School of Medical Biology, South Ural State University, Chelyabinsk, Russian Federation.
Laboratory for Regulatory Mechanisms of Stress and Adaptation, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.
J Appl Physiol (1985). 2021 Mar 1;130(3):759-771. doi: 10.1152/japplphysiol.00694.2019. Epub 2021 Jan 7.
Traumatic stress causes posttraumatic stress disorder (PTSD). PTSD is associated with cardiovascular diseases and risk of sudden cardiac death in some subjects. We compared effects of predator stress (PS, cat urine scent, 10 days) on mechanisms of cardiac injury and protection in experimental PTSD-vulnerable (PTSD) and -resistant (PTSDr) rats. Fourteen days post-stress, rats were evaluated with an elevated plus-maze test, and assigned to PTSD and PTSDr groups according to an anxiety index calculated from the test results. Cardiac injury was evaluated by: ) exercise tolerance; ) ECG; ) myocardial histomorphology; ) oxidative stress; ) pro- and anti-inflammatory cytokines. Myocardial heat shock protein 70 (HSP70) was also measured. Experimental PTSD developed in 40% of rats exposed to PS. Exercise tolerance of PTSD rats was 25% less than control rats and 21% less than PTSDr rats. ECG QRS, QT, and OTc intervals were significantly longer in PTSD rats than in control and PTSDr rats. Only cardiomyocytes of PTSD rats had histomorphological signs of metabolic and hypoxic injury and impaired contractility. Oxidative stress markers were higher in PTSD than in PTSDr rats. Pro-inflammatory IL-6 was higher in PTSD rats than in control and PTSDr rats, and anti-inflammatory IL-4 was lower in PTSD than in control and PTSDr rats. Myocardial HSP70 was lower in PTSD rats than in PTSDr and control rats. Our conclusion was that rats with PTSD developed multiple signs of cardiac injury. PTSDr rats were resistant also to cardiac injury. Factors that limit cardiac damage in PS rats include reduced inflammation and oxidative stress and increased protective HSP70. For the first time, rats exposed to stress were segregated into experimental PTSD (ePTSD)-susceptible and ePTSD-resistant rats. Cardiac injury, ECG changes, and impaired exercise tolerance were more pronounced in ePTSD-susceptible rats. Resistance to ePTSD was associated with decreased inflammation and oxidative stress and with increased protective heat shock protein 70. Results may help identify individuals at high risk of PTSD and also provide a foundation for developing preventive and therapeutic means to restrict PTSD-associated cardiac morbidity.
创伤后应激会导致创伤后应激障碍（PTSD）。PTSD 与心血管疾病和某些患者的心脏性猝死风险相关。我们比较了捕食者应激（PS，猫尿味，10 天）对实验性 PTSD 易感（PTSD）和抗应激（PTSDr）大鼠心脏损伤和保护机制的影响。应激后 14 天，通过高架十字迷宫试验评估大鼠，并根据试验结果计算的焦虑指数将大鼠分为 PTSD 和 PTSDr 组。通过以下方法评估心脏损伤：）运动耐量；）心电图；）心肌组织形态学；）氧化应激；）促炎和抗炎细胞因子。还测量了心肌热休克蛋白 70（HSP70）。40%暴露于 PS 的大鼠出现实验性 PTSD。PTSD 大鼠的运动耐量比对照大鼠低 25%，比 PTSDr 大鼠低 21%。PTSD 大鼠的心电图 QRS、QT 和 OTc 间期明显长于对照和 PTSDr 大鼠。只有 PTSD 大鼠的心肌细胞才有代谢和缺氧损伤以及收缩功能受损的组织形态学迹象。PTSD 大鼠的氧化应激标志物高于 PTSDr 大鼠。PTSD 大鼠的促炎细胞因子 IL-6 高于对照和 PTSDr 大鼠，抗炎细胞因子 IL-4 低于对照和 PTSDr 大鼠。PTSD 大鼠的心肌 HSP70 低于 PTSDr 和对照大鼠。我们的结论是，患有 PTSD 的大鼠出现了多种心脏损伤迹象。PTSDr 大鼠也对心脏损伤具有抗性。在 PS 大鼠中，限制心脏损伤的因素包括炎症和氧化应激减少以及保护性 HSP70 增加。首次将应激暴露的大鼠分为实验性 PTSD（ePTSD）易感和 ePTSD 抗性大鼠。ePTSD 易感大鼠的心脏损伤、心电图变化和运动耐量受损更为明显。对 ePTSD 的抗性与炎症和氧化应激减少以及保护性热休克蛋白 70 增加有关。结果可能有助于确定 PTSD 风险较高的个体，并为开发限制 PTSD 相关心脏发病率的预防和治疗方法提供基础。
