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Electrode-tissue interface impedance reduces efficacy of gastric electrical stimulation
A596
AGA ABSTRACTS
GASTROENTEROLOGY, Vol. 108, No. 4
ELECTRODE-TISSUE INTERFACE IMPEDANCE REDUCES , E F F I C A C Y OF GASTRIC E L E C T R I C A L S T I M U L A T I O N BO Familoni - TL Abell - E Alphonso - A Somjee- G Voeller; Department of Medicine and Department of Biomedical Engineering, University of Tennessee - Memphis; Department of Electrical Engineering, University of Memphis
AN E X P E R I M E N T A L M O D E L O F G A S T R I C P A C I N G IN T H E CANINE STOMACH
BO Familoni, TL Abell, S Moolchandani, P Suresh, E Alphonso, A Somjee-~ G Voeller; Department of Medicine and Department of Biomedical Engineering, University of Tennessee Memphis, Department of Electrical Engineering, University of Memphis, Memphis, TN, USA
BACKGROUND: Treatment of refractory gastroparesis by gastric electrical stimulation at frequencies higher than the intrinsic rhythm has been reported to be successful in improving motility (GE 106(2):A496, 1994). However, the factors necessary for successful long term gastric electrical stimulation are unknown. We investigated the effect on gastric electrical stimulation of the tissue-electrode impedance (resistance) on a patient with gastroparesis. METHODS: Two pairs of intramuscular leads (Medtronie SP5543) were implanted at laparotomy sub-serosally 1 cm apart into the greater curvature of the gastric antral wall, in a 36-year-old caucasian woman with long-standing, insulin-dependent diabetes meUitus. The patient had previously been treated with gastric electrical stimulation for 1 year, with improvement in symptoms and in gastric emptying. Commencing 24 hours after surgery, gastric electrical stimulation (GES) via an Itrel17424 Stimulator (Medtronic - Minneapolis) was performed for 0.5 hours before and 2 hours after every meal. The pacing current was pulse-shaped with a pulse width of 330 Its and an amplitude of 5 mA, delivered at an ON time of 1 second and an O F F time of 5 seconds, (corresponding to a stimulation frequency of 10 cycles/min 0.2 Hz). The electrode-tissue interface impedance was measured every 2 two weeks using a Medtronic programmer 7432. Gastric emptying of radionuclide cornflake meal (defined as T50, normal <45in) was measured at baseline, with the Itretl off at week 2, and with Itrell on at weeks 2 . 5 , 5 and 10, after surgery. RESULTS: Radionuclide gastric emptying changed from a baseline T50 of 110 minutes and at week 2 with Itrell OFF to 80 minutes with Itrell on at week 2.5, and 35 minutes with Itrell on at week 5. T50 at week 10, however, was again > 110 minutes. The tissue-electrode impedance increased linearly (y=3.5x+44% p,<0.05) from 426 ohms intra-operative to 9 l0 ohms at week 10. CONCLUSIONS: We conclude that 1) electrical stimulation at higher than physiological frequencies requires further study as a possible therapy for diabetic gastroparesis; 2) diminishing efficacy of gastric electrical stimulation, as in this patient, may be related to increased impedance, perhaps due to factors at the electrode-tissue interface. Further study of GES needs to focus on techniques to prevent increasing serosal tissue impedance, with subsequent pacer malfunction.
INTRODUCTION: We have previously reported data in animal and human on gastric pacing [GE 98 (2): A362, 1990; GE 106 (2) A496, 1994]. Our current study investigates the optimum frequency and vohage for electrical pacing of the canine stomach. The study design called for serosal electrodes to be paced at increasing frequency and voltage to evaluate its effects on motility. The electrical and mechanical response was recorded and analyzed to determine the optimum frequency and voltage. METHOD: 3 dogs were surgically implanted with an array of 3 pairs of electrodes and 2 strain gauges on the anterior wall of the stomach. The dogs were paced with an ItreU implantable pulse generator [Medtronic, MN] at 4 volts, 330 microsecond pulse width, and frequencies ranging from 6 to 15 cpm. Electrical and mechanical recordings were done before, during and after pacing. RESULTS: Pacing entrained gastric electrical activity and increased contractions. Contractile activity during pacing increased with frequency as shown on the table below. PACING FREQUENCY_ 15 I2
BEFORE Amp 9.52+_ 5.68 Sum 276
DURING 12.23+ 6.45 379
AFTER 6A7-+ 4.72 97
Amp 5.34_+ 5.56 Sum 400
5.94_+8.78 451.5
2.11+ 0.84 165
6
Amp 5.33+ 1.24 1.5+ 0.5 7.64_+2.52 Sum 16 3 14 CONCLUSION: From this study, the optimum pacing frequency for canine stomach is probably higher than the intrinsic rhythm. Similar studies are ' needed in humans to identify if pacing frequencies higher than the intrinsic gastric frequency are effective in inducing gastric mechanical activity.
