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Is the fundo-antral reflex mediated by cholinergic mechanisms?
A618 AGA ABSTRACTS
GASTROENTEROLOGY Vol. 118, No, 4
3172
3174
THE EFFICACY, TOLERABILITY, AND DOSING REQUIREMENTS OF TRICYCLIC ANTIDEPRESSANTS IN 111 PATIENTS WITH FUNCTIONAL BOWEL DISORDERS. Charles W. Randall, Anitha Nair, Carlo Taboada, Methodist Hosp, San Antonio, TX; Univ of Texas Health Sci Ctr, San Antonio, TX. INTRODUCTION Tricyclic agents (TCA) have been used for several years to manage functional bowel syndromes. Their therapeutic effect is thought to be derived from modulation of both acetylcholine and serotonin. This study was designed to determine the effective doses required to improve quality of life and the frequency of side effects (SE). METHODS III patients were followed for a mean time of 16 months. 45 patients had irritable bowel, 37 had non-ulcer dyspepsia, 16 had irritable esophagus, and 13 had overlap syndromes where classic features of 2 or more of the above disorders were observed. Efficacy was judged as remission (R) when no symptoms remained, improved (I) when symptoms were sufficiently reduced in frequency and intensity that no additional treatment was needed by the patients, minimally improved (MI) when symptoms remained intolerable, and no change (NC) when conditions were unchanged from pre-treatment. All patients were followed on amitriptyline (N=IOI) or Desipramine (N = 10). IOmg was the usual starting dose. RESULTS 48 patients (43.2%) achieved R. A total of 55 patients (49.6%) met I criteria, 4 (3.6%) were MI, and 4 (3.6%) had NC. The dose range for amitriptyline (AMI) was 5-150mg and desipramine (DES) 1O-5Omg. The avg dose of AMI needed to achieve I or R was 23.67mg and that for DES was 23.57mg. Of note 39 patients using AMI achieved R (N=21) or I (N= 18) on IOmg only. 32 patients (28.8%) experienced side effects which include fatigue (15), palpitations (2), dizziness and confusion (5), constipation uncontrolled by fiber (3), prolonged antichorinergic effects (3), and miscellaneous causes (4) that included reflux, diaphoresis, nausea, and headache. 8 patients had to stop their medication due to SE. 7 or these patients had achieved a status of R or I. 6 of the 10 patients followed on DES had been treated with AMI but were changed effectively to DES due to SE. 1 patient was switched successfully to Imipramine and 1 patient to Trazadone. Both of these patients achieved I status. CONCLUSIONS 1. 92.8% (R=43.2% and 1=49.6%) of the patients achieved pretreatment goals 2. Benefits have been long term and with relatively inexpensive medications 3. Fatigue was the most common SE 4. SE may be alleviated by change in medications
LACK OF EFFECT OF FUNDIC RELAXATION ON THE DRINKING CAPACITY AND SYMPTOMS AFTER A DRINK TEST IN HEALTHY VOLUNTEERS AND FUNCTIONAL DYSPEPTICS. Guy E. Boeckxstaens, David P. Hirsch, Ingrid Kunst, Guido N. Tytgat, Acad Med Ctr, Amsterdam, Netherlands. Fundic relaxation has recently been suggested as putative treatment for a subgroup of patients with functional dyspepsia. We recently reported a decreased drinking capacity of patients with functional dyspepsia using a simple non-invasive drink test. In the present study, we evaluated the symptoms following these drink tests and investigated the effect of fundic relaxation on the drinking capacity and on symptoms. Methods: Healthy volunteers (HV) (n= 19, 9M, 20-53 yr, Nepean Dyspepsia Index (NDI) :s 5) and functional dyspeptic (FD) patients (n= II, 4M, 23-62 yr, NDI 2: 15, mainly dysmotility-like symptoms) were asked to drink 100 ml of water or a liquid caloric meal (Nutridrink) each min until discomfort, Thereafter, symptoms (nausea, fullness, satiety, pain) were scored on a scale from 0 (no sensation) to 5 (discomfort) at I and 2 h after the drink test. In a separate study, the