二甲双胍和西地那非治疗实验性肺动脉高压的血流动力学影响

Vicente Benavides, Melissa Silva-Medina Weil, S. Castaño, Mauricio Palacios
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引用次数: 0

摘要

据报道,二甲双胍的实验效果可能有利于治疗肺动脉高压,但具体的作用机制仍在推测中。目前这种情况的治疗是西地那非,即使是那些需要二甲双胍作为其他合并症治疗的一部分的患者。二甲双胍和西地那非都能有效降低右心室的收缩压,但没有比较两种治疗对血流动力学影响的报道。本研究的目的是使用一种单苦杏仁碱诱导的PH大鼠模型来做到这一点。将大鼠分为5组,分为3个治疗组(二甲双胍、西地那非及联合治疗)和2个对照组(阳性和阴性)。随访60天,在第30天和第60天进行超声心动图(测量心室射血分数),第60天进行心导管插管,并估计Fulton指数。以右心室射血分数作为参数,没有有效的治疗方案。使用其他结果变量,三个治疗组有积极的反应。与阳性(PH)对照组相比,RVSP得到了改善,无论在何种组,RVSP都没有达到阴性对照组的压力。富尔顿指数仍然是病理性的,但显示出药物治疗的治疗效果。在PH大鼠模型中,二甲双胍并不逊于西地那非,有趣的是,联合治疗显示这些药物之间没有血流动力学协同作用。肾脏和肝脏的安全性评估显示两组之间没有病理或功能差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hemodynamical effects of metformin and sildenafil in the treatment of experimental pulmonary hypertension
Metformin has been reported to have experimental effects that could be beneficial in the treatment of PH (pulmonary hypertension), though the specific mechanism of action is still under speculation. The current management of this condition is sildenafil, even in patients that requiere metformin as part of the treatment for other comorbilities. Both metformin and sildenafil effectively lower the systolic pressure in the right ventricle, however there are no reports comparing the hemodynamical effects of the two treatments. The goal of this study was to do so using a monocrotaline-induced PH rat model. The rats were divided in 5 groups, consisting of 3 treatment groups (metformin, sildenafil and combination therapy) and two control groups (positive and negative). They were followed for 60 days, at day 30 and 60 an echocardiogram was performed (ventricular ejection fraction was measured), and at day 60 cardiac catheterism was carried out, and Fulton index was estimated. No treatment scheme was effective using the right ventricle ejection fraction as a parameter. The three treatment groups had a positive response using the other outcome variables. The RVSP was improved compared to the positive (PH) controls, without reaching the negative control’s pressure regardless of the group. Fulton’s index remained pathological, but demonstrated a therapeutical effect of the pharmacological treatments. Metformin was not inferior to sildenafil in a PH rat model, interestingly combination treatment shows no hemodynamical synergy between these drugs. Safety evaluation of the kidney and liver showed no pathological or functional differences between the groups.
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