Effects Of Cholinergic Anti-inflammatory Pathway On Ventilator-induced Lung Injury

Objective To investigate the effects of cholinergic anti-inflammatory pathway on ventilator-induced lung injury in rats.Methods We established a rat model of Ventilator-induced lung injury by volume-controlled mechanical ventilation with high tidal volume. After anesthesia was administered and tracheotomy was performed, 36 healthy female Sprague-Dawley rats were randomly divided into three groups to receive two ventilation strategies for 2 hours: 1) high-tidal volume (HV_T) ventilation (HV_T group: tidal volume of 25 ml/kg, respiratory rate of 40 breaths/minute, inspiratory:expiratory ratio of 1:2, zero positive end-expiratory pressure, and inspiratory O₂ fraction of 0.21), 2) intraperitoneal injection of nicotine (2 mg/kg) 10 min before HV_T ventilation (HV_T+Nicotine group), and 3) Control group, which did not receive ventilation, served as the control. Hemodynamic parameters were measured throughout the study period. Arterial blood gases were measured every one hour. After maintaining ventilation for 2 hours, rats were sacrificed; a final left lug bronchoalveolar lavage was performed and right lung tissue specimens were harvested. Histological analyses were performed and diffuse alveolar damage (DAD) score were estimated. Lung wet-dry weight ratio, myeloperoxidase (MPO) activity in lung tissue, interleukin [IL]-8 level in BALF and intercellular adhesion molecule [ICAM]-1 level in lung tissue homogenates were assayed respectively.Results Histological and arterial blood gas analyses confirmed that HV_T ventilation induced significant lung injury. PaO₂ is significantly lower and DAD score is significantly higher in HV_T group at 2 h of ventilation. HV_T ventilation also significantly increased lung wet-dry weight ratio, MPO activity in lung tissue, IL-8 level in BALF and ICAM-1 level in lung tissue homogenates at 2 h of ventilation. Nicotine significantly attenuated the effects of HV_T ventilation.Conclusions Nicotine can protect the lung against ventilator-induced lung injury via activating cholinergic anti-inflammatory pathway. The mechanism that cholinergic anti-inflammatory pathway alleviated ventilator-induced lung injury were likely to inhibit the neutrophil aggregation and activity, suppress IL-8 and ICAM-1 synthesis and release.