• SEXUAL DYSFUNCTION IN PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS) AND NON-ULCER DYSPEPSIA (NUD). R. Fass, S. Fullerton, D.L. Diehl, T. Hirsh, E.A. Mayer. CURE: VA/UCLA Gastroenteric Biology Center/Neuroenteric Biology Group, Depts. of Medicine UCLA and West LAVA Medical Center., Los Angeles, CA 90073.
• SLEEP DISTURBANCE (SD) IN PATIENTS WITH FUNCTIONAL BOWEL DISORDERS (FBD). R. Fass, S. Fullerton, D.L. Diebl, E.A. Mayer. CURE: VA/UCLA Gastroenteric Biology Center/Neuroenterie Biology Group, Depts. of Medicine, UCLA and West L A V A Medical Center, Los Angeles, CA 90073.
Dyspareunia and abdominal pain induced by intercourse are thought to be common in female IBS patients. By evaluating the prevalence of sexual dysfunction (SD) in a large number of male and female FBD patients with symptoms arising primarily from the upper GI tract (NUD), lower G1 tract (IBS) or both (1BS+NUD), we tested the following hypotheses: 1) If SD is directly related to pelvic visceral hyperalgesia, it should be most common in the form of pain during intercourse, and more common in IBS and IBS+NUD than in NUD. 2) If SD is secondary to chronic abdominal distress, it should present other than pain, be equally prevalent in all FBD groups and be related to symptom severity. Methods: We prospectively evaluated 710 FBD patients (38%IBS, 22%IBS+NUD, 12%NUD) at the UCLA FBD Center during 1992-94, using a modified Talley bowel symptom questionnaire and compared them to asymptomatic controls and IBS non-patients (IBS-NP), Results: 39% of all FBD patients (36% males, 41% females) reported SD. SD was reported as decreased Sexual drive (29% women; 39% men), GI symptoms directly preventing from intercourse (22%women; 17% men, p<0.05), and dyspareunia (12% women; 4% men, p<0.05). In IBS, SD was more common in constipationpredominant (53%) than in diarrhea-predominant patients (33%), p<0.05. No difference in SD prevalence was reported between any of the patient groups, while asymptomatic controls and IBS-NP reported no SD. Prevalence of SD significantly increased with patient's assessment of GI symptom severity (mild 18%, moderate 23%, severe 45%, very severe 56%) (p< 0.05), but was not related to perceived GI symptom duration. Conclusions: SD is common in both men and women, related primarily to perceived GI distress and manifested as diminished sexual drive regardless of upper or lower GI tract involvement. Pelvic hyperalgesia plays a minor role in women.
Sleep deprivation can lower visceral perception thresholds and non-regenerative sleep has been implicated as an etiologic factor in chronic hyperalgesia syndromes. Insomnia or non-regenerative sleep is a common complaint of patients with non-ulcer dyspepsia (NUD). In the current study we attempted to assess the prevalence and type of sleep disturbances in FBD patients to answer the following questions: 1) Does prevalence differ by diagnosis (IBS vs. NUD vs. NUD+IBS)? 2) Does SD precede the onset of GI symptoms? METHODS: We prospectively evaluated 763 new FBD patients, 15 IBS non-patients (IBS-NP) and 53 asymptomatic controls using validated bowel symptom and sexual function questionnaires. The mean age of groups did not differ. RESULTS:
i
Control IBS-NP IBS °o N=53 N=I5 N~279 SD N('A) 15(28) 4(27) 202(72)* Awakenin~ n/a 5f33) 37168) * p < 0.05 compared to controls
NUD N=I00 75(75)* 54173)
IBS+NUD N=172 143(83)* 09(77)
OtherFBD [ N=2i2 II1(52)* 611561
I
IBS, NUD, IBS+NUD and other FBD reported significantly more SD than controls, while no difference was found between patient groups. Perceived GI symptom seyerity (by VAS ratings) in patients correlated with prevalence of SD (p<0.01). No difference between any groups was found in difficulty falling asleep, waking up repeatedly during the night, waking up in the morning and feeling tired or not rested, and unable to sleep without a sleeping pill. While SD did not differ by gender, SD increased with age in IBS but not in NUD. CONCLUSIONS: 1. Two-thirds of FBD patients report SD regardless of FBD disease classification, while prevalence of reported SD in IBS-NP is similar to controls. 2. In the majority of FBD patients and in 1/3 of IBS-NP, GI symptoms are perceived as awakening them from sleep. These findings demonstrate that while altered sleep is not a necessary condition for the appearance of !BS symptoms, there is a close correlation between GI symptom severity and sleep disturbance in the majority Of FBD patients. The low prevalence of SD in IBS-NP suggests SD as a possible cause for worsening of GI symptoms resulting in health care utilization.
