Yoshikawa Tetsuya, Akiyoshi Yuki, Uchino Tsuyoshi, Kawaguchi Hiroaki
Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories (SNBL), Ltd., Kagoshima, Japan.
Laboratory of Veterinary Pathology, Kitasato University School of Veterinary Medicine, Aomori, Japan
In Vivo. 2025 Jul-Aug;39(4):1992-2003. doi: 10.21873/invivo.13996.
BACKGROUND/AIM: Acute cardiovascular changes following cerebral ischemia are significant contributors to stroke-related mortality, yet their mechanisms remain poorly understood. This study investigated cardiovascular responses in a cynomolgus monkey thromboembolic stroke model.
A thromboembolic stroke model was induced in eight male animals (aged 4 to 6 years) by occlusion of the left middle cerebral artery with an autologous blood clod. Arterial blood pressure, heart rate, respiratory rate, and body temperature were continuously monitored in conscious, free-moving animals for 24 h post-embolization using a telemetry system.
Blood pressure, heart rate, and respiratory rate significantly increased following embolization and these increases persisted for 24 h. Circadian rhythm disruption was suggested by elevated nighttime respiratory rate and body temperature. Three moribund animals exhibited higher blood pressure, heart rate, and respiratory rate compared to five non-moribund animals, along with a drop in body temperature in the hours before death. Electrocardiographic analysis revealed no major abnormalities in non-moribund animals, but the moribund animals showed arrhythmias and ST-segment elevation before death.
These cardiovascular changes closely resemble those observed in stroke-heart syndrome in humans, highlighting the relevance of this non-human primate model in studying acute cardiovascular complications following cerebral ischemia. This model could be applied in the development of therapies for managing post-stroke cardiovascular events.
背景/目的:脑缺血后的急性心血管变化是导致卒中相关死亡的重要因素,但其机制仍知之甚少。本研究调查了食蟹猴血栓栓塞性卒中模型中的心血管反应。
通过用自体血凝块阻塞左大脑中动脉,在8只雄性动物(4至6岁)中诱导建立血栓栓塞性卒中模型。使用遥测系统在清醒、自由活动的动物栓塞后24小时连续监测动脉血压、心率、呼吸频率和体温。
栓塞后血压、心率和呼吸频率显著升高,且这些升高持续24小时。夜间呼吸频率和体温升高提示昼夜节律紊乱。与5只未濒死的动物相比,3只濒死动物的血压、心率和呼吸频率更高,且在死亡前数小时体温下降。心电图分析显示未濒死动物无重大异常,但濒死动物在死亡前出现心律失常和ST段抬高。
这些心血管变化与人类卒中-心脏综合征中观察到的变化非常相似,突出了这种非人灵长类动物模型在研究脑缺血后急性心血管并发症方面的相关性。该模型可应用于开发治疗卒中后心血管事件的疗法。