Effects of nitric oxide on gastric slow waves and spikes

on fasting and postprandial proximal gastric tone and on gastric emptying rate in man. Methods: A) Nine healthy subjects (5 men, age 21-29) underwenttwo consecutive stepwise isobaric distensions to study gastric compliance and sensitivity thresholds, before and after the administration of sildenafil 50 rag. B) Ten healthy subjects (5 men, age 21-29) underwent in randomized order 2 gastric barostat studies to assess gastric tone at MDP+2 mm HO performed 30 rain before and 60 min after a liquid meal (200 ml, 300 kcal). Twenty min prior to the meal, placebo or Sildenafil 50 mg were administered orally. Accommodation was quantified as the difference in mean volume after and before the meal. C) tn 12 healthy subjects (7 men, age 19-29) gastric emptying rate of solids and liquids was assessedtwice in randomizedorder using the ~3Cootanoic acid/~4Cglycin breath tests. Half emptying time (tl/2) for solids and liquid were determined.Twenty min prior to the meal, placeboor Siidenafil 50 mg were administered orally. Results: In the tasting state, sildenaltl did not alter gastric resting tone (163_+27 ml vs. 162__+18ml, NS), compliance (64.7+-3.6 vs. 68.5+-7.8 ml/mm Hg, NS) or sensory thresholds induced by gastric distension (perception pressure 11.5_+0.9 vs, 11.3_+1 mm Hg; discomfort pressure 17.7_+0.9 vs. 17_+1 mm HO, all NS). Prior to the meal, intragastric volumes in the placebo and sildenafil groups were similar (176_+20 vs. 154_+22 ml). After sildenafil a higher gastric relaxationwas recordedthe first 30 rain (357_+38 vs. 253+-42 ml, p<0.05), and 60 min (348+-49 vs. 247_+38 mi, p<0.05) postprandially. Sildenafil did not alter solid emptying (tl/2 65_+6vs. 66_+4 rain, NS), but significantly delayed liquid emptying (tl/2 43_+4 vs. 56-+4 min, p<0.01). Conclusion: Sildenafil significantly increases intragastric volumes after the meal and slows liquid emptying rate, confirming that meal-inducedaccommodationin man involvesthe activationof a nitrergic pathway.Conversely, a nitrergic pathway does not seem to he involved in fasting gastric tone and in sensitivity to gastric distention in man. 1479 Role Of Enteric Nerves In The Regulation And Propagation Of SpontaneousAnd Electrically "Paced" Gastric Slow Waves In Rats. Xiao-Hua Hou, Jieyun Yin, PankajJay Pasricha, Maria Adelaide Micci, Jiande Chen, Univ of Texas Medical Branch, Galveston,TX The aim of this study was to investigatethe role of enteric nerves (EN) in the regulation and propagation of spontaneous and electrically "paced" gastric slow waves (GSWs) in rats. Methods: Denervation of the myenteric plexus in the proximal antrum was performed in 9 rats using BAC (0.46%). Three pairs of serosal electrodes were implanted in the proximal area, the treated area and the distal area, respectively.The same electrodes were placed in 9 rats with saline treatment. GSWs were recorded, 14 days after surgery, for 30-min in the fasting state, for lO-min with electrical pacingvia the proximal electrodes(frequency:5 cycles/ min (cpm); pulse width and amplitude were adjusted to achieve a complete entmnment) and for 20-rain after the termination of electrical pacing. Afterward, a strip of whole-mount tissue of the stomach from the proximal, treated and distal regions was removed, and immunohistochemistry staining for the neuronal marker protein oene product 9.5 (PGP 9.5) and ICCs (c-kit) was performed. Results: 1) Immunohistochemistry staining revealed a loss of PGP 9~5 positive neurons in the BAC-treatedregion in all rats with no changes in the ckit immunoreactivity in any of the rats. 2) The frequency of GSWs and the percentage of normal GSWs (3-6 cpm) in the BAC-treatedarea were significantly lower than the salinetreated area (frequency: 3.8 cpm vs 4.7 cpm, p<0.05; percentage:81% vs 59%, p<0.05). The main pattern of abnormal GSWs in the BAC-treated region was bradyamjthmia. GSW coupling between the treated area and the distal area was significantly lower in BAC-treated rats than the saline-treated rats (21% vs 39%,p<0.05); 3) Electrical pacing completely entrained GSWs in both groups of rats. However, the energy required for the entrainment was significantly higher with BAC than saline (entrainment of treated area: 1266 mS×mA (BAC) vs 566 mS×mA (saline), p
Effects of NO on gastricslowwavesand sp=kesactivity Postprandial

FaMing state

Saline Laeginine L,NAME

DF (cpm} 5.2 5.2

DP(dB)

%

NSPM

DP(dB)

