OBJECTIVE Withdrawal of cardiac vagal activity is considered as one of the important triggers for acute myocardial infarction (MI)-induced ventricular arrhythmias in type 2 diabetes mellitus (T2DM). Our previous study demonstrated that cell excitability of cardiac parasympathetic postganglionic (CPP) neurons was reduced in T2DM rats. This study investigated whether cell excitability of CPP neurons is associated with cardiac vagal activity and MI-induced ventricular arrhythmias in T2DM rats. METHODS Rat T2DM was induced by a high-fat diet plus streptozotocin injection. MI-evoked ventricular arrhythmia was achieved by surgical ligation of the left anterior descending coronary artery. Twenty-four-hour, continuous ECG recording was used to quantify ventricular arrhythmic events and heart rate variability (HRV) in conscious rats. The power spectral analysis of HRV was used to evaluate autonomic function. Cell excitability of CPP neurons was measured by the whole-cell patch-clamp technique. RESULTS Twenty-four-hour ECG data demonstrated that MI-evoked fatal ventricular arrhythmias are more severe in T2DM rats than that in sham rats. In addition, the Kaplan-Meier analysis demonstrated that the survival rate over 2 weeks after MI is significantly lower in T2DM rats (15% in T2DM+MI) compared to sham rats (75% in sham+MI). The susceptibility to ventricular tachyarrhythmia elicited by programmed electrical stimulation was higher in anesthetized T2DM+MI rats than that in rats with MI or T2DM alone (7.0 ± 0.58 in T2DM+MI group vs. 3.5 ± 0.76 in sham+MI). Moreover, as an index for vagal control of ventricular function, changes of left ventricular systolic pressure (LVSP) and the maximum rate of increase of left ventricular pressure (LV dP/dtmax) in response to vagal efferent nerve stimulation were blunted in T2DM rats. Furthermore, T2DM increased heterogeneity of ventricular electrical activities and reduced cardiac parasympathetic activity and cell excitability of CPP neurons (current threshold-inducing action potentials being 62 ± 3.3 pA in T2DM rats without MI vs. 27 ± 1.9 pA in sham rats without MI). However, MI did not alter vagal control of the ventricular function and CPP neuronal excitability, although it also induced cardiac autonomic dysfunction and enhanced heterogeneity of ventricular electrical activities. CONCLUSION The reduction of CPP neuron excitability is involved in decreased cardiac vagal function, including cardiac parasympathetic activity and vagal control of ventricular function, which is associated with MI-induced high mortality and malignant ventricular arrhythmias in T2DM.

中文翻译：

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心脏节后副交感神经元的细胞兴奋性降低与 2 型糖尿病中心肌梗塞引起的致死性室性心律失常相关。

目的 心脏迷走神经活动的停止被认为是 2 型糖尿病 (T2DM) 急性心肌梗死 (MI) 引起的室性心律失常的重要触发因素之一。我们之前的研究表明，T2DM 大鼠心脏副交感神经节后 (CPP) 神经元的细胞兴奋性降低。本研究调查了 CPP 神经元的细胞兴奋性是否与 T2DM 大鼠的心脏迷走神经活动和 MI 诱导的室性心律失常有关。方法通过高脂饮食加链脲佐菌素注射诱导大鼠T2DM。MI诱发的室性心律失常是通过手术结扎左冠状动脉前降支来实现的。24 小时连续心电图记录用于量化清醒大鼠的室性心律失常事件和心率变异性 (HRV)。HRV的功率谱分析用于评估自主神经功能。通过全细胞膜片钳技术测量 CPP 神经元的细胞兴奋性。结果 24 小时心电图数据表明，T2DM 大鼠 MI 诱发的致死性室性心律失常比假手术大鼠更严重。此外，Kaplan-Meier 分析表明，与假手术大鼠（假手术 + MI 中的 75%）相比，T2DM 大鼠（T2DM+MI 中为 15%）在 MI 后 2 周内的存活率显着降低。程序性电刺激引起的室性快速性心律失常的易感性在麻醉的 T2DM+MI 大鼠中高于单独的 MI 或 T2DM 大鼠（T2DM+MI 组为 7.0 ± 0.58，假手术+MI 组为 3.5 ± 0.76）。此外，作为迷走神经控制心室功能的指标，T2DM 大鼠对迷走神经传出神经刺激的左心室收缩压 (LVSP) 和左心室压力最大增加率 (LV dP/dtmax) 的变化减弱。此外，T2DM 增加了心室电活动的异质性，降低了 CPP 神经元的心脏副交感神经活动和细胞兴奋性（没有 MI 的 T2DM 大鼠的电流阈值诱导动作电位为 62 ± 3.3 pA，而没有 MI 的假大鼠为 27 ± 1.9 pA）。然而，MI 并没有改变迷走神经对心室功能和 CPP 神经元兴奋性的控制，尽管它也会引起心脏自主神经功能障碍并增强心室电活动的异质性。结论 CPP神经元兴奋性降低与心脏迷走神经功能降低有关，