OBES SURG (2014) 24:554–560 DOI 10.1007/s11695-013-1109-6
ORIGINAL CONTRIBUTIONS
Altered Postprandial Responses in Gastric Myoelectrical Activity and Cardiac Autonomic Functions in Healthy Obese Subjects Xiaohong Xu & Dennis D. Chen & Jieyun Yin & Jiande D Z Chen
Published online: 13 November 2013 # Springer Science+Business Media New York 2013
Abstract Background It is unknown whether gastric myoelectrical activity (GMA) and autonomic functions are altered in obesity. The aims of this study were to investigate GMA and autonomic functions in obese subjects and to compare their responses to different meals with lean subjects. Methods The study was performed in 12 lean and 12 obese subjects. GMA was measured using electrogastrography, and autonomic functions were assessed using spectral analysis of heart rate variability. Results The study achieved the following key results: (1) Compared to lean subjects, obese subjects showed unaltered gastric slow waves at baseline but enhanced responses to both fatty and protein meals. The lean subjects showed a reduced percentage of normal gastric slow waves with a fatty meal, which was not seen in obese subjects; lean subjects showed no changes in the dominant frequency or power of the gastric slow waves with a protein meal, whereas both of these parameters were increased in obese subjects. (2) Autonomic functions were altered in obese subjects in both fasting and fed states. Obese subjects showed an increased sympathetic activity in the fasting state, but absence of a normal
X. Xu Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA D. D. Chen Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA J. Yin : J. D. Z. Chen University of Texas Medical Branch, Galveston, TX, USA J. D. Z. Chen (*) Ningbo Pace Translational Medical Research Center, Ningbo, Beilun, China e-mail: [email protected]
postprandial response in sympathovagal balance to both fatty and protein meals. Conclusions The findings on gastric slow waves demonstrate that obese subjects are more receptive to fatty meals and more responsive to protein meals. Obese subjects have impaired autonomic functions in both fasting and fed states. The alterations in gastric and autonomic functions may contribute to eating disorders in the obese. Keywords Electrogastrography . Heart rate variability . Gastric slow waves . Autonomic function . Vagal activity . Sympathetic activity . Gastrointestinal motility
Introduction Gastric myoelectrical activity (GMA) plays an important role in the regulation of gastric motility. There are two primary types of myoelectrical activities in the human stomach: slow waves and spike potentials. Slow waves are present all the time and originate near the junction of the proximal one third and distal two thirds of the stomach. The frequency of the normal slow waves is about 3 cycles per minute (cpm) or 0.05 Hz in humans [1, 2]. Spike potentials are directly associated with antral contractions. The antral muscles contract when slow waves are superimposed with spike potentials. The frequency and propagation of the antral contractions are determined by the gastric slow waves. The gastric slow waves can be recorded using electrodes placed on the surface skin of the abdomen. This noninvasive, easily reproducible technique is termed electrogastrography. When appropriately recorded, the dominant frequency of the electrogastrogram (EGG) accurately reflects the frequency of the gastric slow waves, and the relative amplitude change of EGG reflects gastric contractility [2]. Since the EGG method is noninvasive and does not disturb the ongoing activity of the
OBES SURG (2014) 24:554–560
human stomach, it has been attractive to researchers for more than two decades. Electrogastrography has been widely applied to investigate GMA in both normal subjects and patients [3–9]. Obesity is often associated with gastrointestinal motor disorders. However, conflicting results have been reported on gastric motility in obese patients. Our previous studies have shown that a fatty meal or fat preload impairs gastric myoelectrical activity measured by EGG in normal subjects [10, 11]. Previous investigations have shown that clinical motility problems after bariatric surgery were not associated with gastric myoelectrical dysfunction in morbidly obese patients [12]. Another study reported that the body mass index (BMI) was not associated with EGG parameters in children aged 6–12 [9]. However, the spectral power of fasting GMA was reported to be significantly reduced in obese subjects [13]. Although obesity is a disease of eating disorders, little is known whether the gastric slow wave is altered in response to eating or meals. Spectral analysis of heart rate variability (HRV) is a method of assessing vagal activity and sympathovagal balance. It is noninvasive and frequently used in both cardiac and gastrointestinal research to assess sympathetic and parasympathetic activities [14, 15]. The involvement of the autonomic function in obesity is not well understood. One study reported no significant differences in either sympathetic or parasympathetic activity assessed from the HRV between obese and lean subjects [16]. Another study showed an increased sympathovagal balance in the fasting but not fed state in obese women [17]. Yet, Nagai et al. reported that obese boys have normal metabolic and sympathetic responses to high fat [18]. The aim of this study was to investigate possible alterations in gastric slow waves and autonomic functions, and their responses to different meals in healthy obese subjects using the noninvasive methods of electrogastrography and spectral analysis of HRV.
