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Pseudoaffective cardiac response to colonic distention in Sprague-Dawley rats
GASTROENTEROLOGY Vol. 118, No.4
A136 AGA ABSTRACTS
816
818
GASTRIC SLOW WAVE ABNORMALITIES DIFFERENTIATE DIARRHEA·PREDOMINANT AND CONSTIPATION·PREDOMI· NANT ms PATIENTS.
AUTONOMIC NERVOUS SYSTEM FUNCTION IN YOUNG WOMEN WITH ms.
Sigrid Elsenbruch, Jiande Dz Chen, William C. Orr, Lynn Institute for Healthcare Research, Oklahoma City, OK; Univ of Texas Med Sch, Galveston, TX. Introduction: Gastric slow wave abnormalities have been documented in patients with functional dyspepsia, but few studies have assessed gastric myoelectric functioning in patients with irritable bowel syndrome (IBS). Abnormal postprandial small bowel and colonic motility responses have been shown in patients with IBS, and different motility patterns have been documented in constipation-predominant and diarrhea-predominant IBS patients. The aim of this study was to investigate gastric slow wave responses to food intake in patients with diarrhea-predominant and constipation-predominant IBS. Methods: 12 women with diarrhea-predominant IBS (IBS-D), 12 women with constipation-predominant IBS (IBS-C), and 20 healthy women participated. All patients and controls were similar in age and body mass index. Electrogastrogram (EGG) recordings and gastrointestinal (GI) symptom assessment were accomplished at baseline (fasting) and after a standardized meal (two consecutive 30-minute postprandial recording periods). Results: At baseline, IBS-D demonstrated significantly decreased dominant EGG power (p<.05 compared to both controls and IBS-C). In response to the meal, IBS-D and controls showed an increase in the dominant power, while IBS-C did not show this change (p<.05 for the change score). IBS-C also failed to show the normal change in the %2-4cpm activity following the meal (p<.05 compared to controls and IBS-D). Both groups of IBS patients showed a significant increase in both lower and upper GI symptoms postprandially (compared to controls, p<.OI). However, there was no correlation between any EGG parameter and GI symptoms in any patient group. Conclusions: (I) Constipation and diarrhea-predominant IBS patients can be distinguished by their postprandial EGG responses. (2) Constipation-predominant patients have significantly diminished EGG responses to a meal, suggesting abnormal gastric motility. (3) There does not seem to be a good correlation between EGG parameters and GI symptoms in IBS patients.
817 PSEUDOAFFECTIVE CARDIAC RESPONSE TO COLONIC DIS· TENTION IN SPRAGUE-DA WLEY RATS. Bo-Guang Fan, Lu Wang, Ying Chen, Gervais Tougas, McMaster Univ, Hamilton, ON, Canada. Background: Noxious somatic and visceral stimuli elicit pseudoaffective reflex responses such as changes in heart rate (HR) and blood pressure, in addition to causing pain. The nature of the pseudoaffective responses to colonic distention (CD) remains unknown. Purpose: Examine the pseudoaffective cardiac response to CD, and determine the visceral sensory pathways and the types of fibers involved in Sprague Dawley (SD) rats. Methods: A latex balloon was inserted into the sigmoid colon of anaesthetized (ketamine and xylaxine) adult SD rats, and inflated at volumes of 0-3.0 ml. ECG was recorded before, during and after CD. To assess the role of sympathetic and parasympathetic afferents, the cardiac response was also examined after inferior mesenteric ganglionectomy (IMGT) and sacral ganglionectomy (SGT). Involvement of unmyelinated C fibers was assessed by prior treatment with capsaicin (125 mlJ./kg) two weeks prior. The effects of acute stress (restraint for 40 min at 22 C) on the cardiac response to CD was also examined. Results: In anaesthetized rats, CD caused a marked and volume dependent decrease in HR (26.5 :!: 4.3 % decrease with 3 ml, p < 0.0001). IMGT completely prevented the cardioautonomic effects of distention on HR, whereas SGT had no effect. Stress significantly decreased the magnitude of the pseudoaffective cardiac response to CD when compared to the response in non-stressed controls (decrease of 7.5 :!: 1.5% in stressed animals vs. 26.5 :!: 4.3% in controls, p<0.OOO4). Prior capsaicin treatment prevented the pseudoaffective response to CD in both stressed and non-stressed rats. Conclusions: CD produces a volume dependent pseudoaffective cardiac response in SD rats. Acute stress decreases the magnitude of the response, probably through increased sympathetic activity. The response is entirely mediated through activation of capsaicin sensitive unmyelinated C fibers running through the inferior mesenteric sympathetic ganglion. Sensory pathways traveling along parasympathetic tracts do not appear to be involved as evidenced by the lack of effect of the sacral ganglion removal. This study provides a useful model to study the pseudoaffective cardiac response to colonic stimuli and the possible effects of local colonic factors such as inflammation on visceral perception and autonomic responsiveness. These may be relevant to the pathophysiology of functional and inflammatory bowel disorders as well.
