Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema

Ravi Radhakrishnan, Shinil K. Shah, Samuel H. Lance, Hari R. Radhakrishnan, Hasen Xue, Geetha Radhakrishnan, Uma S. Ramaswamy, Peter A. Walker, Karen S. Uray, Glen A. Laine, Randolph H. Stewart, Charles S. Cox

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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. Ements 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.

Original languageEnglish (US)
Pages (from-to)2946-2952
Number of pages7
JournalCritical Care Medicine
Volume37
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

Fingerprint

Aquaporin 4
Resuscitation
Edema
Up-Regulation
Aquaporins
Ascitic Fluid
Immunohistochemistry
Urine
Hypertension
Membranes
Membrane Transport Proteins
Intestinal Mucosa
Oligonucleotide Array Sequence Analysis
Sprague Dawley Rats
Western Blotting
Gene Expression
Pressure
Polymerase Chain Reaction
Water

Keywords

  • Aquaporin
  • Edema
  • Hypertonic saline
  • Ileus
  • Intestines
  • Resuscitation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema. / Radhakrishnan, Ravi; Shah, Shinil K.; Lance, Samuel H.; Radhakrishnan, Hari R.; Xue, Hasen; Radhakrishnan, Geetha; Ramaswamy, Uma S.; Walker, Peter A.; Uray, Karen S.; Laine, Glen A.; Stewart, Randolph H.; Cox, Charles S.

In: Critical Care Medicine, Vol. 37, No. 11, 11.2009, p. 2946-2952.

Research output: Contribution to journalArticle

Radhakrishnan, R, Shah, SK, Lance, SH, Radhakrishnan, HR, Xue, H, Radhakrishnan, G, Ramaswamy, US, Walker, PA, Uray, KS, Laine, GA, Stewart, RH & Cox, CS 2009, 'Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema', Critical Care Medicine, vol. 37, no. 11, pp. 2946-2952. https://doi.org/10.1097/CCM.0b013e3181ab878b
Radhakrishnan, Ravi ; Shah, Shinil K. ; Lance, Samuel H. ; Radhakrishnan, Hari R. ; Xue, Hasen ; Radhakrishnan, Geetha ; Ramaswamy, Uma S. ; Walker, Peter A. ; Uray, Karen S. ; Laine, Glen A. ; Stewart, Randolph H. ; Cox, Charles S. / Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema. In: Critical Care Medicine. 2009 ; Vol. 37, No. 11. pp. 2946-2952.
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T1 - Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema

AU - Radhakrishnan, Ravi

AU - Shah, Shinil K.

AU - Lance, Samuel H.

AU - Radhakrishnan, Hari R.

AU - Xue, Hasen

AU - Radhakrishnan, Geetha

AU - Ramaswamy, Uma S.

AU - Walker, Peter A.

AU - Uray, Karen S.

AU - Laine, Glen A.

AU - Stewart, Randolph H.

AU - Cox, Charles S.

PY - 2009/11

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N2 - 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. Ements 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.

AB - 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. Ements 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.

KW - Aquaporin

KW - Edema

KW - Hypertonic saline

KW - Ileus

KW - Intestines

KW - Resuscitation

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