Bökenkamp Regina, Gittenberger-De Groot Adriana C, Van Munsteren Conny J, Grauss Robert W, Ottenkamp Jaap, Deruiter Marco C
Departments of Pediatric Cardiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Pediatr Res. 2006 Oct;60(4):407-12. doi: 10.1203/01.pdr.0000238243.37116.a6. Epub 2006 Aug 28.
Persistent ductus arteriosus (PDA) is a common cardiovascular anomaly in children caused by the pathologic persistence of the left sixth pharyngeal arch artery. The inbred Brown-Norway (BN) rat presents with increased vascular fragility due to an aortic elastin deficit resulting from decreased elastin synthesis. The strikingly high prevalence of PDA in BN rats in a pilot study led us to investigate this vascular anomaly in 12 adolescent BN rats. In all BN rats, a PDA was observed macroscopically, whereas a ligamentum arteriosum was found in adult controls. The macroscopic appearance of the PDA was tubular (n = 2), stenotic (n = 8), or diverticular (n = 2). The PDA had the structure of a muscular artery with intimal thickening. In the normal closing ductus of the neonatal controls, the media consisted of layers of smooth muscle cells (SMCs) intermingled with layers of elastin. The intima was thin and poor in elastin. By contrast, the media of PDA in BN rats elastin lamellae were absent and the intima contained many elastic fibers. The abnormal distribution of elastin in the PDA of BN rats suggests that impaired elastin metabolism is related to the persistence of the ductus and implicates a genetically determined factor that may link the PDA with aortic fragility.
动脉导管未闭（PDA）是一种常见的儿童心血管异常，由左第六鳃弓动脉的病理性持续存在引起。近交系棕色挪威（BN）大鼠由于弹性蛋白合成减少导致主动脉弹性蛋白缺乏，血管脆性增加。在一项初步研究中，BN大鼠中PDA的惊人高患病率促使我们对12只青春期BN大鼠的这种血管异常进行研究。在所有BN大鼠中，肉眼观察到PDA，而在成年对照组中发现动脉韧带。PDA的宏观外观为管状（n = 2）、狭窄状（n = 8）或憩室状（n = 2）。PDA具有肌肉动脉的结构，伴有内膜增厚。在新生对照组正常闭合的动脉导管中，中膜由平滑肌细胞（SMC）层与弹性蛋白层交织组成。内膜薄且弹性蛋白含量低。相比之下，BN大鼠PDA的中膜缺乏弹性蛋白片层，内膜含有许多弹性纤维。BN大鼠PDA中弹性蛋白的异常分布表明，弹性蛋白代谢受损与动脉导管的持续存在有关，并暗示了一个可能将PDA与主动脉脆性联系起来的遗传决定因素。
