S. Ono1, T. Kudze1, T. Isaji1, T. Hashimoto1, B. Yatsula1, H. Liu1, T. Nishibe2, J. Koizumi3, A. Dardik1,4 1Yale University School of Medicine,Vascular Biology And Therapeutics Program And Department Of Surgery,New Haven, CT, USA 2Tokyo Medical University,Department Of Cardiovascular Surgery,Shinjuku, Tokyo, Japan 3Tokai University School of Medicine,Department Of Diagnostic Radiology,Isehara, KANAGAWA, Japan 4VA Connecticut Healthcare System,Department Of Surgery,West Haven, CT, USA
Introduction: The arteriovenous fistula (AVF) is the preferred method of dialysis access due to its proven superior long term outcomes. However, women have lower rates of AVF maturation than men (38% vs. 60%), preventing optimal AVF use. We used a novel mouse AVF model that recapitulates human AVF maturation to test the hypothesis that there is a difference in male and female AVF maturation.
Methods: Aortocaval fistulae were created in male and female C57BL/6 mice (9-10 wks). At days 0, 3, 7, 14 and 21, infrarenal aortic and IVC diameters and flow velocity were monitored by Doppler ultrasound and used to calculate the resistance index, blood flow and shear stress. AVF were harvested at day 21 and AVF wall thickness was measured by computer morphometry; proteins were examined using immunofluorescence and mRNA by qPCR.
Results: Female mice weighed less throughout the whole period (p<0.0001). At baseline, female mice had lower infrarenal IVC velocity (p=0.0005) and smaller magnitudes of shear stress (p=0.0003); although female mice had smaller infrarenal aortic diameter (p=0.0198), there was no significant difference in infrarenal IVC diameter (p=0.5112). After AVF creation, both the female and male aorta (p=0.5681) and IVC (p=0.5680) dilated similarly and the aortic resistance index decreased similarly (p=0.0743). However, female mice had lower aorta (p=0.0187) and IVC mean velocity (p<0.0001); female mice also showed less blood flow volume in the aorta (p=0.0069) and IVC (p=0.0087) and lower shear stress magnitude in the IVC (p<0.0001) without any significant differences in aortic shear stress magnitude (p=0.31). There were no significant differences in infrarenal IVC wall thickness either at baseline (p=0.9617) or at day 21 (p=0.2931). Although KLF2 mRNA was decreased in the female AVF on day 21 (p=0.048), there were no differences in protein expression (p=0.5224).
Conclusion: AVF in female mice have lower velocity, blood flow volume and magnitudes of shear stress without any differences in wall thickness or protein expression. These findings suggest that hemodynamic changes in the fistula may play an important role underlying the diminished rates of AVF maturation in women.