Margaret M. Heitkemper, Robert L. Burr, Monica E. Jarrett, Kevin C. Cain, Rona L. Levy, Andrew Feld, Vicky Hertig, Univ of Washington, Seattle, WA; Group Health Cooperative, Seattle, WA. Purpose: The purpose of this study was to evaluate autonomic nervous system (ANS) function in women with and without irritable bowel syndrome (IBS). Methods: Women ages 18-49 with and without IBS were recruited through advertisements in newspapers and flyers in the community. In addition, women with IBS who belonged to a local HMO were sent letters inviting them to participate. Women with lBS (n = 107) had a medical diagnosis of lBS and self-reported current gastrointestional symptoms (Rome-I criteria). Women (n = 47) in the control group had no history of chronic gastrointestional symptoms or current symptoms. Participants were initially interviewed then completed a symptom diary for one menstrual cycle. Women with lBS were classified as constipationprone, diarrhea-prone, alternating, or normal based on self-report of usual bowel pattern. During mid-luteal phase, 7 to 9 days after their luteinizing hormone surge (or a comparable time in women on oral contraceptives), the women were scheduled for an assessment of ANS function. Two hours after waking, measures of change in R-R interval were recorded during standardized laboratory tests (expiratory/inspiratory ratio, Valsalva maneuver, and posture changes). Change in heart rate and blood pressure (BP) were measured in response to an ice water immersion test (cold pressor). Heart rate variability was recorded using a Holter electrocardiograph monitor over the following 24 hours. Results: The only difference between the two groups in measures of ANS function was that women with lBS had a greater BP response to the cold pressor test (p = .04) than controls. However, the women with IBS were able to tolerate the ice water immersion for a greater length of time. When immersion time was controlled for, the difference in BP response became marginally non-significant. Within the group of women with lBS, those who were constipation-prone had significantly lower mean 24 hour heart rate (p = .02) relative to other lBS SUbgroups. When controlling for mean heart rate, this subgroup also had less heart rate variability as measured by SDANN (p = .03) and SD24-hr (p = .03). None of the other measures of ANS function differed among the self defined lBS subgroups. Conclusions: These results suggest that no obvious differences in ANS function exist in young women with lBS as compared to controls. Differences in ANS function may exist among subgroups of women with lBS. Further exploration of how best to define these subgroups is warranted.
819 IRRITABLE BOWEL SYNDROME PATIENTS EXHmIT POST· PRANDIAL AUTONOMIC DYSFUNCTION. Margaret M. Leach, Craig Phillips, David Joffe, Charles Fisher, Michael Appleberg, Michael Jones, John E. Kellow, Royal North Shore Hosp, Univ of Sydney, Sydney, Australia; Royal North Shore Hosp, Sydney, Australia. Chronic life event stress is a powerful predictor of symptom intensity in irritable bowel syndrome (lBS) (Gut 1998:43:256-61). The psychophysiological responses to such chronic stress should include alterations in cardiosympathetic and abdominal parasympathetic function; the patterns of autonomic dysfunction reported to date in IBS, however, have been inconsistent, and the evaluation of the above autonomic responses in IBS subgroups of predominant diarrhoea and predominant constipation has received little attention. Methods: We therefore assessed autonomic function non-invasively in 20 female lBS patients [Rome Criteria, 10 predominant diarrhoea (lBS-D) and 10 predominant constipation (lBS-C)] and in 20 age and sex-matched healthy controls (C). Pulse transit time was used as a measure of cardiosympathetic activity, and superior mesenteric artery peak systolic velocity (PSV) - assessed using Doppler ultrasound - as a measure of splanchnic parasympathetic activity. Autonomic measurements were undertaken during fasting and after a 450 kcal isotopically-labelled liquid meal (30% fat), and were adjusted for potential variations in gastric emptying rates. Results: lBS-C exhibited significantly shorter (p
A136 AGA ABSTRACTS
816
818
GASTRIC SLOW WAVE ABNORMALITIES DIFFERENTIATE DIARRHEA·PREDOMINANT AND CONSTIPATION·PREDOMI· NANT ms PATIENTS.
