Hemdahl A-L, Caligiuri G, Hansson G K, Thorén P
Center for Molecular Medicine L8:03 and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Acta Physiol Scand. 2005 Jun;184(2):87-94. doi: 10.1111/j.1365-201X.2005.01421.x.
We have previously shown that mental and hypoxic stress can trigger the development of myocardial infarction (MI) in atherosclerotic apoE(-/-) x LDLR(-/-) mice. The purpose of the present study was to characterize the interval between stress and MI and determine whether electrophysiological changes precede the precipitation of an infarct by assessing telemetry recordings of the electrocardiogram.
Isoflurane anaesthetized apoE(-/-) x LDLR(-/-) (n = 16) and C57BL/6J (n = 8) mice were exposed to systemic hypoxia by reducing the inhaled oxygen concentration to 10% for 10 min. Mental stress was induced in eight conscious apoE(-/-) x LDLR(-/-) and eight C57BL/6J mice by blowing air into the cage. Physiological parameters were recorded every 30 min for 2-6 days by implanted transmitters.
During stress all mice developed transient ischaemic STU-area changes, which returned to normal at the end of stress. During the recovery phase (6 days) 50% (4/8) of the mentally stressed apoE(-/-) x LDLR(-/-) mice developed increased STU-area variability (P < 0.05) followed by dramatic STU-area elevations and spontaneous death at approximately 12-24 h. In hypoxia-exposed apoE(-/-) x LDLR(-/-) mice 56% (9/16) developed MI as determined by elevated serum levels of the infarction marker troponin T which correlated with increased variability in the STU-area (P < 0.05).
This is the first mouse model showing that increased STU-area variability is indicative of MI development in atherosclerotic mice following ischaemic stress. Furthermore, our findings suggest a two-phase pathway for the infarction development: an initial phase comprising a transient ischaemic response which triggers a delayed second phase of ischaemia and MI.
我们之前已经表明，精神压力和低氧应激可触发动脉粥样硬化载脂蛋白E基因敲除（apoE(-/-)）×低密度脂蛋白受体基因敲除（LDLR(-/-)）小鼠发生心肌梗死（MI）。本研究的目的是确定应激与心肌梗死之间的时间间隔，并通过评估心电图遥测记录来确定电生理变化是否先于梗死的发生。
用异氟烷麻醉载脂蛋白E基因敲除×低密度脂蛋白受体基因敲除小鼠（n = 16）和C57BL/6J小鼠（n = 8），通过将吸入氧浓度降至10%持续10分钟使其暴露于全身性低氧环境。对8只清醒的载脂蛋白E基因敲除×低密度脂蛋白受体基因敲除小鼠和8只C57BL/6J小鼠通过向笼内吹气诱导精神压力。通过植入的发射器每30分钟记录一次生理参数，持续2 - 6天。
在应激期间，所有小鼠均出现短暂性缺血性STU段面积变化，应激结束时恢复正常。在恢复阶段（6天），50%（4/8）精神应激的载脂蛋白E基因敲除×低密度脂蛋白受体基因敲除小鼠出现STU段面积变异性增加（P < 0.05），随后在大约12 - 24小时出现STU段面积急剧升高和自发死亡。在暴露于低氧环境的载脂蛋白E基因敲除×低密度脂蛋白受体基因敲除小鼠中，56%（9/16）发生心肌梗死，这通过梗死标志物肌钙蛋白T血清水平升高得以确定，其与STU段面积变异性增加相关（P < 0.05）。
这是首个表明STU段面积变异性增加表明缺血应激后动脉粥样硬化小鼠发生心肌梗死的小鼠模型。此外，我们的研究结果提示梗死发展存在两阶段途径：初始阶段包括短暂性缺血反应，该反应触发延迟的第二阶段缺血和心肌梗死。