effect of 6 mg of sumatriptan (Sum) s.c. on the drinking capacity and symptoms was studied in 10 HV (6M, 21-38 yr) and 6 FD (3M, 22-62 yr) subjects with impaired fundic accommodation in a double blind placebo controlled manner. Results: At the end of the drink test and one hour after the drink tests, symptoms did not differ between the 2 groups. However, 2 hours after the Nutridrink test, FD subjects reported more fullness (3.7 ± 0.35 vs 1.7 ± 0.6, p=0.02), nausea (3.9 ± 0.4 vs 1.0 ± 0.8, p=O.OI), pain (3.2 ± 0.6 vs 0 ± 0, p==O.OI) and satiety (4.2 ± 0.3 vs 2.6 ± 0.4, p=O.OO4) compared to HV. In contrast, only fullness (2.9 ± 0.4 vs 0 ± 0, p=O.OI) was significantly higher in FD 2 hours after the water drink test. In a separate study, Sum did not affect the maximal ingested volume of water (HV plac: 1490 ± 170; Sum: 1420 ± 200/ FD plac: 1080 ± 220; Sum: 1000 ± 220 ml) or Nutridrink (HV plac: 1080 ± 90; Sum: 1120 ± 90/ FD plac: 780 ± 80; Sum: 820 ± 60 ml) in neither FD with impaired fundic accommodation nor HV. Similarly, sum did not affect symptoms up to 3 h after the drink tests. Conclusions: This study shows that FD subjects develop more symptoms following a drink test compared to HV. Fundic relaxation with Sum does not increase the drinking capacity in HV or FD, nor does it improve symptoms during follow up. From these results we conclude that I. our drink test is not sensitive enough to detect fundic relaxation and/or that fundic relaxation is not an important determinant of the drinking capacity, 2. Fundic relaxation does not improve postprandial symptoms arguing against a role of impaired fundic accommodation in the genesis of dyspeptic symptoms.
3173 NASA BIOFEEDBACK TRAINING AS A POTENTIAL TREATMENT FOR PATIENTS WITH CHRONIC GI SYMPTOMS. Hani M. Rashed, Paticia Cowings, Bill Toscano, Ahmed EI-Gammal, Dima Adl, Thomas L. Abell, AFT Lab, UT Bowld Hosp, Univ of Tennessee, Memphis, Memphis, TN; Ames Research Ctr, NASA, Moffitfield, CA; Dept of Psychiatry, UCLA, Los Angeles, CA; Dept of Medicine, Univ of Tennessee, Memphis, Memphis, TN; Univ of Tennessee-Memphis, Memphis, TN. Introduction: Autogenic feedback training (AFTE) is a physiological conditioning procedure developed by NASA as a treatment for space motion sickness. It teaches the individuals how to modulate their Autonomic Nervous System (ANS) responses and thus their physiological functions. We have previously shown (GE 114(4): A825, 1998) the impact of AFTE in alleviating symptoms of Gastrointestinal Motility Disorders (GlMD). We now present additional long-term data using AFrE for patients (pts) with the symptoms of GIMD. Patients: 59 pts (54F, 5M, mean age 35 yrs) with chronic problems of nausea/vomiting, abdominal pain, bloating/distension, anorexia, and/or early satiety were referred to a GI Motility Program for ANS evaluation. Methods: All patients had AFTE in 8 sessions conducted over an 8 wk period and followed up to 16 months. Each session was 42 minutes divided into 5 cycles: each subdivided into 3 min. intervals of relaxation followed by 3 min. of stimulation. GI total symptom scores (TSS) were quantified as: NauseaIVomiting, abdominal pain (AP), bloating/distension (BID), anorexia (AN), and early satiety (ES) were quantified as O=no symptoms, 1=mild, 2=moderate, 3=severe. GI symptoms were evaluated after 4, 8, II & 15 sessions. Data were analyzed by paired t-test and reported as mean ± SE. Results: In all patients the following were observed: eAt baseline: TSS: 8.8±OA, NN: 2 ±0.2, BID: 1.85±0.2, AP: 1.9±0.2, AN: 1.0±0.2, and ES: 1.7±0.2. eAfter4 sessions, All symptoms decreased: TSS: 7.3±0.7, NN: 1.5±0.2, BID == 1.5±0.3, AP == 1.6±0.2, AN = 1.0±0.2 & ES = 1.6±0.2 eAfter 8 sessions, TSS as well as NN & AP were reduced significantly (p
4
Setsion# N=
