Department of Physiology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
Physiol Res. 2013;62(Suppl 1):S191-200. doi: 10.33549/physiolres.932606.
Severe meconium aspiration syndrome (MAS) in newborns is often treated by exogenous surfactant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfactant preparation Curosurf to enhance efficacy of the surfactant therapy in experimental model of MAS. Oxygen-ventilated rabbits were intratracheally given meconium (25 mg/ml, 4 ml/kg) to induce respiratory failure. Thirty minutes later, animals were treated by intratracheal budesonide (0.25 mg/kg) or surfactant lung lavage (10 ml/kg, 5 mg phospholipids/ml) repeated twice, followed by undiluted Curosurf (100 mg phospholipids/kg) or by the above mentioned surfactant treatment with the last surfactant dose fortified with budesonide (0.25 mg/kg) or were untreated. Animals were ventilated for additional 5 hours and respiratory parameters were measured regularly. After sacrificing animals, wet-dry lung weight ratio was evaluated and plasma levels of interleukins (IL)-1beta, -6, -8, and TNF-alpha were measured by ELISA method. Efficacy of the given therapies to enhance lung functions and to diminish lung edema formation and inflammation increased from budesonide-only and surfactant-only therapy to surfactant+budesonide therapy. Combined therapy improved gas exchange from 30 min of administration, and showed a longer-lasting effect than surfactant-only therapy. In conclusions, budesonide additionally improved the effects of exogenous surfactant in experimental MAS.
严重胎粪吸入综合征(MAS)患儿常采用外源性肺表面活性物质治疗。由于胎粪诱导的炎症会降低肺表面活性物质的疗效,因此在 MAS 的实验模型中,将糖皮质激素布地奈德加入到肺表面活性物质制剂固尔苏中,以增强肺表面活性物质治疗的效果。给氧通气的兔经气管内给予胎粪(25mg/ml,4ml/kg)以诱发呼吸衰竭。30 分钟后,通过气管内给予布地奈德(0.25mg/kg)或肺表面活性物质灌洗(10ml/kg,5mg 磷脂/ml)两次,然后给予未稀释的固尔苏(100mg 磷脂/kg)或上述表面活性物质治疗,最后一次表面活性物质治疗时加入布地奈德(0.25mg/kg)或不加,进行治疗。动物继续通气 5 小时,定期测量呼吸参数。处死动物后,通过干湿重法评估肺湿/干重比,并通过 ELISA 法测量血浆中白细胞介素(IL)-1β、-6、-8 和 TNF-α的水平。从单独使用布地奈德和单独使用肺表面活性物质治疗到联合使用肺表面活性物质和布地奈德治疗,增强肺功能、减轻肺水肿形成和炎症的疗效增加。联合治疗从给药 30 分钟开始改善气体交换,并显示出比单独使用肺表面活性物质治疗更长的持续效果。总之,布地奈德额外增强了外源性肺表面活性物质在实验性 MAS 中的作用。