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Articles in PresS. Am J Physiol Gastrointest Liver Physiol (February 2, 2006). doi:10.1152/ajpgi.00487.2005 G-00487-2005.R2 FINAL ACCEPTED VERSION B\B-P\Man\Rectal Traction\Rectal Traction Patients Formatted With Figures.doc Anorectal Manometry.enl COMPARISON OF RECTOANAL AXIAL FORCES IN HEALTH AND FUNCTIONAL DEFECATORY DISORDERS Adil E. Bharucha1 Andrew J. Croak2 John B. Gebhart2 Lawrence J. Berglund3 Barbara M. Seide1 Alan R. Zinsmeister4 Kai-Nan An3 From the 1Clinical Enteric Neuroscience Translational and Epidemiological Research Program (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Department of Medicine, 2Division of Gynecologic Surgery, 3Orthopedics Biomechanics Laboratory, and 4Division of Biostatistics, Mayo Clinic, Rochester, MN Address correspondence and reprints requests to: Adil E. Bharucha, M.D. Clinical Enteric Neuroscience Translational and Epidemiological Research Program (C.E.N.T.E.R.) Mayo Clinic (CH 8-110) 200 First Street S.W. Rochester, MN 55905 Tel: 507-538-5854 Fax: 507-538-5820 Email: [email protected] Running Title: Rectoanal axial forces Copyright © 2006 by the American Physiological Society. 1 G-00487-2005.R2 - 2 ABSTRACT Anal manometry measures circumferential pressures, but not axial forces, which are responsible for defecation and contribute to fecal continence. Our aims were to investigate these mechanisms by measuring axial rectoanal forces with an intra-rectal sphere or a latex balloon, fixed at 8, 6, or 4 cm from the anal verge, and connected to axial force and displacement transducers. Rectoanal forces and rectal pressures within a latex balloon were measured at baseline (i.e., at rest) and during maneuvers (i.e., squeeze, simulated evacuation, and a Valsalva maneuver) in 12 asymptomatic women and 12 women with symptoms of difficult defecation. Anal resting and squeeze pressures were also assessed by manometry and were similar in controls and patients. At rest, axial rectoanal forces were directed inward and increased as the device approached the anal verge. Controls augmented this inward force when they squeezed and exerted an outward force during simulated expulsion and a Valsalva maneuver. The force change during maneuvers was also affected by device location and was highest at 4 cm from the verge. In patients, the force at rest and the change in force during all maneuvers was lower than in controls. The rectal pressure during a Valsalva maneuver was also lower in patients than in controls, suggestive of impaired propulsion. In conclusion, a subset of women with defecatory symptoms had weaker axial forces not only during expulsion but also during a Valsalva maneuver and when they squeezed (i.e., contracted) their pelvic floor muscles, suggestive of generalized pelvic floor weakness. Key Words: anal pressures, axial force, rectoanal, manometry, defecation, continence Word count – 245 G-00487-2005.R2 - 3 INTRODUCTION Current concepts suggest that defecation is accomplished by increased intra-rectal pressure coordinated with relaxation of the pelvic floor muscles. In addition to the internal and external anal sphincters, the pelvic floor muscles, especially the puborectalis, also relax during normal defecation (18). However, several aspects of the anorectal functions responsible for fecal continence and defecation are poorly understood, partly because our understanding is primarily based on manometry, which measures anorectal radial pressures, but not axial forces that are responsible for defecation and contribute to fecal continence. First, although a functional disorder of defecation has been traditionally attributed to impaired relaxation of the anal sphincter and/or pelvic floor muscles (i.e., dyssynergia), recent studies suggest that inadequate propulsive forces may also be important (15, 16). These studies need to be confirmed. Moreover, the mechanisms responsible for generating the propulsive force during defecation, which is assessed by recording pressure in the rectum, are unclear. Specifically, the contributions of increased intraabdominal pressure generated by voluntary effort (12) and rectal contraction (9) to this propulsive force have been disputed. This is an important issue because straining may increase intrarectal pressure but not improve evacuation (16), perhaps because the pelvic floor muscles also contract during straining (17). Second, though clinical observations suggest that the location of stool affects the ease of evacuation, it is unclear if axial rectoanal forces vary along the length of the rectum. Thus, patients with a defecatory disorder often report it is harder to evacuate stool located in the upper rectum (i.e., the vault), than the lower rectum (i.e., the ampulla). Third, though defecatory symptoms are attributed to impaired pelvic floor relaxation during defecation, we recently demonstrated that pelvic floor motion assessed by dynamic MRI was abnormal not only during evacuation, but also when patients contracted their pelvic floor muscles to retain intra-rectal contents (3). These observations need to be confirmed by measuring anorectal forces during contraction and expulsion. G-00487-2005.R2 - 4 To address these questions, we measured anorectal axial forces exerted against a rigid sphere or a latex balloon at specified locations in the anorectum during rectal expulsion and inward traction (REIT) in healthy subjects and patients with symptoms of difficult defecation by a new device (i.e., the REIT device). Previous studies have evaluated axial rectoanal forces to assess the mechanisms of fecal continence, but not defecation (7, 8, 10). These studies have demonstrated that the axial force measured by an intra-rectal solid sphere was correlated with anal pressures measured by manometry (7, 10). Moreover, the inward axial force, reflecting contraction of the anal sphincters and the pelvic floor, was reduced in patients with fecal incontinence (8, 10). G-00487-2005.R2 - 5 MATERIAL & METHODS Participants Twelve healthy women, (age 31.3 ± 2.3 years, Mean ± SEM) and 12 women with symptoms of difficult defecation (age 44.5 ± 4.3 years, Mean ± SEM) consented to participate in this study, which was approved by the Institutional Review Board of the Mayo Clinic. A clinical interview and physical examination were performed in all participants. Healthy controls were recruited by public advertisement. Exclusion criteria for controls included significant cardiovascular, respiratory, neurological, psychiatric or endocrine disease, irritable bowel syndrome as assessed by a validated bowel disease questionnaire (4), medications (with the exception of oral contraceptives or thyroid supplementation), and abdominal surgery (other than appendectomy or cholecystectomy). In addition, healthy subjects who had any previous anorectal operations including hemorrhoid procedures, or had sustained anorectal trauma during delivery (i.e. grade 3 or 4 laceration), as documented by obstetric records, were excluded. Patients were recruited from a specialized clinic devoted to gastrointestinal motility disorders. All patients had two or more symptom-based criteria for functional constipation (18). Colonic motor functions were evaluated by assessing colonic transit with scintigraphy in 8 patients (6) or by assessing colonic motility (i.e., tonic and phasic pressure activity in the descending colon under fasting conditions, after a meal, and after neostigmine by a barostat-manometric assembly) in 1 patient. Overall Study Design On the morning of the study, subjects received 2 magnesium citrate enemas (Fleets ,C.B. Fleet, Lynchburg, VA). Shortly thereafter, anorectal pressures and axial forces were measured by manometry and an axial force transducer respectively. Prior to the anorectal assessments, an investigator, aided by a digital rectal examination, coached subjects to contract the anal sphincter and pelvic floor muscles, simulate the process of expulsion, and to do a Valsalva maneuver. During simulated expulsion, subjects were G-00487-2005.R2 - 6 encouraged to mimic the process they usually employed to defecate. During a Valsalva maneuver, subjects were instructed to expire forcefully against a closed glottis. Anal Manometry, Rectal Balloon Expulsion, and Rectal Sensation After 2 sodium phosphate enemas (Fleets ,C.B. Fleet, Lynchburg, VA), anorectal testing (i.e., manometry, assessment of rectal compliance and sensation by a barostat, and assessment of rectal traction) was conducted in the left lateral position by perfusion manometry. The manometric catheter assembly had 8 sensors, i.e., 4 circumferentially oriented