Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery. Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.
目的： 初步探讨带孔房间隔分流器治疗肺动脉高压犬模型的短期疗效。 方法： 健康雄性比格犬36只，犬龄1~2岁，采用简单随机抽样法分为经导管球囊扩张房间隔造口术（BAS）+分流器组、BAS组和无造口组3组，每组12只。在犬右心房内注射脱氢野百合碱（1.5 mg/kg），建立肺动脉高压模型。建模成功后，BAS+分流器组犬行BAS，术后置入带孔房间隔分流器，BAS组犬行球囊扩张房间隔造口术，无造口组犬不予任何干预。于建模前，建模后2个月，手术治疗后1、3、6个月，分别测量各组犬的血流动力学指标及血N末端B型利钠肽原（NT-proBNP）水平。于手术治疗后1、3、6个月对BAS组和BAS+分流器组犬行超声心动图检查，观察分流器及房间隔造口的开通情况。于手术治疗后1、3、6个月各组分别处死3只犬，取心脏房间隔组织及房间隔分流器进行大体观察，观察分流器内皮化情况；取肺组织进行苏木素-伊红（HE）染色，观察肺中小血管附近炎症细胞浸润以及肺血管内膜增厚和狭窄的情况。 结果： 2只犬在建模后24 h内死亡，剩余34只犬，其中BAS+分流器组12只、BAS组11只、无造口组11只。与BAS组比较，BAS+分流器组犬手术治疗后3个月平均右心房压力（mRAP）和NT-proBNP较低（P均<0.05），手术治疗后6个月心输出量（CO）较高、动脉血氧饱和度（SaO2）较低（P均<0.05）。与无造口组比较，BAS+分流器组犬手术治疗后1、3和6个月mRAP和NT-proBNP较低（P均<0.05），手术治疗后6个月CO较高、SaO2较低（P均<0.05）。与无造口组比较，BAS组犬手术治疗后1个月mRAP和NT-proBNP较低（P均<0.05），手术治疗后3、6个月mRAP、NT-proBNP差异无统计学意义（P均>0.05）。超声心动图检查结果示，手术治疗后1个月BAS组犬房间隔存在极细束右向左分流，手术治疗后3个月BAS组所有犬的造口基本闭合，手术治疗后1、3、6个月BAS+分流器组犬的分流器处仍存在明显右向左分流，分流器成形良好。大体观察结果示，手术治疗后1个月BAS组犬房间隔处有明显穿刺孔，但手术治疗后3个月时房间隔穿刺孔闭合；手术治疗后6个月BAS+分流器组犬分流器表面内皮化进程良好，边缘无血栓形成。HE染色结果示，无造口组犬肺血管内膜明显增厚，肺血管狭窄，肺泡组织塌陷，周围有大量炎症细胞浸润，肺微小血管闭塞、机化，手术治疗6个月后BAS+分流器组犬肺血管内膜厚度与无造口组相仿。 结论： 采用带孔房间隔分流器治疗肺动脉高压犬模型具有长期维持造口开放的优点，疗效优于单纯球囊扩张。.