Luminal oxygen delivery improves small intestinal ischemic damage in a pig model

Intestinal ischemia reperfusion injury (IRI) is mainly caused by lymphocyte recruitment and radical oxygen species release after reoxygenation of a temporary ischemic bowel. Preservation of the intestinal graft with intravascular fluids leads to more IRI and worse graft survival in comparison to other organs. Importantly, with the standard intravascular preservation the lumen of the bowel is not used. Recent findings in rodent models and human intestinal explants show that luminal preservation with specific solutions can reduce intestinal IRI. We developed a pig model of small bowel ischemia, and tested whether luminal administration of gaseous oxygen (O2) ameliorates tissue damage. Segments of pig’s jejunum were chosen for a no-flow ischemia model. These were approached by mid-line laparotomy and opened on both ends for insertion of catheters. Mesenteric vessels were ligated, as were the intramural collaterals by fixing the bowel around tubes placed inside and at the border of the selection. The abdomen was closed after ligation. Ischemia and its treatment lasted for 2 hours. Sham animals (GS, n=6) were not treated with O2. In the treatment group (GT, n=6) small intestine segments were supplied with 100% O2 delivered at low-flow (5ml/min) and high-pressure (2 bar) with a manometry catheter. Heart rate, mean arterial pressure, temperature, intraluminal PCO2, PO2 and pH were recorded. Pulmonary wedge pressure, blood gas and haemoglobin concentration from arterial samples were measured every 30 minutes. Lactate was measured from venous blood. Histology was evaluated (Chiu score) after 2 hours of treatment at different distances from the O2 supply position (up to 60 centimetres proximal and distal from the tip of the catheter (centre) and analysed by a Mann-Whitney rank sum test (p<0.05 considered statistically significant). Systemic hemodynamics, acid-base variables and biochemical markers did not vary between groups. Intraluminal PO2 decreased to nearly 0 mmHg in GS after 30 minutes. It increased to 679 mmHg after 90 minutes in GT. PCO2 peaked at 135 mmHg after 30 minutes in GS and decreased to 43 mmHg after 2 hours in GT. GS showed severe histological damage at all points (mean Chiu score 3 ±0.1). GT showed a gradual increase in mucosal damage, directly related to the distance from the centre of oxygenation (mean Chiu score 1.5±1.1). Statistically significant differences between the scores for both groups were found in the centre (p<0.005) and up to 20 centimetres proximal and distal (p<0.05). This study shows that 2 hours ischemia leads to severe mucosal damage in the small bowel of pigs and can be largely prevented by luminal application of gaseous O2. This is the first model in large animals that shows the beneficial effect of direct oxygenation through the lumen of the small bowel and prompts further research on luminal perfusion and oxygenation of the bowel in order to reduce IRI.