AGA ABSTRACTS
GASTROENTEROLOGY, Vol. 108, No. 4
ELECTRODE-TISSUE INTERFACE IMPEDANCE REDUCES , E F F I C A C Y OF GASTRIC E L E C T R I C A L S T I M U L A T I O N BO Familoni - TL Abell - E Alphonso - A Somjee- G Voeller; Department of Medicine and Department of Biomedical Engineering, University of Tennessee - Memphis; Department of Electrical Engineering, University of Memphis
AN E X P E R I M E N T A L M O D E L O F G A S T R I C P A C I N G IN T H E CANINE STOMACH
BO Familoni, TL Abell, S Moolchandani, P Suresh, E Alphonso, A Somjee-~ G Voeller; Department of Medicine and Department of Biomedical Engineering, University of Tennessee Memphis, Department of Electrical Engineering, University of Memphis, Memphis, TN, USA
BACKGROUND: Treatment of refractory gastroparesis by gastric electrical stimulation at frequencies higher than the intrinsic rhythm has been reported to be successful in improving motility (GE 106(2):A496, 1994). However, the factors necessary for successful long term gastric electrical stimulation are unknown. We investigated the effect on gastric electrical stimulation of the tissue-electrode impedance (resistance) on a patient with gastroparesis. METHODS: Two pairs of intramuscular leads (Medtronie SP5543) were implanted at laparotomy sub-serosally 1 cm apart into the greater curvature of the gastric antral wall, in a 36-year-old caucasian woman with long-standing, insulin-dependent diabetes meUitus. The patient had previously been treated with gastric electrical stimulation for 1 year, with improvement in symptoms and in gastric emptying. Commencing 24 hours after surgery, gastric electrical stimulation (GES) via an Itrel17424 Stimulator (Medtronic - Minneapolis) was performed for 0.5 hours before and 2 hours after every meal. The pacing current was pulse-shaped with a pulse width of 330 Its and an amplitude of 5 mA, delivered at an ON time of 1 second and an O F F time of 5 seconds, (corresponding to a stimulation frequency of 10 cycles/min 0.2 Hz). The electrode-tissue interface impedance was measured every 2 two weeks using a Medtronic programmer 7432. Gastric emptying of radionuclide cornflake meal (defined as T50, normal <45in) was measured at baseline, with the Itretl off at week 2, and with Itrell on at weeks 2 . 5 , 5 and 10, after surgery. RESULTS: Radionuclide gastric emptying changed from a baseline T50 of 110 minutes and at week 2 with Itrell OFF to 80 minutes with Itrell on at week 2.5, and 35 minutes with Itrell on at week 5. T50 at week 10, however, was again > 110 minutes. The tissue-electrode impedance increased linearly (y=3.5x+44% p,<0.05) from 426 ohms intra-operative to 9 l0 ohms at week 10. CONCLUSIONS: We conclude that 1) electrical stimulation at higher than physiological frequencies requires further study as a possible therapy for diabetic gastroparesis; 2) diminishing efficacy of gastric electrical stimulation, as in this patient, may be related to increased impedance, perhaps due to factors at the electrode-tissue interface. Further study of GES needs to focus on techniques to prevent increasing serosal tissue impedance, with subsequent pacer malfunction.
INTRODUCTION: We have previously reported data in animal and human on gastric pacing [GE 98 (2): A362, 1990; GE 106 (2) A496, 1994]. Our current study investigates the optimum frequency and vohage for electrical pacing of the canine stomach. The study design called for serosal electrodes to be paced at increasing frequency and voltage to evaluate its effects on motility. The electrical and mechanical response was recorded and analyzed to determine the optimum frequency and voltage. METHOD: 3 dogs were surgically implanted with an array of 3 pairs of electrodes and 2 strain gauges on the anterior wall of the stomach. The dogs were paced with an ItreU implantable pulse generator [Medtronic, MN] at 4 volts, 330 microsecond pulse width, and frequencies ranging from 6 to 15 cpm. Electrical and mechanical recordings were done before, during and after pacing. RESULTS: Pacing entrained gastric electrical activity and increased contractions. Contractile activity during pacing increased with frequency as shown on the table below. PACING FREQUENCY_ 15 I2
BEFORE Amp 9.52+_ 5.68 Sum 276
DURING 12.23+ 6.45 379
AFTER 6A7-+ 4.72 97
Amp 5.34_+ 5.56 Sum 400
5.94_+8.78 451.5
2.11+ 0.84 165
6
Amp 5.33+ 1.24 1.5+ 0.5 7.64_+2.52 Sum 16 3 14 CONCLUSION: From this study, the optimum pacing frequency for canine stomach is probably higher than the intrinsic rhythm. Similar studies are ' needed in humans to identify if pacing frequencies higher than the intrinsic gastric frequency are effective in inducing gastric mechanical activity.
