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Table 1 Pre-clinical studies of nebulised heparin treatment for acute lung injury

From: Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence

Dosage (Timing) Species Model (Sacrifice) Nebulizer Outcomes Side effects Reference
Animal models of acute lung injury treated with nebulised heparin
 1000 IU/kg
(30min before injury and every 6h)
Rat it. Streptococcus pneumoniae (40h) Aeroneb Pro Nebulizer ↓ Pulmonary coagulation NR Hofstra et al, 2009 [104]
 1000 IU/kg
(30min before, 6h and 12h after injury)
Rat iv. LPS (7.5 mg/kg) (16h) Aeroneb Pro Nebulizer ↓ Coagulation NR Hofstra et al, 2010 [105]
 1000 IU/kg
(30min before injury and every 6h)
Rat it. Pseudomonas aeruginosa (16h) Aeroneb Pro Nebulizer = NR Cornet et al, 2011 [106]
 Dose NR
(5 min after injury)
Mouse inh. Chlorine (400 ppm for 30min) (6h) AirLife Brand Misty Max 10 ↓ Decreased inflammation No side effects Zarogiannis et al, 2014 [107]
 1000 IU/kg
(4h and 8h after injury
or 30min before, 4h and 8h after injury)
Rat it. LPS (10μg/g) (24h) Aeroneb Pro Nebulizer ↓ Pulmonary coagulation and inflammation NR Chimenti et al, 2017 [80]
Animal models of acute lung injury treated with nebulised heparin and combined with another treatment
 10000 IU (1h after injury, every 4h) Sheep Smoke inh. and it. Pseudomonas aeruginosa (24h) AirLife Brand Misty Max 10 ↓ Lung injury and airways obstruction
↑ PaO2
No side effects Murakami et al, 2002 [108]
 10000 IU (30min after injury, every 4h for 24h) or combined with intravenous 10 mg/kg/h lisofylline Sheep Smoke inh. (48h) AirLife Brand Misty Max 10 ↓ Need for MV
↑ PaO2
No side effects Tasaki et al, 2002 [109]
 10000 IU (2h after injury, every 4h) or combined with nebulized 290 IU recombinant antithrombin Sheep Cutaneous burn and smoke inh. (48h) AirLife Brand Misty Max 10 Combination:
↓ Pulmonary inflammation and airways obstruction
↑ PaO2
No side effects Enkhbataar et al, 2007 [110]
 10000 IU (1h after injury, every 4h) combined with intravenous 0.34 mg/kg/h recombinant antithrombin Sheep Cutaneous burn and smoke inh. (48h) AirLife Brand Misty Max 10 ↓ Inflammation, oedema, airways obstruction
↑ PaO2
No side effects Enkhbataar et al, 2008 [111]
 10000 IU (2h after injury, every 4h) combined with intravenous 6 IU/kg/h recombinant antithrombin (from 1h after injury until the end of the study) and nebulized 2 mg tissue plasminogen inhibitor (4h after injury, every 4h) Sheep Cutaneous burn and smoke inh. (48h) AirLife Brand Misty Max 10 ↓ Lung injury, oedema and airways obstruction
↑ PaO2
No side effects Rehberg et al, 2014 [112]
 1000 IU/kg (4h, 12h and 28h after injury) combined with nebulized 500 IU/kg antithrombin (4h and 28h after injury) Rat it. HCl and LPS (30 μg/g) (72h) Aeroneb Pro Nebulizer ↓ Pulmonary coagulation and inflammation No side effects Camprubí-Rimblas et al, 2020 [113]
  1. ↓: reduced, ↑: increased, =: equal, inh inhalation, it. intratracheal, iv. intravenous, LPS lipopolysaccharide, MV mechanical ventilation, NR not reported