The general objective of this proposal is to understand the biomechanical and mechanosensory properties of the small intestine as they relate to partial small intestinal obstruction. Guinea pigs with obstruction will be compared to age- and sex-matched normal guinea pigs to analyze possible differences in afferent nerve signal transduction (Specific Aim 3) and how it relates to the geometric (Specific Aim 1) and biomechanical remodeling (Specific Aim 2) during obstruction. The goals are to obtain detailed morphometric and mechanical data including muscle contraction characteristics on the normal and obstructed guinea-pig small intestine and to relate them to the tissue remodeling elicited by the intestinal obstruction. Hence, new distention protocols, new theory and methods need to be used and further developed. The abovementioned data together with afferent nerve signals will be used to characterize the stimulus-response function for mechanoreceptor responses. The main hypothesis is that partial intestinal obstruction will lead to changes in the mechanosensory properties and that a mathematical relationship can be established between the geometric and biomechanical remodeling and the changes in afferent nerve signal transduction. Although previous studies have shown morphological and biomechanical remodeling including muscle cell hypertrophy, increased stiffness of the intestinal wall and altered motility, much remains to be determined from a bioengineering point of view. The studies will focus on determination of multidimensional stress-strain properties of the small intestinal wall with the zero-stress state taking into account, and on the integration of the passive mechanical properties, the muscle contractile properties, and afferent nerve signals. The studies will shed light on the relation between the mechanical stimulus (stress and strain) and the afferent nerve response, i.e. information on mechanoreceptor behavior will be obtained. The rationale is that a bioengineering model is needed in order to deal with the complexity of intestinal obstruction. A major goal is to demonstrate that the understanding of Gl diseases can be greatly enhanced by using a multidisciplinary approach including material and mathematical sciences, imaging analysis, cell and tissue bioengineering, biology, and medical science and diagnostics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK072616-03
Application #
7617128
Study Section
Special Emphasis Panel (ZRG1-DIG-F (50))
Program Officer
Hamilton, Frank A
Project Start
2007-05-05
Project End
2011-10-31
Budget Start
2009-05-01
Budget End
2011-10-31
Support Year
3
Fiscal Year
2009
Total Cost
$288,731
Indirect Cost
Name
La Jolla Institute
Department
Type
DUNS #
114215473
City
San Diego
State
CA
Country
United States
Zip Code
92121
Zhao, Jingbo; Liao, Donghua; Yang, Jian et al. (2011) Stress and strain analysis of contractions during ramp distension in partially obstructed guinea pig jejunal segments. J Biomech 44:2077-82
Zhao, Jingbo; Liao, Donghua; Yang, Jian et al. (2010) Biomechanical remodelling of obstructed guinea pig jejunum. J Biomech 43:1322-9
Liao, Donghua; Zhao, Jingbo; Gregersen, Hans (2010) 3d Mechanical properties of the partially obstructed guinea pig small intestine. J Biomech 43:2079-86
Yang, Jian; Zhao, Jingbo; Nakaguchi, Toshiya et al. (2009) Biomechanical changes in oxazolone-induced colitis in BALB/C mice. J Biomech 42:811-7
Liao, Dong-Hua; Zhao, Jing-Bo; Gregersen, Hans (2009) Gastrointestinal tract modelling in health and disease. World J Gastroenterol 15:169-76
Chen, Xudong; Zhao, Jingbo; Gregersen, Hans (2008) The villi contribute to the mechanics in the guinea pig small intestine. J Biomech 41:806-12
Li, Jiang; Zhao, Jingbo; Liao, Donghua et al. (2008) Effect of smooth muscle tone on morphometry and residual strain in rat duodenum, jejunum and ileum. J Biomech 41:2667-72
Zhao, Jingbo; Liao, Donghua; Gregersen, Hans (2008) Phasic and tonic stress-strain data obtained in intact intestinal segment in vitro. Dig Dis Sci 53:3145-51
Storkholm, Jan Henrik; Zhao, Jingbo; Villadsen, Gerda E et al. (2008) Spontaneous and bolus-induced motility in the chronically obstructed guinea-pig small intestine in vitro. Dig Dis Sci 53:413-20