Simvastatin attenuates sympathetic hyperinnervation to prevent atrial fibrillation during the postmyocardial infarction remodeling process

Yu T, Zhu W, Gu B, Li S, Wang F, Liu M, Wei M, Li J. Simvastatin attenuates sympathetic hyperinnervation to prevent atrial fibrillation during the postmyocardial infarction remodeling process. J Appl Physiol 113: 1937-1944, 2012. First published September 13, 2012; doi: 10.1152/japplphysiol.00451.2012.-Statin, as a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, has been shown to prevent atrial fibrillation (AF) due to its anti-inflammatory and antioxidant effects. However, it is still not known whether statin can improve autonomic remodeling to prevent AF. In the present study, using an in vivo rat myocardial infarction (MI) model, we aimed to test whether simvastatin can attenuate nerve sprouting and sympathetic hyperinnervation to prevent AF during the post-MI remodeling process. Our data demonstrate that simvastatin, delivered 3 days after MI for 4 wk, can result in significant decreases in plasma levels of both TNF-alpha (239 +/- 23 pg/ml) and IL-1 beta (123 +/- 11 pg/ml) compared with MI rats without therapy (TNF-alpha, 728 +/- 57 pg/ml; IL-1 beta, 213 +/- 21 pg/ml; P < 0.05), which, however, were still higher than sham-operated rats (TNF-alpha, 194 +/- 20 pg/ml; IL-1 beta, 75 +/- 8 pg/ml; P < 0.05). The similar pattern of changes in inflammation responses was also observed in TNF-alpha and IL-1 beta protein expression in the left atrium free wall. The suppressed inflammation responses were associated with reduced superoxide and malondialdehyde generation in the atrium. These changes account for decreases in neural growth factor expression at levels of both mRNA (1.2 +/- 0.09 AU vs. MI group, 1.78 +/- 0.16 AU) and protein (1.57 +/- 0.17 AU vs. MI group, 2.24 +/- 0.19 AU; P < 0.05), thus resulting in reduced nerve sprouting and sympathetic hyperinnervation. Accordingly, the rate adaptation of the atrial effective refractory period also recovered, leading to the decreased inducibility of AF. These data suggest that simvastatin administration after MI can prevent AF through reduced sympathetic hyperinnervation.