A688 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4

• CHANGES IN GASTROINTESTINAL SMOOTH MUSCLE REACTIVITY DURING PREGNANCY MAY BE INDUCED BY NITRIC OXIDE S.N. Shah. J.M. Cuevas. A.J. Hobbs. E. Whanu. S.W. Ashley. L.J. Ignarro & G. Chandhuri. Departments of Pharmacology, Obstetrics & Gynecology and Surgery, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90024.

Gastrointestinal (GI) disorders represent one of the most frequent complaints during pregnancy. Nitric oxide (NO) functions as a non- adrenergic non-cholinergic (NANC) inhibitory neurotransmitter in many regions including the GI tract. In this study, we attempted to determine whether NO plays a role in changes in GI motility and smooth muscle reactivity which may contribute to the problems associated with pregnancy. To investigate this possibility, different regions of the GI U'act were examined using organ bath preparations. Tissues were taken from non-pregnant (control), mid-pregnant (11-13 days) and late pregnant ( 18- 20 days) female rats. Following constriction with carbachol, elecu'ic field stimulation (EFS) resulted in frequency dependent relaxations of the esophagus. However, there was no significant difference in EFS stimulated relaxations between pregnant and fion-pregnant animals. Addition of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), was only effective in the late pregnant animals. In the fundus, EFS elicited frequency-dependent relaxations of serotonin- induced tone. In late-pregnant animals, the relaxant response to EFS was maa'kedly enhanced, as compm~ed to control and mid-pregnant animals. Further, L-NAME significantly reduced EFS-induced relaxations in control, mid-, and late-pregnant animals. In ileal preparations, EFS of the resting smooth muscle resulted in frequency-dependent contractions. Addition of L-NAME was effective in potentiating EFS-induced contractions in control, mid-, and late-pregnant animals, but was significantly more potent in late-pregnant tissue especiaUy at higher frequencies as compared to the other groups. In contrast to the ileum, EFS elicited frequency-dependent relaxations of the quiescent colonic smooth muscle. In the colon, L-NAME reduced EFS-induced relaxation in control, mid-, and late-pregnant animal. In this tissue however, L- NAME was significantly more potent at inhibiting relaxations in both mid- and late-pregnant animals as compared to controls. These data suggest that the control of the GI smooth muscle function varies markedly between regions and may be significantly altered during pregnancy. (Funded by NIH Grant HL46843)

• AUGMENTATION OF DEGLUTITIVE UES OPENING IN THE ELDERLY BY EXERCISE. R. Shaker. M. Kern, R.C. Arndorfer, C. Hofmann, J. Ren, J. Bonnevier. M e w Dysphagia Institute, Depts. of Medicine, Radiology and Otolaryngology and Communicative Disorders, Medical College of Wisconsin and VA Medical Center, Milwaukee, WI

Earlier studies have shown that normal deglutitive upper esophageal (UES) opening is multifactorial. These factors include relaxation of the cricopharyngeal (CP) muscle, the main component of LIES, distensibility of the CP and distraction forces imparted on the CP by the LIES opening muscles of the suprahyoid muscle group. Among these, only the function of the opening muscles are currently amenable to physiologic manipulation. The aim of this study was to determine the effect of a simple isotonic and isometric exercise of the neck muscles on deglutitive UES opening. Methods: Since earlier studies have shown that the cross-sectionai area of UES opening in healthy elderly is reduced, we chose to study this age group. We determined maximal deglutitive, superior hyoid (A), anterior hyoid (B), superior laryngeal (C), anterior laryngeal (D), anteroposterior UES diameter (E), lateral UES diameter (F), and cross-sectional area of UES opening (G) in seven healthy elderly without any swallowing problems before and following six weeks of simple neck flexion exercise. The exercise was performed three times a day (three 1-n-tin. sustained head raising, interrupted by l-rain, of rest followed by 30 repetitions of head raising in supine position). We also studied six healthy elderly before and after 6-weeks of sham exercise (fist clenching). Subjects were studied in lateral and AP projection during dry and 5 ml barium swallows. Videofluoroscopic recordings were analyzed in blinded fashion. Results:

% Change from Pre-Exercise (ANOVA all subjects, Mean _+ SEM)

Results A B C D E F G

RealExercise -13+7 9:t:13 -6:1:8 21±4" 27+5* 2+2 26+6

Sham Exercise -0.8_+_2 3+7 -2±3 0-J:4 -2+2 15-2 0+5

After real exercise, in six of seven volunteers, laryngeal anterior excursion and LIES AP diameter as well as cross-sectional area of the sphincter increased significantly (*p<0.05). In one subject, exercise did, not result in detectable augmentation. In the sham group, there was no change in measured parameters after exercise. Conclusion: In normal elderly, deglutitive UES opening is amenable to augmentation by exercise. This approach may be useful in some patients with disorders of LIES opening.

