Pentoxifylline associated to hypertonic saline solution attenuates pulmonary and intestinal inflammatory process and increases Bcl-2 expression following intestinal ischemia/reperfusion in rats

Geraldo NM Marques¹, Roberto Rasslan¹, Alessandro R Belon¹, Juliana G Carvalho, Edivaldo M Utiyama¹, Samir Rasslan¹, EDNA FS MONTERO¹

¹SURGERY, UNIVERSITY OF SÃO PAULO, Santana de Parnaíba- SP, Brazil

This work aims to evaluate pulmonary and intestinal inflammatory and apoptotic process after intestinal ischemia-reperfusion injury, modulated by pentoxifylline (PTX) and hypertonic saline solution (HS). It was used 24 male Wistar rats weighing 200 to 250g. Rats were randomized into 4 groups with 6 animals in each: I/R group, intestinal ischemia for 40 min and reperfusion for 80 min; HS group, same procedure but adding HS (4ml/kg), before reperfusion; PTX group, same procedure but adding PTX (30mg/kg), before reperfusion; HS+PTX group, same procedure but adding HS and PTX (same dosage), before reperfusion. All animals were heparinized (100 U/kg) and anesthetized with ketamine (60 mg/kg) and xylazine (10 mg/kg) intraperitoneally. Femoral artery was dissected for blood samples and solution infusion. After laparotomy, the superior mesenteric artery and vein were dissected and clamped to promote ischemia. Blood samples were collected after ischemia and at 40 and 80 minutes of reperfusion for gas analysis. Intestinal and pulmonary fragments were removed for morphological, by hematoxylin-eosin staing, and histochemical studies for COX2, Bcl2 and cleaved caspase-3. Morphologic tissue injuries, evaluated by hematoxylin-eosin staining, showed higher grades on IR, in contrast to other groups.The histochemical study showed lesser expression of COX2 and BCL2 on HS+PTX group, in contrast to other groups. The values of sO₂ were higher on treated groups at 40(p=0.0099) and 80(p=0.0074) minutes of reperfusion. Serum lactate values were closer to normal on treated groups after 40(p=0.0069) and 80(p=0.0098) minutes of reperfusion. Based on our data, we conclude that the combined use of pentoxifylline and hypertonic saline offers best results on metabolic, inflammatory and apoptotic inhibitory aspects after intestinal I/R.