sensors at each of 2 levels separated by 2 cm. Average anal resting and squeeze pressures measured by the distal group of 4 sensors using the station pull-through technique, and summarized as described previously (5). The recto-anal pressure gradient was measured during expulsion; data were summarized by the difference between rectal and anal pressure, averaged over a 10 second interval during which anal pressure was at its lowest. The amount of external traction required to facilitate expulsion of a rectal balloon filled with 50 ml of warm water was also assessed in patients (3, 14). Rectal compliance and sensation were recorded using previously validated techniques by an “infinitely” compliant 7-cm long balloon with a maximum volume of 500 ml (Hefty Baggies, Mobil Chemical Co., Pittsford, NY) linked to an electronic rigid piston barostat (Mayo Clinic, Rochester, MN) (2, 5). An initial or conditioning distention followed by a rectal staircase distention (0-32 mm Hg in 4-mm Hg steps at 1 minute intervals) was performed. Rectal compliance and sensory thresholds for first sensation, desire to defecate (DD), and urgency were recorded during the staircase distention; the threshold was the first sensation of each symptom. Rectal pressure-volume relationships were analyzed by a power exponential function and summarized by the pressure corresponding to half maximum volume (Prhalf) (2, 11). G-00487-2005.R2 - 7 Rectal Traction Procedure – Rectoanal axial forces were measured by a customized device (i.e., Rectal Expulsion and Inward Traction (REIT) Device), adapted after a similar device described previously (7) (Figure 1). This device comprised an intra-rectal device (i.e., either a latex balloon or a rigid sphere 2.5 cm diameter) which was connected to tension-compression (Transducer Techniques, Temecula, Ca) and linear displacement transducers (Novotechnik, Ostfildern, Germany) and interfaced to a computer. The intrarectal device was fixed at 8, 6, or 4 cm from the anal verge. We chose to use a sphere 2.5 cm in diameter, because Bannister et al demonstrated that normal subjects could invariably expel a sphere of this size (1). The latex balloon was inflated with 60 ml of water and the intra-balloon pressure was also measured during maneuvers. Each maneuver began with a baseline period of 20 seconds during which the resting force was assessed. Thereafter, subjects were asked to squeeze (i.e., contract) their pelvic floor and anal sphincter muscles for 30 seconds, or to expel the device for 30 seconds, or, to do a Valsalva maneuver for 20 seconds in that order. A rest period of 30 seconds separated consecutive maneuvers. Data were acquired, displayed and analyzed by a customized Labview™ based program (National Instruments, Austin, Tx). Data Analysis – In each subject, the baseline resting force was averaged over 10 seconds immediately prior to each maneuver. The force change during maneuvers was calculated by subtracting the baseline force from the force during maneuvers. Statistical Analysis Axial rectoanal forces at baseline and the force change during maneuvers (i.e., squeeze, expulsion, and a Valsalva maneuver) were analyzed by a mixed-model analysis of covariance, fitting terms for location, maneuver, and subject status (i.e., patient or control). To validate the measurements of force, the relationship between force and pressure was assessed separately for each maneuver with a latex balloon in each subject. The relationship between the recto-anal pressure gradient during expulsion measured by G-00487-2005.R2 manometry and the force change during expulsion was also assessed. All results are expressed as Mean ± SEM. 8 G-00487-2005.R2 - 9 RESULTS Clinical Features Consistent with the Rome II criteria, all patients reported two or more symptoms of functional constipation for H 25% of time. Symptoms included excessive straining during defecation (92% patients), hard stools (62 %), sense of incomplete evacuation after defecation (92%), sense of anorectal blockage or obstruction (69%), infrequent stools (i.e., less than 3 times per week; 85%) and digital removal of stool from the rectum (77%). The duration of symptoms ranged from < 1 year (n = 2), 1 to 5 years (n = 4), 5 to 10 years (n = 2), or more than 10 years (n = 4). Anorectal Manometry, Standard Rectal Balloon