Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, United States.
J Appl Physiol (1985). 2023 Nov 1;135(5):1186-1198. doi: 10.1152/japplphysiol.00372.2023. Epub 2023 Oct 5.
Epidemiological studies report higher risks of cardiovascular disease in humans exposed to heat stroke earlier in life. Previously, we explored mechanistic links between heat stroke and developing cardiac abnormalities using a preclinical mouse model of exertional heat stroke (EHS). Profound metabolic abnormalities developed in the ventricles of females but not males after 2 wk of recovery. Here we tested whether this lack of response in males could be attributed to the lower exercise performances or reduced thermal loads they experienced with the same running protocol. We systematically altered environmental temperature (T) during EHS to manipulate heat exposure and exercise performance in the males. Three groups of adult C57BL/6 male mice were studied: "EHS-34" (T = 34°C), "EHS-41" (T = 41°C), and "EHS-39.5" (T = 39.5°C). Mice ran until symptom limitation (unconsciousness), reaching max core temperature (T). After a 2-wk recovery, the mice were euthanized, and the ventricles were removed for untargeted metabolomics. Results were compared against age-matched nonexercise controls. The EHS-34 mice greatly elevated their exercise performance but reached lower T and lower thermal loads. The EHS-41 mice exhibited equivalent thermal loads, exercise times, and T compared with EHS-39.5. The ventricles from EHS-34 mice exhibited the greatest metabolic disturbances in the heart, characterized by shifts toward glucose metabolism, reductions in acylcarnitines, increased amino acid metabolites, elevations in antioxidants, altered TCA cycle flux, and increased xenobiotics. In conclusion, delayed metabolic disturbances following EHS in male myocardium appear to be greatly amplified by higher levels of exertion in the heat, even with lower thermal loads and max core temperatures. Epidemiological data demonstrate greater cardiovascular risk in patients with previous heat stroke exposure. Using a preclinical mouse model of exertional heat stroke, male mice were exposed to one of three environmental temperatures (T) during exercise. Paradoxically, after 2 wk, the mice in the lowest T, exhibiting the largest exercise response and lowest heat load, had the greatest ventricular metabolic disturbances. Metabolic outcomes resemble developing left ventricular hypertrophy or stress-induced heart disease.
流行病学研究报告称，早年暴露于热射病的人类患心血管疾病的风险更高。此前，我们使用一种体力性热射病（EHS）的临床前小鼠模型探索了热射病与心脏异常发展之间的机制联系。在恢复 2 周后，雌性小鼠的心室出现了严重的代谢异常，但雄性小鼠则没有。在这里，我们测试了雄性小鼠是否缺乏反应是否归因于它们较低的运动表现或相同跑步方案下较低的热负荷。我们系统地改变了 EHS 期间的环境温度（T），以操纵男性的热暴露和运动表现。我们研究了三组成年 C57BL/6 雄性小鼠：“EHS-34”（T=34°C）、“EHS-41”（T=41°C）和“EHS-39.5”（T=39.5°C）。当小鼠出现症状限制（失去意识），即达到最大核心温度（T）时，它们会继续跑步。恢复 2 周后，处死小鼠并取出心室进行非靶向代谢组学分析。将结果与同龄非运动对照进行比较。EHS-34 组的小鼠大大提高了它们的运动表现，但达到了更低的 T 和更低的热负荷。EHS-41 组的小鼠与 EHS-39.5 组的小鼠具有相同的热负荷、运动时间和 T。EHS-34 组的心室显示出最大的心脏代谢紊乱，其特征是向葡萄糖代谢转移、酰基辅酶 A 减少、氨基酸代谢物增加、抗氧化剂升高、三羧酸循环通量改变以及外源化学物增加。总之，即使热负荷和最大核心温度较低，男性心肌 EHS 后延迟的代谢紊乱似乎因热应激下更高水平的劳累而大大放大。流行病学数据表明，有过热射病暴露史的患者心血管疾病风险更大。使用一种体力性热射病的临床前小鼠模型，在运动期间将雄性小鼠暴露于三种环境温度（T）之一。矛盾的是，在 2 周后，T 值最低、表现出最大运动反应和最低热负荷的小鼠，心室代谢紊乱最大。代谢结果类似于左心室肥厚或应激性心脏病的发展。
