Effect of acute, slightly increased intra-abdominal pressure on intestinal permeability and oxidative stress in a rat model.

INTRODUCTION: Intra-abdominal hypertension (IAH) is known as a common, serious complication in critically ill patients. Bacterial translocation and permeability changes are considered the pathophysiological bases for IAH-induced enterogenic endotoxemia and subsequent multiorgan failure. Nevertheless, the effects of slightly elevated intra-abdominal pressures (IAPs) on the intestinal mucosa and the associated mechanisms remain unclear. METHODS: To investigate the acute effects of different nitrogen pneumoperitoneum grades on colonic mucosa, male Sprague-Dawley rats were assigned to six groups with different IAPs (0 [control], 4, 8, 12, 16, and 20 mmHg, n = 6/group). During 90 min of exposure, we dynamically monitored the heart rate and noninvasive hemodynamic parameters. After gradual decompression, arterial blood gas analyses were conducted. Thereafter, structural injuries to the colonic mucosa were identified using light microscopy. Colon permeability was determined using the expression of tight junction proteins, combined with fluorescein isothiocyanate dextran (FD-4) absorption. The pro-oxidant-antioxidant balance was determined based on the levels of malondialdehyde (MDA) and antioxidant enzymes. RESULTS: IAH significantly affected the histological scores of the colonic mucosa, tight junction protein expression, mucosal permeability, and pro-oxidant-antioxidant balance. Interestingly, elevations of IAP that were lower than the threshold for IAH also showed a similar, undesirable effect. In the 8 mmHg group, mild hyponatremia, hypocalcemia, and hypoxemia occurred, accompanied by reduced blood and abdominal perfusion pressures. Mild microscopic inflammatory infiltration and increased MDA levels were also detected. Moreover, an 8-mm Hg IAP markedly inhibited the expression of tight junction proteins, although no significant differences in FD-4 permeability were observed between the 0- and 8-mmHg groups. CONCLUSIONS: Acute exposure to slightly elevated IAP may result in adverse effects on intestinal permeability and the pro-oxidant-antioxidant balance. Therefore, in patients with critical illnesses, IAP should be dynamically monitored and corrected, as soon as possible, to prevent intestinal mucosal injury and subsequent gut-derived sepsis

The effects of the different grades of nitrogen pneumoperitoneum on colonic pro-oxidant-antioxidant balance.

<p>A: Malondialdehyde (MDA), the product of lipid peroxidation. B–D: The antioxidant enzymes of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD). At 4 mmHg, the pro-oxidant-antioxidant balance was stable, and no significant differences in related parameters were detected between the 0- and 4-mmHg groups. Intra-abdominal pressures of ≥8 mmHg showed adverse effects on colonic pro-oxidant-antioxidant balance. Compared with that in the 0-mmHg group, the MDA concentrations in the 8, 12, 16, and 20-mmHg groups were significantly higher, whereas the CAT and GSH-Px concentrations tended to decline. No obvious changes in the SOD levels were detected. All data are shown as means ± SD. *P<0.05, **P<0.01, vs. 0 mmHg; ^▴P<0.05, ^▴▴P<0.01, vs. 4 mmHg; ^★P<0.05, ^★★P<0.01, vs. 8 mmHg. ^▪P<0.05, ^▪▪P<0.01, vs. 12 mmHg, ^⧫P<0.05, vs. 16 mmHg.</p

The effects of different grades of nitrogen pneumoperitoneum on the expression levels of TJ proteins.

<p>i: Immunohistochemical localization of claudin 5 and occludin (×200). Increased intra-abdominal pressures tended to reduce the expression levels of claudin 5 and occludin. A–D: Claudin 5. The black arrow indicates the positive signals for claudin 5 in the lateral membrane of the epithelia. E–H: Occludin. The white arrows indicate the positive signals for occludin in the apical cell borders of the colonic epithelia. ii: Western blotting results for claudin 5 and occludin. The expression levels of the proteins were normalized relative to actin. Compared with the 0-mmHg group, the 8-, 12-, 16-, and 20-mmHg groups had significantly reduced densities of claudin 5 and occludin. All data are shown as means ± SD. *P<0.05, **P<0.01, vs. 0 mmHg; ^▴P<0.05, ^▴▴P<0.01, vs. 4 mmHg;^★★P<0.01, vs. 8 mmHg; ^▪P<0.05, ^▪▪P<0.01, vs. 12 mmHg.</p

The effects of different grades of nitrogen pneumoperitoneum on intestinal permeability to FD-4.

