Intestinal Intestinal Ischemia-reperfusion Research Articles

Protective effect of bilirubin in ischemia-reperfusion injury in the rat intestine.

Although bilirubin, which crosses the blood-brain barrier, can cause irreversible brain damage, it also possesses antioxidant properties that may be protective against oxidative stress. Intestinal ischemia-reperfusion (IR) injury results in cell destruction, mediated via the generation of reactive oxygen species. Although increased serum bilirubin is correlated with increased antioxidant potential in the face of hyperoxia, evidence of bilirubin-associated protective effect against IR injury remains nonspecific. We therefore sought to investigate whether hyperbilirubinemia would be protective against IR injury to the intestine. Young adult rats were randomly assigned to one of three groups: 1) IR/control (n = 12); 2) IR/hyperbilirubinemia (n = 10), in which IR was generated while the rats were treated with a continuous infusion of bilirubin; and 3) hyperbilirubinemia controls (n = 10). Blood and intestinal tissue samples were obtained to determine serial thiobarbituric acid reducing substances (index of lipid peroxidation) and for xanthine oxidase/xanthine dehydrogenase and glutathione/glutathione disulfide ratios. Intestinal histopathology was graded from 1 (normal) to 4 (severe necrotic lesions). Histopathologic scoring and circulating and tissue thiobarbituric acid reducing substances were highest in the IR/control animals compared with either the IR/hyperbilirubinemics or the controls. All of these are consistent with the most severe injury in this group. Xanthine oxidase/xanthine dehydrogenase ratios were not significantly different among the groups. Hyperbilirubinemia ameliorates the extent of intestinal IR injury in our model and appears to act as an antioxidant. This study supports the concept that bilirubin possesses some beneficial properties in vivo, although no direct clinical conclusions can be drawn from these data.

Protective Effect of Bilirubin in Ischemia‐Reperfusion Injury in the Rat Intestine

ABSTRACTBackgroundAlthough bilirubin, which crosses the blood–brain barrier, can cause irreversible brain damage, it also possesses antioxidant properties that may be protective against oxidative stress. Intestinal ischemia–reperfusion (IR) injury results in cell destruction, mediated via the generation of reactive oxygen species. Although increased serum bilirubin is correlated with increased antioxidant potential in the face of hyperoxia, evidence of bilirubin‐associated protective effect against IR injury remains nonspecific. We therefore sought to investigate whether hyperbilirubinemia would be protective against IR injury to the intestine.MethodsYoung adult rats were randomly assigned to one of three groups: 1) IR/control (n = 12); 2) IR/hyperbilirubinemia (n = 10), in which IR was generated while the rats were treated with a continuous infusion of bilirubin; and 3) hyperbilirubinemia controls (n = 10). Blood and intestinal tissue samples were obtained to determine serial thiobarbituric acid reducing substances (index of lipid peroxidation) and for xanthine oxidase/xanthine dehydrogenase and glutathione/glutathione disulfide ratios. Intestinal histopathology was graded from 1 (normal) to 4 (severe necrotic lesions).ResultsHistopathologic scoring and circulating and tissue thiobarbituric acid reducing substances were highest in the IR/control animals compared with either the IR/hyperbilirubinemics or the controls. All of these are consistent with the most severe injury in this group. Xanthine oxidase/xanthine dehydrogenase ratios were not significantly different among the groups.ConclusionHyperbilirubinemia ameliorates the extent of intestinal IR injury in our model and appears to act as an antioxidant. This study supports the concept that bilirubin possesses some beneficial properties in vivo, although no direct clinical conclusions can be drawn from these data.

Role of integrins and intracellular adhesion molecule-1 in lung injury after intestinal ischemia-reperfusion

Background: We tested the hypothesis that lung injury after intestinal ischemia-reperfusion (IR) requires the activation of CD11/CD18 glycoprotein complex and its ligand, intracellular adhesion molecule-1 (ICAM-1), on pulmonary endothelial surface. Methods: Rats were assigned to one of six groups including sham operation, intestinal IR (60/120 min) and IR plus treatment with one of the following monoclonal antibodies against CD11a, CD11b, CD18, and ICAM-1. Pulmonary microvascular permeability, neutrophil accumulation, and expression of adhesion molecules were evaluated. Results: Intestinal IR resulted in lung injury characterized by a marked increase in microvascular permeability, neutrophil accumulation and upregulated expression of leukocyte integrins and ICAM-1. The increase in pulmonary microvascular permability and neutrophil accumulation elicited by intestinal reperfusion was effectively prevented by administration of blocking antibodies against ICAM-1, CD11, and CD18. Conclusions: These results indicate that adhesion molecules contribute to the lung injury after intestinal IR. Immunoneutralization of certain of these adhesion molecules may prevent intestinal IR-induced lung injury.

Intestinal Motility in an In Vivo Rat Model of Intestinal Ischemia–Reperfusion With Special Reference to the Effects of Nitric Oxide on the Motility Changes

ABSTRACTBackgroundTo clarify the relation between intestinal ischemia–reperfusion (IR) and dysmotility, the authors investigated changes in the motility pattern in the duodenum and jejunum in an in vivo rat model of IR when artery‐ (and vein‐) fed jejunum was clamped transiently. The authors also studied the effect of nitric oxide on the motility changes in this model by means of the administration of l ‐NAME (NG ‐nitro‐ l ‐arginine methyl ester) or S‐methylisothiourea sulfate (SMT).Materials and MethodsA force transducer was sutured onto the serosal side of the duodenum or jejunum. After a 3‐to 4‐day recovery period, contractions were recorded during periods of preischemia, ischemia (60 minutes), and reperfusion (90 minutes). An intestinal IR was produced by clamping and releasing the mesenteric artery and vein with artery forceps.ResultsIn the jejunum, there was a prolongation in the duration of contraction and there were decreases in the number of contractions (NC) during the IR. When treated with L‐NAME, no decrease in the NC was observed during the 45 to 90 minutes after reperfusion. S‐methylisothiourea sulfate did not affect the IR‐induced motility changes significantly. In the duodenum, there was a prolongation in the duration of contraction and a decrease in the NC and AC only during the reperfusion. l ‐NAME or S‐methylisothiourea sulfate inhibited the decreases in the NC during the reperfusion.ConclusionsIntestinal IR causes motility changes in the ischemic site during the IR and in the nonischemic site during the reperfusion. The IR‐induced motility changes partly depend on nitric oxide production.

