Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran.
Shock. 2012 Feb;37(2):219-27. doi: 10.1097/SHK.0b013e318240b4be.
Cardiac cycle is regulated by a complex interplay between autonomic nervous system and cardiac pacemaker cells. Decreased heart rate variability (HRV) and increased cardiac rhythm regularity are associated with poor prognosis in patients with systemic inflammation (e.g., sepsis). However, the underlying mechanism of decreased HRV in systemic inflammation is not understood. It is known that greater regularity in a complex system could indicate uncoupling of the system's components. The present study aimed to test the hypothesis that impaired responsiveness of cardiac pacemaker to autonomic nervous system may lead to uncoupling of the cardiovascular regulatory mechanisms during systemic inflammation. Systemic inflammation was induced by intraperitoneal injection of endotoxin (lipopolysaccharide, 1 mg/kg) in rats. Cardiovascular signals were recorded in conscious animals using a telemetric system. Heart rate dynamics was analyzed using Poincaré plot, and cardiac cycle regularity was assessed by sample entropy analysis. Spontaneously beating atria were isolated, and chronotropic responsiveness to adrenergic and cholinergic stimulation was assessed using standard organ bath. Sample entropy decreased significantly 4 h after endotoxin injection in conscious rats. Vagal modulation of cardiac cycle (as assessed by Poincaré plot) also exhibited a significant reduction in endotoxemic rats. Acute endotoxin challenge was associated with a significant hyporesponsiveness of isolated spontaneously beating atria to cholinergic stimulation. The chronotropic responsiveness to adrenergic stimulation was identical in controls and endotoxin-treated rats. These data propose that systemic inflammation is linked to reduced cardiac responsiveness to cholinergic stimulation. This may lead to partial uncoupling of cardiac pacemaker cells from autonomic neural control and can explain decreased HRV during systemic inflammation.
心动周期受自主神经系统和心脏起搏细胞之间复杂相互作用的调节。心率变异性（HRV）降低和心脏节律规则性增加与全身炎症（如败血症）患者的预后不良相关。然而，全身炎症中 HRV 降低的潜在机制尚不清楚。已知复杂系统中的更大规则性可能表明系统组件的解耦。本研究旨在检验以下假设：即心脏起搏对自主神经系统的反应能力受损可能导致全身炎症期间心血管调节机制的解耦。通过腹腔内注射内毒素（脂多糖，1mg/kg）在大鼠中诱导全身炎症。使用遥测系统在清醒动物中记录心血管信号。使用 Poincaré 图分析心率动力学，并用样本熵分析评估心脏周期规则性。分离出自发跳动的心房，并使用标准器官浴评估肾上腺素能和胆碱能刺激的变时反应性。在注射内毒素后 4 小时，清醒大鼠的样本熵显着降低。迷走神经对心脏周期的调制（如 Poincaré 图评估）在内毒素血症大鼠中也显着降低。急性内毒素挑战与分离的自发跳动心房对胆碱能刺激的反应性显着降低有关。肾上腺素能刺激的变时反应性在对照组和内毒素处理组大鼠中相同。这些数据表明，全身炎症与心脏对胆碱能刺激的反应性降低有关。这可能导致心脏起搏细胞与自主神经控制的部分解耦，并解释了全身炎症期间 HRV 降低。
