A. The mouse aortocaval fistula recapitulates human arteriovenous fistula maturation. Am J Physiol Heart Circ Physiol 305: H1718 -H1725, 2013. First published October 4, 2013 doi:10.1152/ajpheart.00590.2013.-Several models of arteriovenous fistula (AVF) have excellent patency and help in understanding the mechanisms of venous adaptation to the arterial environment. However, these models fail to exhibit either maturation failure or fail to develop stenoses, both of which are critical modes of AVF failure in human patients. We used high-resolution Doppler ultrasound to serially follow mice with AVFs created by direct 25-gauge needle puncture. By day 21, 75% of AVFs dilate, thicken, and increase flow, i.e., mature, and 25% fail due to immediate thrombosis or maturation failure. Mature AVF thicken due to increased amounts of smooth muscle cells. By day 42, 67% of mature AVFs remain patent, but 33% of AVFs fail due to perianastomotic thickening. These results show that the mouse aortocaval model has an easily detectable maturation phase in the first 21 days followed by a potential failure phase in the subsequent 21 days. This model is the first animal model of AVF to show a course that recapitulates aspects of human AVF maturation. aortocaval fistula; arteriovenous fistula; maturation; mouse; model THE ARTERIOVENOUS FISTULA (AVF) is the most common access chosen for hemodialysis as the first-line therapy before renal replacement. Despite the superiority of AVF access compared with its alternatives, AVFs are still far from perfect. AVFs fail to "mature," e.g., dilate, thicken, and increase flow, before the beginning of dialysis in ϳ20 -50% of cases, with the majority of AVFs requiring some additional therapeutic intervention to mature successfully (9,14,20,21). In addition, 1-yr primary AVF patency rates are typically only 60 -65%, with many mature AVFs subsequently failing secondarily due to neointimal hyperplasia, generally perianastomotic (2,4,7,19,21,22). The poor patency of AVFs clearly reflects our imperfect understanding of the biology of venous remodeling to the arterial environment.The AVF has been studied using several models, including the surgical anastomosis model as well as the puncture model (1, 5, 6, 8, 10 -12, 15-17). All of these models have strengths and weakness, including technical difficulty due to surgery as well as the use of animals larger than mice (1,5,8,12,15,16). A common feature of all these models is that they are good models of surgical access, with good patency; unfortunately, they fail to exhibit a percentage of animals that either fail to mature or fail to develop stenoses in long-term followup, both of which are both important aspects of understanding modes of failure of human AVF.Recent advances in ultrasound technology have allowed increasingly accurate analysis of blood flow within small vessels, such as in a mouse, as well as allowing the ability to serially examine the same mouse over time. We used this technology to observe the time course of venous remodeling in the mouse ao...

Veins are exposed to the arterial environment during two common surgical procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both cases veins adapt to the arterial environment that is characterized by different hemodynamic conditions and increased oxygen tension compared to the venous environment. Successful venous adaptation to the arterial environment is critical for long term success of the vein graft or AVF, and in both cases is generally characterized by venous dilation and wall thickening. However, AVF are exposed to a high flow, high shear stress, low pressure arterial environment, and adapt mainly via outward dilation with less intimal thickening. Vein grafts are exposed to a moderate flow, moderate shear stress, high pressure arterial environment, and adapt mainly via increased wall thickening with less outward dilation. We review the data that describe these differences, as well as the underlying molecular mechanisms that mediate these processes. Despite extensive research, there are few differences in the molecular pathways that regulate cell proliferation and migration or matrix synthesis, secretion, or degradation currently identified between vein graft adaptation and AVF maturation that account for the different types of venous adaptation to arterial environments.

Pelvic ischemia associated with IOHA may be severe and lead to fatality after EVAR. Our data show that BC may lead to severe quality of life impairment when it does not regress during follow-up.

Background The poor clinical results that are frequently reported for arteriovenous fistulae (AVF) for hemodialysis are typically due to failure of AVF maturation. We hypothesized that early AVF maturation is associated with generation of reactive oxygen species and activation of the HIF-1 pathway, potentially promoting neointimal hyperplasia. We tested this hypothesis using a previously reported mouse AVF model that recapitulates human AVF maturation. Methods Aortocaval fistulae were created in C57Bl/6 mice, and compared to sham-operated mice. AVFs or inferior vena cavas were analysed using a microarray, Amplex Red for extracellular H2O2, qPCR, immunohistochemistry, and immunoblotting for HIF-1α, and immunofluorescence for NOX-2, nitrotyrosine, HO-1 and VEGF-A. Results Oxidative stress was higher in AVF compared to control veins, with more H2O2 (p=0.007) and enhanced nitrotyrosine immunostaining (p=0.005). Immunohistochemistry and immunoblot showed increased HIF-1α immunoreactivity in the AVF endothelium; HIF-1 targets NOX-2, HO-1 and VEGF-A were overexpressed in the AVF (p<0.01). AVF expressed increased numbers of HIF-1α (p<0.0001) and HO-1 (p<0.0001) mRNA transcripts. Conclusions Oxidative stress increases in mouse AVF during early maturation, with increased expression of HIF-1α and its target genes NOX-2, HO-1 and VEGF-A. These results suggest that clinical strategies to improve AVF maturation could target the HIF-1 pathway.