MATRIX METALLOPROTEINASE INHIBITION LIMITS ARTERIAL ENLARGEMENT IN A RODENT ARTERIOVENOUS-FISTULA MODEL

Background, We administered a specific, nonselective matrix metallopro teinase (MMP) inhibitor (RS-113, 456) to examine the effect of MMP inh ibition on flow-mediated arterial enlargement in a rodent arteriovenou s fistula (ATF) model. Methods. Four groups of male Sprague-Dawley rat s were created: sham (sham operated; n = 10), control (2.0 mm left com mon femoral AVF alone; n = 16), vehicle (AVF plus 0.5 mt vehicle orall y twice a day; n = 20), and treatment (AVF plus 25 mg/kg RS-113, 456 i n 0.5 mL vehicle orally twice a day; n = 16). Heart rate, mean arteria l pressure, and body weight were recorded on postoperative days 0, 7; 14, and 21. On day 21, AVF patency was confirmed the infrarenal aorta and common iliac arteries were exposed blood flow velocity and externa l diameter were measured, and wall shear stress (WSS) was calculated. Analysis was performed by paired two-tailed Student t test, one-way an alysis of variance, and the Bonferroni/Dunn procedure for Post hoc tes ting. Results. Heart rate mean arterial pressure, and weight did not v ary at any time between groups. Aortic and left iliac diameter was lar ger in the AVF groups than in sham groups (P <.001), and control and v ehicle groups were larger than treatment groups (P <.0001). Changes in aortic and left iliac flow were also significant (AVF was more than s ham and control, and vehicle was more than treatment). No difference i n aortic and left iliac artery velocity and WSS or right iliac diamete r velocity, flow, or WSS was observed between groups. Conclusions. MMP inhibition diminishes flow-mediated arterial enlargement in the rat A VF model.