Does microcirculation play a role in the pathogenesis of inflammatory bowel diseases? Answers from intravital microscopic studies in animal models

The potential role of intestinal microcirculation for the development of inflammatory bowel diseases (IBD) has not been systematically investigated, mainly because of methodological problems. Using a well-established rodent model of IBD and intravital microscopy, the present study investigated whether (and when) gut microcirculation is disturbed in IBD, and whether microcirculatory disorders contribute to histological and functional alterations in the development of IBD. Colitis was induced by rectal injection of trinitrobenzene sulfonic acid. After 1, 3, and 15 days rats were laparotomized for intravital microscopic determination of mucosal colonic blood flow. In a second series it was examined whether enhancing colonic capillary blood flow by hemodilution therapy stabilizes colonic wall resistance and other electrophysiological parameters of gut permeability. Additional measurements involved hemodynamic monitoring and histological examinations. Colonic capillary blood flow was significantly decreased 3 days after colitis induction (1.8 +/- 0.05 vs. 2.6 +/- 0.04 nl/min in healthy control animals) when histology revealed signs of acute inflammation, and normal values after 15 days (2.4 +/- 0.06 nl/min) when chronic histological changes were evident. Hemodilution therapy enhanced colonic capillary blood flow in the initial stage (2.1 +/- 0.02 vs. 1.6 +/- 0.02 nl/min in saline-treated animals with trinitrobenzene sulfonic acid colitis) and improved gut resistance and electronic chloride secretion (73 +/- 15 vs. 33 +/- 8 microA cm2). Histological alterations were not significantly attenuated. Impaired colonic capillary blood flow in the initial stage of experimental colitis and improved mucosal microcirculation with stabilized gut permeability suggests that the early microcirculatory disturbances precede chronic histological changes and influence functional alterations in the course of the disease. Research should be continued in this field because important mechanisms in the pathogenesis of IBD and potentially therapeutic (vasoactive) substances may otherwise be overlooked.