Increased Dopamine and DA2 Receptor Expression in the Gastric Myenteric Plexus (MP) is Responsible for Gastroparesis in Parkinson's Disease Rat Model Treated With 6-Ohda

Abstract

Introduction Gastric smooth muscle layers are electrically excited by slow waves. In the normal stomach, slow waves propagate longitudinally in ring wavefronts from the upper corpus to the distal antrum. Circumferential propagation does not appear to occur, likely because there is no excitable tissue available circumferentially in these rings. However, rapid circumferential propagation has been observed in isolated gastric tissues and during gastric pacing. In this study, the propagation profiles of slow wave behaviors in diabetic gastroparesis were defined at high resolution (HR). The hypothesis was that circumferential propagation occurs during dysrhythmia, presenting a novel marker of gastric electrical dysfunction. Methods HR (multi-electrode) mapping was performed in 7 patients with diabetic gastroparesis undergoing laparotomy for stimulator implantation. Anterior serosal recordings were taken using flexible PCB arrays (256 electrodes; 4 mm spacing; 36cm2), and activation mapping was performed. Velocity fields were calculated using a finite difference approach incorporating a Gaussian filter smoothing function. Amplitudes were calculated using a peak-trough detection algorithm. Longitudinal and circumferential propagation data from corpus recordings were compared with Student's t-test. Means±SEM are reported. Results Atypical or dysrhythmic propagation was observed in 6/7 patients, including incomplete conduction block, complete block with escape, ectopic pacemaking in the corpus and antral tachygastria (freq range: 2.7-4.2 cpm). Circumferential propagation was associated with all of these events (circumferential velocity 6.6 ± 0.9 mm/s vs longitudinal velocity 2.9 ± 0.2 mm/s; p<0.01). Extracellular slow wave amplitudes were also ~2.5x higher during circumferential propagation (411±66 uV vs 170±27 uV; p<0.01). Isochronalmapping demonstrated that circumferential propagation led to the rapid restoration of a normal longitudinal wavefront distal to the source of the dysrhythmia. However, circumferential propagation also promoted organized retrograde propagation in the case of antral tachygastria. Conclusions Propagation abnormalities in diabetic gastroparesis include conduction blocks, escape, and ectopic events, potentially as a consequence of known ICC network degradation. Circumferential propagation emerges in many of these abnormal patterns because excitable tissue becomes available in the circumferential direction. Circumferential conduction is found to be associated with high velocities and high amplitudes, which could therefore serve as useful clinical indicators for abnormal slow wave propagation. Functionally, rapid circumferential propagation serves to restore normal slow wave propagation distal to conduction defects, however it can also promote organized retrograde tachygastria.