Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo: implications for novel left ventricular assist devices with a peripheral anastomosis.

Nonphysiologic blood flow triggers endothelial and arterial remodeling in vivo: implications for novel left ventricular assist devices with a peripheral anastomosis.
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DOI:
10.1016/j.jtcvs.2013.10.027
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发表时间:
2014-07
影响因子:
6
通讯作者:
Dowling, Robert D.
Dowling, Robert D.
中科院分区:
医学1区
文献类型:
--
作者:
Bartoli, Carlo R.;Spence, Paul A.;Siess, Thorsten;Raess, Daniel H.;Koenig, Steven C.;Dowling, Robert D.

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已经开发了需要与外周动脉吻合的侵入性较小的循环支持装置。Symphony心脏辅助系统是一种缝合在锁骨下动脉上的容量置换泵,可提供部分循环支持。手术配置在锁骨下动脉中产生非生理血压和双向血流。我们的目的是确定血流动力学改变对动脉结构和功能的影响。在小牛(n=23,80- 100 kg)中,将Symphony泵端侧缝合到颈动脉。急性期记录颈动脉血压和血流,评价血流动力学变化。在中期支持(1-4周)后,研究颈动脉横截面。组织学和分子测定评价了结构变化。实时定量PCR检测基质金属蛋白酶(MMP)-2和MMP-9及结缔组织生长因子(CTGF)基因表达。体外颈动脉环研究评价了生理反应。Symphony支持期间,颈动脉压为200/15 mmHg。前向血流从1.40±0.32升/分增加到4.29± 0.33升/分(p<0.05),吻合口近端颈动脉血流从0.25±0.05升/分完全逆转到-4.15 ± 0.38升/分。中期支持后,颈动脉显著扩张,与对照组相比,图尼卡中膜显著变薄,图尼卡外膜显著变厚。MMP-9基因表达显著降低,CTGF基因表达显著增加,胶原、弹性蛋白和总细胞外基质显著增加。内皮细胞明显肥大,产生更多的血管性血友病因子。内皮细胞凋亡明显增加。血小板-内皮相互作用显著降低。内皮非依赖性收缩显著减少,而内皮依赖性舒张适度增加。左心室辅助装置(LVAD)辅助循环触发动脉重塑,允许外周动脉适应新型部分支持泵的血流动力学改变。重构途径的进一步描绘可能对部分循环支持的新兴领域具有重要意义。
Less-invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System is a volume displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces non-physiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. In calves (n=23, 80-100kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery cross sections were studied. Histology and molecular assays evaluated architectural changes. Quantitative real-time PCR evaluated gene expression of matrix metalloproteinase (MMP)-2 and MMP-9 and connective tissue growth factor (CTGF). In vitro carotid arterial-ring studies evaluated physiological responses. During Symphony support, carotid arterial pressure was 200/15mmHg. Antegrade flow increased significantly (p<0.05) from 1.40±0.32 to 4.29±0.33L/min. Flow during native cardiac diastole reversed completely from 0.25±0.05 to -4.15±0.38L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia versus controls. MMP-9 gene expression decreased significantly, CTGF gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial-independent contraction decreased significantly, whereas endothelial-dependant relaxation increased modestly. Assisted circulation with a left ventricular assist device (LVAD) triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support.
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