Effects Of Propranolol And Benazepril Treatment On Atrial Neural Remodeling Induced By Levothyroxine In Rabbits

Objective To determin the effect of propranolol and benazepril on cardiac neural remodeling in rabbits with hyperthyroidism induced by levothyroxine and to investigate the role of cardiac neural remodeling in the genesis of atrial fibrillation.Methods Forty New Zealand rabbits were randomly divided into 4 groups: control group (saline only, n=10), L-thy group (45μg/kg/day levothyroxine, n=10), Prop group (45μg/kg/day levothyroxine plus 5mg/kg/day propranolol, n=10), Bena group (45μg/kg/day levothyroxine plus 3mg/kg/day benazepril, n=10). All medications were administered by intraperitoneal injection. After 4 weeks of treatment, left atrial appendages were harvested for immunohistological staining of sympathetic nerve markers tyrosine hydroxylase (TH), parasympathetic marker choline acetyltransferase (ChAT) and growth-associated protein 43 (GAP43). Nerve density quantification was performed by a computer assisted histomorphometry system.Results Compared with control group, atrial tissues from L-thy and Bena group had a higher density of nerve structures immunopositive to the TH, ChAT and GAP43 (P < 0.01). There was no difference in TH, ChAT and GAP43 positive nerve density between rabbits from control group and Prop group (P > 0.05).Conclusion Levothyroxine induces rabbit atrial nerve sprouting and neural remodeling with the involvement of sympathoadrenal system (SAS) instead of rennin-agiotension system (RAS), which may be one of the mechanisms by which hyperthyroidism predisposes to atrial fibrillation. Objective This study sought to quantify and determine the cardiac autonomic innervations in different regions of the left atria and pulmonary veins in dogs and investigate its implications in atial fibrillation.Methods Eight healthy adult mongrel dogs of either sex, weighing from 15 to 20 kg, were euthanized with an intravenous overdose of pentobarbital sodium immediately after acute physiological experiments not expected to result in modification of the cardiac ANS being studied. The heart and great vessels were rapidly removed en bloc through a median sternotomy. Tissue samples were obtained from the posterior left atrium (PLA), left atrial roof (LAR), anterior left atrium (ALA), interatrial septum (IAS), left atrial appendage (LAA) and pulmonary veins (PVs). Nerve density of tissue samples were determined by immunohistochemical staining and 25omputer-assisted morphometric analysis system.Results Sympathetic and parasympathetic nerve are distributed through the LA and PVs in a similar way. Both sympathetic and parasympathetic nerve densities decreased in the order: PLA > PV > IAS > LAR > ALA > LAA. For sympathetic nerve, multiple comparisons between any two regions showed a significant difference (P < 0.05 or P < 0.01) except for PV versus PLA (P = 0.211), IAS versus LAR (P = 0.140), and LAR versus ALA (P = 0.204); for parasympathetic nerve, all the differences between any pair of regions were statistically significant (P < 0.05 or P < 0.01) with the exception of PV versus PLA (P = 0.256), IAS versus LAR (P = 0.130), LAR versus ALA (P = 0.238), and ALA versus LAA (P = 0.124). For both nerve types, a decreasing gradient of nerve densities from the external to internal layer (P < 0.001,each comparisons). Nerve density for either nerve type was significantly higher at the ostia than the distal segments of PVs (P < 0.001).Conclusion The left atria and PVs are innervated by sympathetic and parasympathetic nerves in a regionally heterogeneous way, which may has close relation with the initiation and perpetuation of AF and the formation and distribution of CFAE, and be of important significance for AF ablation. Objective To evaluate the role of the cardiac intrinsic autonomic nerve innervation in the formation of complex fractionated atrial electrogram (CFAE).Methods Twelve anesthetized mongrel canines weighing 15-20kg were randomized into isoprenaline group (Iso, n=6) and acetylcholine chloride group (Ach, n=6). After the left 4th thoracotomy and pericardiotomy, atrial fibrillation (AF) was induced by atria topical application of Iso or Ach. After the induction of AF, epicardium mapping was performed. CFAEs and Non-CFAEs were located and labeled respectively. All animals were euthanized by intravenous injection of a lethal does of sodium pentobarbital immediately after the surgical and electrophysiological procedure. Labeled atrial tissues were collected and sectioned for immunohistochemistry. Nerve density of tissue samples were determined by immunohistochemical staining and comupter-assisted morphometric analysis system.Results Compared with non-CFAE sites, both sympathetic nerve density of CFAE sites in Iso group (4.23±1.15 vs 0.33±0.13, P<0.001) and parasympathetic nerve density of CFAE sites in Ach group (7.37±1.43 vs 0.53±0.14, P<0.001) was significantly higher.Conclusion This study demonstrates significantly higher autonomic nerve density at CFAE sites, suggesting an autonomic basis for CFAE formation.