Development and validation of a multiwavelength spatial domain near-infrared oximeter to detect cerebral hypoxia-ischemia.

Detection of cerebral hypoxia-ischemia in infants remains problematic, as current monitors in clinical practice are impractical, insensitive, or nonspecific. Our study develops a multiwavelength spatial domain construct for near-infrared spectroscopy (NIRS) to detect cerebral hypoxia-ischemia and evaluates the construct in several models. The NIRS probe contains photodiode detectors 2, 3, and 4 cm from a three-wavelength, light-emitting diode. A construct determines cerebral O(2) saturation based on spatial domain principles. Device performance and construct validity are examined in in-vitro models simulating the brain, and in piglets subjected to hypoxia, hypoxia-ischemia, and hyperoxic conditions using a weighted average of arterial and cerebral venous O(2) saturation measured by CO-oximetry. The results in the brain models verify key equations in the construct and demonstrate reliable performance of the device. In piglets, the device measures cerebral O(2) saturation with bias +/-4% and precision +/-8%. In conclusion, this NIRS device accurately detects cerebral hypoxia-ischemia and is of a design that is practical for clinical application.

Selective inhibition of the epidermal growth factor receptor impairs intestinal adaptation after small bowel resection.

BACKGROUND: Prior indirect studies have suggested that a functional epidermal growth factor receptor (EGFR) appears to be indispensable for the adaptive response of the remnant intestine to massive small bowel resection (SBR). The recent availability of a specific pharmacologic EGFR inhibitor enabled us to more directly test the hypothesis that EGFR signaling is required for postresection intestinal adaptation. METHODS: Mice (C57B1/6, n = 26) underwent a 50% SBR or sham operation and were then given orogastric EGFR inhibitor (ZD1839, 50 mg/kg/day) or vehicle. After 3 days, indices of adaptation (wet weight, crypt depth, and villus height) and apoptotic index (number of apoptotic bodies per crypt) were calculated in the ileum. The expression of proliferating cell nuclear antigen (PCNA) and activated EGFR was measured by Western blotting. RESULTS: ZD1839 prevented EGFR activation and the normal postresection increases in ileal wet weight, villus height, and crypt depth. Enterocyte proliferation was reduced twofold in the SBR group by ZD1839. Although not statistically significant, rates of enterocyte apoptosis were the highest in the inhibitor-treated mice. CONCLUSION: Following massive SBR, pharmacologic inhibition of the EGFR attenuates proliferation and the normal adaptive response of the intestine. These results more directly confirm the requirement of a functional EGFR as a mediator of the postresection adaptation response. This study demonstrates an in vivo application of a novel selective EGFR inhibitor and offers a unique experimental model to gain mechanistic insight into understanding postresection intestinal adaptation.

Intestinal and hepatic response to combined partial hepatectomy and small bowel resection in mice.

BACKGROUND: Both partial-hepatectomy (PHx) and massive small bowel resection (SBR) are strong mitogenic signals to the remnant liver and intestine, respectively. This study tested the hypothesis that PHx was an additive signal for intestinal adaptation after massive SBR. METHODS: Male mice underwent either sham SBR or 50% proximal SBR. Mice from these two groups were then subjected to a 70% PHx or sham PHx. After 3 days, parameters of intestinal adaptation and liver regeneration were recorded in the remnant intestine and liver, respectively. RESULTS: Intestinal adaptation following SBR occurred normally, but was not enhanced after concomitant PHx. On the other hand, SBR impaired the regenerative ability of the liver following PHx. CONCLUSIONS: Intestinal adaptation after SBR takes priority over liver regeneration after PHx. These data implicate a hierarchy with regard to adaptive alterations to organ loss and endorse an important role for the intestinal mucosa in the regulation of hepatic regeneration.

Intestinal permeability and bacterial translocation are uncoupled after small bowel resection.

BACKGROUND/PURPOSE: Gut barrier failure and bacterial translocation have been proposed to cause infection and sepsis in patients with the short bowel syndrome. This study tested the hypothesis that permeability is increased in the adapting remnant ileum after massive small bowel resection (SBR). METHODS: Male ICR mice underwent a 50% proximal SBR or sham operation. At 3, 7, and 14 days, the ileum was mounted in an Ussing chamber. Mucosal-to-serosal flux of low (dextran) and high (horseradish peroxidase; HRP) molecular weight markers was determined. Additionally, bacterial translocation was measured by culturing blood, mesenteric lymph nodes, liver, and spleen at 3 and 14 days after SBR or sham operation. RESULTS: Permeability to dextran was reduced immediately after SBR but was no different at later time-points. HRP permeability was no different at any time-point. Translocation of Gram-negative bacteria to the mesenteric lymph nodes and liver was more frequent in the SBR animals 3 and 14 days postoperatively. CONCLUSIONS: Intestinal permeability to macromolecules is not increased after massive SBR, but the rate of translocation to the mesenteric lymph nodes and liver is elevated. This suggests that the mechanism for bacterial translocation after SBR does not involve alterations in gut permeability.