西地那非与前列腺素E_1治疗猪肺动脉高压

Sildenafil and prostaglandin E_1 treated pulmonary hypertension on piglet model

目的比较西地那非和前列腺素E1对幼猪肺动脉高压模型的影响。方法体质量约5kg实验用健康幼猪24只,用经气管内吸入胎粪法诱发幼猪产生肺动脉高压,2h后建立急性缺氧性肺动脉高压模型。随机将幼猪分成4组:对照组,不给予任何药物治疗;西地那非组,静脉注射枸橼酸西地那非(2mg/kg)、前列腺素E1组,持续静脉滴注前列腺素E120ng/(kg·min)至实验结束;合用组同时给予西地那非组和前列腺素E1。结果吸入胎粪2h后,记录动物的肺动脉压、肺血管阻力(pulmonary vascular resistance,PVR)和体循环血管阻力(systemic vascular resistance,SVR)。发现肺动脉压、PVR和PVR/SVR均随时间明显增加。施加药物干预以后,西地那非组与合用组的上述指标均明显迅速下降,并且心输出量和心脏指数明显提高;前列腺素E1组肺动脉压、PVR以及PVR/SVR下降程度不如西地那非组明显,心输出量、心脏指数无改善;对照组的肺动脉压、PVR以及PVR/SVR无下降。结论西地那非降低肺动脉压和肺血管阻力,改善心功能,同时对体循环血流动力学无不良影响;在本实验用量,西地那非扩张肺血管和降低肺血管阻力的作用比前列腺素E1强;两者联合应用没有发生协同降低肺动脉压作用。

Objectives To investigate the effects of intravenous sildenafil on pulmonary and systemic hemodynamics in a piglet model of acute pulmonary hypertension secondary to meconium aspiration, to compare these effects of prostaglandin E1 and the combination of sildenafil and prostaglandin E1. Methods Pulmonary hypertension was induced in 24 piglets by endotracheal instillation of human meconium. Animals were assigned to four groups randomly after meconium aspiration over 2 hours. Each group had six piglets. Group A received no any additional intervention, group B received an infusion of intravenous sildenail 2 mg/kg for 2 hours, group C received continually intravenous infusion prostaglandin E1 20 ng/kg per min for 2 hours, group D received both of what were done in A and B groups. Results All piglets＇ pulmonary artery pressure （PAP）, pulmonary vascular resistance （PVR） and the rate of pulmonary-to-systemic vascular resistance （PVR/ SVR） increased remarkably after meconium aspiration over 2 hours. There was no further change of the PAP, PVR and PVR/SVR of group A after medicine intervention. Those of group B and D decreased remarkably. The cardiac output （CO） and cardiac index （CI） of group B and D increased at the same time. Similar changes were seen in both group B and D. PAP, PVR, PVR/SVR of group C also decreased, but less than those of group B and D. CO and CI in group C were not improved. Conclusions Sildenafil decreases PAP and PVR, improves heart function, unchanges systemic hemodynamics. Its potency is stronger than that of prostaglandin E1 at this experiment dosage. Effects can be augdmented under combination of two drugs.