Table 1.
Pre-clinical studies investigating the role of acetylsalicylic acid in lung injury
| Reference | Lung injury model | Drug (dose; (pre)-treatment) | Animal (n/group) | Conclusion |
|---|---|---|---|---|
| Leeman et al[26] (1988) | Oleic acid iv | ASA (1 g iv; Treatment) | Dog (n=8 all groups) | ↑ PaO2, ↓venous admixture ↓ intra pulmonary shunt |
| Sigurdsson et al[27] (1989) | Ethanolamine oleate iv. | ASA (10 mg/kg, Pretreatment) | Sheep(n=7 vs 8 control) | prevent PHT prevent lung edema preserved PaO2 |
| Chelucci et al[28] (1992) | Oleic acid i.v. | ASA (10 mg/kg; Pretreatment) | Sheep (n=6 vs 8 control) | no morphological benefit no significant change of static compliance of respiratory system and on flow resistance of the airway at 3h |
| Gonçalves de Moraes et al[29] (1996) | LPS inhalation | ASA (50mg/kg; Pretreatment) | Mice (n=5 or 6) | ↑ inflammation |
| Fukunaga et al[30] (2005) | HCl intrabronchial | ASA (125mg/kg; Treatment and Pretreatment) | Mice (n=3–5) | ↓ inflammation |
| Zarbock et al[31] (2006) | HCL-intratracheal | ASA ( 1 g/kg; Pretreatment) | Mice (n=4–5) | ↓ inflammation ↑ PaO2/FiO2 (mmHg) |
| Jin et al[32] (2007) | LPS inhalation | AT-LX4 (0.7mg/kg; Treatment) | Mice (n=6) | ↓ lung edema ↓ microvascular permeability ↓ Inflammation ↑ survival ( at 72 h) |
| El Kebir et al[33] (2009) | Carrageenan + MPO intratracheal or E. coli intraperitoneal | AT-15 epiLXA4 (200 μg/kg; Treatment) | Mice (n=6–10) | ↓ inflammation |
| Eickmeier et al[34] (2013) | HCL intrabronchial | AT-RvD1 (0,5–5ug/kg; Treatment and Pretreatment) | Mice (n≥3–6) | ↓ lung edema ↓ resistance ↓ inflammation ↑restitution of lung- barrier function |
| Tuinman et al[35] (2013) | LPS intranasal | ASA(12.5 mg/kg) or 100 mg/kg; Pretreatment) | Mice (n=8 all groups) | ASA protects against ARDS. High dose ASA is superior to low-dose ASA. |
| Ortiz-Muñoz et al[38] (2014) | LPS intratracheal | ASA (100mg/kg Pretreatment with or without AT-15 epiLXA4 (100–5000ng; Pretreatment and Treatment) | Mice (n=3–10) | ↓ inflammation ↓ permeability |
| Two-event LPS-primed/MHC 1 mAb TRALI model | ASA (100mg/kg Pretreatment with or without AT-15 epiLXA4 (100–5000ng; Pretreatment and Treatment) | ↓inflammation lower dose: not effective |
||
| Tang et al[39] (2014) | Anti-BSA IgG intratracheal and iv. | AT-RvD1 (500 ng; Pretreatment) | Mice (n=3–5) | ↓ lung injury and mortality |
| Cox et al[40] ( 2015) | Hyperoxia | AT-RvD1 (100 ng; Treatment) | Mice (n=6–10) | ↓ inflammation ↓ permeability |
| Looney et al[36] (2009) | Two-event LPS-primed/MHC I mAb TRALI model | ASA (100mg/kg; Pretreatment) | Mice (n=4–10) | ↓ inflammation ↓ permeability ↓ mortality |
| Caudrillier et al[37] (2012) | Two-event LPS-primed/MHC I mAb TRALI model | ASA (100mg/kg; Pretreatment) | Mice (n=6–9) | ↓NETs (leading to ↓ lung injury) |
ARDS: acute respiratory distress syndrome; ASA: acetylsalicylic acid;AT-LXA4: ASA-Triggered Lipoxin A4 ;AT-15 epiLXA4 : ASA-triggered 15-epi-lipoxin A4 ; AT-RvD1: ASA-triggered resolving D1; ; pAT-RvD1: 17R-hydroxy-19-para-fluorophenoxy-resolvin D1 methyl ester ; BALF-N: Broncho alveolar lavage fluid neutrophil; EVLW: extra vascular lung water; EVPE: lung vascular permeability; HCL: hydrochloric acid; IgG-IC: immune globulin G complex LPS: lipopolysaccharide; NET: neutrophil extravascular traps; Pap: pulmonary artery pressure; PHT: pulmonary hypertension; TRALI: transfusion-related cute lung injury; ↓: decrease; ↑: increase