title: Regional and systemic hemodynamic responses following the creation of a murine arteriovenous fistula.
abstract: The study of hemodynamic alterations following the creation of an arteriovenous fistula (AVF) is relevant to vascular adaptive responses and hemodialysis access dysfunction. This study examined such alterations in a murine AVF created by anastomosing the carotid artery to the jugular vein. AVF blood flow was markedly increased due to reduced AVF vascular resistance. Despite such markedly increased basal blood flow, AVF blood flow further increased in response to acetylcholine. This AVF model exhibited increased cardiac output and decreased systemic vascular resistance; the kidney, in contrast, exhibited decreased blood flow and increased vascular resistance. Augmentation in AVF blood flow was attended by increased arterial heme oxygenase-1 (HO-1) mRNA and protein expression, the latter localized to smooth muscle cells of the AVF artery; AVF blood flow was substantially reduced in HO-1(-/-) mice compared with HO-1(+/+) mice. Finally, in a murine model of a representative disease known to exhibit impaired hemodynamic responses (sickle cell disease), the creation of an AVF was attended by decreased AVF flow and impaired AVF function. We conclude that this AVF model exhibits markedly increased AVF blood flow, a vasodilatory reserve capacity, increased cardiac output, decreased renal blood flow, and a dependency on intact hemodynamic responses, in general, and HO-1 expression, in particular, in achieving and maintaining AVF blood flow. We suggest that these findings support the utility of this model in investigating the basis for and the consequences of hemodynamic stress, including shear stress, and the pathobiology of hemodialysis AVF dysfunction.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester 55905, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Kang
authors.forename: Satsuki
authors.initials: S
authors.lastname: Yamada
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Hernandez
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Croatt
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Grande
authors.forename: Julio P
authors.initials: JP
authors.lastname: Juncos
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Vercellotti
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hebbel
authors.forename: Zvonimir S
authors.initials: ZS
authors.lastname: Katusic
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
authors.forename: Karl A
authors.initials: KA
authors.lastname: Nath
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000755:Anemia, Sickle Cell / Q000503:physiopathology; D000818:Animals; D001164:Arteriovenous Fistula / Q000201:enzymology / Q000503:physiopathology*; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002339:Carotid Arteries; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007601:Jugular Veins; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D012039:Regional Blood Flow; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D051547:Heme Oxygenase-1; D000109:Acetylcholine