The effectiveness of unfractionated heparin vs. low molecular weight (Enoxaparin) in Acute Respiratory Distress Syndrom (ARDS) and metabolic dysfunction: an old drug for new indication!

Acute Respiratory Distress Syndrome is a lung disorder defined by the acute onset of hypoxemia, the commonest being abdominal sepsis.Many biomarkers have been studied for diagnostic prognostication and ARDS pharmacotherapy. The current study aim to assess the protective effects of UFH versus Enoxaparin in sepsis-induced ARDS and related metabolic sequelae. Sepsis was initiated through cecal ligation and puncture (CLP). Wistar rats were divided to: sham, CLP, CLP + unfractionated Heparin, and CLP + Enoxaparin and CLP + distilled water groups. Levels of serum Lipoxin A4 (LXA4), lipoprotein lipase (LPL), leukotriene E4 (LTE4), leukotriene B4 (LTB4), interleukin-8 (IL-8), were quantified. Furthermore, mRNA expression of receptors for advanced glycation end products (RAGE) and angiopoietin-2 (ANG-2) were assessed. Histopathological study was conducted to assess any lung injuries. Septic rats demonstrated higher levels of leukotriene E4, leukotriene B4, and interleukin-8, while treatment with unfractionated Heparin attenuated these levels but enoxaparin effectiveness on LTB-4 and IL-8 was not as significant as heparin while its was equally effective on LTE-4. Moreover, mRNA levels of RAGE and ANG-2 were enhanced in CLP rats. These elevations were mitigated by treatment with unfractionated Heparin and reduced by enoxaparin to a lesser extent. Treatment with unfractionated Heparin increased the lipoxin A4 and lipoprotein lipase levels but enoxaparin had no effect on the LPL level. Lung protective effect of unfractionated Heparin was further confirmed by histopathological observations of lung tissue samples. Our study demonstrates that UFH can modulate ARDS and metabolic dysfunction in hyperinflammatory conditions like sepsis.