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

Abstract

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 prooxidant-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.