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Deglutitive inhibition affects esophageal smooth muscle contractions but not basal tone: An analysis using a barostat
April 1995
• REPETITIVE ACTIVATION OF SIGMOID MECHANORECEPTORS RESULTS IN THE DEVELOPMENT OF RECTAL HYPERALGESIA IN IBS PATIENTS. J. Munakata L. Chang, C. An, B. Naliboff, E.A. Mayer. CURE: VA/UCLA Gastroenteric Biology Center/Neurobiology Group; Depts. of Medicine UCLA, West LAVA Med. Ctr. and Harbor-UCLA, Los Angeles, CA. 90073. In the current study we wanted to answer the following questions 1) Does repetitive activation of sigmoid mechanorecepto~'sby phasic balloon distension result in the development of rectosigmoid hyperalgesia and altered rectal motor function; 2) Do IBS patients differ from healthy controls in their response to sigmoid sensitization? Methods: 7 IBS patients and 7 normal controls (N) were studied using a double-balloon catheter (1 rectal, 1 sigmoid) and an electronic distension device (SVS, Synectics). Perception thresholds for discomfort, stimulus-response (SR) functions using verbal descriptor ratings for affective and sensory intensity, rectal and sigmoid tone and compliance were measured before and after a 10 rain period of intermittent rapid sigmoid (SIG) distension (60mmHg, 30 s pressure steps, 30 s interv.). Sympathetic activation was monitored by skin conductance measurements. Results: Compliance in the SIG was significantly lower in IBS patients (1.7±2ml/mmHg) when compared to N (3.9+3ml/mmHg; p<0.01) while resting tone was similar. In IBS (but not N) SIG stimulation resulted in secondary hyperalgesia referred to the lower abdomen, outlasting the stimulus by up to 60 rain. Following SIG sensitization, intensity of REC perception was decreased in N and increased in IBS (p<0.05). REC thresholds in IBS decreased from 27±6 to 18±2 in IBS (p<0.05) while no effect was seen in N. SIG sensitization was accompanied by a significant increase in skin conductance in both IBS and N. Summary and conclusions: 1. In IBS, repetitive stimulation of splanchnic afferents (sigmoid) afferents results in the development of central (spinal) sensitization manifested as secondary hyperalgesia and rectal hypersensitivity. 2. The differential effect on rectal perception in IBS patients and C is consistent with an inappropriate activation of descending bulbospinal control systems in IBS patients. Repetitive sigmoid contractions may therefore play a role in the development of rectal hypersensitivity.
EFFECT O F INCREASING INTRABOLUS PRESSURES ON E S O P H A G E A L PERISTALTIC MECHANICS: AN ANALYSIS USING A BAROSTAT. P.P. Murphy, B.T. Massey, R.C. Arndorfer, M. IL Kern, C. Hofmann, W.J. Hogan. MCW Dysphagia Institute, Medical College of Wisconsin, Milwaukee, Wl. Esophageal outflow obstruction is known to increase intrabolus pressure. We used a barostat to generate a constant-pressure pseudobolus to investigate in more detail the effects of intrabolus pressure on peristaltic mechanics. Methods: 9 normal subjects (5M/4F, age 24-48) were studied. A solid state pressure transducer manometry catheter was positioned with the transducers 2, 5, 8, 11, 18 and 21cm above the LES. A catheter with an infinitely compliant polyethylene balloon (length 10cm, diameter 3cm, volume 50ml) was positioned over the 4 distal transducers. This balloon was connected to an electronic barostat so that pressures were recorded and the balloon filled at the distal end, thus allowing the balloon to be emptied while maintaining a constant intraluminal pressure as the peristaltic wave progressed. 5 dry swallows were taken at balloon inflations of 0, 2, 5, 10, 15, 20 and 25 mmHg. Results: Median pressure at which secondary peristalsis (SP) occurred was 15mmHg, volume l l m m H g . Primary peristalsis (PP) was more effective than SP for balloon emptying. During PP larger volumes were cleared with larger pressures, but the fractional volume decreased (10mmHg 86% clearance, 25mmHg 75%, p < 0.01), whereas fractional clearance was constant at all pressures for SP (10mmHg, 67%; 25mmHg, 63%, p=0.63). Increasing balloon pressures decreased PP velocity from 3cm/s (0mmHg) to 1.8cm/s (25 mmHg) p<0.001. Peristaltic amplitude and duration increased above the balloon with increasing pressures (0mmHg, 74.6mmHg; 25mmHg, 102.6mmHg), whereas the response adjacent to the balloon was variable. Conclusions: PP is more effective than SP at esophageal clearance when the bolus offers a constant resistance. For PP fractional clearance decreases with increasing intraluminal pressures. In response to higher intraluminal pressure/wall tension the esophageal peristaltic velocity slows, while contractions above the distension increase in amplitude and duration. Supported by NIH DK25731 and CRC 00058-32S2.
