The syndrome of critical illness is a complex physiological stressor that can be triggered by diverse pathologies. It is widely believed that organ dysfunction and death result from bioenergetic failure caused by inadequate cellular oxygen supply. Teleologically, life has evolved to survive in the face of stressors by undergoing a suite of adaptive changes. Adaptation not only comprises alterations in systemic physiology but also involves molecular reprogramming within cells. The concept of cellular adaptation in critically ill patients is a matter of contention, in part because medical interventions mask underlying physiology, creating the artificial construct of "chronic critical illness", without which death would be imminent. Thus far, the intensive care armamentarium has not targeted cellular metabolism to preserve a temporary equilibrium, but instead attempts to normalize global oxygen and substrate delivery. Here, we review adaptations to hypoxia that have been demonstrated in cellular models and in human conditions associated with hypoxia, including the hypobaric hypoxia of high altitude, the intrauterine low oxygen environment and adult myocardial hibernation. Common features include upregulation of glycolytic ATP production; enhancement of respiratory efficiency; downregulation of mitochondrial density and suppression of energy-consuming processes. We argue that these innate cellular adaptations to hypoxia represent potential avenues for intervention that have thus far remained untapped by intensive care medicine.

中文翻译：

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人类适应重大疾病中的缺氧。

危重症候群是一种复杂的生理应激源，可由多种病理触发。人们普遍认为，器官功能障碍和死亡是由细胞供氧不足引起的生物能衰竭引起的。目的论上，生活经历了一系列适应性变化，可以生存以面对压力源。适应不仅包括系统生理学的改变，而且还涉及细胞内的分子重编程。重症患者的细胞适应性概念尚待解决，部分原因是医学干预掩盖了潜在的生理机能，造成了“慢性危重病”的人工构造，如果没有这种构造，将可能导致死亡。迄今，重症监护武器库并未针对细胞代谢来维持暂时的平衡，而是试图使总体氧气和底物的输送正常化。在这里，我们回顾了在细胞模型和与缺氧相关的人类状况（包括高海拔地区的低压缺氧，子宫内低氧环境和成人心肌冬眠）中已证明的对缺氧的适应性。共同特征包括糖酵解ATP产生的上调；增强呼吸效率；下调线粒体密度并抑制耗能过程。我们认为，这些先天性的细胞对缺氧的适应性代表了迄今为止仍未被重症监护医学开发的潜在干预途径。而是尝试使总体氧气和底物输送正常化。在这里，我们回顾了在细胞模型和与缺氧相关的人类状况（包括高海拔地区的低压缺氧，子宫内低氧环境和成人心肌冬眠）中已证明的对缺氧的适应性。共同特征包括糖酵解ATP产生的上调；增强呼吸效率；下调线粒体密度并抑制耗能过程。我们认为，这些先天性的细胞对缺氧的适应性代表了迄今为止仍未被重症监护医学开发的潜在干预途径。而是尝试使总体氧气和底物的输送正常化。在这里，我们回顾了在细胞模型和与缺氧相关的人类状况（包括高海拔地区的低压缺氧，子宫内低氧环境和成人心肌冬眠）中已证明的对缺氧的适应性。共同特征包括糖酵解ATP产生的上调；增强呼吸效率；下调线粒体密度并抑制耗能过程。我们认为，这些先天性的细胞对缺氧的适应性代表了迄今为止仍未被重症监护医学开发的潜在干预途径。包括高海拔的低压缺氧，宫内低氧环境和成人心肌冬眠。共同特征包括糖酵解ATP产生的上调；增强呼吸效率；下调线粒体密度并抑制耗能过程。我们认为，这些先天性的细胞对缺氧的适应性代表了迄今为止仍未被重症监护医学开发的潜在干预途径。包括高海拔的低压缺氧，宫内低氧环境和成人心肌冬眠。共同特征包括糖酵解ATP产生的上调；增强呼吸效率；下调线粒体密度并抑制耗能过程。我们认为，这些先天性的细胞对缺氧的适应性代表了迄今为止仍未被重症监护医学开发的潜在干预途径。