Expulsion, and Colonic Motor Functions Average anal resting pressures were comparable in controls (66 ± 6 mm Hg, Mean ± SEM) and patients (65 ± 7 mm Hg). Average squeeze pressures were also comparable in controls (150 ± 17 mm Hg, Mean ± SEM) and patients (137 ± 16 mm Hg). Ten patients had an abnormal rectal balloon expulsion test and/or an abnormal recto-anal pressure gradient during simulated expulsion. The rectal balloon expulsion test was normal (i.e., 100 gm traction required) in 4 and abnormal in 8 patients. The recto-anal pressure gradient during expulsion was also abnormal in 8 patients, including 2 patients in who had a normal rectal balloon expulsion test. Seven patients had normal colonic motility assessed by scintigraphy (6 patients) or by an intraluminal colonic barostat-manometric assembly (1 patient). Two patients had delayed colonic transit. Rectal Compliance and Sensation During rectal staircase balloon distention, 9 of 12 subjects tolerated distention up to the highest pressure, i.e., 32 mmHg. Due to significant discomfort, this distention was terminated at 12 mmHg and 24 mmHg in 2 subjects, precluding an assessment of rectal compliance in these subjects. Among the remaining subjects, the Prhalf for rectal compliance was within normal limits, i.e., 14.4 ± 0.5 mmHg. Three patients - G-00487-2005.R2 10 had a stiff rectum, as evidenced by a Prhalf which was above the 90th percentile value for healthy subjects in our laboratory. During rectal staircase distention, the sensory thresholds for first sensation, desire to defecate, and constant urgency averaged 11.5 ± 1.4 mmHg, 15.7 ± 1.1 mmHg, and 23.5 ± 1.8 mmHg; these values were within 10th – 90th percentile normal values for our laboratory. The corresponding volume thresholds were 110 ± 20 ml, 150 ± 17 ml, and 216 ± 19 ml respectively. While sensory thresholds expressed as pressure were within the normal range for all subjects, volume thresholds for the desire to defecate were above the 90th percentile value in 2 patients. Assessment of Axial Forces With a Sphere Figure 2 provides representative tracings of axial forces recorded by a solid sphere during squeeze, expulsion, and a Valsalva maneuver. Axial forces directed inward (i.e., orad) and outward (i.e., caudad) were designated negative and positive respectively. At rest (i.e., before maneuvers), the sphere recorded an inwardly oriented force at 4 and 6 cm and an outwardly oriented force at 8 cm from the verge (Figure 3). Therefore, the resting force was influenced (p < 0.0001) by the location of the sphere in controls and patients. Moreover, the inward resting force was weaker (p = 0.01) in patients compared to controls (Figure 3). Both controls and patients exerted an outwardly directed force against a sphere during expulsion and a Valsalva maneuver (Figures 3 and 5). Conversely, both controls and patients generated an inwardly directed force when they squeezed (i.e., contracted) their pelvic floor muscles. Compared to controls, patients generated a significantly (p < 0.0001) lower outward force during expulsion and a Valsalva maneuver; these differences were most pronounced at 4 cm from the verge (Figure 5). However, the inward force during squeeze was comparable in controls and patients. - G-00487-2005.R2 11 Similar to the resting force, the force change during maneuvers was also affected by location of the sphere in controls (p = 0.0002), but not in patients. Thus, in controls, the outward force during expulsion and a Valsalva maneuver was highest at 4cm, intermediate at 6 cm, and lowest at 8 cm from the verge. During squeeze, the force change was higher at 4 cm compared to 6 cm, and in turn, compared to 8 cm from the verge; however differences among locations were not significant. Assessment of Axial Forces by a Latex Balloon At rest, forces measured by a latex balloon were comparable to a sphere, affected (p < 0.0001) by device location (i.e., inward at 4 and 6 cm, and outward at 8 cm from the verge), and of smaller magnitude in patients than controls (Figure 4). During voluntary maneuvers, controls and patients generated an inward force when they squeezed their pelvic floor muscles, and an outward force during expulsion and a Valsalva maneuver. Both controls and patients exerted a stronger outward force during expulsion against a latex balloon