Motility and Nerve-Gut Interactions
A653
DEGLUTIT1VE INHIBITION AFFECTS E S O P H A G E A L SMOOTH MUSCLE CONTRACTIONS BUT N O T BASAL TONE: AN ANALYSIS USING A BAROSTAT. P.P. Murphy. B.T. Massey, R.C. Arndorfer, M.K. Kern, C. Hofmann, W.J. Hogan. MCW Dysphagia Institute, Medical College of Wisconsin, Milwaukee WI. Previous studies have demonstrated that deglutitive inhibition can block esophageal peristaltic contractions and transiently interrupt the propulsive force. We tested whether such inhibition can also affect basal tone generated in response to esophageal distension. METHODS: 9 healthy subjects (5M/4F, mean age 24-48) underwent esophageal manometry using a catheter with 6 solid state pressure transducers positioned 2, 5, 8, 11, 18 and 21cm above the LES. In addition an orally swallowed catheter with an infinitely compliant polyethylene balloon (length 10cm, diameter 3cm, volume 50ml) was positioned with the balloon alongside the 4 distal transducers. The balloon was inflated to 2, 5, 10, 15, 20 and 25 m m H g constant pressures controlled by the barostat, with pressures being sampled and the balloon filled at its distal end. Balloon volume changes in response to dry swallows and secondary peristalsis were recorded. Results: Pressure-volume curves were essentially linear. The median pressure and volume at which secondary peristalsis occurred were 15 mmHg and 11 ml; these secondary peristaltic contractions decreased the balloon volume. Amyl nitrite at this balloon pressure increased basal balloon volume by 103%, indicating the presence of active myogenic tone. In 7 subjects degtutition did not increase basal volume before the contraction wave reached the balloon, indicating no inhibition of tone. In 2 subjects a small rise in volume of 14% was seen with less than 15% of swallows. Swallowing just after the onset of a secondary peristaltic contraction wave transiently inhibited that wave and arrested the ongoing fall in balloon volume, with volume either remaining constant or sometimes rising to but not above baseline levels. Conclusions: Deglutition inhibits active contractions evoked by esophageal distension but not the basal tone produced by such distension. Previous studies suggesting such tone is inhibited used intraluminal pressures that may have been inducing active contractions. Supported by DK25731 and CRC 00058-32S2.
