Cardiac Dysregulation and Myocardial Injury in a 6-Hydroxydopamine-Induced Rat Model of Sympathetic Denervation

Abstract

BackgroundCardiac sympathetic denervation is found in various cardiac pathologies; however, its relationship with myocardial injury has not been thoroughly investigated.MethodsTwenty-four rats were assigned to the normal control group (NC), sympathectomy control group (SC), and a sympathectomy plus mecobalamin group (SM). Sympathectomy was induced by injection of 6-OHDA, after which, the destruction and distribution of sympathetic and vagal nerve in the left ventricle (LV) myocardial tissue were determined by immunofluorescence and ELISA. Heart rate variability (HRV), ECG and echocardiography, and assays for myocardial enzymes in serum before and after sympathectomy were examined. Morphologic changes in the LV by HE staining and transmission electron microscope were used to estimate levels of myocardial injury and concentrations of inflammatory cytokines were used to reflect the inflammatory reaction.ResultsInjection of 6-OHDA decreased NE (933.1 ± 179 ng/L for SC vs. 3418.1± 443.6 ng/L for NC, P < 0.01) and increased NGF (479.4± 56.5 ng/mL for SC vs. 315.85 ± 28.6 ng/mL for NC, P < 0.01) concentrations. TH expression was reduced, while ChAT expression showed no change. Sympathectomy caused decreased HRV and abnormal ECG and echocardiography results, and histopathologic examinations showed myocardial injury and increased collagen deposition as well as inflammatory cell infiltration in the cardiac tissue of rats in the SC and SM groups. However, all pathologic changes in the SM group were less severe compared to those in the SC group.ConclusionsChemical sympathectomy with administration of 6-OHDA caused dysregulation of the cardiac autonomic nervous system and myocardial injuries. Mecobalamin alleviated inflammatory and myocardial damage by protecting myocardial sympathetic nerves.

Increased Epicardial Adipose Tissue Volume Correlates With Cardiac Sympathetic Denervation in Patients With Heart Failure

“…In this regard, the interaction between cardiac sympathetic and parasympathetic innervation and its effect on cardiac parasympathetic activity has been largely unexplored. The evidence comes only from few experimental studies conducted in non-HF animal models, 36 thus avoiding comparisons with our results obtained in the clinical setting.…”

“…In fact, when the failing myocardium shows depletion of norepinephrine stores because of reduced mechanisms of norepinephrine uptake, 7 circulating catecholamines derived from peripheral organs might play a prominent role in perpetuating the progression of cardiac sympathetic denervation. This is particularly relevant given the importance of cardiac sympathetic nerves in cardiac homeostasis 36 and repair. 37 In this regard, it has been demonstrated that cardiac chemical sympathectomy in rats induces LV contractility dysfunction, increased circulating levels of markers of severe myocardial damage, and cardiac inflammatory reactions.…”

“…37 In this regard, it has been demonstrated that cardiac chemical sympathectomy in rats induces LV contractility dysfunction, increased circulating levels of markers of severe myocardial damage, and cardiac inflammatory reactions. 36 In addition, sympathetic denervation completely blocks cardiac regenerative responses after injury in neonatal hearts. 37 In our analysis, the EAT thickness was an independent predictor of 123 I-MIBG planar and SPECT parameters and provided additional predictive information on cardiac adrenergic nerve activity respect to important demographic, clinical, and LV function parameters.…”

Cardiac Sympathetic Denervation in the Failing Heart

“…This means that, in the context of SNS hyperactivity in HF, the production of catecholamines within the EAT seems to play an additive role in generating the final net effect leading to cardiac sympathetic denervation (Figure). Such denervation of the SNS would have dramatic effects on the progression of HF not only because of a loss in responsiveness to ionotropic stimulation but also because of a loss of trophic support that we and others have demonstrated to be critical for the maintenance of cardiac homeostasis 22 and repair. 23 Although the authors present data to indicate that the density of SNS fibers is similar between EAT and SCAT, their data suggest that EAT is more biosynthetically active with regard to catecholamine production.…”

Efeitos da simpatectomia no miocárdio

“…Há poucos dados relacionados à análise tecidual após simpatectomia em modelos não patológicos. Jiang et al 35 concluíram que a simpatectomia química induziu degeneração de cardiomiócitos com necrose e infiltração inflamatória focal, hiperplasia dos tecidos conectivos intersticiais, além de deposição de colágeno. Contudo, estes achados podem estar relacionados a provável efeito tóxico da 6-hidroxidopamina no miócito, como descrito previamente.…”