AUTONOMIC NERVOUS SYSTEM FUNCTION IN YOUNG WOMEN WITH ms.
Sigrid Elsenbruch, Jiande Dz Chen, William C. Orr, Lynn Institute for Healthcare Research, Oklahoma City, OK; Univ of Texas Med Sch, Galveston, TX. Introduction: Gastric slow wave abnormalities have been documented in patients with functional dyspepsia, but few studies have assessed gastric myoelectric functioning in patients with irritable bowel syndrome (IBS). Abnormal postprandial small bowel and colonic motility responses have been shown in patients with IBS, and different motility patterns have been documented in constipation-predominant and diarrhea-predominant IBS patients. The aim of this study was to investigate gastric slow wave responses to food intake in patients with diarrhea-predominant and constipation-predominant IBS. Methods: 12 women with diarrhea-predominant IBS (IBS-D), 12 women with constipation-predominant IBS (IBS-C), and 20 healthy women participated. All patients and controls were similar in age and body mass index. Electrogastrogram (EGG) recordings and gastrointestinal (GI) symptom assessment were accomplished at baseline (fasting) and after a standardized meal (two consecutive 30-minute postprandial recording periods). Results: At baseline, IBS-D demonstrated significantly decreased dominant EGG power (p<.05 compared to both controls and IBS-C). In response to the meal, IBS-D and controls showed an increase in the dominant power, while IBS-C did not show this change (p<.05 for the change score). IBS-C also failed to show the normal change in the %2-4cpm activity following the meal (p<.05 compared to controls and IBS-D). Both groups of IBS patients showed a significant increase in both lower and upper GI symptoms postprandially (compared to controls, p<.OI). However, there was no correlation between any EGG parameter and GI symptoms in any patient group. Conclusions: (I) Constipation and diarrhea-predominant IBS patients can be distinguished by their postprandial EGG responses. (2) Constipation-predominant patients have significantly diminished EGG responses to a meal, suggesting abnormal gastric motility. (3) There does not seem to be a good correlation between EGG parameters and GI symptoms in IBS patients.
817 PSEUDOAFFECTIVE CARDIAC RESPONSE TO COLONIC DIS· TENTION IN SPRAGUE-DA WLEY RATS. Bo-Guang Fan, Lu Wang, Ying Chen, Gervais Tougas, McMaster Univ, Hamilton, ON, Canada. Background: Noxious somatic and visceral stimuli elicit pseudoaffective reflex responses such as changes in heart rate (HR) and blood pressure, in addition to causing pain. The nature of the pseudoaffective responses to colonic distention (CD) remains unknown. Purpose: Examine the pseudoaffective cardiac response to CD, and determine the visceral sensory pathways and the types of fibers involved in Sprague Dawley (SD) rats. Methods: A latex balloon was inserted into the sigmoid colon of anaesthetized (ketamine and xylaxine) adult SD rats, and inflated at volumes of 0-3.0 ml. ECG was recorded before, during and after CD. To assess the role of sympathetic and parasympathetic afferents, the cardiac response was also examined after inferior mesenteric ganglionectomy (IMGT) and sacral ganglionectomy (SGT). Involvement of unmyelinated C fibers was assessed by prior treatment with capsaicin (125 mlJ./kg) two weeks prior. The effects of acute stress (restraint for 40 min at 22 C) on the cardiac response to CD was also examined. Results: In anaesthetized rats, CD caused a marked and volume dependent decrease in HR (26.5 :!: 4.3 % decrease with 3 ml, p < 0.0001). IMGT completely prevented the cardioautonomic effects of distention on HR, whereas SGT had no effect. Stress significantly decreased the magnitude of the pseudoaffective cardiac response to CD when compared to the response in non-stressed controls (decrease of 7.5 :!: 1.5% in stressed animals vs. 26.5 :!: 4.3% in controls, p<0.OOO4). Prior capsaicin treatment prevented the pseudoaffective response to CD in both stressed and non-stressed rats. Conclusions: CD produces a volume dependent pseudoaffective cardiac response in SD rats. Acute stress decreases the magnitude of the response, probably through increased sympathetic activity. The response is entirely mediated through activation of capsaicin sensitive unmyelinated C fibers running through the inferior mesenteric sympathetic ganglion. Sensory pathways traveling along parasympathetic tracts do not appear to be involved as evidenced by the lack of effect of the sacral ganglion removal. This study provides a useful model to study the pseudoaffective cardiac response to colonic stimuli and the possible effects of local colonic factors such as inflammation on visceral perception and autonomic responsiveness. These may be relevant to the pathophysiology of functional and inflammatory bowel disorders as well.
