Supplement Abstracts Submitted for the 70th Annual Scientific Meeting of the American College of Gastroenterology: STOMACH
Purpose: Implantable gastric stimulation (IGS) has been shown to reduce appetite, increase satiety and induce weight loss in obese patients. However, possible central mechanisms of hypothalamus involved with the IGS treatment of obesity are still unclear.
Aim: The purpose of this study was to investigate the effects of IGS with different parameters on the neuronal activity of gastric related neurons in the PVN and VMH.
Methods: Extracellular potentials of single neurons in the PVN and VMH were recorded in 58, 52 anesthetized rats, respectively. Gastric distension (GD) was produced by air inflation of a latex balloon surgically placed in the stomach to identify as GD-excitatory (GD-E) neurons or GD-inhibitory (GD-I) neurons. One pair of platinum electrodes (0.3 cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. IGS with four sets of parameters was applied for one minute on GD-Responsive (GD-R, both GD-E and GD-I) neurons: IGS-A (the parameters currently used in clinical trials for the treatment of obesity): 6 mA, 0.3 ms, 40 Hz, 2s-on, 3s-off; IGS-B: same as IGS-A but decreased train on-time of 0.1s; IGS-C: same as IGS-A but increased pulse width3ms; IGS-D: same as IGS-A but decreased pulse frequency of 20 Hz.
Results: (1) Of 115 PVN and 96 VMH neurons tested by GD, 104 and 82 neurons were responsive to GD, respectively. (2) Among these GD-responsive neurons 79%, 63.2%, 91.4% and 69.8% of them in the PVN and 55.0%, 17.6%, 77.8%, and 14.3% of them in the VMH were activated by IGS-A, B, C and D respectively. (3) In the PVN, neuronal activity was affected more frequently with IGS-C than IGS-B (P < 0.001) or IGS-D (P < 0.01); however, no significant difference was noted between IGS-C and IGS-A; IGS-A was significantly more effective than IGS-B (P<0.05). In the VMH, more GD-E neurons were excited by IGS-C (P < 0.001, vs. IGS-B; P = 0.02, vs. IGS-D) and by IGS-A (P = 0.002, vs. IGS-B; P = 0.016 vs. IGS-D); in addition, 63.6%, 73.3%, 37.9% and 51.8% of GD-I neurons were excited by IGS-A, B, C, D respectively (P < 0.05, IGS-B vs. IGS-A/IGS-C).
Conclusions: IGS with appropriate parameters can activate gastric-related neurons in both PVN and VMH and the effect seems related to stimulation strength (pulse frequency, pulse width as well pulse train on-time). The activation of neurons in the hypothalamus of the PVN and the VMH indicates the central mechanism of IGS in the treatment of obesity.