<p>Intra-abdominal hypertension significantly stimulated the intestinal permeability to FD-4.Compared with that in the 0-mmHg group, the FD-4 concentration in the 12-, 16-, and 20-mmHg groups were increased 5.2-,12.4- and 26.7-fold, respectively. Slightly elevated intra-abdominal pressures of 4 and 8 mmHg did not affect the FD-4 concentrations. No significant differences were observed between the 0-mmHg group and the 4- and 8-mmHg groups. All data are shown as means ± SD. **P<0.01, vs. 0 mmHg; ^▴▴P<0.01, vs. 4 mmHg; ^★★P<0.01, vs. 8 mmHg; ^▪P<0.05, vs. 12 mmHg; ^⧫P<0.05, vs. 16 mmHg.</p

Scoring criteria for histologic damage in colon sections.

<p>Scoring criteria for histologic damage in colon sections.</p

Effects of the different grades of nitrogen pneumoperitoneum on arterial blood gas parameters.

<p>PO₂,partial pressure of arterial oxygen; PCO₂, arterial carbon dioxide; SO₂C, arterial oxygen saturation; Lac, lactic acid; Glu, glucose; Na, sodium; K, potassium; Ca,calcium.</p><p>All data are shown as means ± SD values.</p><p>*P<0.05, **P<0.01, vs. 0 mmHg; ^▴P<0.05, ^▴▴P<0.01, vs. 4 mmHg; ^★P<0.05, ^★★P<0.01 vs. 8 mmHg; ^▪P<0.05, ^▪▪P<0.01, vs. 12 mmHg.</p><p>Effects of the different grades of nitrogen pneumoperitoneum on arterial blood gas parameters.</p

Literature overview of the currently published animal experiments related to the present study.

<p>MDA, malondialdehyde; GSH, glutathione; GSH-Px, glutathione peroxidase; MPO, myeloperoxidase; SOD, superoxide dismutase, FITC, fluorescein isothiocyanate.</p><p>Literature overview of the currently published animal experiments related to the present study.</p

Effects of different grades of nitrogen pneumoperitoneum on heart rate (HR) and noninvasive hemodynamic parameters.

<p>A: HR; 90-min exposure to intra-abdominal hypertension caused a significant reduction in HR. Compared with the 0-mmHg group, the HR in the 12-, 16-, and 20-mmHg groups were significantly lower. B: Noninvasive hemodynamic parameters; the 90-min exposure to intra-abdominal pressures (IAPs) ≥8 mmHg caused significant reductions in the systolic blood pressure (SBP) and abdominal perfusion pressure (APP). The SBP and APP in the 8-, 12-, 16-, and 20-mmHg groups were significantly lower than those in the 0-mmHg group. As the IAPs increased, the noninvasive hemodynamic parameters deteriorated. All data are shown as means ± SD *P<0.05, **P<0.01, vs. 0 mmHg; ^▴P<0.05, ^▴▴P<0.01, vs. 4 mmHg; ^★P<0.05, ^★★P<0.01, vs. 8 mmHg; ^▪P<0.05, ^▪▪P<0.01, vs. 12 mmHg.</p

The effects of the different grades of nitrogen pneumoperitoneum on intestinal histologic damage.

<p>A–F (0–20 mmHg, ×100): Morphological changes under the different grades of nitrogen pneumoperitoneum. The parts in the black box are magnified and listed from A1 to F1 (0–20 mmHg, ×200). As the intra-abdominal pressure (IAP) increased, the severity of the histologic changes increased. At 8 mmHg, nitrogen pneumoperitoneum induced slight inflammatory cell infiltration. When the IAP reached 20 mmHg, almost no intact intestinal mucosa was observed. G: Histological scores in the different groups. Compared with the 0-mmHg group, the 8-, 12-, 16-, and 20-mmHg groups had significantly higher histological scores. All data are shown as means ± SD. **P<0.01, vs. 0 mmHg; ^▴▴P<0.01, vs. 4 mmHg; ^★P<0.05, ^★★P<0.01, vs. 8 mmHg; ^▪P<0.05, ^▪▪P<0.01, vs. 12 mmHg.</p