The concept of gastric pacing for the treatment of obesity originated with the observation of a 6-month-old infant with vomiting and failure to thrive because of an abnormal endogenous antral pacemaker.20
In 1992, a single pig named Lucky lost weight in a cyclical manner and reduced food intake during gastric pacing.21
This led to antral stimulation in three groups of pigs. The stimulus parameters in group 2 were an amplitude of 10 V, a pulse width of 450 μs, and a frequency of 100 Hz, with an on time of 3.2 s and an off time of 5.1 s. This group decreased food intake by 12–16% and gained 10% less than group 1 controls over 35 weeks. Group 3 was similar to group 2 but the amplitude was 5 V, which was ineffective in causing weight loss.20
Human gastric pacing for obesity began in 1995. There have now been more than 500 subjects treated for obesity with gastric pacing. With proper screening, weight loss is now in the range of 40% excess body weight. Excess body weight is defined as the weight above the midpoint of the 1983 Metropolitan Life Insurance tables for a given height and gender. Excess body weight loss divided in half is approximately equivalent to the percentage loss of initial body weight. Most surgical studies report results in terms of excess body weight lost, whereas most medical studies report results in terms of percentage body weight loss.
reported on four series of subjects. The first 5 subjects were operated upon in 1995 and maintained a 70% loss of excess body weight over 2 years. Ten additional subjects were operated upon in 1998 and maintained a 20% loss of excess body weight over a year. Ten more subjects operated upon in 2000 lost 30% of excess body weight over 1 year. The fourth group of 40 patients was operated upon beginning in 2002, and the entire group lost 20% of excess body weight over 1 year. A screening algorithm was developed through retrospective analysis of weight loss in all prior trials. Subjects enrolled into the fourth group were screened with this algorithm beginning in 2003. Subjects screened in this way lost an average of 40% of excess body weight over 1 year.21
Subjects in these trials decreased their mean blood pressure 12/12 mm Hg, normalized bowel habits despite decreased food intake, were relieved of gastric reflux symptoms, and increased metabolic rate 10%. Insulin sensitivity was increased in proportion to weight loss as measured by the homeostatis model.21
These and other studies with the gastric stimulator for obesity are summarized in
. These studies have been performed with the Transcend® stimulator manufactured by Transneuronix (Mt. Arlington, NJ) (
). The pacemaker is implanted laparoscopically below the pes anserinus 3 cm from the edge of the lesser gastric curvature and 6 cm from the pyloris. The lead is fixed within a tunnel in the gastric muscular wall by a suture, and gastroscopy is performed to ensure that the lead does not perforate the stomach wall. The operative time is less than an hour, and the stimulator is activated 30 days after implantation. Stimulus parameters are an amplitude of 10 mA, a pulse width of 208 μs, and a frequency of 40 Hz with 2 s on time and 3 s off time.22
Clinical Studies with the Transcend Gastric Pacemaker
(A) Transcend pacemaker device. (B) Position of device. Reprinted with permission from Obesity Surgery Journal 2004;14:S14-S22.
All the clinical trials are open label studies with the exception of one study done in the United States. This study enrolled 103 patients who lost minimal weight over the blinded period. This study randomized patients to pacemaker on or pacemaker off in a 1:1 fashion for the first 6 months. Because this trial was done prior to the appreciation that the lead needed to be sutured in place, there were problems with lead displacement. There were 34 patients remaining in the trial at 29 months who lost 20% of excess body weight.23
Because proper patient selection is important in optimizing weight loss after pacemaker implantation, a retrospective analysis of the elements of success in prior trials was conducted and a predictive algorithm was created. Use of this algorithm has allowed selection of patients who lose an average of 40% of excess body weight.21
Since the trials to date have shown placement of the gastric pacemaker to be the safest and simplest operation for morbid obesity, there has been considerable interest in defining the mechanism by which it works.24
Several lessons have been learned through experience. The improvement in quality of life is proportional to the weight loss. In contrast to the original studies, the screening algorithm, the elimination of binge eaters, and a behavior modification program have been added to the more recent Screened Health Assessment and Pacer Evaluation trial, which is presently in progress.23
Nineteen subjects in the study reported by DeLuca and colleagues25
experienced increased satiety without the increase in ghrelin anticipated to accompany weight loss. Cigaina evaluated leptin, cholecystokinin (CCK), somatostatin, and glucagon-like peptide 1 (GLP-1) at baseline, 1 month, and 6 months following pacemaker implantation, as administration of these hormones is associated with weight loss.26
Subjects in this trial lost 10.4 kg, but the meal-related rise in all four hormones was reduced paradoxically. Although leptin is expected to fall with weight loss, the release of other hormones is dependent on the vagus nerve. Thus, these results are consistent with the pacemaker blocking efferent vagal nerve transmission.27
Other investigations into the mechanism by which the gastric pacemaker induces weight loss have focused on gastric myoelectrical activity. Obese patients have accelerated gastric emptying compared to nonobese patients.28
Two methods have been used to delay gastric emptying and increase satiety—long pulse width, low-frequency stimulation and short pulse width, high-frequency stimulation. The Transcend gastric pacemaker has been the most extensively studied and uses the latter. Its mechanism of action will be discussed first.
Short pulse width (a few hundred milliseconds) and high-frequency (a few times higher than physiological frequency of the gastric slow wave) stimulation increases afferent vagal activity as measured by spectral analysis, and vagotomy abolishes this effect, something that does not occur with long pulse width, low-frequency stimulation.29
This vagal effect is mediated by the afferent vagus through the nucleus of the tractus solitarius and may involve central circuits.30
Vagal afferents have been demonstrated to synapse with glucose-sensitive neurons in the ventromedial hypothalamus, and input from the cerebellar nucleus interpositus augments this vagal stimulation through an integrated pathway.31
Studies with positron emission tomography demonstrated higher metabolism in the right hippocampus with lower emotional eating scores when the Transcend pacemaker was in the “on” position compared to the “off” position.32
Although short pulse, high-frequency pacing increases vagal afferent activity, it blocks vagal efferent activity. The decrease in vagally controlled satiety hormones (CCK, GLP-1, and somatostatin) and an absence of the expected rise in ghrelin with fasting during stimulation are examples of efferent vagal inhibition.27,33
Ascribing the mechanism of short pulse width and high-frequency stimulation to blocking of the efferent vagus while activating the afferent vagus is based on the aforementioned studies and should be regarded as speculative until confirmed by further investigations.
Short pulse width, high-frequency stimulation induces gastric distention, inhibits postprandial antral contractions, and slows gastric emptying, which leads to early satiety and reduced food intake with weight loss.34
Cholinergic vagal efferents increase gastric tone, whereas nitric oxide pathways decrease it.35
Gastric stimulation blocks the efferent vagal pathway and releases nitric oxide pathways from inhibition, resulting in gastric dilatation.14,36,37
The gastric slow waves are inhibited postprandially, which may also contribute to the delay of gastric emptying with a promotion of satiety.38