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Background: Arteriovenous fistula (AVF) creation may negatively affect cardiac structure and function and impact cardiovascular mortality. The objective of this study was to develop and characterize the cardiac changes following AVF creation in a murine AVF model., Methods: AVFs were constructed using the carotid artery and jugular vein in C57BL/6 mice. Sham-operated AVF mice served as the control group. 2D-echocardiography was performed prior to AVF creation (baseline) and at 7 and 21 days after creation in AVF and sham-operated mice. Picrosirius red was used to stain the left ventricle for collagen production., Results: The cardiac output (CO), left ventricular end diastolic (LVEDD) and systolic (LVESD) diameter, and end-diastolic (LVEDV) and systolic (LVESV) volume was significantly increased at 7 and 21 days in AVF compared to sham-operated mice. There was also a significant increase in CO, LVEDD, LVESD, LVEDV, and LVESV from baseline to 21 days within the AVF group, but not the sham-operated mice. There was a significant decrease in ejection fraction and fractional shortening at 21 days in AVF compared to sham-operated mice. Picrosirius red was significantly more prominent around both the perivascular and interstitial areas of the cardiac tissue from AVF mice compared to sham-operated AVF mice at 21 days., Conclusions: The creation of an AVF in our murine model leads to cardiac changes such as increased cardiac output, left ventricular dilation, and cardiac fibrosis, while showing reductions of ejection fraction and fractional shortening.

Purpose: Venous stenosis secondary to neointimal hyperplasia is a major etiology of early arteriovenous fistula (AVF) failure. The natural history of AVF failure is likely influenced by progressive vascular insults to the vein prior to and after AVF creation. The main objectives of this study were to (1) provide a histologic and morphometric description of non-chronic kidney disease (CKD), upper extremity vein specimens and (2) perform a morphometric analysis to study venous histology from non-CKD upper extremity veins, veins collected at the time of new vascular access surgery and veins collected from failed stenotic AVFs., Methods: Vein samples from 11 non-CKD deceased donors, 29 subjects receiving new vascular access creation and 20 subjects with stenotic failed AVFs were collected for histologic and morphometric analysis., Results: The mean values of average intima/media thickness ± S.E. from veins collected from non-CKD subjects, subjects receiving new vascular access and subjects with stenotic AVFs were 0.16±0.02, 0.43±0.07 and 3.84±0.55, respectively (p<0.0001). Among donor, non-CKD, vein samples, only diabetes (p=0.0007) was associated with increased average intima/media thickness., Conclusions: Our results demonstrate a progressively increasing venous neointimal hyperplasia development from the non-CKD period through the period of AVF creation and failure. Vascular injuries from complications of progressive CKD prior to access placement and vascular injuries after vascular access placement may play important roles in these progressive vascular changes, and need to be further elucidated.