IS THE FUNDO-ANTRAL REFLEX MEDIATED BY CHOLINERGIC MECHANISMS? Brent Harris, Satish SC Rao, Bruce Brown, Vani Vernuri, Konrad Schulze, Univ of Iowa Coli of Medicine, Iowa City, IA. In man, distention of the fundus induces a characteristic reflex contractile response of the antrum, the fundo-antral reflex. Whether this reflex is mediated by cholinergic mechanisms is not known? In 6 healthy subjects, we placed a probe with 2 sensors, 3 em apart in antrum and a large compliant balloon in the fundus. Isobaric balloon distensions were performed at 3mm Hg increments using a barostat. Distentions were maintained for 8 min followed by 8 minute rest. We examined intragastric pressures, fundic tone, and gastric sensation before and after giving 0.6 mg IV atropine sulphate. Simultaneously, we evaluated antral contractions and configurational changes with ultrasound. Blood pressure and pulse rate were monitored. RESULTS: Fundic distention induced antral phasic activity in all subjects before atropine confirming the reflex. The motor activity peaked at distending pressure of 12-15 mm Hg. After atropine, pressure waves showed a significant reduction (p<0.05) in their incidence, area under the curve, and amplitude(Table). After atropine, the fundic tone decreased as shown by an increase in balloon volume. Thresholds for definite perception (mean ± s.d), pre vs post atropine, (1O±4 vs II ±2mmHg), moderate sensation (13±3 vs 12±3) and discomfort (l7±3 vs 14±4) were not different. At higher distentions some antral pressure activity was seen possibly due to a loss of atropine effect. This was associated with normalization of heart rate. Conclusions: Atropine attenuates the fundo-antral reflex in man suggesting that cholinergic mechanisms may mediate this reflex. However, because the gastric muscle tone decreased and the response was not abolished, other mechanisms such as enteric regulation may playa role.
lOP
Waves/min
Table 1.
TSS
3175
59 a.a±OA
27 7.3±O.7
25 6A±0.a'
11
15
14 5.7±0.a
6.5±0.a
a
AUC mm Hg xs
Amplitude mm Hg
Pre Post Pre Post Pre Post
1.0 0.06 779 9.2 69 10
1.3 0.03 1820 4.4 60 12
1.1 0.6 1690 157 40 11
12
15
18
1.3 0.5 1980 1100 75 63
11
0.4 2433 206 66 51
08 0.4 1606 902 53 88
Antral motor activity pre & post-atropine. Header-balloon pressure, mm Hg Bold=p<0.05 'p < 0.05 significant difference from thebasal by paired t-tests.
GASTROENTEROLOGY Vol. 118, No, 4
3172
3174
THE EFFICACY, TOLERABILITY, AND DOSING REQUIREMENTS OF TRICYCLIC ANTIDEPRESSANTS IN 111 PATIENTS WITH FUNCTIONAL BOWEL DISORDERS. Charles W. Randall, Anitha Nair, Carlo Taboada, Methodist Hosp, San Antonio, TX; Univ of Texas Health Sci Ctr, San Antonio, TX. INTRODUCTION Tricyclic agents (TCA) have been used for several years to manage functional bowel syndromes. Their therapeutic effect is thought to be derived from modulation of both acetylcholine and serotonin. This study was designed to determine the effective doses required to improve quality of life and the frequency of side effects (SE). METHODS III patients were followed for a mean time of 16 months. 45 patients had irritable bowel, 37 had non-ulcer dyspepsia, 16 had irritable esophagus, and 13 had overlap syndromes where classic features of 2 or more of the above disorders were observed. Efficacy was judged as remission (R) when no symptoms remained, improved (I) when symptoms were sufficiently reduced in frequency and intensity that no additional treatment was needed by the patients, minimally improved (MI) when symptoms remained intolerable, and no change (NC) when conditions were unchanged from pre-treatment. All patients were followed on amitriptyline (N=IOI) or Desipramine (N = 10). IOmg was the usual starting dose. RESULTS 48 patients (43.2%) achieved R. A total of 55 patients (49.6%) met I criteria, 4 (3.6%) were MI, and 4 (3.6%) had NC. The dose range for amitriptyline (AMI) was 5-150mg and desipramine (DES) 1O-5Omg. The avg dose of AMI needed to achieve I or R was 23.67mg and that for DES was 23.57mg. Of note 39 patients using AMI achieved R (N=21) or I (N= 18) on IOmg only. 32 patients (28.8%) experienced side effects which include fatigue (15), palpitations (2), dizziness and confusion (5), constipation uncontrolled by fiber (3), prolonged antichorinergic effects (3), and miscellaneous causes (4) that included reflux, diaphoresis, nausea, and headache. 