Antiarrhythmic and proarrhythmic effects of subcutaneous nerve stimulation in ambulatory dogs

Abstract

Background High output subcutaneous nerve stimulation (ScNS) remodels the stellate ganglia and suppresses cardiac arrhythmia. Objective To test the hypothesis that long duration low output ScNS causes cardiac nerve sprouting, increases plasma norepinephrine concentration and the durations of paroxysmal atrial tachycardia (PAT) in ambulatory dogs. Methods We prospectively randomized 22 dogs (11 males and 11 females) into 5 different output groups for 2 months of ScNS: 0 mA (sham) (N=6), 0.25 mA (N=4), 1.5 mA (N=4), 2.5 mA (N=4) and 3.5 mA (N=4). Results As compared with baseline, the changes of the durations of PAT episodes per 48 hours were significantly different among different groups (sham, -5.0±9.5 s; 0.25 mA 95.5±71.0 s; 1.5 mA, -99.3±39.6 s; 2.5 mA, -155.3±87.8 s and 3.5 mA, -76.3±44.8 s, p<0.001). The 3.5 mA group had greater reduction of sinus heart rate than the sham group (-29.8±15.0 bpm vs -14.5±3.0 bpm, p=0.038). Immunohistochemical studies showed that the 0.25 mA group had a significantly increased while 2.5 mA and 3.5 mA stimulation had a significantly reduced growth-associated protein 43 nerve densities in both atria and ventricles. The plasma Norepinephrine concentrations in 0.25 mA group was 5063.0±4366.0 pg/ml, which was significantly higher than other groups of dogs (739.3±946.3, p=0.009). There were no significant differences in the effects of simulation between males and females. Conclusions In ambulatory dogs, low output ScNS causes cardiac nerve sprouting, increases plasma norepinephrine concentration and the duration of PAT episodes while high output ScNS is antiarrhythmic.