Department of Intensive Care Medicine and Neonatology, University Children's Hospital Zurich, Zurich, Switzerland.
Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland.
J Transl Med. 2022 Feb 5;20(1):77. doi: 10.1186/s12967-022-03281-2.
Cardiovascular impairment contributes to increased mortality in preterm infants with chronic lung disease. Macitentan, an endothelin-1 receptor antagonist, has the potential to attenuate pulmonary and cardiovascular remodelling.
In a prospective randomized placebo-controlled intervention trial, Sprague-Dawley rats were exposed to 0.21 or 1.0 fraction of inspired oxygen (FiO) for 19 postnatal days. Rats were treated via gavage with placebo or macitentan from days of life 5 to 19. Alveoli, pulmonary vessels, α-smooth muscle actin content in pulmonary arterioles, size of cardiomyocytes, right to left ventricular wall diameter ratio, and endothelin-1 plasma concentrations were assessed.
FiO 1.0 induced typical features of chronic lung disease with significant alveolar enlargement (p = 0.012), alveolar (p = 0.048) and pulmonary vessel rarefaction (p = 0.024), higher α-smooth muscle actin content in pulmonary arterioles (p = 0.009), higher right to left ventricular wall diameter ratio (p = 0.02), and larger cardiomyocyte cross-sectional area (p < 0.001). Macitentan treatment significantly increased pulmonary vessel count (p = 0.004) and decreased right to left ventricular wall diameter ratios (p = 0.002). Endothelin-1 plasma concentrations were higher compared to placebo (p = 0.015). Alveolar number and size, α-smooth muscle actin, and the cardiomyocyte cross-sectional area remained unchanged (all p > 0.05).
The endothelin-1 receptor antagonist macitentan attenuated cardiovascular remodelling in an infant rat model for preterm chronic lung disease. This study underscores the potential of macitentan to reduce cardiovascular morbidity in preterm infants with chronic lung disease.
心血管损伤导致患有慢性肺疾病的早产儿死亡率增加。内皮素-1 受体拮抗剂马西替坦具有减轻肺和心血管重塑的潜力。
在一项前瞻性随机安慰剂对照干预试验中，将 Sprague-Dawley 大鼠暴露于 0.21 或 1.0 的吸入氧分数（FiO）中 19 天。从第 5 天到第 19 天，大鼠通过灌胃接受安慰剂或马西替坦治疗。评估肺泡、肺血管、肺小动脉中α-平滑肌肌动蛋白含量、心肌细胞大小、右心室与左心室壁直径比以及内皮素-1 血浆浓度。
FiO 1.0 诱导出慢性肺疾病的典型特征，表现为肺泡显著增大（p=0.012）、肺泡（p=0.048）和肺血管稀疏（p=0.024）、肺小动脉中α-平滑肌肌动蛋白含量增加（p=0.009）、右心室与左心室壁直径比升高（p=0.02）和心肌细胞横截面积增大（p<0.001）。马西替坦治疗显著增加了肺血管计数（p=0.004），降低了右心室与左心室壁直径比（p=0.002）。与安慰剂相比，内皮素-1 血浆浓度更高（p=0.015）。肺泡数量和大小、α-平滑肌肌动蛋白和心肌细胞横截面积保持不变（均 p>0.05）。
内皮素-1 受体拮抗剂马西替坦减轻了早产慢性肺疾病婴儿模型中的心血管重塑。这项研究强调了马西替坦降低患有慢性肺疾病的早产儿心血管发病率的潜力。
Zotero 插件