8 patients had to stop their medication due to SE. 7 or these patients had achieved a status of R or I. 6 of the 10 patients followed on DES had been treated with AMI but were changed effectively to DES due to SE. 1 patient was switched successfully to Imipramine and 1 patient to Trazadone. Both of these patients achieved I status. CONCLUSIONS 1. 92.8% (R=43.2% and 1=49.6%) of the patients achieved pretreatment goals 2. Benefits have been long term and with relatively inexpensive medications 3. Fatigue was the most common SE 4. SE may be alleviated by change in medications
LACK OF EFFECT OF FUNDIC RELAXATION ON THE DRINKING CAPACITY AND SYMPTOMS AFTER A DRINK TEST IN HEALTHY VOLUNTEERS AND FUNCTIONAL DYSPEPTICS. Guy E. Boeckxstaens, David P. Hirsch, Ingrid Kunst, Guido N. Tytgat, Acad Med Ctr, Amsterdam, Netherlands. Fundic relaxation has recently been suggested as putative treatment for a subgroup of patients with functional dyspepsia. We recently reported a decreased drinking capacity of patients with functional dyspepsia using a simple non-invasive drink test. In the present study, we evaluated the symptoms following these drink tests and investigated the effect of fundic relaxation on the drinking capacity and on symptoms. Methods: Healthy volunteers (HV) (n= 19, 9M, 20-53 yr, Nepean Dyspepsia Index (NDI) :s 5) and functional dyspeptic (FD) patients (n= II, 4M, 23-62 yr, NDI 2: 15, mainly dysmotility-like symptoms) were asked to drink 100 ml of water or a liquid caloric meal (Nutridrink) each min until discomfort, Thereafter, symptoms (nausea, fullness, satiety, pain) were scored on a scale from 0 (no sensation) to 5 (discomfort) at I and 2 h after the drink test. In a separate study, the effect of 6 mg of sumatriptan (Sum) s.c. on the drinking capacity and symptoms was studied in 10 HV (6M, 21-38 yr) and 6 FD (3M, 22-62 yr) subjects with impaired fundic accommodation in a double blind placebo controlled manner. Results: At the end of the drink test and one hour after the drink tests, symptoms did not differ between the 2 groups. However, 2 hours after the Nutridrink test, FD subjects reported more fullness (3.7 ± 0.35 vs 1.7 ± 0.6, p=0.02), nausea (3.9 ± 0.4 vs 1.0 ± 0.8, p=O.OI), pain (3.2 ± 0.6 vs 0 ± 0, p==O.OI) and satiety (4.2 ± 0.3 vs 2.6 ± 0.4, p=O.OO4) compared to HV. In contrast, only fullness (2.9 ± 0.4 vs 0 ± 0, p=O.OI) was significantly higher in FD 2 hours after the water drink test. In a separate study, Sum did not affect the maximal ingested volume of water (HV plac: 1490 ± 170; Sum: 1420 ± 200/ FD plac: 1080 ± 220; Sum: 1000 ± 220 ml) or Nutridrink (HV plac: 1080 ± 90; Sum: 1120 ± 90/ FD plac: 780 ± 80; Sum: 820 ± 60 ml) in neither FD with impaired fundic accommodation nor HV. Similarly, sum did not affect symptoms up to 3 h after the drink tests. Conclusions: This study shows that FD subjects develop more symptoms following a drink test compared to HV. Fundic relaxation with Sum does not increase the drinking capacity in HV or FD, nor does it improve symptoms during follow up. From these results we conclude that I. our drink test is not sensitive enough to detect fundic relaxation and/or that fundic relaxation is not an important determinant of the drinking capacity, 2. Fundic relaxation does not improve postprandial symptoms arguing against a role of impaired fundic accommodation in the genesis of dyspeptic symptoms.
