Hyperbaric oxygen inhibits venous neointimal hyperplasia following arteriovenous fistulization

Abstract

Hypoxia following arteriovenous fistulization results in venous neointimal hyperplasia (VNH), potentially causing early arteriovenous fistula (AVF) dysfunction. In this study, we used hyperbaric oxygen (HBO) in a rabbit model of AVF to determine whether it could ameliorate early AVF failure. Chronic renal failure was induced by adenine in 96 adult rabbits randomly divided into 3 groups (n=32 in each group). The sham + HBO group underwent sham operation and received HBO. The AVF alone group underwent fistulization, but did not receive HBO. The AVF + HBO group underwent fistulization and received HBO. Each group was further divided into 4 subgroups of 8 rabbits each that were euthanized at 1, 7, 14 or 28 days post-operatively. At each time point, blood flow changes in the AVF venous segment were detected using a high-frequency duplex ultrasonography system. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), and hematoxylin and eosin staining were performed to evaluate VNH. Western blot analysis was performed to confirm the expression of hypoxia-inducible factor (HIF)-1α. At 14 and 28 days following HBO treatment, blood flow in the AVF + HBO group was greater than that at day 0. The AVF + HBO group had a smaller ratio of intima to media area, a lower HIF-1α protein expression, and a smaller percentage of PCNA-positive cells in the proximal vein than did the AVF alone group. Our results thus suggest that continuous HBO treatment following AVF significantly inhibits VNH and promotes blood flow. Therefore, early AVF failure may be prevented by the use of HBO therapy.

The Hyperoxic-Hypoxic Paradox

“…The dose-response curve related to the applied pressure, time, and number of HBOT exposures and its relation to HIF expression is still not fully understood, and further studies are needed to find the optimal HBOT protocols. It should be noted that when HBOT is administrated to an ischemic tissue, which overexpresses HIF, tissue hypoxia is being reversed and corrected, accordingly the overexpressed HIF is reduced towards the normalized baseline [ 65 , 66 , 67 , 68 , 69 , 70 ]. Moreover, when HBOT is being used as preconditioning therapy for hypoxia (by HIF induction), the tissue will tolerate the ischemic insult better, less ischemic injury induced, and the overall post insult HIF expression will be lower than expected for the same insult [ 71 , 72 ].…”

Vascularization of the arteriovenous fistula wall and association with maturation outcomes

“…These results suggest that IH thrives under hypoxic conditions, as observed in femoral arteries 35 and contrasts the proposed association between AVF vascularization and IH in experimental arteriovenous grafts and fistulas. [1][2][3]36 In experimental AVFs, inadequate oxygenation was associated with IH and activation of hypoxia-associated transcription factors (e.g. hypoxia-inducible factor 1-alpha (HIF-1α)), [1][2][3] which in turn is thought to trigger vascular endothelial growth factor (VEGF)-mediated neoangiogenesis.…”

“…[1][2][3]36 In experimental AVFs, inadequate oxygenation was associated with IH and activation of hypoxia-associated transcription factors (e.g. hypoxia-inducible factor 1-alpha (HIF-1α)), [1][2][3] which in turn is thought to trigger vascular endothelial growth factor (VEGF)-mediated neoangiogenesis. 4 In agreement with our results, only a minority of veins in the Hemodialysis Fistula Maturation Study presented foci of neoangiogenesis in the intima, 31 indicating that the mechanisms of neointima formation in human pre-access veins and AVFs differ from those in experimental models.…”

“…oxygenation of the fistula. [1][2][3][4] However, the premises of this notion are built upon interpretation of other vascular pathologies and experimental AVF models, while observational clinical studies to support this hypothesis are not available.…”

Acupuncture attenuates renal interstitial fibrosis via the TGF‑β/Smad pathway

“…The CRF model was created by gavaging the rabbits with adenine for 3 weeks, as previously described (26). Adenine (purity >98%; FW: 135.14) was purchased from Guangzhou Weijia Technology Co., Ltd. (Guangzhou, China).…”