Table 2.
beneficial mechanisms of ASA in pre-clinical studies investigating the role of acetylsalicylic acid in lung injury in relation to the pathophysiology in ARDS
| Study | Pathophysiology in ARDS | Beneficial mechanism of ASA in ARDS |
|---|---|---|
|
| ||
| Edema and Inflammation | ↓ edema and inflammation by: | |
| Eickmeier et al[34] (2013) | - improved epithelial and endothelial barrier integrity through ↓ leukocyte lung recruitment and regulation of vasoactive mediators | |
| Jin et al[32] (2007) | - ↑HO-1 protein (cytoprotective effects) | |
|
Zarbock et al[31] (2006) Caudrillier et al[37] (2012) |
- ↓ TXA2 | |
| Eickmeier et al[34] (2013) | - ↓ NETs through ↓ TXA2 | |
| Jin et al[32] (2007) | - inhibiting neutrophil – platelet heterotypic interactions by ↓ P-selectin and its ligand CD24; ↑ HO-1 protein it ↓ TNF-α,↓ NO, ↓ MDA leading to a mitigation of neutrophilic lung inflammation |
|
| Zarbock et al[31] (2006) | - ↓ neutrophil recruitment by ↓ TXA2 | |
| Tuinman et al[35] (2013) | - ↓ neutrophil activation by ↓ TXA2 | |
| Ortiz-Muñoz et al[38] (2014) | - ↓ influx neutrophils through inhibition of COX-1 and -2 | |
|
| ||
| Leeman et al[26] (1988) | Increased intrapulmonary shunt | ↓ intrapulmonary shunt by: - accentuating hypoxic pulmonary vasoconstriction; presumed mechanism are ↓ vasodilating prostacyclin or ↑ vasoconstricting leukotrienes |
|
| ||
| Not reported | Increased pulmonary dead space | - decrease in microvascular thrombi |
|
| ||
| Sigurdsson et al[27] (1989) | Pulmonary hypertension | through attenuating increased vascular tone |
|
| ||
| - | Microvascular thrombosis | Not reported by the included studies |
|
| ||
| Resolution of inflammation and fibrosis | ↑ resolution by: | |
| Fukunaga et al[30] (2005) | - ↑ COX-2 mediated anti-inflammatory LX | |
| Kebir et al[33] (2009) | - overriding antiapoptosis signal from MPO | |
| Eickmeier et al[34] (2013) | - through resolvin D1 | |
| Jin et al[32] (2007) | - through lipoxins generated HO-1 protein | |
HO-1 protein: Heme oxygenase-1 protein; TXA2: thromboxane2; NET: neutrophil extracellular traps; IL-1β: interleukin-1β; IL-6:interleukin-6; TNFα: tumor necrosis factor-α; NF-κB p65: nuclear factor-κB p65; NO:nitric oxide ; MDA: malondialdehyde; PGE2: prostaglandin E2; COX-2: cyclooxygenase-2; MPO: myeoloperoxidase; ↑: increase; ↓: reduction