Effect of peritoneal dialysis solution with different pyruvate concentrations on intestinal injury

Abstract

To investigate the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (Pyr-PDS) of different concentrations combined with intravenous resuscitation on acid–base imbalance and intestinal ischemia reperfusion injury in rats with hemorrhagic shock. Sixty rats were randomly assigned to group SHAM, group intravenous resuscitation, and four direct peritoneal resuscitation groups combined with intravenous resuscitation: group NS, LA, PY1, and PY2, that is, normal saline, lactate-PDS (Lac-PDS), lower concentration Pyr-PDS (Pyr-PDS1), and higher concentration Pyr-PDS (Pyr-PDS2), respectively. Two hours after hemorrhagic shock and resuscitation, the pH, oxygen partial pressure, carbon dioxide partial pressure (PCO₂), base excess, and bicarbonate ion concentration (HCO₃⁻) of the arterial blood were measured. The intestinal mucosal damage index and intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor-α, interleukin-6, zonula occludens-1, claudin-1, and occludin levels in intestinal issues were detected. Two hours after resuscitation, group PY2 had higher mean arterial pressure, pH, oxygen partial pressure, and base excess and lower PCO₂ of arterial blood than group PY1 (P < 0.05). Tumor necrosis factor-α and interleukin-6 levels in group PY2 were significantly lower than those in group PY1 (P < 0.05). Zonula occludens-1, claudin-1, and occludin expression levels were significantly higher in group PY2 than in group PY1 (P < 0.05). Direct peritoneal resuscitation with Pyr-PDS2 combined with intravenous resuscitation enhanced the hemodynamics, improved the acid–base balance, and alleviated intestinal ischemia reperfusion injury from hemorrhagic shock and resuscitation in rats. The mechanisms might include correction of acidosis, inhibition of inflammatory response, enhancement of systemic immune status, regulation of intestinal epithelial permeability, and maintenance of intestinal mucosal barrier function.

Impact statement: Hemorrhagic shock is a life-threatening condition after trauma or during surgery. Acid–base imbalance and intestinal ischemia reperfusion injury are two significant causes in the pathogenetic process and multiple organ dysfunction. As a result, it is urgent and necessary to find an effective method of resuscitation in order to reverse the acid–base imbalance and protect organ function. This current study confirmed the protection against hypoxic acidosis and intestinal ischemia reperfusion injury by peritoneal resuscitation with pyruvate combined with intravenous resuscitation in rats with hemorrhagic shock. And the peritoneal dialysis solution with pyruvate of high concentration plays a crucial role in the process. It provided a new idea and possible direction of fluid resuscitation for alleviating organ injuries, protecting organ functions, and improving clinical prognosis after hemorrhagic shock and resuscitation.

Keywords: Direct peritoneal resuscitation; acid–base balance; inflammatory response; intestinal barrier function; pyruvate; tight junction.

Figure 1.

The effect of Pyr-PDS on morphological changes in the intestinal mucosa of rats (n = 10). Photomicrographs of hematoxylin-eosin-stained sections of the small intestine of rats at 2 h after resuscitation (original magnification, ×100 for the six panels). (a) Group SHAM. (b) Group VR. (c) Group NS. (d) Group LA. (e) Group PY1. (f) Group PY2. In (b) and (c), the arrows highlight the shedding of massive epithelium down the sides of villi with a few tips desquamated, partial disintegration of lamina propria, and infiltration of a large number of lymphocytes and neutrophils. In (d), the arrows highlight the widened subepithelial space in the villi tips, mild separation of the epidermis, and lamina propria with denudation of few tips, and infiltration of many lymphocytes and neutrophils. In (e) and (f), the arrows highlight the infiltration of few neutrophils and lymphocytes. (A color version of this figure is available in the online journal.)

Figure 2.

Immunohistochemical staining of ICAM-1 in the sections of the intestinal mucosa of rats at 2 h after resuscitation (n = 10) (original magnification, ×400 for the six panels). (a) Group SHAM. (b) Group VR. (c) Group NS. (d) Group LA. (e) Group PY1. (f) Group PY2. The arrows highlight the expression of intestinal ICAM-1. (A color version of this figure is available in the online journal.)

Figure 3.

Immunohistochemical staining of TNF-α in the sections of the intestinal mucosa of rats at 2 h after resuscitation (n = 10) (original magnification, ×400 for the six panels). (a) Group SHAM. (b) Group VR. (c) Group NS. (d) Group LA. (e) Group PY1. (f) Group PY2. The arrows highlight the expression of intestinal TNF-α. (A color version of this figure is available in the online journal.)

Figure 4.

Effects of Pyr-PDS on the expression of IL-6 in the intestinal tissue as represented by grayscale value and determined by Western blot analysis at 2 h after HS and resuscitation in rats (n = 10).

Figure 5.

Effects of Pyr-PDS on the expression of tight junction proteins ZO-1, claudin-1, and occludin as represented by grayscale value and determined by Western blot analysis at 2 h after HS and resuscitation in rats (n = 10).

Figure 6.

Effects of Pyr-PDS on the expression of tight junction proteins ZO-1, claudin-1, and occludin as represented by the grayscale ratio at 2 h after HS and resuscitation in rats (n = 10). Data are expressed as mean ± SD. *P < 0.05 versus group SHAM. ^†P < 0.05 versus group VR. ^‡P < 0.05 versus group NS. ^§P < 0.05 versus group LA. ^‖P < 0.05 versus group PY1.