Role of activated protein C on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis induced by cecal ligation and puncture: an experimental study in the rat.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. The delaying effects of intra-abdominal sepsis on wound healing process in colonic anastomoses have been previously demonstrated. This study was designed to investigate the role of APC on wound healing process in left colonic anastomoses in the presence of intra-abdominal sepsis. METHODS: The left colonic anastomosis was performed in 48 rats that were divided into four groups: (1) sham-operated group, laparatomy plus cecal mobilization (n = 12); (2) sham + APC group, identical to group I except for APC treatment (n = 12); (3) CLP group, cecal ligation and puncture (n = 12); 4) CLP + APC-treated group, 100 microg/kg, 15 min before the construction of colonic anastomosis (n = 12). Anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), and nitrate/nitrite (NO3(-) /NO2(-)) levels. The plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and D-dimer also were measured. RESULTS: Intra-abdominal sepsis led to significant decreases in colonic anastomotic bursting pressures and tissue HP contents, along with increases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). However, APC treatment led to significant increases in anastomotic bursting pressures and tissue HP ontents, along with decreases in MPO activity, MDA and NO3(-) /NO2(-) levels, and also plasma levels of TNF-alpha, IL-6, and D-dimer (P < 0.05). CONCLUSIONS: This study clearly showed that APC treatment prevented the delaying effects of intra-abdominal sepsis on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of anastomotic healing during particular surgeries in which sepsis-induced injury occurs.

Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and ant-inflammatory activities. APC has been shown to attenuate deleterious effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to investigate the effects of APC on intestinal mucosal injury induced by superior mesenteric occlusion. MATERIALS AND METHODS: Male Wistar-albino rats were allocated into four groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to Group 1 except for APC treatment (n = 12); (3) I/R group, 60 min of ischemia followed by 3-h of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 mug/kg injection of APC intravenously, 15 min before reperfusion (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale from 0 to 5, histopathologically, and by measuring activities of oxidative and antioxidative enzymes as well as nitrate/nitrite levels, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. Animal survival was observed up to 1 wk. RESULTS: Intestinal mucosal injury scores were significantly decreased with APC administration (P < 0.05). APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the intestinal tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes in the intestinal tissues (P < 0.05). Intestinal edema was significantly alleviated with APC treatment (P < 0.05). The survival rate of rats in the APC-treated group were significantly higher than that of the I/R-treated group (P < 0.05). CONCLUSIONS: This study clearly showed that APC treatment significantly attenuated intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether APC has a useful role in reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.

Activated protein C prevents deleterious effects of remote reperfusion injury caused by intestinal ischemia on wound healing in the left colonic anastomoses: an experimental study in the murine model.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and antiinflammatory activities. The delaying effects of remote reperfusion injury on the wound-healing process in colonic anastomoses have been previously shown. In this study, we aimed to investigate whether APC protects against deleterious systemic effects of intestinal ischemia/reperfusion (I/R) injury on colonic anastomotic wound healing process. METHODS: Male Wistar-albino rats were randomly allocated into 4 groups, and a left colonic anastomosis was performed in all animals: (1) sham-operated group, simultaneously with left colonic anastomosis, the superior mesenteric artery and collateral branches were divided from the celiac axis, and the inferior mesenteric artery were isolated but not occluded (group 1, n = 12), (2) sham + APC group, identical to group 1 except for APC treatment (100 microg/kg, intravenously, 15 minutes before construction of the colonic anastomosis), (group 2, n = 12), (3) intestinal I/R group, 60 minutes of superior mesenteric ischemia followed by reperfusion (group 3, n = 12), and (4) APC-treated group, (100 microg/kg, intravenously, 15 minutes before reperfusion) (group 4, n = 12). All animals were sacrificed, and colonic anastomotic bursting pressures were measured in vivo on day 7. Tissue samples were obtained for analysis of hydroxyproline contents, nitrate/nitrite levels, and activities of oxidative and antioxidative enzymes. The plasma levels of proinflammatory cytokines and D-dimer were also measured. RESULTS: Intestinal I/R led to significant decreases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with increases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). However, APC treatment led to significant increases in colonic anastomotic bursting pressures, tissue hydroxyproline contents, and activities of antioxidative enzymes, along with decreases in tissue nitrate/nitrite levels, activities of oxidative enzymes, and plasma levels of proinflammatory cytokines and D-dimer (P < .05). CONCLUSION: This study clearly showed that APC treatment prevented the delaying effects of remote I/R injury on colonic anastomotic wound healing process. Further clinical studies are required to determine whether APC has a useful role in the enhancement of colonic anastomotic wound healing after particular operations in which I/R injury occurs.

Activated protein C attenuates intestinal reperfusion-induced acute lung injury: an experimental study in a rat model.

BACKGROUND: Activated protein C (APC) is a serine protease with anticoagulant and anti-inflammatory activities. APC has been shown to attenuate local deleterious effects of ischemia/reperfusion (I/R) injury in many organs. We aimed to investigate the effects of APC on lung reperfusion injury induced by superior mesenteric occlusion. METHODS: Male Wistar-Albino rats were allocated into 4 groups: (1) sham-operated group, laparotomy without I/R injury (n = 12); (2) sham + APC group, identical to group 1 except for APC treatment (n = 12); (3) intestinal I/R group, 60 minutes of ischemia followed by 3 hours of reperfusion (n = 12); and (4) I/R + APC-treated group, 100 microg/kg injection of APC intravenously, 15 minutes before reperfusion (n = 12). Evans blue dye was injected into half of the rats in all groups. We assessed the degree of pulmonary tissue injury by measuring activities of oxidative and antioxidative enzymes, as well as nitrate (NO(3)(-))/nitrite (NO(2)(-)) levels, biochemically. We evaluated acute lung injury (ALI) by establishing pulmonary neutrophil sequestration and ALI scoring histopathologically. Pulmonary edema was estimated by using Evans blue dye extravasation and wet/dry ratios. The plasma levels of proinflammatory cytokines and D-dimer were measured. RESULTS: APC treatment significantly reduced activities of oxidative enzymes and nitrate/nitrite levels in the lung tissues, and plasma levels of proinflammatory cytokines and D-dimer, and also significantly increased activities of antioxidative enzymes (P < .05). Pulmonary neutrophil sequestration and ALI scores were decreased significantly with APC administration (P < .05). In addition, APC treatment significantly alleviated pulmonary edema (P < .05). CONCLUSIONS: This study clearly showed that APC treatment significantly attenuated the lung reperfusion injury. Further clinical studies are required to clarify whether APC has a useful role in the reperfusion injury during particular surgeries in which I/R-induced organ injury occurs.