Intestinal motility in an in vivo rat model of intestinal ischemia-reperfusion with special reference to the effects of nitric oxide on the motility changes.

To clarify the relation between intestinal ischemia-reperfusion (IR) and dysmotility, the authors investigated changes in the motility pattern in the duodenum and jejunum in an in vivo rat model of IR when artery- (and vein-) fed jejunum was clamped transiently. The authors also studied the effect of nitric oxide on the motility changes in this model by means of the administration of L-NAME (N(G)-nitro-L-arginine methyl ester) or S-methylisothiourea sulfate (SMT). A force transducer was sutured onto the serosal side of the duodenum or jejunum. After a 3-to 4-day recovery period, contractions were recorded during periods of preischemia, ischemia (60 minutes), and reperfusion (90 minutes). An intestinal IR was produced by clamping and releasing the mesenteric artery and vein with artery forceps. In the jejunum, there was a prolongation in the duration of contraction and there were decreases in the number of contractions (NC) during the IR. When treated with L-NAME, no decrease in the NC was observed during the 45 to 90 minutes after reperfusion. S-methylisothiourea sulfate did not affect the IR-induced motility changes significantly. In the duodenum, there was a prolongation in the duration of contraction and a decrease in the NC and AC only during the reperfusion. L-NAME or S-methylisothiourea sulfate inhibited the decreases in the NC during the reperfusion. Intestinal IR causes motility changes in the ischemic site during the IR and in the nonischemic site during the reperfusion. The IR-induced motility changes partly depend on nitric oxide production.

Amelioration of ischemia-reperfusion injury in rat intestine by pentoxifylline-mediated inhibition of xanthine oxidase.

Intestinal ischemia-reperfusion (IR) injury results in cell destruction, which may be mediated by the generation of reactive oxygen species, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can improve capillary flow and tissue oxygenation. Because of these combined effects, it has been hypothesized that pentoxifylline would protect against intestinal IR. Young adult rats were randomly assigned to one of four experimental groups: IR/Placebo (n = 12) in which superior and inferior mesenteric arteries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in which IR was induced as in the Placebo group, but with 25 mg/kg PTX at 0, 30, and 60 minutes; No IR/Placebo (n = 12); and No IR/PTX (n = 6) in which placebo and PTX were applied with no IR. Blood and intestinal samples were taken for serial thiobarbituric acid-reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase-xanthine dehydrogenase ratios, glutathione, myeloperoxidase, and histopathology. Animals in the IR/PTX group had lower TBARS and the least severe histopathologic injury. Xanthine oxidasexanthine dehydrogenase ratios were elevated only in IR/ Placebo (0.67+/-0.22 vs. 0.45+/-0.14 in IR/PTX; 0.42+/-0.22 in No IR/Placebo; and 0.40+/-0.11 in No IR/PTX; p = 0.0009). Reduced glutathione was diminished in IR/PTX animals (38.9 +/-1.35 vs. 46.1+/-7.0 in IR/Placebo; 41.1+/-2.5 in No IR/ Placebo; 43.6+/-1.0 in No IR/PTX; p = 0.048). No differences were recorded in myeloperoxidase levels among groups. Pentoxifylline ameliorates histopathologic signs of injury and decreases lipid peroxidation (TBARS). Normal xanthine oxidase-xanthine dehydrogenase ratios in the treated compared with IR-only animals imply that the protective effect of PTX is at least partially mediated through inhibition of xanthine oxidase.

Lipid peroxidation contributes to cardiac deficits after ischemia and reperfusion of the small bowel.

Our previous studies showed that intestinal ischemia-reperfusion (IR) impairs cardiac contractile function. The present study examined the contribution of oxygen free radicals and lipid peroxidation of cardiac cell membrane to cardiac dysfunction after intestinal IR in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and collateral arcade ligation. Controls were sham operated (group 1, n = 25). In group 2, 30 rats with SMA occlusion were killed 3-4 h after reperfusion without treatment. Aminosteroid (U-74389F), a pharmacological agent known to inhibit lipid peroxidation of membranes, was given 1 min before occlusion of the SMA (group 3, n = 19). All rats were killed 3-4 h after reperfusion of the ischemic intestine, and the hearts were harvested for in vitro assessment of cardiac function (Langendorff preparation). Cardiac contractile depression occurred in the untreated group as indicated by a fall in left ventricular pressure (from 76 +/- 3 to 64 +/- 3 mmHg, P = 0.01), maximum +dP/dt (from 1,830 +/- 60 to 1,577 +/- 64 mmHg/s, P = 0.05), and maximum -dP/dt (from 1,260 +/- 50 to 950 +/- 60 mmHg/s, P = 0.005). Lipid peroxidation of cardiac membranes occurred after untreated IR as indicated by the rise in cardiac malondialdehyde levels (MDA) (from 0.203 +/- 0.046 to 0.501 +/- 0.044 nM/mg protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)