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Noninvasive Monitoring of Small Intestinal Oxygen in a Rat Model of Chronic Mesenteric Ischemia

Significance Statement

We noninvasively monitored the partial pressure of oxygen (pO2) in rat small intestine using a model of chronic mesenteric ischemia by electron paramagnetic resonance oximetry (EPR) over a 7-day period. The particulate probe lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) was embedded into the oxygen permeable material polydimethyl siloxane (PDMS) by cast-molding and polymerization (Oxy-Chip).  A one-time surgical procedure was performed to place the Oxy-Chip on the outer wall of the small intestine (SI). The superior mesenteric artery (SMA) was banded to approximately 30% blood flow for experimental rats. Noninvasive measurement of pO2 was performed at baseline for control rats or immediate post-banding and on days 1, 3, and 7. The SI pO2 for control rats remained stable over the 7-day period. The pO2 on day 7 was 54.5 ± 0.9 mm Hg (mean ± SE). SMA banded rats were significantly different from controls with a noted reduction in pO2 post banding with a progressive decline to a final pO2 of 20.9 ± 4.5 mm Hg (mean ± SE; p = 0.02). All SMA-banded rats developed adhesions around the Oxy-Chip yet remained asymptomatic. The hypoxia marker HypoxyprobeTM was used to validate low tissue pO2. Brown cytoplasmic staining was consistent with hypoxia. Mild brown staining was noted predominantly on the villus tips in control animals. SMA-banded rats had an extended region of hypoxic involvement in the villus with a higher intensity of cytoplasmic staining. Deep brown staining of the enteric nervous system neurons and connective tissue both within layers and in the mesentery were noted. SMA banded rats with lower pO2 values had a higher intensity of staining. Thus, monitoring SI pO2 using the probe Oxy-Chip provides a valid measure of tissue oxygenation. Tracking pO2 in conditions that produce chronic mesenteric ischemia will contribute to our understanding of intestinal tissue oxygenation and how changes impact symptom evolution and the trajectory of chronic disease.

Figure Legend: Deep brown staining of the enteric nervous system neurons and connective tissue in SMA banded rats with lower pO2 values.

Noninvasive Monitoring of Small Intestinal Oxygen in a Rat Model of Chronic Mesenteric Ischemia- Global Medical Discovery

 

 

 

 

 

 

 

 

 

 

 

 

Journal Reference

Fisher EM, Khan M, Salisbury R, Kuppusamy P.

Cell Biochem Biophys. 2013 May 1.

School of Nursing, The University of Akron, Akron, OH, 44325, USA, [email protected].

 

Abstract

We noninvasively monitored the partial pressure of oxygen (pO2) in rat’s small intestine using a model of chronic mesenteric ischemia by electron paramagnetic resonance oximetry over a 7-day period. The particulate probe lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) was embedded into the oxygen permeable material polydimethyl siloxane by cast-molding and polymerization (Oxy-Chip). A one-time surgical procedure was performed to place the Oxy-Chip on the outer wall of the small intestine (SI). The superior mesenteric artery (SMA) was banded to ~30 % of blood flow for experimental rats. Noninvasive measurement of pO2 was performed at the baseline for control rats or immediate post-banding and on days 1, 3, and 7. The SI pO2 for control rats remained stable over the 7-day period. The pO2 on day-7 was 54.5 ± 0.9 mmHg (mean ± SE). SMA-banded rats were significantly different from controls with a noted reduction in pO2 post banding with a progressive decline to a final pO2 of 20.9 ± 4.5 mmHg (mean ± SE; p = 0.02). All SMA-banded rats developed adhesions around the Oxy-Chip, yet remained asymptomatic. The hypoxia marker Hypoxyprobe™ was used to validate the low tissue pO2. Brown cytoplasmic staining was consistent with hypoxia. Mild brown staining was noted predominantly on the villus tips in control animals. SMA-banded rats had an extended region of hypoxic involvement in the villus with a higher intensity of cytoplasmic staining. Deep brown stainings of the enteric nervous system neurons and connective tissue both within layers and in the mesentery were noted. SMA-banded rats with lower pO2 values had a higher intensity of staining. Thus, monitoring SI pO2 using the probe Oxy-Chip provides a valid measure of tissue oxygenation. Tracking pO2 in conditions that produce chronic mesenteric ischemia will contribute to our understanding ofintestinal tissue oxygenation and how changes impact symptom evolution and the trajectory of chronic disease.

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