FUNCTIONAL CHANGES IN ENTERIC NEUROMUSCULAR ACTIVITY AFTER SMALL BOWEL TRANSPLANTATION (SBTx) IN RATS. M.M. Mur(, M.G. Sarr. Dept. of Surg., Mayo Clinic, Rochester, MN BACKGROUND: The effects of SBTx on integrated function of the enteric nervous system (ENS) and smooth muscle are poorly understood. AIM: To evaluate in vitro mechanical responses of enteric smooth muscle to electric field stimulation (EFS) after SBTx. METHODS: Five groups of Lewis rats (n>8 each) were utilized: naive controls (NC); operative controls that were studied 1 and 8 wk (OC1, OC8) after intestinal transection/reanastomosis of the proximal jejunum and terminal ileum, and rats studied after total orthotopic SBTx at 1 and 8 wk (TX1, TX8). Fullthickness circular muscle strips suspended in tissue chambers were stretched to Lo. Square wave currents were delivered every 3 min with varying frequency (1-50 Hz) and pulse-width (0.5-8.0 reset) keeping stimulus duration and volta~ge constant at 10 see and 20 V. EFS was repeated with phentolamine (10".J,M), propranolol (5x10-6M) and atropine (10-7M) to study the response of non-adrenergic, non-cholinergic-(NANC) neurons. Active responses (on-response) during the period of stimulation were standardized to wet weight and/or expressed as percent of the baseline spontaneous activity. RESULTS: Spontaneous contractile activity (Sp Act) was increased in OC1, TX1 and TX8 (Table). EFS induced inhibition at low frequencies (1-5 Hz) and frequency-dependent contraction at higher frequencies in all groups. The frequency at which the response was equal to spontaneous activity, Ft00, was similar in all groups. Under NANC conditions, EFS caused inhibition at low and high frequencies in all groups; in TX1 and OC1 the F100 was greater (p<0.01) and there was more inhibition at 2 and 20 Hz (p<0.01). Pulse-width dependent contractions occurred in all groups but were greater in OC1 and TX1 at 0.5 msec (p<0.01); however, under NANC conditions inhibition prevailed at 0.5-4.0 reset. CONCLUSIONS: SBTx and interruption of the continuity of the ENS increase inhibitory output from NANC neurons during electric field stimulation suggesting a possible upregulation of NANC nerves. (Support: NIH DK 39337) Group Sp Act:~ Ft00~ NANC/F100~t 0.5 msec:~ NANC/0.5 msecl: NC 1.6:~0.2 4.2:~0.4 19.8±2.2 0.10±0,03 -0.03±0.02 OC1 2.9:~0.3" 3.1~:1.9 36.1:~7.3" 0.28±0.04* -0.10:~0.03 OC8 1.7±0.2 6.0:t0.9 15.7±2.1 0.11 ~:0.03 -0.07~:0.01 TX1 3.1±0.3" 3.7~:0.4 33.6±4.4* 0.30±0.05* -0.06~0.02 TX8 2.7±0.3* 5.3 :~0.9 21.4±4.0 0.29±0.08 -0.11 :t0.03 All data are .~±SEM tHz; :[:g'sec/mg; *Differs from NC, p<0.01
• REPETITIVE ACTIVATION OF SIGMOID MECHANORECEPTORS RESULTS IN THE DEVELOPMENT OF RECTAL HYPERALGESIA IN IBS PATIENTS. J. Munakata L. Chang, C. An, B. Naliboff, E.A. Mayer. CURE: VA/UCLA Gastroenteric Biology Center/Neurobiology Group; Depts. of Medicine UCLA, West LAVA Med. Ctr. and Harbor-UCLA, Los Angeles, CA. 90073. In the current study we wanted to answer the following questions 1) Does repetitive activation of sigmoid mechanorecepto~'sby phasic balloon distension result in the development of rectosigmoid hyperalgesia and altered rectal motor function; 2) Do IBS patients differ from healthy controls in their response to sigmoid sensitization? Methods: 7 IBS patients and 7 normal controls (N) were studied using a double-balloon catheter (1 rectal, 1 sigmoid) and an electronic distension device (SVS, Synectics). Perception thresholds for discomfort, stimulus-response (SR) functions using verbal descriptor ratings for affective and sensory intensity, rectal and sigmoid tone and compliance were measured before and after a 10 rain period of intermittent rapid sigmoid (SIG) distension (60mmHg, 30 s pressure steps, 30 s interv.). Sympathetic activation was monitored by skin conductance measurements. Results: Compliance in the SIG was significantly lower in IBS patients (1.7±2ml/mmHg) when compared to N (3.9+3ml/mmHg; p<0.01) while resting tone was similar. In IBS (but not N) SIG stimulation resulted in secondary hyperalgesia referred to the lower abdomen, outlasting the stimulus by up to 60 rain. Following SIG sensitization, intensity of REC perception was decreased in N and increased in IBS (p<0.05). REC thresholds in IBS decreased from 27±6 to 18±2 in IBS (p<0.05) while no effect was seen in N. SIG sensitization was accompanied by a significant increase in skin conductance in both IBS and N. Summary and conclusions: 1. In IBS, repetitive stimulation of splanchnic afferents (sigmoid) afferents results in the development of central (spinal) sensitization manifested as secondary hyperalgesia and rectal hypersensitivity. 2. The differential effect on rectal perception in IBS patients and C is consistent with an inappropriate activation of descending bulbospinal control systems in IBS patients. Repetitive sigmoid contractions may therefore play a role in the development of rectal hypersensitivity.
