Department of Cardiology, Tianjin First Central Hospital, Tianjin, China.
J Cardiovasc Pharmacol. 2020 Nov;76(5):602-609. doi: 10.1097/FJC.0000000000000899.
Heart failure (HF) affects around 100 million people and is a staggering burden for health care system worldwide. Rapid and sustained activation of inflammatory response is an important feature of HF after myocardial infarction. Sympathetic overactivation is also an important factor in the occurrence and progression of HF. The beneficial effect of renal denervation (RDN) has been demonstrated in HF. In the current study, we hypothesized that RDN improves cardiac function in HF canine models due to acute myocardial infarction (AMI) and reduced inflammation might be involved. Twenty-four beagles were randomized into the control (n = 8), HF (n = 8), and HF + RDN group (n = 8). The HF model after AMI was established by embolization the anterior descending distal artery with anhydrous ethanol in the HF and HF + RDN group. Bilateral renal artery ablation was performed in the HF + RDN group. Cardiac function, serum creatine kinase, creatine kinase-MB and NT-Pro BNP level, and expression of inflammation-related proteins in myocardial were examined. Because the paraventricular nucleus of the hypothalamus might be involved in inflammation-induced central neural excitation in HF and plays an important role in regulating extracellular fluid volume and sympathetic activity, expression of inflammation-related proteins in hypothalamus was also examined. AMI and post-AMI HF model was created successfully. Compared with the HF group, dogs in the HF + RDN group showed better cardiac function 4 weeks after AMI: lower left ventricular end-diastolic pressure, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension and higher LEVF and left ventricular systolic pressure (P < 0.05 for all) were observed in the HF + RDN group. In addition, dogs in the HF + RDN group had slightly less ventricular fibrosis. Interestingly, RDN had lower expression of inflammation-related proteins including interleukin-6, tumor necrosis factors-α, nuclear factor κB, and monocyte chemotactic protein 1 (P < 0.05 for all) in both myocardial tissue and hypothalamus. RDN can improve cardiac function in dogs with HF after myocardial infarction. Our results suggested that RDN might affect cytokine-induced central neural excitation in HF and later affect sympathetic activity. Our results suggested a potential beneficial mechanism of RDN independent of mechanism involving renal afferent and efferent sympathetic nerves.
心力衰竭（HF）影响全球约 1 亿人，给全球医疗保健系统带来了巨大的负担。心肌梗死后，炎症反应的快速和持续激活是 HF 的一个重要特征。交感神经过度激活也是 HF 发生和发展的重要因素。肾去神经支配（RDN）对 HF 的有益作用已得到证实。在目前的研究中，我们假设 RDN 通过减轻炎症改善心肌梗死后 HF 犬模型的心脏功能。24 只比格犬随机分为对照组（n = 8）、HF 组（n = 8）和 HF + RDN 组（n = 8）。HF 模型通过无水乙醇栓塞前降支远端动脉在 HF 和 HF + RDN 组中建立。HF + RDN 组行双侧肾动脉消融术。检测心功能、血清肌酸激酶、肌酸激酶同工酶和 NT-Pro BNP 水平以及心肌炎症相关蛋白的表达。由于下丘脑室旁核可能参与 HF 中炎症诱导的中枢神经兴奋，并在调节细胞外液体积和交感神经活动中发挥重要作用，因此还检测了下丘脑炎症相关蛋白的表达。成功建立了心肌梗死后 HF 模型。与 HF 组相比，AMI 后 4 周，HF + RDN 组犬心功能更好：左心室舒张末期压、左心室舒张末期内径和左心室收缩末期内径降低，左心室射血分数和左心室收缩压升高（所有 P < 0.05）。此外，HF + RDN 组犬心室纤维化程度略低。有趣的是，HF + RDN 组心肌和下丘脑炎症相关蛋白的表达均降低，包括白细胞介素 6、肿瘤坏死因子-α、核因子 κB 和单核细胞趋化蛋白 1（所有 P < 0.05）。RDN 可改善心肌梗死后 HF 犬的心脏功能。我们的研究结果表明，RDN 可能影响 HF 中细胞因子诱导的中枢神经兴奋，进而影响交感神经活性。我们的研究结果表明，RDN 可能具有独立于肾传入和传出交感神经的潜在有益机制。
