Review article: gastric electrical stimulation for gastroparesis--physiological foundations, technical aspects and clinical implications

Abstract

Background: Application of electrical stimulation to the gut, primarily the stomach, has rapidly advanced in the last two decades, from mostly animal studies to the clinical arena. Most studies focused on the use of electrical stimulation for gastroparesis, the only approved indication for such intervention.

Aim: To review the physiological basis of gastric electrical activity and the technical aspects and clinical outcome of gastric electrical stimulation (GES) for gastroparesis.

Methods: PubMed search from 1966 to 2009, using gastroparesis and GES as search terms. Areas in focus were systematically reviewed.

Results: The literature consists of open-label studies, mostly from single centres, published in the last decade. Improvement in symptoms, quality of life and nutritional status was reported by most studies. Physiologically, stimulation parameters approved in clinical practice do not regulate gastric slow wave activity and have inconsistent effect on gastric emptying. The mechanism of action of GES is not fully known, but data support modulation of gastric biomechanical activity and afferent neural mechanisms.

Conclusions: Gastric electrical stimulation is a helpful intervention in recalcitrant gastroparesis. Controlled studies and better understanding of mechanisms of action of electrical stimulation are needed to evaluate further the clinical utility of this intervention and to exploit its therapeutic potential better.

Figure 1

Schematic representation of efferent control of gastrointestinal smooth muscle function. Phasic smooth muscle contractions are controlled by electrical slow waves generated by pacemaker ICC. Chronotropic regulation of slow waves and control of non-phasic contractile activity are provided by the autonomic nervous system either directly or indirectly via intramuscular ICC that mediate neuromuscular neurotransmission. Depending on stimulus parameters, electrical stimulation can influence smooth muscle function indirectly by triggering neurotransmitter release from intramural nerve fibers or, superimposed upon the neurally mediated effect, more directly via ICC and smooth muscle cells.

Figure 2

Innervation of intramuscular ICC by enteric nerves in the circular muscle layer of the murine fundus. Synaptotagmin-like immunopositive nerve varicosities (green) form close morphological associations with intramuscular ICC labeled with an anti-Kit antibody (red). The region outlined by the white dashed box in A is shown in greater magnification in B. Scale bars: 10 μm in A and 5 μm in B. Reproduced, with permission of Wiley-Liss, Inc. a subsidiary of John Wiley & Sons, Inc., from reference .

Figure 3

Role of mitochondria in the generation of slow wave activity by ICC. A, rhythmic pacemaker activity in cultured small intestinal ICC purified by immunomagnetic sorting of Kit⁺ cells. Slow wave activity was detected by monitoring oscillations in mitochondrial [Ca²⁺] using the Ca²⁺-sensing fluorescent dye rhod-2 and confocal line-scanning microscopy. B, tetramethylrhodamine methyl ester (TMRM) fluorescence in immunomagnetically purified ICC. TMRM is a positively charged, membrane-permeable dye that rapidly redistributes between the extracellular space, the cytoplasm and the mitochondria depending on transmembrane potential differences. Note predominantly mitochondrial localization of TMRM. A.U., arbitrary units. Scale bar, 30 μm. C, rhythmic pacemaker activity in immunomagnetically purified ICC reported by rhythmic oscillations in mitochondrial TMRM fluorescence detected by confocal line-scanning microscopy. Reproduced, with permission, from reference .

Figure 4

Role of ICC in the control of smooth muscle function by ICC. See text for details. (Reproduced, with permission, from reference 41)

Figure 5

Schematic depiction of a biphasic square wave pulse. The positive and negative components have the same amplitude and duration, hence the total net charge is zero.

Figure 6

Gastric electrical stimulation in a patient with gastroparesis. The recording is obtained from an electrode positioned in the antrum (S4), while stimulation is delivered through an electrode positioned in the mid body of the stomach. Pacing stimuli, marked by dots, drive the electrical frequency as recorded in the antrum on a 1:1 ratio, indicating pacing (entrainment). In this experiment, stimulation with rectangular pulses of 30 ms, amplitude of 4 mA, and frequency up to 10% higher than the intrinsic gastric frequency is able to completely entrain the gastric slow wave and normalize gastric dysrhythmia. (Reproduced, with permission, from reference .)

Figure 7

An illustration of the type of electrical stimulation used by the Enterra system. Short bursts of short duration rectangular pulses pulses (330 μs each) are given at a frequency of 14Hz in each burst. Bursts in turn last 0.1 s, and are delivered every 5 s.