Materials and Methods Subjects Twelve lean (7 M, 5 F; ages 19–45; mean age 31.5; BMI 22.8 ±0.7, ranging from 19.5 to 27.6) and 12 obese (8 M, 4 F; age range 32–59, mean age 45.3; BMI 35.3±4.6, ranging from 31.0 to 42.4) subjects were enrolled in this project. The sample size was determined based on previous EGG studies using power analysis [9, 10]. No difference was noted in age, gender, or ethnicity between the lean and obese groups except the difference in BMI. The subjects were free of gastrointestinal symptoms and had no history of gastrointestinal surgeries; they were taking no medications except oral contraceptives. Every subject signed the consent
555
form before enrollment in the study. The study protocol was approved by the Institutional Review Board at the University of Texas Medical Branch in Galveston, TX, and the VA Medical Center in Oklahoma City, OK. Study Protocol The experiment consisted of two sessions (fatty soup session and protein soup session) performed on separate days in a randomized order. After an overnight fast, the EGG and electrocardiogram (ECG) were recorded in the fasting state for 30 min. Once the recording was done, either a protein soup (two steamed eggs) or a fatty soup (Campbell’s Cream of Chicken, Campbell Soup Company, Camden, NJ, USA) was given to the subject to be consumed within 10–15 min. The two soups were designed to maximize the contribution from either protein or fat and contained 160 kcal in 325 mL, 90 % of which was from the nutrient of interest (protein or fat). After that, the EGG and ECG were recorded for 30 more minutes. The liquid instead of solid meal was chosen because the liquid meal was emptied from the stomach to the small intestine faster than the solid meal so that absorption could take place sooner. Measurement and Analysis of the EGG Before the placement of electrodes, three abdominal areas for electrodes were cleaned with abrasive skin-prep jelly (Nuprep, D.O. Weaver and Co., Aurora, CO, USA) to reduce impedance. The jelly was applied to the skin and rubbed gently until the skin turned pinkish. To reduce skin–electrode impedance, electrode gel (Signa gel, Parker Laboratories, Inc., Orange, NJ, USA) was applied to the areas and left to dry for about 1 min. Then, the areas were thoroughly cleaned, on which were placed three silver– silver chloride ECG electrodes (Red Dot; 3M Health Care, St. Paul, MN, USA) as follows: the first one at the midpoint of a line connecting the xiphoid process and the umbilicus; the second one placed 5 cm away, 45° to the upper left of the first one; and the third one at the left costal margin of the abdomen horizontal to the first one used as a ground electrode [1]. A portable EGG recorder (Digitrapper EGG; MedtronicSynectics, Shoreview, MN, USA) was used to record the EGG signal with a sampling frequency of 1 Hz. At the completion of each study session, the EGG data stored on the recorder were downloaded to a personal computer. Each session was divided into two 30-min segments (fasting state and fed state), and EGG tracings were carefully reviewed and artifacts were checked and deleted. The EGG signal was then subjected to spectral analysis using previously validated software [19] to compute the following EGG parameters: dominant frequency and power, and percentage of normal slow waves:
556
Dominant Frequency and Dominant Power of Gastric Slow Waves The frequency at which the power spectrum of the 30min recording had a peak power in the range of 0.5–9.0 cpm was defined as the dominant frequency. The power corresponding to the dominant frequency in the power spectrum was defined as the dominant power [19]. Percentage of Normal Slow Waves This is a parameter reflecting the regularity of gastric slow waves calculated from the EGG. It was defined as the percentage of time during which regular two to four slow waves were detected from the adaptive running spectral analysis [1, 20].
