BACKGROUND: Intestinal ischemia/reperfusion causes intestinal mucosal injury, which may result in bacterial translocation (BT) and multiple organ failure. Lung injury is a common complication after intestinal ischemia/reperfusion. Adiponectin is an antiinflammatory adipokine, and it plays an important role in the development of metabolic syndrome in hypoadiponectinemia. In atherosclerosis with hypoadiponectinemia, BT also may aggravate injuries induced by intestinal ischemia/reperfusion. METHODS: Wistar rats were divided into 3 groups: Normal group (normal diet), Chol group (2% high cholesterol diet), and Chol+1400W group (Chol group plus 1400W, an inducible nitric oxide [iNOS] inhibitor, at 1 mg/kg intraperitoneally 30 minutes preoperatively). The serum concentrations of lipids and adiponectin and vascular responses were measured. After midline laparotomy (time, T0), the superior mesenteric artery was occluded with a microvascular clamp for 30 minutes, followed by 360 minutes of reperfusion (T1). Intestinal injury was assessed from microcirculatory flow, histology, serum diamine oxidase activity, and permeability. Lung injury was assessed by histology, pulmonary permeability index (PPI), and wet-to-dry lung weight (W/D) ratio. Intestinal and lung nitric oxide (NO) concentrations were also measured. BT was assessed by serum peptidoglycan (PG) concentration. RESULTS: The Chol and Chol+1400W groups developed hyperlipidemia and hypoadiponectinemia; the 2 groups also had vascular endothelial dysfunction without histological changes, indicating early atherosclerosis. These groups also showed poor recovery of intestinal microcirculatory flow at T1. The serum diamine oxidase activity, histological intestinal damage, and permeability were elevated at T1 in the Chol group; however, these findings were not significant in the Normal and Chol+1400W groups. Histological lung damage and lung PPI and W/D ratio were increased only in the Chol group. Intestinal and lung NO concentrations were significantly elevated at T1 in the Chol group. The serum PG concentration was elevated significantly in the Chol group. CONCLUSION: In atherosclerotic rats with hypoadiponectinemia, intestinal microcirculatory flow does not recover adequately after intestinal ischemia/reperfusion because of endothelial dysfunction. Atherosclerosis with hypoadiponectinemia increased the incidence of BT further by aggravating intestinal mucosal injury and, moreover, it aggravated lung injury. Although inhibition of iNOS does not lead to adequate recovery of intestinal microcirculatory flow, it reduces injury by decreasing the amount of NO derived from high enzymatic iNOS activity in the intestine.
BACKGROUND:Intestinal ischemia/reperfusion causes intestinal mucosal injury, which may result in bacterial translocation (BT) and multiple organ failure. Lung injury is a common complication after intestinal ischemia/reperfusion. Adiponectin is an antiinflammatory adipokine, and it plays an important role in the development of metabolic syndrome in hypoadiponectinemia. In atherosclerosis with hypoadiponectinemia, BT also may aggravate injuries induced by intestinal ischemia/reperfusion. METHODS:Wistar rats were divided into 3 groups: Normal group (normal diet), Chol group (2% high cholesterol diet), and Chol+1400W group (Chol group plus 1400W, an inducible nitric oxide [iNOS] inhibitor, at 1 mg/kg intraperitoneally 30 minutes preoperatively). The serum concentrations of lipids and adiponectin and vascular responses were measured. After midline laparotomy (time, T0), the superior mesenteric artery was occluded with a microvascular clamp for 30 minutes, followed by 360 minutes of reperfusion (T1). Intestinal injury was assessed from microcirculatory flow, histology, serum diamine oxidase activity, and permeability. Lung injury was assessed by histology, pulmonary permeability index (PPI), and wet-to-dry lung weight (W/D) ratio. Intestinal and lung nitric oxide (NO) concentrations were also measured. BT was assessed by serum peptidoglycan (PG) concentration. RESULTS: The Chol and Chol+1400W groups developed hyperlipidemia and hypoadiponectinemia; the 2 groups also had vascular endothelial dysfunction without histological changes, indicating early atherosclerosis. These groups also showed poor recovery of intestinal microcirculatory flow at T1. The serum diamine oxidase activity, histological intestinal damage, and permeability were elevated at T1 in the Chol group; however, these findings were not significant in the Normal and Chol+1400W groups. Histological lung damage and lung PPI and W/D ratio were increased only in the Chol group. Intestinal and lung NO concentrations were significantly elevated at T1 in the Chol group. The serum PG concentration was elevated significantly in the Chol group. CONCLUSION: In atheroscleroticrats with hypoadiponectinemia, intestinal microcirculatory flow does not recover adequately after intestinal ischemia/reperfusion because of endothelial dysfunction. Atherosclerosis with hypoadiponectinemia increased the incidence of BT further by aggravating intestinal mucosal injury and, moreover, it aggravated lung injury. Although inhibition of iNOS does not lead to adequate recovery of intestinal microcirculatory flow, it reduces injury by decreasing the amount of NO derived from high enzymatic iNOS activity in the intestine.