compared to a sphere (Figures 3-5). Similar to a sphere, outward forces during expulsion and a Valsalva maneuver were weaker in patients, compared to controls. However, in contrast to a sphere, (i) the inward force during squeeze was also weaker in patients compared to controls; and (ii) the force change during maneuvers with a balloon was not significantly different across locations (i.e., at 4, 6, and 8 cm from the verge), in controls nor patients. The recto-anal pressure gradient during expulsion measured by anal manometry was correlated (r = 0.44, p = 0.04) with the axial force during expulsion of a latex balloon at 4 cm from the verge. However, the recto-anal pressure gradient was not correlated with axial forces during expulsion of a latex balloon located at 6 or at 8 cm from the anal verge. Relationship Between Force and Pressure Assessed by a Latex Balloon Table 1 provides the pressures recorded by a latex balloon at rest and the change in pressure during maneuvers. Compared to rest, rectal pressures generally increased during all maneuvers. In controls, the - G-00487-2005.R2 12 rectal pressure change during expulsion and a Valsalva maneuver was comparable (i.e., 95% confidence intervals overlapped). Among patients, the axial force during a Valsalva maneuver was significantly lower than during expulsion. To validate force measurements, we examined the correlation between axial forces and pressures measured by the latex balloon. Figure 6 and Table 2 demonstrate that force and pressure during maneuvers with a latex balloon were correlated. These correlations were modest to excellent at all locations during expulsion and a Valsalva maneuver, and at 4 and 6 cm during squeeze. During squeeze, these correlations were negative because forces were negative (i.e., directed inward). - G-00487-2005.R2 13 DISCUSSION Anal manometry measures circumferential pressures, but not axial forces which are responsible for expulsion when directed outwardly or contribute to continence when directed inwardly. In previous studies, the axial force measured by an intra-rectal solid sphere was correlated with anal pressures measured by manometry (7, 10). Moreover, the inward axial force, reflecting contraction of the anal sphincters and the pelvic floor, was reduced in patients with fecal incontinence (8, 10). Similar to previous studies, we observed that when subjects squeezed, they exerted an inward axial force even when an intra-rectal device was located above the anal canal, reflecting pelvic floor contraction (8). Using a new device (REIT), we measured axial forces not only during squeeze, but also during expulsion and a Valsalva maneuver at specified locations within the anorectum. Consistent with the length of the anal sphincter (i.e., between 2-5 cm from the anal verge), the resting force was strongest at 4 cm from the anal verge, (i.e., within the anal canal). Moreover, the inward force was augmented during squeeze to a greater extent as the intra-rectal device approached the anal verge. Simultaneous measurements of axial force and pressure by a latex balloon during maneuvers were significantly correlated at most locations, validating force measurements by the REIT device against the existing standard (i.e., pressure). Four observations from this study provide insights into the mechanisms of normal and disordered continence and expulsion. First, healthy subjects augmented the resting inward force when they squeezed (i.e., contracted) their pelvic muscles, and exerted an outward force during expulsion and a Valsalva maneuver. Second, compared to controls, patients with defecatory symptoms exerted a weaker inward force when they squeezed the pelvic floor and a weaker outward force not only during expulsion, but also during a Valsalva maneuver, supporting the concept of generalized pelvic floor weakness. Third, rectoanal forces were higher for a latex balloon, which provides a closer approximation to a normally formed stool than does a sphere. Lastly, forces were influenced by the location of the device relative to the anal verge. Thus, the - G-00487-2005.R2 14 outward force during expulsion and a Valsalva maneuver was strongest at 4 cm from the verge, perhaps explaining why patients find it easier to evacuate stool located in the lower, compared to the upper rectum. During