Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema
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OBJECTIVE: To characterize membrane conductivity by applying mathematical modeling techniques and immunohistochemistry and to localize and predict areas of the bowel where aquaporins may be associated with edema resolution/prevention associated with hypertonic saline. Intestinal edema induced by resuscitation and mesenteric venous hypertension impairs intestinal transit/contractility. Hypertonic saline decreases intestinal edema and improves transit. Aquaporins are water transport membrane proteins that may be up-regulated with edema and/or hypertonic saline. DESIGN: Laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague Dawley rats, weighing 270 to 330 g. INTERVENTIONS: Rats were randomized to control (with and without hypertonic saline) and mesenteric venous hypertension with either 80 mL/kg normal saline (RESUS + VH + VEH) or 80 mL/kg normal saline with hypertonic saline (RESUS + VH + HTS). After 6 hrs, intestinal wet/dry ratios, urine output, peritoneal fluid, and intraluminal fluid were measured. Hydraulic conductivity was calculated from our previously known and published pressure-flow data. The cDNA microarray, Western blot, polymerase chain reaction, and immunohistochemistry studies were conducted for candidate aquaporins and distribution in intestinal edema resolution. MEASUREMENTS AND MAIN RESULTS: Hypertonic saline decreased edema and increased urine, intraluminal, and peritoneal fluid volume. RESUS + VH favors fluid flux into the interstitium. Hypertonic saline causes increased hydraulic conductivity at the seromuscular and mucosal surfaces at the same time limiting flow into the interstitium. This is associated with increased aquaporin 4 expression in the intestinal mucosa and submucosa. CONCLUSIONS: Hypertonic saline mitigates intestinal edema development and promotes fluid redistribution secondary to increased membrane conductivity at the mucosal and seromuscular surfaces. This is associated with up-regulation of aquaporin 4 gene expression and protein. Aquaporin 4 may be a useful therapeutic target for strategies to enhance edema resolution.
author list (cited authors)
Radhakrishnan, R. S., Shah, S. K., Lance, S. H., Radhakrishnan, H. R., Xue, H., Radhakrishnan, G. L., ... Cox, C. S.