• CHARACTERIZATION OF VOCAL CORDS AND I N T R A T R A C H E PRESSURE PHENOMENA DURING SWALLOWING, COUGHING AND PHONATION. R. Shaker, J. Ren, R.M. Schapira, K. Dua, Z. Sui, A. Funahashi. MCW Dysphagia Institute, Depts. of Medicine, Radiol. and Otoluryngol., Medical College of Wisconsin and VAMC, Milwankee, WI

Deglutitive vocal cord closure comprises the first tier of airway protection during swallowing; However, their degiutitive closure pressure in humans is not known. Similarly, their closure pressure during other physiologic functions such as coughing and phonation has not been systematically studied. The aim of the present study was to characterize and correlate these pressures with that of subglottal tracheal pressure phenomenon. We utilized a 3-site strain gauge (SG) transducer probe (2.2 mm OD, frequency response rate = 2000 Hz) to measure the vocal cord closure and tracheal pressures of 11 healthy adult volunteers (ago [mean + SE] = 41.0-+2.0 yrs) during dry swallow, cough, phonation and straining. Following the application of topical anesthesia to the larynx, the transducer probe was placed transnasally between the vocal cords under direct visualization using a video fiberoptic bronchoscopc (FOB). Transducer position was verified by video FOB. The most proximal SG was held between the cords while the two distal gauges were in the trachea. All pressure measurement s were made in sitting position and referenced to atmospheric pressure. Results: During swallowing the proximal SG invariably recorded a short duration high amplitude pressure (Table).

]Swallow } Cough ] Swain I Phonation Vocal Cord Pressure (mrang) 7~SE 298+_23 ] 280±20 330-2--45 ] 222-5:25

Simultaneously, intratracheal gauges recorded a hiphasic pressure wave. The first phase (subatmospheric) averaged -9.2_+0.6 mmHg in amplitude and 464+28 ms in duration and was followed by a positive phase of 7.5-2-0.9 mmHg, 106+70 ms. In one subject the subatmospheric tracheal pressure was preceded by a positive pressure of 5_+0 mmHg. Vocal cord closure pressuro during swallowing and coughing was significantly higher than that of phonation (p<0.05). Straining induced pressures significantly higher than all other events (p<0.05). The tracheal pressure generated during cough was 107-+10 mrnHg and significantly lower than that of corresponding vocal cord closure pressure (I)<0,05). Conclusions: 1) The vocal cords generate closure pressures that vary depending on the maneuvers performed. 2) Swallowing and coughing generates significantly greater vocal cord closure pressures than those generated during phonation. 3) The vocal cord closure pressures are significantly greater than those of the trachea during cough. 4) Swallowing is associated with a short duration subaimosl~heric intratracheal pressure.

DISTRIBUTION OF CHOLINERGIC ENZYMES IN MUSCLES OF PHARYNGO-ESOPHAGEAL REGION IN TWO SPECIES. R. Shaker. E. Mustin, B. Medda, L Bonnevier, I, Lung, T.R. Koch. MCW Dysphagia Institute, Departments of Medicine, Radiology, Otolaryngology and Communicative Disorders, Medical College of Wisconsin and VA Medical Center, Milwaukee) WI

As striated muscles, pressures generated by pharyngeal constrictors, cricopharyngeus and proximal esophagus are produced by contractions induced through acetylcholine release. Acetylcholine is synthesized by the activity of choline acetyltransferase (CHAT) and can be degraded by acetylcholinesterase (AChEst). It is known that parameters of deglutitive- peristaltic pressure wave in the pharynx differs from that of the upper esophageal sphincter and proximal esophagus~ These differences could be due to one or a combination of differences in mnscle mass, receptor density, or rate of production of neurotransmitters. The aim of the present study was to test the hypothesis that a gradient in ChAT activity exists between the pharyngeal and the upper esophageal muscles. Methods: Thyropharyngens (TP), cricopharyngeus (CP), and proximal esophagus were obtained from 6 young (Fischer 344) rats (3 moO, 6 elderly rats (15-18 too.), and 9 cats. After extraction into phosphate buffers, validated spectrophotometdc assays were used to quantitate AChEst and CHAT. In each assay, external standard curves were prepared using ChAT and AChEst from Sigma Chemical Co, St. Louis, MO. In the ChAT assay, activity was blocked by bromoacetyl- choline bromide; in the AChEst assay, activity was blocked by neostigmine sulfate. Enzymatic activities were expressed in U/g wet tissue (Mear~+SE). Results: :~p<.001; *p<.05; "~p<.05; §p=.05

TP, CP Proximal Esophagus Tissue ChAT AChEst ChAT AChEst ChAT AChEst

Young Rat 27±2* 1.86+.12:~ 19+3" 1.36+.07:~ 22+2* 1.04±.07~. Elderly Rat 28+45 - - 16±3I - - 18±3~" - - Cat 63+7§ 1.1:!:.2 70t:11§ 0.8+.1 34±6§ 0.7±.2 ~3.1]11111~: In both feline and rodent species, the choline acetyltransferase activity in the hypopharynx is significantly higher than the most proximal part of esophagus. ChAT activity of the CP muscle in feline is similar to pharynx, whereas in rodent it resembles proximal esophagus. Acetylcholinesterase activity in the rat hypopharynx is higher than in proximal esophagus, paralleling ChAT activity.