a Valsalva maneuver in controls, the axial force, which reflects the net outward force, was comparable to the outward force during expulsion. The intrarectal pressure, which is a surrogate marker of the propulsive effort, increased by an average of 31 mm Hg during a Valsalva maneuver. This increase in intrarectal pressure is similar to that reported in a previous study, in which intra-abdominal pressure increased by 36 mm Hg during a Valsalva maneuver (13). Among patients, the axial force and intrarectal pressure change during a Valsalva maneuver were lower than in controls. Taken together, these observations suggest that the lower outward axial force during a Valsalva maneuver in patients may be explained by a weaker propulsive effort. The outward axial force during expulsion was correlated with the recto-anal pressure gradient during expulsion measured by manometry. However, in contrast to a Valsalva maneuver, the intrarectal pressure during expulsion was comparable in patients and controls, suggesting that increased outlet resistance accounted for the weaker outward force during expulsion in patients. These observations expand on the concept introduced by Rao et al that symptoms of obstructive defecation are associated with inadequate propulsive forces and/or with increased resistance to expulsion (16). They also reinforce the concept that impaired expulsion in obstructive defecation is not a fixed process but is strongly influenced by voluntary actions. Similar to anal manometry, forces were assessed in the decubitus position. Further studies are necessary to compare forces in the seated and decubitus positions. In addition to a weaker outward force, the inward force during squeeze against a latex balloon was also weaker in patients than in controls. However, the inward force exerted against a sphere was not significantly different in patients and controls. These results confirm previous observations that the rectoanal axial force is influenced by the size of the intra-rectal device (7). They also corroborate recent observations that pelvic floor motion during squeeze, assessed by dynamic MRI, was reduced in women - G-00487-2005.R2 15 with defecatory symptoms (3). Taken together, these findings (i.e., reduced axial forces during expulsion, Valsalva maneuver, and squeeze), are consistent with the hypothesis that a subset of patients with defecatory symptoms have generalized pelvic floor weakness, rather than an isolated impairment of pelvic floor relaxation during expulsion. This hypothesis needs to be substantiated by simultaneous assessments of abdominal wall activity, (e.g., by EMG) and axial forces during voluntary maneuvers. The intrarectal sphere or balloon was connected to the transducers by a solid, inelastic segment, thus avoiding the drawback of an elastic connection that stretches and affects the force measured during maneuvers (10). In contrast to a previous study, the intra-rectal latex balloon or sphere was fixed relative to the anal verge during assessments to avoid reflex sphincter contraction induced by movement of the device (7). However, we cannot exclude the possibility that the resting axial force was influenced by proprioceptive input resulting from an object within the anorectum. The force change during maneuvers was substantially higher with a balloon compared to a sphere, perhaps because the balloon was in contact with, and therefore measured forces exerted by a larger surface area (~ 100 cm2) compared to a sphere (16 cm2 ). It is also conceivable that a hydraulic effect, (i.e., displacement of fluid within a balloon during a maneuver), also increased the axial force exerted against a balloon. From a practical perspective, a latex balloon may be preferable to a sphere because it approximates more closely to stool, and also because it is easier to introduce a deflated balloon compared to a sphere into the rectum in subjects with high resting anal pressure. On the other hand, a sphere was more useful for characterizing the effects of location on rectoanal forces, probably because it had a smaller surface area than the balloon. Diamant et al showed previously that the axial force was not influenced by friction, because similar forces were recorded by a regular sphere and another sphere with a smooth Teflon surface (7). In summary, our