Measurement of ECG and Spectral Analysis of HRV The autonomic function was assessed from the spectral analysis of HRV that was derived from the ECG recording. The ECG was recorded from three surface electrodes: one at the manubrium of the sternum, a second one at the V5 position (just above the fifth interspace in the anterior axillary line), and a third one (used as ground) at the right chest. To improve the quality of the ECG, the same skin preparation as for EGG was performed before the placement of electrodes for ECG. A special UFI amplifier (UFI model 2,283 ft/I, Morrow Bay, CA, USA) was used to record the ECG signal with a sampling frequency of 6,000 Hz (digitized using the sound card on the PC). The software developed in our own lab was then used to down-sample the ECG signal to 500 Hz, detect R–R intervals, and perform spectral analysis on the HRV signal [21]. Sympathetic and Vagal Activity The spectral analysis of HRV is a well-established noninvasive method for the assessment of the autonomic function [22, 23]. The sum of spectral power P1 in the low-frequency (LF) band (0.04–0.15 Hz) reflects mainly sympathetic activity, whereas the sum of spectral power P2 in the high-frequency (HF) band (0.15–0.50 Hz) stands purely for parasympathetic or vagal activity. In this study, the ratio P1/(P1 + P2) was defined as the LF (sympathetic), and the ratio P2/(P1+P2) was considered as vagal activity HF. The ratio of LF/HF was defined as the sympathovagal balance.
Statistical Analysis All data are presented as mean ± SE. Paired or unpaired Student’s t tests were used to determine the differences in EGG parameters and HRV parameters between fasting and fed states in each session (paired test), between two sessions within the same group (paired test), or between the lean subjects and the obese subjects (unpaired test). P 0.05) and so was the dominant frequency of the EGG (2.97 ± 0.11 vs. 3.01 ± 0.06 cpm, P >0.05); however, the DP was significantly reduced in the obese subjects in comparison with that in lean subjects (30.84±2.33 vs. 44.90±2.77 dB, P
ORIGINAL CONTRIBUTIONS
Altered Postprandial Responses in Gastric Myoelectrical Activity and Cardiac Autonomic Functions in Healthy Obese Subjects Xiaohong Xu & Dennis D. Chen & Jieyun Yin & Jiande D Z Chen
Published online: 13 November 2013 # Springer Science+Business Media New York 2013
Abstract Background It is unknown whether gastric myoelectrical activity (GMA) and autonomic functions are altered in obesity. The aims of this study were to investigate GMA and autonomic functions in obese subjects and to compare their responses to different meals with lean subjects. Methods The study was performed in 12 lean and 12 obese subjects. GMA was measured using electrogastrography, and autonomic functions were assessed using spectral analysis of heart rate variability. Results The study achieved the following key results: (1) Compared to lean subjects, obese subjects showed unaltered gastric slow waves at baseline but enhanced responses to both fatty and protein meals. The lean subjects showed a reduced percentage of normal gastric slow waves with a fatty meal, which was not seen in obese subjects; lean subjects showed no changes in the dominant frequency or power of the gastric slow waves with a protein meal, whereas both of these parameters were increased in obese subjects. (2) Autonomic functions were altered in obese subjects in both fasting and fed states. Obese subjects showed an increased sympathetic activity in the fasting state, but absence of a normal
X. Xu Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA D. D. Chen Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA J. Yin : J. D. Z. Chen University of Texas Medical Branch, Galveston, TX, USA J. D. Z. Chen (*) Ningbo Pace Translational Medical Research Center, Ningbo, Beilun, China e-mail: [email protected]
postprandial response in sympathovagal balance to both fatty and protein meals. Conclusions The findings on gastric slow waves demonstrate that obese subjects are more receptive to fatty meals and more responsive to protein meals. Obese subjects have impaired autonomic functions in both fasting and fed states. The alterations in gastric and autonomic functions may contribute to eating disorders in the obese. Keywords Electrogastrography . Heart rate variability . Gastric slow waves . Autonomic function . Vagal activity . Sympathetic activity . Gastrointestinal motility