3173 NASA BIOFEEDBACK TRAINING AS A POTENTIAL TREATMENT FOR PATIENTS WITH CHRONIC GI SYMPTOMS. Hani M. Rashed, Paticia Cowings, Bill Toscano, Ahmed EI-Gammal, Dima Adl, Thomas L. Abell, AFT Lab, UT Bowld Hosp, Univ of Tennessee, Memphis, Memphis, TN; Ames Research Ctr, NASA, Moffitfield, CA; Dept of Psychiatry, UCLA, Los Angeles, CA; Dept of Medicine, Univ of Tennessee, Memphis, Memphis, TN; Univ of Tennessee-Memphis, Memphis, TN. Introduction: Autogenic feedback training (AFTE) is a physiological conditioning procedure developed by NASA as a treatment for space motion sickness. It teaches the individuals how to modulate their Autonomic Nervous System (ANS) responses and thus their physiological functions. We have previously shown (GE 114(4): A825, 1998) the impact of AFTE in alleviating symptoms of Gastrointestinal Motility Disorders (GlMD). We now present additional long-term data using AFrE for patients (pts) with the symptoms of GIMD. Patients: 59 pts (54F, 5M, mean age 35 yrs) with chronic problems of nausea/vomiting, abdominal pain, bloating/distension, anorexia, and/or early satiety were referred to a GI Motility Program for ANS evaluation. Methods: All patients had AFTE in 8 sessions conducted over an 8 wk period and followed up to 16 months. Each session was 42 minutes divided into 5 cycles: each subdivided into 3 min. intervals of relaxation followed by 3 min. of stimulation. GI total symptom scores (TSS) were quantified as: NauseaIVomiting, abdominal pain (AP), bloating/distension (BID), anorexia (AN), and early satiety (ES) were quantified as O=no symptoms, 1=mild, 2=moderate, 3=severe. GI symptoms were evaluated after 4, 8, II & 15 sessions. Data were analyzed by paired t-test and reported as mean ± SE. Results: In all patients the following were observed: eAt baseline: TSS: 8.8±OA, NN: 2 ±0.2, BID: 1.85±0.2, AP: 1.9±0.2, AN: 1.0±0.2, and ES: 1.7±0.2. eAfter4 sessions, All symptoms decreased: TSS: 7.3±0.7, NN: 1.5±0.2, BID == 1.5±0.3, AP == 1.6±0.2, AN = 1.0±0.2 & ES = 1.6±0.2 eAfter 8 sessions, TSS as well as NN & AP were reduced significantly (p
4
Setsion# N=
IS THE FUNDO-ANTRAL REFLEX MEDIATED BY CHOLINERGIC MECHANISMS? Brent Harris, Satish SC Rao, Bruce Brown, Vani Vernuri, Konrad Schulze, Univ of Iowa Coli of Medicine, Iowa City, IA. In man, distention of the fundus induces a characteristic reflex contractile response of the antrum, the fundo-antral reflex. Whether this reflex is mediated by cholinergic mechanisms is not known? In 6 healthy subjects, we placed a probe with 2 sensors, 3 em apart in antrum and a large compliant balloon in the fundus. Isobaric balloon distensions were performed at 3mm Hg increments using a barostat. Distentions were maintained for 8 min followed by 8 minute rest. We examined intragastric pressures, fundic tone, and gastric sensation before and after giving 0.6 mg IV atropine sulphate. Simultaneously, we evaluated antral contractions and configurational changes with ultrasound. Blood pressure and pulse rate were monitored. RESULTS: Fundic distention induced antral phasic activity in all subjects before atropine confirming the reflex. The motor activity peaked at distending pressure of 12-15 mm Hg. After atropine, pressure waves showed a significant reduction (p<0.05) in their incidence, area under the curve, and amplitude(Table). After atropine, the fundic tone decreased as shown by an increase in balloon volume. Thresholds for definite perception (mean ± s.d), pre vs post atropine, (1O±4 vs II ±2mmHg), moderate sensation (13±3 vs 12±3) and discomfort (l7±3 vs 14±4) were not different. At higher distentions some antral pressure activity was seen possibly due to a loss of atropine effect. This was associated with normalization of heart rate. Conclusions: Atropine attenuates the fundo-antral reflex in man suggesting that cholinergic mechanisms may mediate this reflex. However, because the gastric muscle tone decreased and the response was not abolished, other mechanisms such as enteric regulation may playa role.
lOP
Waves/min
Table 1.
TSS
3175
59 a.a±OA
27 7.3±O.7
25 6A±0.a'
11
15
14 5.7±0.a
6.5±0.a
a
AUC mm Hg xs
Amplitude mm Hg
Pre Post Pre Post Pre Post
1.0 0.06 779 9.2 69 10
1.3 0.03 1820 4.4 60 12
1.1 0.6 1690 157 40 11
12
15
18
1.3 0.5 1980 1100 75 63
11
0.4 2433 206 66 51
08 0.4 1606 902 53 88
Antral motor activity pre & post-atropine. Header-balloon pressure, mm Hg Bold=p<0.05 'p < 0.05 significant difference from thebasal by paired t-tests.