Structural and Electrical Myocardial Remodeling in a Rodent Model of Depression
Structural and Electrical Myocardial Remodeling in a Rodent Model of Depression
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DOI：
10.1097/psy.0b013e318276cb0d
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Sgoifo, Andrea
中科院分区：
文献类型：
--
作者：
Carnevali, Luca;Trombini, Mimosa;Sgoifo, Andrea
目的：尽管压力和抑郁症与心脏病发病率和死亡率之间的相关性有充分的证据，但情感障碍和心脏病之间的联系机制还没有令人满意的解释。本研究探讨了抑郁症动物模型的心脏电生理特性。研究方法：在间歇性社交失败应激（n = 12）或空笼暴露（对照，n = 11）期间和之后，在成年雄性野生型大鼠中测量抑郁相关的生理和行为参数。末次失败/空融合器暴露后9天，在麻醉下进行高清心外膜标测。结果如下：与对照组相比，应激组动物的心率昼夜节律幅度降低幅度更大（-32% [3%] vs 13 [2%]; p = .001）和体温（-33% [4%]对比-5% [2%]; p = .001）节律，体重增加较小（+11% [1%]对比+17% [1%]; p < .001），并显示蔗糖溶液摄入量的较大减少（-19% [6%]对比7% [4%]; p = .006）。心外膜标测分析显示，应激动物的波前横向传导速度降低（0.23 [0.0] vs 0.27 [0.1] m/s; p = 0.02），有效不应期缩短（86.8 [2.1] vs 95.9 [3.0]毫秒; p = 0.01）。处死后，在应激组中观察到中度左心室纤维化。结论：间歇性社会应激过程与抑郁样症状和心肌电稳定性改变相关，可能具有预防作用。特别是，心肌不应性降低和传导受损，这被认为是心肌梗死的主要决定因素，代表了心脏脆弱性的可能机制。
Objective: Despite a well-documented association between stress and depression with cardiac morbidity and mortality, there is no satisfactory explanation for the mechanisms linking affective and cardiac disorders. This study investigated cardiac electrophysiological properties in an animal model of depression. Methods: Depression-relevant physiological and behavioral parameters were measured in adult male wild-type rats during and after a period of intermittent social defeat stress (n = 12) or empty cage exposure (control, n = 11). Nine days after the last defeat/empty cage exposure, high-definition epicardial mapping was performed under anesthesia. Results: Stressed animals versus controls displayed a larger reduction in the circadian amplitude of heart rate (-32% [3%] versus 13 [2%]; p = .001) and body temperature (-33% [4%] versus -5% [2%]; p = .001) rhythms, had smaller body weight gain (+11% [1%] versus +17% [1%]; p < .001), and showed a larger reduction in sucrose solution intake (-19% [6%] versus 7% [4%]; p = .006). Epicardial mapping analysis revealed a decrease in the transversal conduction velocity of the wavefront (0.23 [0.0] versus 0.27 [0.1] m/s; p = .02) and a shortening of the effective refractory period (86.8 [2.1] versus 95.9 [3.0] milliseconds; p = .01) in stressed animals. Upon killing, moderate left ventricular fibrosis was observed in the stressed group. Conclusions: Intermittent social stress procedure is associated with depression-like symptoms and altered myocardial electrical stability in a potentially proarrhythmic manner. In particular, reduced myocardial refractoriness and impaired conduction, which are considered major determinants of arrhythmogenesis, represent possible mechanisms underlying cardiac vulnerability.