• SEXUAL DYSFUNCTION IN PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS) AND NON-ULCER DYSPEPSIA (NUD). R. Fass, S. Fullerton, D.L. Diehl, T. Hirsh, E.A. Mayer. CURE: VA/UCLA Gastroenteric Biology Center/Neuroenteric Biology Group, Depts. of Medicine UCLA and West LAVA Medical Center., Los Angeles, CA 90073.
• SLEEP DISTURBANCE (SD) IN PATIENTS WITH FUNCTIONAL BOWEL DISORDERS (FBD). R. Fass, S. Fullerton, D.L. Diebl, E.A. Mayer. CURE: VA/UCLA Gastroenteric Biology Center/Neuroenterie Biology Group, Depts. of Medicine, UCLA and West L A V A Medical Center, Los Angeles, CA 90073.
Dyspareunia and abdominal pain induced by intercourse are thought to be common in female IBS patients. By evaluating the prevalence of sexual dysfunction (SD) in a large number of male and female FBD patients with symptoms arising primarily from the upper GI tract (NUD), lower G1 tract (IBS) or both (1BS+NUD), we tested the following hypotheses: 1) If SD is directly related to pelvic visceral hyperalgesia, it should be most common in the form of pain during intercourse, and more common in IBS and IBS+NUD than in NUD. 2) If SD is secondary to chronic abdominal distress, it should present other than pain, be equally prevalent in all FBD groups and be related to symptom severity. Methods: We prospectively evaluated 710 FBD patients (38%IBS, 22%IBS+NUD, 12%NUD) at the UCLA FBD Center during 1992-94, using a modified Talley bowel symptom questionnaire and compared them to asymptomatic controls and IBS non-patients (IBS-NP), Results: 39% of all FBD patients (36% males, 41% females) reported SD. SD was reported as decreased Sexual drive (29% women; 39% men), GI symptoms directly preventing from intercourse (22%women; 17% men, p<0.05), and dyspareunia (12% women; 4% men, p<0.05). In IBS, SD was more common in constipationpredominant (53%) than in diarrhea-predominant patients (33%), p<0.05. No difference in SD prevalence was reported between any of the patient groups, while asymptomatic controls and IBS-NP reported no SD. Prevalence of SD significantly increased with patient's assessment of GI symptom severity (mild 18%, moderate 23%, severe 45%, very severe 56%) (p< 0.05), but was not related to perceived GI symptom duration. Conclusions: SD is common in both men and women, related primarily to perceived GI distress and manifested as diminished sexual drive regardless of upper or lower GI tract involvement. Pelvic hyperalgesia plays a minor role in women.
Sleep deprivation can lower visceral perception thresholds and non-regenerative sleep has been implicated as an etiologic factor in chronic hyperalgesia syndromes. Insomnia or non-regenerative sleep is a common complaint of patients with non-ulcer dyspepsia (NUD). In the current study we attempted to assess the prevalence and type of sleep disturbances in FBD patients to answer the following questions: 1) Does prevalence differ by diagnosis (IBS vs. NUD vs. NUD+IBS)? 2) Does SD precede the onset of GI symptoms? METHODS: We prospectively evaluated 763 new FBD patients, 15 IBS non-patients (IBS-NP) and 53 asymptomatic controls using validated bowel symptom and sexual function questionnaires. The mean age of groups did not differ. RESULTS:
i
Control IBS-NP IBS °o N=53 N=I5 N~279 SD N('A) 15(28) 4(27) 202(72)* Awakenin~ n/a 5f33) 37168) * p < 0.05 compared to controls
NUD N=I00 75(75)* 54173)
IBS+NUD N=172 143(83)* 09(77)
OtherFBD [ N=2i2 II1(52)* 611561
I
IBS, NUD, IBS+NUD and other FBD reported significantly more SD than controls, while no difference was found between patient groups. Perceived GI symptom seyerity (by VAS ratings) in patients correlated with prevalence of SD (p<0.01). No difference between any groups was found in difficulty falling asleep, waking up repeatedly during the night, waking up in the morning and feeling tired or not rested, and unable to sleep without a sleeping pill. While SD did not differ by gender, SD increased with age in IBS but not in NUD. CONCLUSIONS: 1. Two-thirds of FBD patients report SD regardless of FBD disease classification, while prevalence of reported SD in IBS-NP is similar to controls. 2. In the majority of FBD patients and in 1/3 of IBS-NP, GI symptoms are perceived as awakening them from sleep. These findings demonstrate that while altered sleep is not a necessary condition for the appearance of !BS symptoms, there is a close correlation between GI symptom severity and sleep disturbance in the majority Of FBD patients. The low prevalence of SD in IBS-NP suggests SD as a possible cause for worsening of GI symptoms resulting in health care utilization.