Cannabidiol Reduces Inflammatory Lung Damage After Meconium Aspiration in Newborn Piglets

AimTo assess the effects of cannabidiol (CBD) on lung damage in a piglet model of meconium aspiration syndrome (MAS). Materials and MethodsMeconium aspiration syndrome was modelled in newborn piglets via intratracheal instillation of 20% meconium in saline collected from healthy newborn humans. Piglets were treated i.v. with 5 mg/kg CBD (MAS + CBD) or Vehicle (MAS + VEH) 30 min after MAS induction and monitored for 6 h. Ventilated piglets without meconium instillation served as controls (CTL). Ventilatory and haemodynamic monitoring, histological and biochemical studies assessed the effects of treatment. ResultsPost-insult administration of CBD reduced MAS-induced deterioration of gas exchange, improving respiratory acidosis (final pH 7.38 +/- 0.02, 7.22 +/- 0.03 and 7.33 +/- 0.03 and final pCO(2) 39.8 +/- 1.3, 60.4 +/- 3.8 and 45.7 +/- 3.1 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). These beneficial effects were obtained despite the less aggressive ventilatory settings required for CBD-treated animals (final minute volume 230 +/- 30, 348 +/- 33 and 253 +/- 24 mL/kg/min and final Oxygenation Index 1.64 +/- 0.04, 12.57 +/- 3.10 and 7.42 +/- 2.07 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). CBD's beneficial effects on gas exchange were associated with reduced histological lung damage, reduced leucocyte infiltration and oedema (histopathological score 1.6 +/- 0.3, 8.6 +/- 1.4 and 4.6 +/- 0.7 points for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05), as well as reduced TNF alpha production (0.04 +/- 0.01, 0.34 +/- 0.06 and 0.12 +/- 0.02 A.U. for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). Moreover, CBD improved blood pressure stability (final mean blood pressure 74.5 +/- 0.2, 62.2 +/- 6.2, and 78.67 +/- 4.1 mmHg for CTL, MAS + VEH and MAS + CBD, respectively, p < 0.05). ConclusionCannabidiol reduces histologic lung damage and inflammation in a piglet model of MAS. This translates into improved gas exchange and blood pressure stability.