Linking Myometrial Physiology to Intrauterine Pressure; How Tissue-Level Contractions Create Uterine Contractions of Labor
Linking Myometrial Physiology to Intrauterine Pressure; How Tissue-Level Contractions Create Uterine Contractions of Labor
复制标题
DOI：
10.1371/journal.pcbi.1003850
复制
发表时间：
2014-10-01
影响因子：
4.3
通讯作者：
Barendse, Peter
中科院分区：
文献类型：
--
作者：
Young, Roger C.;Barendse, Peter
用于协调子宫收缩的机制尚不清楚。我们开发了一个新的模型的基础上的建议，有一个最大的距离，动作电位可以在子宫壁中传播。这建立了“区域”，其中一个动作电位爆发可以迅速招募所有组织。区域通过牵张引发的收缩机制（子宫肌源性反应）被招募到器官水平的收缩中。每次子宫收缩开始于局部收缩，这会轻微增加子宫内压。更高的压力会增加整个子宫壁的张力，从而引发更多区域的收缩并进一步增加压力。正反馈将局部收缩转化为器官水平的收缩。元胞自动机（CA）模拟与Mathematica。每个“细胞”是一个被分配了动作电位阈值的区域。解剖敏感性因子通过拉普拉斯定律将子宫内压力转换为局部张力。当区域紧张局势超过区域阈值时，就会出现区域收缩。其他输入变量为：起始和最小压力、爆发和不应期持续时间、电爆发期间增强的收缩活动以及不应期期间减少的活动。压力发展的复杂模式被认为是模仿劳动妇女中观察到的收缩模式。观察到的紧急行为，包括全球同步，多个起搏区域，和系统记忆的先决条件。硝苯地平和催产素暴露的复杂影响进行了模拟。所产生的力可以作为区域数量的非线性函数而变化。模拟直接将组织水平的生理学与人类劳动联系起来。子宫起搏器的概念被重新评估，因为起搏活动可能发生在宫缩表达之前。我们提出了一个新的生物CA分类系统，该系统与Wolfram的4类系统平行。然而，生物CA不应该对规则进行分类，而应该对描述相关生物学的规则的输入值集进行分类。
The mechanisms used to coordinate uterine contractions are not known. We develop a new model based on the proposal that there is a maximum distance to which action potentials can propagate in the uterine wall. This establishes "regions", where one action potential burst can rapidly recruit all the tissue. Regions are recruited into an organ-level contraction via a stretch-initiated contraction mechanism (myometrial myogenic response). Each uterine contraction begins with a regional contraction, which slightly increases intrauterine pressure. Higher pressure raises tension throughout the uterine wall, which initiates contractions of more regions and further increases pressure. The positive feedback synchronizes regional contractions into an organ-level contraction. Cellular automaton (CA) simulations are performed with Mathematica. Each "cell" is a region that is assigned an action potential threshold. An anatomy sensitivity factor converts intrauterine pressure to regional tension through the Law of Laplace. A regional contraction occurs when regional tension exceeds regional threshold. Other input variables are: starting and minimum pressure, burst and refractory period durations, enhanced contractile activity during an electrical burst, and reduced activity during the refractory period. Complex patterns of pressure development are seen that mimic the contraction patterns observed in laboring women. Emergent behavior is observed, including global synchronization, multiple pace making regions, and system memory of prior conditions. The complex effects of nifedipine and oxytocin exposure are simulated. The force produced can vary as a nonlinear function of the number of regions. The simulation directly links tissue-level physiology to human labor. The concept of a uterine pacemaker is re-evaluated because pace making activity may occur well before expression of a contraction. We propose a new classification system for biological CAs that parallels the 4-class system of Wolfram. However, instead of classifying the rules, biological CAs should classify the set of input values for the rules that describe the relevant biology.