T. M. Gisinger1,2, V. M. Baratta2, M. Barahona2, J. Ollodart2, D. Mulligan2, J. P. Geibel2,3 1Paracelsus Medical University,Department Of Medicine,Salzburg, SALZBURG, Austria 2Yale University School of Medicine,Department Of Surgery,New Haven, CT, USA 3Yale University School of Medicine,Department Of Cellular And Molecular Physiology,New Haven, CT, USA
Introduction: Ischemic colitis (IC) is the most common type of intestinal ischemia and arises when the colonic blood supply does not meet cellular metabolic demands. Though clinical evidence is lacking, many patients with IC are nonoperatively managed with empiric antibiotics. It has been proposed that antibiotics mitigate ischemia by reducing bacterial translocation and preventing breakdown of the epithelial barrier. In this study, we demonstrate that colonic tissue perfused with Penicillin G is more resilient to ischemic injury than tissues not exposed to the drug. These findings suggest a new clinical management paradigm of preventing ischemic conditions of the gastrointestinal tract.
Methods: Colon segments from rats were obtained and perfused with an ex-vivo intestinal perfusion device. The perfusion device consists of concentric chambers that contain the bowel segments perfused at 37°C. FITC-Inulin, fluorescein isothiocyanate, was used to assess the ischemic conditions of the intestinal grafts in real-time; a drop in fluorescence (FITC-Inulin concentration) is indicative of cellular ischemic injury. Intestinal segments were perfused with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, HEPES-Ringer. To create an ischemic environment, the HEPES-Ringer was pre-saturated with 100% N2 and perfused on extraluminal surface of all rat colonic segments. The intraluminal components of experimental colons were perfused with 5 mM Penicillin G, whereas control segments were not.
Results: Control (without Penicillin G) distal colon samples showed a significant decrease in FITC-inulin fluorescence compared with experimental (with Penicillin G) distal colons, (26.98 ± 5.035 μM FITC vs 43.62 ± 1.569 μM FITC, respectively p 0.0083, Figure 1). This indicates that Penicillin G minimizes colonic fluid secretion, which is a marker for cell death. A similar trend was seen with proximal colon rat segments (42.7 ± 1.984 μM vs. 33.28 ± 3.455 μM FITC, p 0.0356).
Conclusion: Patients with ischemic colitis are often clinically treated with antibiotics, though the pathophysiological basis of their use is not well-proven. Our study shows that Penicillin G exposure prolongs colonic viability under ischemic conditions. This result will help further guide clinical management of ischemia in the gastrointestinal tract. Further investigation of the precise mechanism by which Penicillin G mitigates ischemia needs to be conducted.
