title: Cardiovascular remodeling during arteriovenous fistula maturation in a rodent uremia model.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Vascular Surgery, University Hospital RWTH Aachen, Aachen, Germany. slanger@ukaachen.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Langer
authors.forename: Niklas
authors.initials: N
authors.lastname: Paulus
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Koeppel
authors.forename: Andreas
authors.initials: A
authors.lastname: Greiner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Buhl
authors.forename: Gabriele A
authors.initials: GA
authors.lastname: Krombach
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Jacobs
authors.forename: Lieven
authors.initials: L
authors.lastname: Kennes
authors.forename: Maria
authors.initials: M
authors.lastname: Kokozidou
mesh_terms: D000225:Adenine; D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D002302:Cardiac Output; D006332:Cardiomegaly / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D005260:Female; D005263:Femoral Artery / Q000473:pathology / Q000601:surgery*; D005268:Femoral Vein / Q000473:pathology / Q000601:surgery*; D006339:Heart Rate; D006439:Hemodynamics; D006965:Hyperplasia; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014511:Uremia / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D061205:Vascular Calcification / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D000225:Adenine