studies demonstrate that the rectoanal forces responsible for defecation and contributing to fecal continence can be measured at specific locations within the anorectum by a new - G-00487-2005.R2 16 device. Rectoanal axial forces during voluntary actions (i.e., squeeze, expulsion, and a Valsalva maneuver) were influenced by device location within the anorectum. Both devices recorded weaker axial forces during expulsion and a Valsalva maneuver in patients compared to controls. The force during squeeze against a latex balloon was also weaker in patients, consistent with the concept that some patients with defecatory symptoms have generalized abdomino-pelvic weakness, rather than an isolated impairment of pelvic floor relaxation. - G-00487-2005.R2 17 ACKNOWLEDGEMENTS This study was supported in part by USPHS NIH Grants R01 HD38666 and R01 HD41129, and by the General Clinical Research Center grant #RR00585 from the National Institutes of Health in support of the Physiology Laboratory and Patient Care Cores. - G-00487-2005.R2 18 REFERENCES 1. Bannister JJ, Davison PA, Timms JA, Gibbons C, and Read NW. Effect of stool size and consistency on defecation. Gut 28: 1246-1250, 1987. 2. Bharucha AE, Fletcher JG, Harper CM, Hough D, Daube JR, Stevens C, Seide B, Riederer SJ, and Zinsmeister AR. Relationship between symptoms and disordered continence mechanisms in women with idiopathic fecal incontinence. Gut 54: 546-555, 2005. 3. Bharucha AE, Fletcher JG, Seide B, Riederer SJ, and Zinsmeister AR. Phenotypic Variation in Functional Disorders of Defecation. Gastroenterology 128: 1199-1210, 2005. 4. Bharucha AE, Locke GR, Seide B, and Zinsmeister AR. A New Questionnaire for Constipation and Fecal Incontinence. Aliment Pharmacol Ther 20: 355-364, 2004. 5. Bharucha AE, Seide B, Fox JC, and Zinsmeister AR. Day-to-day reproducibility of anorectal sensorimotor assessments in healthy subjects. Neurogastroenterol Motil 16: 241-250, 2004. 6. Burton DD, Camilleri M, Mullan BP, Forstrom LA, and Hung JC. Colonic transit scintigraphy labeled activated charcoal compared with ion exchange pellets. Journal of Nuclear Medicine 38: 1807-1810, 1997. 7. Diamant NE and Harris LD. Comparison of objective measurement of anal sphincter strength with anal sphincter pressures and levator ani function. Gastroenterology 56: 110-116, 1969. 8. Fernandez-Fraga X, Azpiroz F, and Malagelada JR. Significance of pelvic floor muscles in anal incontinence. Gastroenteroogy 123: 1441-1450, 2002. 9. Halpert A, Keck L, Drossman DA, and Whitehead WE. Rectal Contractions are Part of Normal Defecation. Gastroenterology 126: A-362, 2004. 10. Hiltunen KM and Matikainen M. Simplified solid sphere test to investigate anal sphincter strength in patients with anorectal diseases. Dis Colon Rectum 37: 564-567, 1994. 11. Law N-M, Bharucha AE, Undale AS, and Zinsmeister AR. Cholinergic stimulation enhances colonic motor activity, transit and sensation in humans. Am J Physiol 281: G1228-G1237, 2001. 12. MacDonald A, Paterson PJ, Baxter JN, and Finlay IG. Relationship between intra-abdominal and intrarectal pressure in the proctometrogram. Br J Surg 80: 1070-1071, 1993. 13. Neumann P and Gill V. Pelvic floor and abdominal muscle interaction: EMG activity and intraabdominal pressure. International Urogynecology Journal 13: 125-132, 2002. 14. Pezim ME, Pemberton JH, Levin KE, Litchy WJ, and Phillips SF. Parameters of anorectal and colonic motility in health and in severe constipation. Dis Col Rectum 36: 484-491, 1993. 15. Rao SS, Mudipalli RS, Stessman M, and Zimmerman B. Investigation of the utility of colorectal function tests and Rome II criteria in dyssynergic defecation (Anismus). Neurogastroenterol Motil 16: 589596, 2004. 16. Rao SS, Welcher KD, and Leistikow JS. Obstructive defecation: a failure of rectoanal coordination. Am J Gastroenterol 93: 1042-1050, 1998. 17. Sapsford RR, Hodges PW, Richardson CA, Cooper DH, Markwell SJ, and Jull GA. Coactivation of the abdominal and pelvic floor muscles during voluntary exercises. Neurourology & Urodynamics 20: 31-42, 2001. 