EFFECT O F INCREASING INTRABOLUS PRESSURES ON E S O P H A G E A L PERISTALTIC MECHANICS: AN ANALYSIS USING A BAROSTAT. P.P. Murphy, B.T. Massey, R.C. Arndorfer, M. IL Kern, C. Hofmann, W.J. Hogan. MCW Dysphagia Institute, Medical College of Wisconsin, Milwaukee, Wl. Esophageal outflow obstruction is known to increase intrabolus pressure. We used a barostat to generate a constant-pressure pseudobolus to investigate in more detail the effects of intrabolus pressure on peristaltic mechanics. Methods: 9 normal subjects (5M/4F, age 24-48) were studied. A solid state pressure transducer manometry catheter was positioned with the transducers 2, 5, 8, 11, 18 and 21cm above the LES. A catheter with an infinitely compliant polyethylene balloon (length 10cm, diameter 3cm, volume 50ml) was positioned over the 4 distal transducers. This balloon was connected to an electronic barostat so that pressures were recorded and the balloon filled at the distal end, thus allowing the balloon to be emptied while maintaining a constant intraluminal pressure as the peristaltic wave progressed. 5 dry swallows were taken at balloon inflations of 0, 2, 5, 10, 15, 20 and 25 mmHg. Results: Median pressure at which secondary peristalsis (SP) occurred was 15mmHg, volume l l m m H g . Primary peristalsis (PP) was more effective than SP for balloon emptying. During PP larger volumes were cleared with larger pressures, but the fractional volume decreased (10mmHg 86% clearance, 25mmHg 75%, p < 0.01), whereas fractional clearance was constant at all pressures for SP (10mmHg, 67%; 25mmHg, 63%, p=0.63). Increasing balloon pressures decreased PP velocity from 3cm/s (0mmHg) to 1.8cm/s (25 mmHg) p<0.001. Peristaltic amplitude and duration increased above the balloon with increasing pressures (0mmHg, 74.6mmHg; 25mmHg, 102.6mmHg), whereas the response adjacent to the balloon was variable. Conclusions: PP is more effective than SP at esophageal clearance when the bolus offers a constant resistance. For PP fractional clearance decreases with increasing intraluminal pressures. In response to higher intraluminal pressure/wall tension the esophageal peristaltic velocity slows, while contractions above the distension increase in amplitude and duration. Supported by NIH DK25731 and CRC 00058-32S2.
Motility and Nerve-Gut Interactions
A653
DEGLUTIT1VE INHIBITION AFFECTS E S O P H A G E A L SMOOTH MUSCLE CONTRACTIONS BUT N O T BASAL TONE: AN ANALYSIS USING A BAROSTAT. P.P. Murphy. B.T. Massey, R.C. Arndorfer, M.K. Kern, C. Hofmann, W.J. Hogan. MCW Dysphagia Institute, Medical College of Wisconsin, Milwaukee WI. Previous studies have demonstrated that deglutitive inhibition can block esophageal peristaltic contractions and transiently interrupt the propulsive force. We tested whether such inhibition can also affect basal tone generated in response to esophageal distension. METHODS: 9 healthy subjects (5M/4F, mean age 24-48) underwent esophageal manometry using a catheter with 6 solid state pressure transducers positioned 2, 5, 8, 11, 18 and 21cm above the LES. In addition an orally swallowed catheter with an infinitely compliant polyethylene balloon (length 10cm, diameter 3cm, volume 50ml) was positioned with the balloon alongside the 4 distal transducers. The balloon was inflated to 2, 5, 10, 15, 20 and 25 m m H g constant pressures controlled by the barostat, with pressures being sampled and the balloon filled at its distal end. Balloon volume changes in response to dry swallows and secondary peristalsis were recorded. Results: Pressure-volume curves were essentially linear. The median pressure and volume at which secondary peristalsis occurred were 15 mmHg and 11 ml; these secondary peristaltic contractions decreased the balloon volume. Amyl nitrite at this balloon pressure increased basal balloon volume by 103%, indicating the presence of active myogenic tone. In 7 subjects degtutition did not increase basal volume before the contraction wave reached the balloon, indicating no inhibition of tone. In 2 subjects a small rise in volume of 14% was seen with less than 15% of swallows. Swallowing just after the onset of a secondary peristaltic contraction wave transiently inhibited that wave and arrested the ongoing fall in balloon volume, with volume either remaining constant or sometimes rising to but not above baseline levels. Conclusions: Deglutition inhibits active contractions evoked by esophageal distension but not the basal tone produced by such distension. Previous studies suggesting such tone is inhibited used intraluminal pressures that may have been inducing active contractions. Supported by DK25731 and CRC 00058-32S2.
