Cardiovascular remodeling after AVF surgery in rats assessed by a clinical MRI scanner.

PURPOSE: To evaluate a cardiovascular magnetic resonance imaging (MRI) technique which allows the longitudinal analysis of cardiovascular remodeling in a rodent femoral arteriovenous fistula (AVF) model by means of a clinical scanner. MATERIALS AND METHODS: Eight rats underwent femoral AVF surgery and four rats served as controls. Vascular and cardiac morphology as well as cardiac function was assessed from Week 3 to 12 using contrast-enhanced, time-resolved magnetic resonance angiography (MRA) and cardiac MRI (cine gradient-echo sequence) at 3 T in one imaging session. RESULTS: Arteriovenous surgery resulted in progressive venous dilation and a subsequent cardiac adaptation. This procedure led to downstream vasodilation of the iliac vein and inferior vena cava of 179% and 188%, respectively (3 weeks). To accommodate the increased returning blood volume, cardiac output (CO) increased significantly (P=.014; 6 weeks). This was caused by increased end-diastolic volume (EDV), stroke volume (SV) and heart rate (HR) consistent with an increased volume load. A continuous increase in heart weight peaked at 12 weeks. This increase combined with a distinct end-diastolic left ventricular dilation implied eccentric hypertrophy. CONCLUSION: Small rodent MRI is feasible and clearly depicts fistula maturation and cardiac alterations. This technique proved to be a valuable tool for longitudinal in vivo monitoring in this model, which strongly resembles clinical findings in hemodialysis patients.

Cardiovascular remodeling during arteriovenous fistula maturation in a rodent uremia model.

PURPOSE: The aim of this study was to evaluate cardiovascular remodeling after arteriovenous fistula (AVF) surgery and to characterize the effect of chronic kidney disease (CKD) in a rodent femoral AVF model. METHODS: Sixteen rats (8 healthy; 8 CKD) underwent femoral AVF surgery; 4 animals served as controls. AVF and cardiac morphology as well as function were assessed during the fistula maturation process (until day 84 after surgery) using magnetic resonance imaging and histopathological analyses. RESULTS: Histopathological analysis revealed that a glomerular and interstitial nephropathy caused CKD. In healthy and CKD animals, AVF surgery resulted in progressive downstream vein dilation and a subsequent cardiac adaptation. This vein dilation during maturation was less in CKD rats during the early postoperative course (day 21: p=0.0475) and similar thereafter until day 84. The dilation was accompanied by an aggravation of neointimal hyperplasia (NIH) and calcification in AVFs of CKD rats. The chronic volume overload resulted in both groups in a significantly increased end-diastolic volume (healthy rats: p=0.0087; CKD rats: p=0.0333). Simultaneously, cardiac output increased 195% in healthy and 244% in uremic rats, which was caused by both a significantly increased stroke volume and heart rate. The left ventricular mass rose in AVF animals and was increased at the end of the study period, indicating a distinct cardiac hypertrophy. CONCLUSION: Our rat model showed typical cardiovascular features of the AVF maturation process, which strongly resemble clinical findings in patients. Uremia caused inferior dilation in the early phase after surgery and an exacerbation of NIH. This model should help to identify the cellular and molecular mechanisms that contribute to AVF failure.

Chronic kidney disease aggravates arteriovenous fistula damage in rats.

Neointimal hyperplasia (NIH) and impaired dilatation are important contributors to arteriovenous fistula (AVF) failure. It is unclear whether chronic kidney disease (CKD) itself causes adverse remodeling in arterialized veins. Here we determined if CKD specifically triggers adverse effects on vascular remodeling and assessed whether these changes affect the function of AVFs. For this purpose, we used rats on a normal diet or on an adenine-rich diet to induce CKD and created a fistula between the right femoral artery and vein. Fistula maturation was followed noninvasively by high-resolution ultrasound (US), and groups of rats were killed on 42 and 84 days after surgery for histological and immunohistochemical analyses of the AVFs and contralateral femoral vessels. In vivo US and ex vivo morphometric analyses confirmed a significant increase in NIH in the AVFs of both groups with CKD compared to those receiving a normal diet. Furthermore, we found using histological evaluation of the fistula veins in the rats with CKD that the media shrank and their calcification increased significantly. Afferent artery dilatation was significantly impaired in CKD and the downstream fistula vein had delayed dilation after surgery. These changes were accompanied by significantly increased peak systolic velocity at the site of the anastomosis, implying stenosis. Thus, CKD triggers adverse effects on vascular remodeling in AVFs, all of which contribute to anatomical and/or functional stenosis.

Functional and structural response of arterialized femoral veins in a rodent AV fistula model.

BACKGROUND: Neointimal hyperplasia is considered to be the major cause of arteriovenous fistula (AVF) failure, resulting in vein wall thickening, stenosis and, ultimately, occlusion. Ultrasound (US) has been shown to be effective for detecting these morphological changes in patients. The aim of this study was to develop an experimental AVF model in the rat that shows typical features of fistula maturation and allows longitudinal monitoring of fistula veins by high-resolution ultrasound. METHODS: AVFs were created by a handsewn end-to-side anastomosis between the femoral vein and the femoral artery in 15 rats. A group of sham-operated animals (n = 3) served as controls. Time-related functional and morphological AVF characteristics were assessed up to 12 weeks using ultrasound (15-MHz transducer) and were correlated to histopathological changes. RESULTS: All rats survived surgery, and the patency rate was 93%. US showed a 2-fold increase in the fistula vein diameter and mean flow velocity as well as a 4-fold increase in the intima-media thickness without significant luminal loss. The afferent femoral artery exhibited no change in intima-media thickness and only minimal adaptive increases in diameter and flow velocity. Histological evaluation confirmed these observations. CONCLUSIONS: Our AVF model in the rat demonstrates maturation effects in fistula veins similar to typical clinical findings in haemodialysis patients. Noninvasive ultrasound proved to be a valuable tool for longitudinal in vivo monitoring of the fistulas in this rodent model.