Cannabidiol Reduces Inflammatory Lung Damage After Meconium Aspiration in Newborn Piglets

Luis Arruza; Lorena Barata; Eva Vierge; Maria José Rodríguez; Aaron Del Pozo; William Hind; José Martínez-Orgado

doi:10.3389/fped.2022.862035

Cannabidiol Reduces Inflammatory Lung Damage After Meconium Aspiration in Newborn Piglets

Front Pediatr. 2022 Jun 6:10:862035. doi: 10.3389/fped.2022.862035. eCollection 2022.

Authors

Luis Arruza¹, Lorena Barata¹, Eva Vierge¹, Maria José Rodríguez¹, Aaron Del Pozo¹, William Hind², José Martínez-Orgado¹

Affiliations

¹ Department of Neonatology, Hospital Clinico San Carlos-Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
² GW Research Ltd., Cambridge, United Kingdom.

Abstract

Aim: To assess the effects of cannabidiol (CBD) on lung damage in a piglet model of meconium aspiration syndrome (MAS).

Materials and methods: Meconium 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.

Results: Post-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 pCO₂ 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 TNFα 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).

Conclusion: Cannabidiol reduces histologic lung damage and inflammation in a piglet model of MAS. This translates into improved gas exchange and blood pressure stability.

Keywords: cannabidiol; inflammation; meconium aspiration syndrome (MAS); piglet; translational research.