Physiology Laboratory, Faculty of Medicine, Université Libre de Bruxelles, 808 Lennik Road, 1070 Brussels, Belgium.
Eur Heart J. 2012 Apr;33(8):1017-26. doi: 10.1093/eurheartj/ehr111. Epub 2011 May 23.
Three-month chronic systemic-to-pulmonary shunting in growing piglets has been reported as an early pulmonary arterial hypertension (PAH) model with preserved right ventricular (RV) function. We sought to determine whether prolonged shunting might be associated with more severe PAH and RV failure.
Fourteen growing piglets were randomized to a sham operation or the anastomosis of the left innominate artery to the pulmonary arterial trunk. Six months later, the shunt was closed and the animals underwent haemodynamic evaluation followed by tissue sampling for pathobiological assessment. Prolonged shunting had resulted in increased mean pulmonary artery pressure (22 ± 2 versus 17 ± 1 mmHg) and pulmonary arteriolar medial thickness, while cardiac output was decreased. However, RV-arterial coupling was markedly deteriorated, with a ~50% decrease in the ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Lung tissue expressions of endothelin-1, angiopoietin-1, and bone morphogenetic protein receptor-2 were similarly altered compared with previously observed after 3-month shunting. At the RV tissue level, pro-apoptotic ratio of Bax-to-Bcl-2 expressions and caspase-3 activation were increased, along with an increase in cardiomyocyte size, while expressions in voltage-gated potassium channels (Kv1.5 and Kv2.1) and angiogenic factors (angiopoietin-2 and vascular endothelial growth factor) were decreased. Right ventricular expressions of pro-inflammatory cytokines [interleukin (IL)-1α, IL-1β, tumour necrosis factor-α (TNF-α)] and natriuretic peptide precursors (NPPA and NPPB) were increased. There was an inverse correlation between RV Ees/Ea and pro-apoptotic Bax/Bcl-2 ratios.
Prolonged left-to-right shunting in piglets does not further aggravate pulmonary vasculopathy, but is a cause of RV failure, which appears related to an activation of apoptosis and inflammation.
据报道，3 个月的慢性体肺分流可作为一种保留右心室（RV）功能的早期肺动脉高压（PAH）模型。我们试图确定长期分流是否与更严重的 PAH 和 RV 衰竭有关。
14 只生长中的小猪被随机分为假手术组或左无名动脉与肺动脉干吻合术组。6 个月后，关闭分流并进行血流动力学评估，然后进行组织取样进行病理生物学评估。长期分流导致平均肺动脉压（22±2 对 17±1mmHg）和肺小动脉中层厚度增加，而心输出量降低。然而，RV-动脉偶联明显恶化，收缩末期与肺动脉弹性比值（Ees/Ea）下降约 50%。与之前观察到的 3 个月分流后相比，肺组织中内皮素-1、血管生成素-1 和骨形态发生蛋白受体-2 的表达也发生了类似的改变。在 RV 组织水平上，促凋亡 Bax/Bcl-2 比值增加，caspase-3 激活增加，心肌细胞增大，同时电压门控钾通道（Kv1.5 和 Kv2.1）和血管生成因子（血管生成素-2 和血管内皮生长因子）的表达减少。右心室促炎细胞因子[白细胞介素（IL）-1α、IL-1β、肿瘤坏死因子-α（TNF-α）]和利钠肽前体（NPPA 和 NPPB）的表达增加。RV Ees/Ea 与促凋亡 Bax/Bcl-2 比值呈负相关。
猪的长期左向右分流不会进一步加重肺血管病变，但会导致 RV 衰竭，这似乎与细胞凋亡和炎症的激活有关。
