Hilderink Bashar N, Crane Reinier F, Baysan Meryem, Arbous Sesmu M, van den Bogaard Bas, Mik Egbert G, Ince Can, Pillay Janesh, Juffermans Nicole P
Department of Intensive Care, OLVG Hospital, Amsterdam, The Netherlands.
Department of Intensive Care, Leiden University Medical Center, Leiden, The Netherlands.
J Appl Physiol (1985). 2023 May 1;134(5):1165-1176. doi: 10.1152/japplphysiol.00621.2022. Epub 2023 Mar 17.
Circulatory shock is the inadequacy to supply mitochondria with enough oxygen to sustain aerobic energy metabolism. A novel noninvasive bedside measurement was recently introduced to monitor the mitochondrial oxygen tension in the skin (mitoPo). As the most downstream marker of oxygen balance in the skin, mitoPo may provide additional information to improve shock management. However, a physiological basis for the interpretation of mitoPo values has not been established yet. In this paper, we developed a mathematical model of skin mitoPo using a network of parallel microvessels, based on Krogh's cylinder model. The model contains skin blood flow velocity, heterogeneity of blood flow, hematocrit, arteriolar oxygen saturation, and mitochondrial oxygen consumption as major variables. The major results of the model show that normal physiological mitoPo is in the range of 40-60 mmHg. The relationship of mitoPo with skin blood flow velocity follows a logarithmic growth curve, reaching a plateau at high skin blood flow velocity, suggesting that oxygen balance remains stable while peripheral perfusion declines. The model shows that a critical range exists where mitoPo rapidly deteriorates if skin perfusion further decreases. The model intuitively shows how tissue hypoxia could occur in the setting of septic shock, due to the profound impact of microcirculatory disturbance on mitoPo, even at sustained cardiac output. MitoPo is the result of a complex interaction between all factors of oxygen delivery and microcirculation. This mathematical framework can be used to interpret mitoPo values in shock, with the potential to enhance personalized clinical trial design. This is the first paper to simulate mitochondrial oxygen tension in skin in circulatory shock. The relationships of mitoPo with parameters of (microcirculatory) oxygen delivery aid in the understanding of noninvasive bedside measurement of mitoPo values and show that mitochondrial oxygen tension is two orders of magnitude higher than classically assumed. The model can be used to enhance clinical trial design investigating mitoPo as a resuscitation target in circulatory shock.
循环性休克是指无法为线粒体提供足够的氧气以维持有氧能量代谢。最近引入了一种新型的非侵入性床边测量方法来监测皮肤中的线粒体氧张力（mitoPo）。作为皮肤中氧平衡的最下游标志物，mitoPo可能为改善休克管理提供额外信息。然而，尚未建立用于解释mitoPo值的生理学基础。在本文中，我们基于克罗格圆柱体模型，使用平行微血管网络开发了皮肤mitoPo的数学模型。该模型包含皮肤血流速度、血流异质性、血细胞比容、小动脉血氧饱和度和线粒体氧消耗作为主要变量。该模型的主要结果表明，正常生理状态下的mitoPo在40 - 60 mmHg范围内。mitoPo与皮肤血流速度的关系遵循对数增长曲线，在高皮肤血流速度时达到平台期，这表明在周围灌注下降时氧平衡仍保持稳定。该模型表明存在一个临界范围，如果皮肤灌注进一步降低，mitoPo会迅速恶化。该模型直观地展示了在脓毒症休克情况下组织缺氧是如何发生的，因为即使在心输出量持续的情况下，微循环紊乱对mitoPo也有深远影响。mitoPo是氧输送和微循环所有因素之间复杂相互作用的结果。这个数学框架可用于解释休克中的mitoPo值，有可能加强个性化临床试验设计。这是第一篇模拟循环性休克中皮肤线粒体氧张力的论文。mitoPo与（微循环）氧输送参数的关系有助于理解mitoPo值的非侵入性床边测量，并表明线粒体氧张力比经典假设高两个数量级。该模型可用于加强临床试验设计，将mitoPo作为循环性休克的复苏目标进行研究。