18. Whitehead WE and Wald A. Functional disorders of the anus and rectum. Gut 45: II55-II59, 1999. G-00487-2005.R2 19 Table 1. Rectoanal Pressures Measured by a Balloon at Rest and During Maneuvers in Healthy Subjects Epoch Resting pressure (i.e. before maneuver) Latex balloon pressure (95% CI) 4 cm 6 cm 8 cm Controls Patients Controls Patients Controls Patients 25 (13, 36) 28 (17, 39) 22 (12, 34) 24 (14, 35) 38 (27, 50) 31 (20, 42) Squeeze (During – Before) 26 (16, 37) 11 (1, 20) 14 (3, 25) 8 (-2, 17) -5 (-16, 6) 6 (-3, 16) Expulsion (During – Before) 17 (2, 32) 29 (16, 43) 29 (14, 43) 37 (24, 51) 35 (20, 50) 39 (25, 52) Valsalva (During – Before) 24 (12, 35) 13 (2, 24) 27 (16, 38) 13 (2, 24) 32 (20, 43) 11 (0.0, 22) All values are mean (95% C.I.) for pressure measured in mm Hg G-00487-2005.R2 20 Table 2. Relationship Between Axial Force and Pressure Measured by a Latex Balloon During Maneuvers Maneuver Squeeze 4 cm -0.71 (-0.97, -0.51) Location 6 cm -0.65 (-0.96, -0.44) Expulsion 0.62 (0.27, 0.9) 0.80 (0.72, 0.96) 0.69 (0.52, 0.97) Valsalva 0.54 (0.15, 0.93) 0.87 (0.83, 0.96) 0.87 (0.85, 0.98) 8 cm -0.01 (-0.61, 0.49) All values are mean (95% C.I.) for the correlation coefficient (r) - G-00487-2005.R2 21 Figure Legends Figure 1. Rectal expulsion and inward traction (REIT) device. A sphere (thin arrow) or a latex balloon (not shown) were connected to a pressure transducer (thick arrow) and to axial force and linear displacement transducers (arrowhead). Figure 2. Representative example of rectoanal axial forces during squeeze (left panel), expulsion (center panel), and a Valsalva maneuver (right panel). During squeeze, forces were more negative (i.e., directed inward) when the sphere was located at 4, compared to 6 and 8 cm from the verge. During expulsion, the positive (i.e., outward) force during expulsion was considerably higher at 4 compared to 6 and 8 cm from the verge. During a Valsalva maneuver, outward forces were generated at all locations. Figure 3. Rectoanal axial forces measured by a sphere during voluntary maneuvers in controls (left panel) and patients (right panel). Positive and negative values represent outward and inward forces respectively. Values are for absolute force at rest and the force change (during – before) during maneuvers. Particularly at 4 cm, outward forces during expulsion and a Valsalva maneuver were weaker in patients compared to controls. Inward forces were augmented by squeeze to a similar extent in patients and controls. Values are mean ± 95% CI. Figure 4. Rectoanal axial forces measured by a latex balloon during voluntary maneuvers in controls (left panel) and patients (right panel). Positive and negative values represent outward and inward forces respectively. Values are for absolute force at rest and the force change (during – before) during maneuvers. Values are mean ± 95% CI. Figure 5. Rectoanal axial forces measured by a sphere (left panel) and a latex balloon (right panel) at 4 cm from the anal verge. Values are for absolute force at rest and the force change (during – before) during maneuvers. Figure 6. G-00487-2005.R2 22 Tracings of axial force and pressure measured during simulated expulsion of a latex balloon fixed at 6 cm from the anal verge. Observe the correlation between force and pressure. Figure 1 G-00487-2005.R2 23 G-00487-2005.R2 24 Figure 2 6 cm 4 cm 800 800 600 600 600 400 400 400 200 0 -200 -400 -600 -800 Squeeze (30 s.) Force (gm) 800 Force (gm) Force (gm) 8 cm 200 0 -200 -400 -600 -800 Expulsion (30 s.) Out 200 0 -200 -400 -600 -800 Valsalva Maneuver (20 s.) In G-00487-2005.R2 25 Figure 3 Controls Patients 500 400 300 200 100 0 -100 -200 -300 -400 6 cm 8 cm 4 cm Mean + 95% C.I. * 0 5 Rest Squeeze 10 15 Expulsion Valsalva 20 Force (gm) Force (gm) 4 cm 500 400 300 200 100 0 -100 -200 -300 -400 6 cm 8 cm Mean + 95% C.I. 0 5 Rest 10 15 Squeeze Expulsion Valsalva 20 G-00487-2005.R2 26 Figure 4 Controls Patients 500 400 300 200 100 0 -100 -200 -300 -400 6 cm 4 cm 8 cm Mean + 95% C.I. 0 5 Rest Squeeze 10 15 Evacuation Valsalva 20 Force (gm) Force (gm) 4 cm 500 400 300 200 100 0 -100 -200 -300 -400 -500 6 cm 8 cm Mean + 95% C.I. 0 5 Rest Squeeze 10 15 Evacuation Valsalva 20 G-00487-2005.R2 27 Figure 5 Controls Patients 1000 800 600 600 400 400 Force (gm) Force (gm) Controls Patients 800 200 200 0 -200 -400 0 -200 -600 -400 -800 -1000 Rest Squeeze Expulsion Valsalva -600 Rest Squeeze Expulsion Valsalva G-00487-2005.R2 28 Figure 6 Pressure (mmHg) Force (gms) 500 Force (g-force) Pressure (gm) 400 110 100 90 80 70 300 60 50 40 30 200 100 20 0 10 0 0 20 40 60 Time (s) 80 100