Mechanisms of Improving Fecal Continence Muscles Motor Function in Health and Disease - Abstract The overall aim of this proposal is an in-depth investigation of mechanisms for enhancing the motor function of fecal continence muscles to improve fecal incontinence in patients. Fecal incontinence (FI), characterized by involuntary loss of solid and/or liquid stools, is a common problem in the United States and worldwide affecting all adult age groups and especially women and elderly. Although, it is known that muscle weakness is one of the important components of FI pathophysiology and its improvement may remedy or reduce the severity of incontinence, to-date basic knowledge to enhance the contractility of various continence muscles such as their fatigability; a pre-requisite for strength training rehabilitation, tools and methods for inducing and measuring their fatigue leading to increased contractility and improved function and quality of life remain unknown. Supported by preliminary data, we have developed tools and techniques for inducing and reliably measuring fatigue in continence muscles and determining their fatigue characteristics necessary for devising methods for increasing their contractility and reducing incontinence. Our specific aims are: Specific Aim 1: Characterization of the fatigability of various continence muscles across adult age spectrum and sex. SA1A: We will determine and characterize the fatigue characteristics of the striated: a. anal canal continence muscle complex (comprised of external anal sphincter muscle group and puborectalis muscle), and b. Puborectalis muscle alone induced by various loads, intervals, and repetitions. SA1B: We will compare and characterize the differences in fatigue characteristics of the continence muscles induced by isotonic and isometric contractions with and without load. Specific Aim 2: Determination of the effect of daily fatigue on continence muscles' motor function and incontinence severity and its related patient quality of life. SA2A: We will determine the effect of repetitive fatigue by isometric and isotonic contractions on physiologic response of the continence muscles, severity of incontinence and related quality of life in FI patients. SA2B: We will determine the effect of continued exercise for three and six months in a subset of patients who do not develop significant response. We have assembled a multi-disciplinary team comprised of gastroenterologists, OB/Gynecologists, exercise Physiologists, surgeons, bio-feedback specialists and occupational therapists to design and execute the mandate of this proposal.
