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Mechanosensory properties in the partially obstructed guinea pig small intestin

Principal Investigator: Hans Gregersen, Ph.D.

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.