Introduction Gastric myoelectrical activity (GMA) plays an important role in the regulation of gastric motility. There are two primary types of myoelectrical activities in the human stomach: slow waves and spike potentials. Slow waves are present all the time and originate near the junction of the proximal one third and distal two thirds of the stomach. The frequency of the normal slow waves is about 3 cycles per minute (cpm) or 0.05 Hz in humans [1, 2]. Spike potentials are directly associated with antral contractions. The antral muscles contract when slow waves are superimposed with spike potentials. The frequency and propagation of the antral contractions are determined by the gastric slow waves. The gastric slow waves can be recorded using electrodes placed on the surface skin of the abdomen. This noninvasive, easily reproducible technique is termed electrogastrography. When appropriately recorded, the dominant frequency of the electrogastrogram (EGG) accurately reflects the frequency of the gastric slow waves, and the relative amplitude change of EGG reflects gastric contractility [2]. Since the EGG method is noninvasive and does not disturb the ongoing activity of the
OBES SURG (2014) 24:554–560
human stomach, it has been attractive to researchers for more than two decades. Electrogastrography has been widely applied to investigate GMA in both normal subjects and patients [3–9]. Obesity is often associated with gastrointestinal motor disorders. However, conflicting results have been reported on gastric motility in obese patients. Our previous studies have shown that a fatty meal or fat preload impairs gastric myoelectrical activity measured by EGG in normal subjects [10, 11]. Previous investigations have shown that clinical motility problems after bariatric surgery were not associated with gastric myoelectrical dysfunction in morbidly obese patients [12]. Another study reported that the body mass index (BMI) was not associated with EGG parameters in children aged 6–12 [9]. However, the spectral power of fasting GMA was reported to be significantly reduced in obese subjects [13]. Although obesity is a disease of eating disorders, little is known whether the gastric slow wave is altered in response to eating or meals. Spectral analysis of heart rate variability (HRV) is a method of assessing vagal activity and sympathovagal balance. It is noninvasive and frequently used in both cardiac and gastrointestinal research to assess sympathetic and parasympathetic activities [14, 15]. The involvement of the autonomic function in obesity is not well understood. One study reported no significant differences in either sympathetic or parasympathetic activity assessed from the HRV between obese and lean subjects [16]. Another study showed an increased sympathovagal balance in the fasting but not fed state in obese women [17]. Yet, Nagai et al. reported that obese boys have normal metabolic and sympathetic responses to high fat [18]. The aim of this study was to investigate possible alterations in gastric slow waves and autonomic functions, and their responses to different meals in healthy obese subjects using the noninvasive methods of electrogastrography and spectral analysis of HRV.
Materials and Methods Subjects Twelve lean (7 M, 5 F; ages 19–45; mean age 31.5; BMI 22.8 ±0.7, ranging from 19.5 to 27.6) and 12 obese (8 M, 4 F; age range 32–59, mean age 45.3; BMI 35.3±4.6, ranging from 31.0 to 42.4) subjects were enrolled in this project. The sample size was determined based on previous EGG studies using power analysis [9, 10]. No difference was noted in age, gender, or ethnicity between the lean and obese groups except the difference in BMI. The subjects were free of gastrointestinal symptoms and had no history of gastrointestinal surgeries; they were taking no medications except oral contraceptives. Every subject signed the consent
555
form before enrollment in the study. The study protocol was approved by the Institutional Review Board at the University of Texas Medical Branch in Galveston, TX, and the VA Medical Center in Oklahoma City, OK. Study Protocol The experiment consisted of two sessions (fatty soup session and protein soup session) performed on separate days in a randomized order. After an overnight fast, the EGG and electrocardiogram (ECG) were recorded in the fasting state for 30 min. Once the recording was done, either a protein soup (two steamed eggs) or a fatty soup (Campbell’s Cream of Chicken, Campbell Soup Company, Camden, NJ, USA) was given to the subject to be consumed within 10–15 min. The two soups were designed to maximize the contribution from either protein or fat and contained 