%

16 23

DF (cPM} 4.5 4.6

-1.9 -0.8

77 78

NSPM , 39 42

-5.4 -6.3

87 81

5.3

4.4

72

46*

48

-1.3

80

47

1481 GaMdc Elesldcat S#mulatinn: A Five Year Follow-up Thomas L. Abell, Jean Lug, A Aljuburi, Univ of Arkansas for Medical Science, Little Rock, AR; Paula Eaton, Medtronic, Inc, Memphis, TN; Less Gann, Univ of Arkansas for Medical Science, Little Rock, AR; Guy voeller, Univ of TennesseeHealth Science Ctr, Memphis, TN; J Famitoni, Univ of Memphis, Memphis, TN INTRODUCTION: Gastric Electrical Stimulation GES can significantly reduce gastroparesis symptoms, as reported for 30 months (GE 116 (4) 2: A949, April 99). We now report a 5 year follow-up of 10 consecutive GES patients (pts) a subset of the GEMStrial. PATIENTS: 10 pts (2m, 8f, mean age 35.3 yrs) were implanted with Temporary (T) electrodes,connected to a GES device. 2 pts had Diabetes Mellitus (DM), 1 pt had a post-surgical disorder, and 7 had idiopathic disease; all had delayed solid and~or liquid gastric emptying. After a 2 week Ttrial, pts improved by both gastric emptying and symptoms receivedPermanent(P) electrodes and device. METHODS: GES employed an implantable neurostimulator (Itrel, Medtronic) programmed to the following parameters: pulse width: 330 microsec, frequency 12 bpm, current: 5 mA. Symptoms were recordedas total symptom scores (TSS: nausea(N), vomiting (V), bloating, abdominal pain and anorexia). Quality of life was rated as -3 to + 3, worst to best. Results were compared by pairedt-tests, and reported as mean+-S.E. RESULTS:Of the original 10 patients, 3 met the symptom improvement but not the gastric emptying criteria for P implantation. Of the 7 who underwent P implantation, 1 patent (with DM) died within 24 months of complications related to Kidney-PancreasTransplantation. The remaining 6 patients hadthe following at 5 years:Symptoms by TSS decreasedfrom 34.8_+3.1 to 20.7_+4.8, (p>O.01); N decreasedfrom 8.7+-0.6 to 5.6+-1.7, and V decreasedfrom 6.3+-1.6 to 3.3+-1.5. Quality of life improved from -2.8 to 1.5 (p< 0.01). Of the 3 patients who did not receive P implantation, one later received a GES, one is currently hospitalized,and the third (also with DM) recentlydied, after recurring hospitalizations.CONCLUSION:In this group of GESpatients followed for 5 years, the majority of patients continue to have symptomatic relief with associatedimprovement in OOL.This data suggeststhat the efficacy of GES may not diminish over time and is associated with improved and sustained quality of life, 1482 tnMbltoqt Effects Of Cbra~ic Retrograde Gastric Electrical Stimulation On Food Intake, WoioM And Postprandial Gastric Myoatectrical Activity Hui Ocyang, Univ of Texas Medical Branch, Galveston,TX; Steve Aidler, Transneuronix Inc, Mt Arlington, NJ; Jieyun Yin, Jlande Chen, Univ of Texas Medical Branch, Galveston, TX A preliminary study in obese patients suggested weight loss with chronic gastric electrical stimulation. The mechanism is, however unclear. The aim of this study was to investigate effects of chronic retrograde gastric electrical stimulation (RGES) on food intake and gastric myoelectrical activity. Methods: Five female dogs were implanted with bipolar stimulation electrodeson the distal lesser curvature connectedto a subcutaneouslyimplanted pacemaker and 3 pairs of serosal recording electrodes on the greater curvature. The pacemaker was turned on during the 4= month with pulse trains of 2-sec on and 3-sec off (pulse frequency: 40 Hz, amplitude: 6mA, width: 0.2mS) and all data were comparedwith those obtained during the preceding month and following month when the pacemakerwas turned off. During the study period, the dogs were given unlimited accessto food and daily food intake was noted. Gastric myoelectrical activity was recorded weekly and gastric slow waves were analyzed using the previously validated software to derive the following parameters:frequency, power (amplitude), percentageand coupling of normal slow waves. Results: 1. The average daily food intake was decreased by about 10% during the month of RGES (492.5+-34.4 g) in comparison with the preceding (532.1 _+39.4 g, p
1480 Effects Of Nitric Oxide On Gastric Slow Waves And Spikes. Xiaohua Hou, Hui Ouyang, Jieyun Yin, Zhishun Wang, Jiande Chen, Univ of Texas Medical Branch, Galveston,TX While numerous studies have investigatedthe effect of nitric oxide (NO) on gastric motility, gastric slow waves which regulate gastric motility is unknown. The aim of this study was to test our hypothesis that NO would impair the gastric slow wave by reducing its regularity and amplitude as well as contraction-relatedspike activity. Methods: The study was performed in 3 sessions in 8 dogs 2 weeks after the implantation of four pairs of electrodes along the greater curvature. In each session, saline, L-arginine (75mg/kg), or L-NAME(5mg/kg) was given intravenously (IV) after a 30-rain baseline recording in the fasting state. A solid test meal (200g) was ingested 30-rain after the IV injection. Gastric myoelectrical activity was recorded for 30-min at baseline,30-rain after IV injection and 60-min after the meal. Results: 1) Gastric slow waveswere not affected by NO. There were no changesamong the 3 sessions in the dominant frequency (DF), amplitude (DP) and percentageof normal slow waves (%) in either proximal or distal (see table) stomach. 2) L-arginine did not reduce the number of spikes per minute (NSPM) in the fed state. However,L-NAMEsignificantly increasedthe spike activity in the fasting state (*: p
1483

Ckanges in Elestragastrogram, Antral Motility and Autonomic Function by Ailmlnislration of CRH Yasuhiro Sagami, Taisuke Nomura, Manabu Satake, Yuka Endo, Tomotaka Shouji, Kazuto Kamhashi, Michio Hongo, Tohoku Univ, Sendal Japan [Background] Gastric motility is affected by stress via corticotrophin releasinghormone (CRH) and sympathetic discharges. Delayedgastric emptying, increasedsmall intestinal and colonic motility was induced by administration of CRH in humans. [Aim] Our aim of this study is to

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