Clinical-alimentary tractAcquired microvascular dysfunction in inflammatory bowel disease: loss of nitric oxide-mediated vasodilation☆
Section snippets
General preparation
All protocols were approved by the institutional review board of the Medical College of Wisconsin. Human submucosal arterioles were dissected from full-thickness intestinal specimens obtained from patients undergoing bowel operations. Immediately following resection in the operating room, excised tissues were placed in Krebs’ buffer solution (4°C) with the following composition (in mmol/L): NaCl, 118; KCl, 4.7; CaCl2, 2.5; KH2PO4, 1.2; MgSO4, 1.2; NaHCO3, 20; Na2/ethylenediaminetetraacetic
Isolation of microvessels
Submucosal microvessels were isolated from 34 controls and 33 patients with IBD (19 with CD and 14 with UC). Microvessels ranging from 56 to 302 μm in diameter were dissected from full-thickness intestinal specimens and used in all experiments (Figure 1A). Clinical data on the patients with IBD are included in Table 1. Mean passive luminal diameters of intestinal microvessels isolated from these clinical groups were similar (Table 2).
Impaired endothelium-dependent dilation in IBD
Vessels isolated from histologically normal bowel in
Discussion
This study is the first to directly examine vasodilator responses in human intestinal microvessels in healthy subjects and in patients with CD and UC. Our investigation shows a profound impairment in microvascular endothelial function in chronically inflamed IBD patient tissues that is absent in adjacent ”normal” segments or in vessels from patients with active inflammatory intestinal conditions. This is significant, because the microvasculature plays a fundamental role in health and tissue
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Supported by the Cardiovascular Center and Impulse Dynamics, the Crohn’s and Colitis Foundation of America (to D.G.B.), and the Digestive Disease Center at the Medical College of Wisconsin.