Margaret M. Heitkemper, Robert L. Burr, Monica E. Jarrett, Kevin C. Cain, Rona L. Levy, Andrew Feld, Vicky Hertig, Univ of Washington, Seattle, WA; Group Health Cooperative, Seattle, WA. Purpose: The purpose of this study was to evaluate autonomic nervous system (ANS) function in women with and without irritable bowel syndrome (IBS). Methods: Women ages 18-49 with and without IBS were recruited through advertisements in newspapers and flyers in the community. In addition, women with IBS who belonged to a local HMO were sent letters inviting them to participate. Women with lBS (n = 107) had a medical diagnosis of lBS and self-reported current gastrointestional symptoms (Rome-I criteria). Women (n = 47) in the control group had no history of chronic gastrointestional symptoms or current symptoms. Participants were initially interviewed then completed a symptom diary for one menstrual cycle. Women with lBS were classified as constipationprone, diarrhea-prone, alternating, or normal based on self-report of usual bowel pattern. During mid-luteal phase, 7 to 9 days after their luteinizing hormone surge (or a comparable time in women on oral contraceptives), the women were scheduled for an assessment of ANS function. Two hours after waking, measures of change in R-R interval were recorded during standardized laboratory tests (expiratory/inspiratory ratio, Valsalva maneuver, and posture changes). Change in heart rate and blood pressure (BP) were measured in response to an ice water immersion test (cold pressor). Heart rate variability was recorded using a Holter electrocardiograph monitor over the following 24 hours. Results: The only difference between the two groups in measures of ANS function was that women with lBS had a greater BP response to the cold pressor test (p = .04) than controls. However, the women with IBS were able to tolerate the ice water immersion for a greater length of time. When immersion time was controlled for, the difference in BP response became marginally non-significant. Within the group of women with lBS, those who were constipation-prone had significantly lower mean 24 hour heart rate (p = .02) relative to other lBS SUbgroups. When controlling for mean heart rate, this subgroup also had less heart rate variability as measured by SDANN (p = .03) and SD24-hr (p = .03). None of the other measures of ANS function differed among the self defined lBS subgroups. Conclusions: These results suggest that no obvious differences in ANS function exist in young women with lBS as compared to controls. Differences in ANS function may exist among subgroups of women with lBS. Further exploration of how best to define these subgroups is warranted.
819 IRRITABLE BOWEL SYNDROME PATIENTS EXHmIT POST· PRANDIAL AUTONOMIC DYSFUNCTION. Margaret M. Leach, Craig Phillips, David Joffe, Charles Fisher, Michael Appleberg, Michael Jones, John E. Kellow, Royal North Shore Hosp, Univ of Sydney, Sydney, Australia; Royal North Shore Hosp, Sydney, Australia. Chronic life event stress is a powerful predictor of symptom intensity in irritable bowel syndrome (lBS) (Gut 1998:43:256-61). The psychophysiological responses to such chronic stress should include alterations in cardiosympathetic and abdominal parasympathetic function; the patterns of autonomic dysfunction reported to date in IBS, however, have been inconsistent, and the evaluation of the above autonomic responses in IBS subgroups of predominant diarrhoea and predominant constipation has received little attention. Methods: We therefore assessed autonomic function non-invasively in 20 female lBS patients [Rome Criteria, 10 predominant diarrhoea (lBS-D) and 10 predominant constipation (lBS-C)] and in 20 age and sex-matched healthy controls (C). Pulse transit time was used as a measure of cardiosympathetic activity, and superior mesenteric artery peak systolic velocity (PSV) - assessed using Doppler ultrasound - as a measure of splanchnic parasympathetic activity. Autonomic measurements were undertaken during fasting and after a 450 kcal isotopically-labelled liquid meal (30% fat), and were adjusted for potential variations in gastric emptying rates. Results: lBS-C exhibited significantly shorter (p