Abstract
Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate the clinical and anti-inflammatory effects of RIC in patients with active ulcerative colitis (UC). We included 22 patients with active UC in this explorative, randomized, sham-controlled clinical trial. The patients were randomly assigned 1:1 to RIC (induced in the arm through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) or sham (incomplete inflation of the blood-pressure cuff) once daily for 10 days. Outcome variables were measured at baseline and on day 11. When compared with sham, RIC did not affect inflammation in the UC patients measured by fecal calprotectin, plasma C-reactive protein, Mayo Score, Mayo Endoscopic Subscore, Nancy Histological Index or inflammatory cytokines involved in UC and RIC. The mRNA and miRNA expression profiles in the UC patients were measured by RNA sequencing and multiplexed hybridization, respectively, but were not significantly affected by RIC. We used the Langendorff heart model to assess activation of the organ protective mechanism induced by RIC, but could not confirm activation of the organ protective mechanism in the UC patients.
Highlights
Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury
RIC reduced the mean infarct size/area-at-risk ratio (IS/AAR)% from 80.06 to 63.04 (p-value 0.034) in the healthy controls confirming the ability the Langendorff setup to detect the cardioprotective effect of RIC. This is the first study of RIC in active ulcerative colitis (UC) patients and in an inflammatory condition in humans
After 10 days of daily RIC or sham intervention, we did not observe a reduction in fecal calprotectin (FC), clinical symptoms, endoscopic or histological activity scores in the RIC group compared to the sham group
Summary
Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. Studies suggest that RIC reduces activation of neutrophils after ischemic preconditioning[16] and down-regulates genes involved in pro-inflammatory pathways including leukocyte activation, innate immunity, cell adhesion, and intracellular signaling[17]. In animal models RIC reduced transcription factors NF-κB, TNF-α, IL-1β, and intercellular adhesion molecule 1 (ICAM-1) in intestinal I/R injury[19,20], as well as TNF-α, IL-1β, IL-6, and IL-10 in mice with lipopolysaccharide induced sepsis[21]. These secondary effects are overall desirable in UC patients with active disease
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