Division of Nephrology and Hypertension, Mayo Clinic, Rochester 55905, USA.
Am J Physiol Renal Physiol. 2011 Oct;301(4):F845-51. doi: 10.1152/ajprenal.00311.2011. Epub 2011 Jun 22.
The study of hemodynamic alterations following the creation of an arteriovenous fistula (AVF) is relevant to vascular adaptive responses and hemodialysis access dysfunction. This study examined such alterations in a murine AVF created by anastomosing the carotid artery to the jugular vein. AVF blood flow was markedly increased due to reduced AVF vascular resistance. Despite such markedly increased basal blood flow, AVF blood flow further increased in response to acetylcholine. This AVF model exhibited increased cardiac output and decreased systemic vascular resistance; the kidney, in contrast, exhibited decreased blood flow and increased vascular resistance. Augmentation in AVF blood flow was attended by increased arterial heme oxygenase-1 (HO-1) mRNA and protein expression, the latter localized to smooth muscle cells of the AVF artery; AVF blood flow was substantially reduced in HO-1(-/-) mice compared with HO-1(+/+) mice. Finally, in a murine model of a representative disease known to exhibit impaired hemodynamic responses (sickle cell disease), the creation of an AVF was attended by decreased AVF flow and impaired AVF function. We conclude that this AVF model exhibits markedly increased AVF blood flow, a vasodilatory reserve capacity, increased cardiac output, decreased renal blood flow, and a dependency on intact hemodynamic responses, in general, and HO-1 expression, in particular, in achieving and maintaining AVF blood flow. We suggest that these findings support the utility of this model in investigating the basis for and the consequences of hemodynamic stress, including shear stress, and the pathobiology of hemodialysis AVF dysfunction.
研究动静脉瘘（AVF）形成后血流动力学的改变与血管适应性反应和血液透析通路功能障碍有关。本研究通过将颈总动脉吻合到颈静脉来建立小鼠的 AVF，以此来研究这种变化。由于 AVF 血管阻力降低，AVF 血流量明显增加。尽管基础血流量明显增加，但 AVF 血流量在乙酰胆碱的作用下进一步增加。该 AVF 模型表现为心输出量增加和全身血管阻力降低；相反，肾脏表现为血流量减少和血管阻力增加。AVF 血流量的增加伴随着动脉血红素加氧酶-1（HO-1）mRNA 和蛋白表达的增加，后者定位于 AVF 动脉的平滑肌细胞；与 HO-1(+/+)小鼠相比，HO-1(-/-)小鼠的 AVF 血流量明显减少。最后，在一种已知表现出血流动力学反应受损的代表性疾病（镰状细胞病）的小鼠模型中，AVF 的建立伴随着 AVF 流量减少和 AVF 功能受损。我们得出结论，该 AVF 模型表现出明显增加的 AVF 血流量、扩张储备能力、增加的心输出量、减少的肾血流量，以及对完整血流动力学反应的依赖性，特别是对 HO-1 表达的依赖性，以实现和维持 AVF 血流量。我们认为这些发现支持该模型在研究血流动力学应激（包括剪切应力）的基础和后果以及血液透析 AVF 功能障碍的病理生物学方面的效用。
