t). Almitrine (Alm), a pulmonary vasoconstrictor has been suggested to reduce Q_s/Q_t by amplification of hypoxic pulmonary vasoconstriction. We compared the effects of iNO and Aim on arterial oxygenation and intrapulmonary shunt in an animal model of ALI. Methods: In 22 anesthetized piglets (25±5 kg), ALI was Induced by surfactant depletion. Animals were paralyzed, ventilated in a volume-controlled mode (FIO₂ 1.0) and were randomly assigned to either receive increasing doses of Aim i.v. (0.5, 1.0, 2.0, 4.0 μg kg^-1min^-1 for a 30 min period each, n=7) or to inhale 20 ppm NO continuously (n=7), or to receive no further treatment (n=8, controls). Statistics were performed by Kruskal-Wallis-ANOVA followed by posthoc comparisons using Mann-Whitney-U test with Bonferroni correction (*denotes p<0.05 compared to controls, # denotes p<0.05 compared to iNO). Results: (Mean ±SEM) Induction of ALI decreased PaO₂ from 542±11 mmHg (pre-lavage) to 68±3 mmHg, and increased Q_s/Q_t from 11±1 to 46±3%. Aim (0.5, 1.0, 2.0, 4.0 μg kg^-1min^-1) induced an increase in PaO₂ to 107±12*, 122±6*, 98±7*, and 73±5 mmHg (corresponding changes in Q_s/Q_t from ALI were -16±6, -21±5*, -16±5, and -7±6%). During iNO, PaO₂ at time points corresponding to Aim infusion periods increased to 102±7*, 108±9*, 110±11*, and 109±10*# mmHg (changes in Q_s/Q_t were -16±5*. -15±4*, -14±5, and -14±6%). Controls remained at low PaO₂ levels of 66±7, 61 ±5, 58±6, and 58±7 mmHg, corresponding changes in Q_s/Q_t from ALI were 1±3, 3±4, 5±7, and 9±5%. During the protocol, n=3 animals from the control group died. Conclusion: In experimental ALI, low doses of Aim (0.5, 1.0 and 2.0 μg kg^-1 min^-1) are as effective as iNO (20 ppm) in improving pulmonary gas exchange. However, higher doses of Aim (4.0 pg kg^-1 min^-1) impaired arterial oxygenation.