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Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Reperfusion injury after critical intestinal ischemia and its correction with perfluorochemical emulsion "perftoran"
Vyacheslav Leontjevich Kozhura1, Dmitriy Alexeevich Basarab, Marina Innokentievna Timkina
1Laboratory of Experimental Therapy, Research Institute of General Reanimatology, Russian Academy of Medical Sciences, Moscow 107031, Russia.
Aim:
To investigate the anti-ischemic properties of perfluorochemical emulsion "perftoran" in mesenteric region.
Methods:
Experiments were conducted on 146 nonlinear white male rats weighing 200-350 g. Partial critical intestinal ischemia was induced by thorough atraumatic strangulation of 5-6 cm jejunal loop with its mesentery for 90 min. Global critical intestinal ischemia was made by atraumatic occlusion of the cranial mesenteric artery (CMA) for 90 min also. Perftoran (PF, 0.8-1.0 mL per 100 g) in experimental groups or 0.9% sodium chloride in control groups was injected at 75 min of ischemic period. Mean systemic arterial blood pressure (BP(M)) registration, intravital microscopy and morphological examination of ischemic intestine and its mesentery were performed in both groups.
Results:
During 90 min of reperfusion, BP(M) progressively decreased to 27.3+/-7.4% after PF administration vs 38.6+/-8.0% in the control group of rats with partial intestinal ischemia (NS) and to 50.3+/-6.9% vs 53.1+/-5.8% in rats after global ischemia (NS). During the reperfusion period, full restoration of microcirculation was never registered; parts with restored blood flow had leukocyte and erythrocyte stasis and intra-vascular clotting, a typical "non-reflow" phenomenon. The reduction of mesenteric 50-400 mum feeding artery diameter was significantly less in the PF group than in the control group (24+/-5.5% vs 45.2+/-3.6%, P<0.05) 5 min after partial intestinal ischemia. This decrease progressed but differences between groups minimized at the 90(th) min of reperfusion (41.5+/-4.2% and 50.3+/-2.8%, respectively). In reperfusion of rat's intestine, a significant mucosal alteration was registered. Villous height decreased 2.5-3 times and the quantity of crypts decreased more than twice. In the group of rats administered PF, intestinal mucosal layer was protected from irreversible post-ischemic derangement during reperfusion. Saved cryptal epithelial cells were the source of regeneration of the epithelium, which began to cover renewing intestinal villi after 24 h of blood flow restoration. View of morphological alterations was more heterogeneous in CMA groups.
Conclusion:
Systemic administration of perftoran promotes earlier and more complete structural regeneration during reperfusion in rats after partial and global critical intestinal ischemia.
Insights
Perfluorochemical emulsion "perftoran" administration improved intestinal recovery after ischemia in rats. It protected the mucosal layer, promoting faster regeneration of villi and crypts during reperfusion.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Surgical Research
Background:
- Intestinal ischemia poses significant clinical challenges, often leading to severe tissue damage and impaired recovery.
- Perfluorochemical emulsions are investigated for their potential to improve oxygen delivery and tissue preservation during ischemic events.
Purpose of the Study:
- To evaluate the anti-ischemic and regenerative effects of perfluorochemical emulsion "perftoran" in a rat model of mesenteric ischemia.
- To assess the impact of perftoran on microcirculation, tissue morphology, and mucosal regeneration following partial and global intestinal ischemia.
Main Methods:
- Induction of partial (jejunal loop strangulation) and global (cranial mesenteric artery occlusion) intestinal ischemia in rats.
- Intravenous administration of perftoran or saline (control) during the ischemic period.
- Monitoring of systemic blood pressure, intravital microscopy, and morphological examination of the ischemic intestine and mesentery.
Main Results:
- Perftoran administration showed a trend towards better blood pressure maintenance during reperfusion but did not fully prevent microcirculatory disturbances like stasis and non-reflow.
- Significantly reduced mesenteric feeding artery constriction was observed in the perftoran group after partial ischemia.
- Perftoran protected the intestinal mucosal layer from irreversible damage, preserving cryptal epithelial cells crucial for regeneration.
Conclusions:
- Systemic administration of perftoran promotes earlier and more complete structural regeneration in the rat intestine following partial and global ischemia.
- Perftoran demonstrates protective effects on intestinal mucosa, facilitating epithelial regeneration during reperfusion.