160 kcal in 325 mL, 90 % of which was from the nutrient of interest (protein or fat). After that, the EGG and ECG were recorded for 30 more minutes. The liquid instead of solid meal was chosen because the liquid meal was emptied from the stomach to the small intestine faster than the solid meal so that absorption could take place sooner. Measurement and Analysis of the EGG Before the placement of electrodes, three abdominal areas for electrodes were cleaned with abrasive skin-prep jelly (Nuprep, D.O. Weaver and Co., Aurora, CO, USA) to reduce impedance. The jelly was applied to the skin and rubbed gently until the skin turned pinkish. To reduce skin–electrode impedance, electrode gel (Signa gel, Parker Laboratories, Inc., Orange, NJ, USA) was applied to the areas and left to dry for about 1 min. Then, the areas were thoroughly cleaned, on which were placed three silver– silver chloride ECG electrodes (Red Dot; 3M Health Care, St. Paul, MN, USA) as follows: the first one at the midpoint of a line connecting the xiphoid process and the umbilicus; the second one placed 5 cm away, 45° to the upper left of the first one; and the third one at the left costal margin of the abdomen horizontal to the first one used as a ground electrode [1]. A portable EGG recorder (Digitrapper EGG; MedtronicSynectics, Shoreview, MN, USA) was used to record the EGG signal with a sampling frequency of 1 Hz. At the completion of each study session, the EGG data stored on the recorder were downloaded to a personal computer. Each session was divided into two 30-min segments (fasting state and fed state), and EGG tracings were carefully reviewed and artifacts were checked and deleted. The EGG signal was then subjected to spectral analysis using previously validated software [19] to compute the following EGG parameters: dominant frequency and power, and percentage of normal slow waves:
556
Dominant Frequency and Dominant Power of Gastric Slow Waves The frequency at which the power spectrum of the 30min recording had a peak power in the range of 0.5–9.0 cpm was defined as the dominant frequency. The power corresponding to the dominant frequency in the power spectrum was defined as the dominant power [19]. Percentage of Normal Slow Waves This is a parameter reflecting the regularity of gastric slow waves calculated from the EGG. It was defined as the percentage of time during which regular two to four slow waves were detected from the adaptive running spectral analysis [1, 20].
Measurement of ECG and Spectral Analysis of HRV The autonomic function was assessed from the spectral analysis of HRV that was derived from the ECG recording. The ECG was recorded from three surface electrodes: one at the manubrium of the sternum, a second one at the V5 position (just above the fifth interspace in the anterior axillary line), and a third one (used as ground) at the right chest. To improve the quality of the ECG, the same skin preparation as for EGG was performed before the placement of electrodes for ECG. A special UFI amplifier (UFI model 2,283 ft/I, Morrow Bay, CA, USA) was used to record the ECG signal with a sampling frequency of 6,000 Hz (digitized using the sound card on the PC). The software developed in our own lab was then used to down-sample the ECG signal to 500 Hz, detect R–R intervals, and perform spectral analysis on the HRV signal [21]. Sympathetic and Vagal Activity The spectral analysis of HRV is a well-established noninvasive method for the assessment of the autonomic function [22, 23]. The sum of spectral power P1 in the low-frequency (LF) band (0.04–0.15 Hz) reflects mainly sympathetic activity, whereas the sum of spectral power P2 in the high-frequency (HF) band (0.15–0.50 Hz) stands purely for parasympathetic or vagal activity. In this study, the ratio P1/(P1 + P2) was defined as the LF (sympathetic), and the ratio P2/(P1+P2) was considered as vagal activity HF. The ratio of LF/HF was defined as the sympathovagal balance.
Statistical Analysis All data are presented as mean ± SE. Paired or unpaired Student’s t tests were used to determine the differences in EGG parameters and HRV parameters between fasting and fed states in each session (paired test), between two sessions within the same group (paired test), or between the lean subjects and the obese subjects (unpaired test). P 0.05) and so was the dominant frequency of the EGG (2.97 ± 0.11 vs. 3.01 ± 0.06 cpm, P >0.05); however, the DP was significantly reduced in the obese subjects in comparison with that in lean subjects (30.84±2.33 vs. 44.90±2.77 dB, P
