Departments of Anatomy & Physiology, Kinesiology, Kansas State University, Manhattan, Kansas.
Department of Engineering Science, University of Electro-Communications, Tokyo, Japan.
Microcirculation. 2019 Jul;26(5):e12497. doi: 10.1111/micc.12497. Epub 2018 Oct 10.
The oxygen transport pathway from air to mitochondria involves a series of transfer steps within closely integrated systems (pulmonary, cardiovascular, and tissue metabolic). Small and finite O stores in most mammalian species require exquisitely controlled changes in O flux rates to support elevated ATP turnover. This is especially true for the contracting skeletal muscle where O requirements may increase two orders of magnitude above rest. This brief review focuses on the mechanistic bases for increased microvascular blood-myocyte O flux (V̇O ) from rest to contractions. Fick's law dictates that V̇O elevations driven by muscle contractions are produced by commensurate changes in driving force (ie, O pressure gradients; ΔPO ) and/or effective diffusing capacity (DO ). While previous evidence indicates that increased DO helps modulate contracting muscle O flux, up until recently the role of the dynamic ΔPO across the capillary wall was unknown. Recent phosphorescence quenching investigations of both microvascular and novel interstitial PO kinetics in health have resolved an important step in the O cascade between the capillary and myocyte. Specifically, the significant transmural ΔPO at rest was sustained (but not increased) during submaximal contractions. This supports the contention that the blood-myocyte interface provides a substantial effective resistance to O diffusion and underscores that modulations in erythrocyte hemodynamics and distribution (DO ) are crucial to preserve the driving force for O flux across the capillary wall (ΔPO ) during contractions. Investigation of the O transport pathway close to muscle mitochondria is key to identifying disease mechanisms and develop therapeutic approaches to ameliorate dysfunction and exercise intolerance.
氧气从空气到线粒体的运输途径涉及一系列紧密整合的系统（肺、心血管和组织代谢）中的转移步骤。大多数哺乳动物物种的氧气储备量小而有限，需要对氧气通量率进行精确控制，以支持升高的 ATP 周转率。对于收缩的骨骼肌来说尤其如此，其中氧气需求可能会增加两个数量级以上。本综述重点介绍了从休息到收缩时微脉管血液-肌细胞氧气通量（V̇O ）增加的机制基础。菲克定律规定，肌肉收缩驱动的 V̇O 升高是由驱动力（即氧气压力梯度；ΔPO ）和/或有效扩散能力（DO ）的相应变化产生的。尽管先前的证据表明增加 DO 有助于调节收缩肌肉的氧气通量，但直到最近，毛细血管壁上动态ΔPO 的作用仍不清楚。最近对健康状态下微血管和新型间质 PO 动力学的磷光猝灭研究解决了毛细血管和肌细胞之间氧气级联中的一个重要步骤。具体来说，在亚最大收缩期间，休息时的显著壁间ΔPO 保持不变（但未增加）。这支持了血液-肌细胞界面对氧气扩散提供了实质性有效阻力的观点，并强调了红细胞血液动力学和分布（DO ）的调节对于在收缩期间维持毛细血管壁氧气通量的驱动力（ΔPO ）至关重要。接近肌肉线粒体的氧气运输途径的研究是确定疾病机制和开发治疗方法以改善功能障碍和运动不耐受的关键。