FUNCTIONAL CHANGES IN ENTERIC NEUROMUSCULAR ACTIVITY AFTER SMALL BOWEL TRANSPLANTATION (SBTx) IN RATS. M.M. Mur(, M.G. Sarr. Dept. of Surg., Mayo Clinic, Rochester, MN BACKGROUND: The effects of SBTx on integrated function of the enteric nervous system (ENS) and smooth muscle are poorly understood. AIM: To evaluate in vitro mechanical responses of enteric smooth muscle to electric field stimulation (EFS) after SBTx. METHODS: Five groups of Lewis rats (n>8 each) were utilized: naive controls (NC); operative controls that were studied 1 and 8 wk (OC1, OC8) after intestinal transection/reanastomosis of the proximal jejunum and terminal ileum, and rats studied after total orthotopic SBTx at 1 and 8 wk (TX1, TX8). Fullthickness circular muscle strips suspended in tissue chambers were stretched to Lo. Square wave currents were delivered every 3 min with varying frequency (1-50 Hz) and pulse-width (0.5-8.0 reset) keeping stimulus duration and volta~ge constant at 10 see and 20 V. EFS was repeated with phentolamine (10".J,M), propranolol (5x10-6M) and atropine (10-7M) to study the response of non-adrenergic, non-cholinergic-(NANC) neurons. Active responses (on-response) during the period of stimulation were standardized to wet weight and/or expressed as percent of the baseline spontaneous activity. RESULTS: Spontaneous contractile activity (Sp Act) was increased in OC1, TX1 and TX8 (Table). EFS induced inhibition at low frequencies (1-5 Hz) and frequency-dependent contraction at higher frequencies in all groups. The frequency at which the response was equal to spontaneous activity, Ft00, was similar in all groups. Under NANC conditions, EFS caused inhibition at low and high frequencies in all groups; in TX1 and OC1 the F100 was greater (p<0.01) and there was more inhibition at 2 and 20 Hz (p<0.01). Pulse-width dependent contractions occurred in all groups but were greater in OC1 and TX1 at 0.5 msec (p<0.01); however, under NANC conditions inhibition prevailed at 0.5-4.0 reset. CONCLUSIONS: SBTx and interruption of the continuity of the ENS increase inhibitory output from NANC neurons during electric field stimulation suggesting a possible upregulation of NANC nerves. (Support: NIH DK 39337) Group Sp Act:~ Ft00~ NANC/F100~t 0.5 msec:~ NANC/0.5 msecl: NC 1.6:~0.2 4.2:~0.4 19.8±2.2 0.10±0,03 -0.03±0.02 OC1 2.9:~0.3" 3.1~:1.9 36.1:~7.3" 0.28±0.04* -0.10:~0.03 OC8 1.7±0.2 6.0:t0.9 15.7±2.1 0.11 ~:0.03 -0.07~:0.01 TX1 3.1±0.3" 3.7~:0.4 33.6±4.4* 0.30±0.05* -0.06~0.02 TX8 2.7±0.3* 5.3 :~0.9 21.4±4.0 0.29±0.08 -0.11 :t0.03 All data are .~±SEM tHz; :[:g'sec/mg; *Differs from NC, p<0.01