Significance of critical closing pressures (starling resistors) in arterial circulation,Critical Care

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Significance of critical closing pressures (starling resistors) in arterial circulation
Critical Care ( IF 15.1 ) Pub Date : 2024-04-18 , DOI: 10.1186/s13054-024-04912-4
Michael R. Pinsky , M. Ignacio Monge García , Arnaldo Dubin

Arterial pressure is the input pressure driving tissue blood flow. However, under most conditions organ blood flow is independent of arterial pressure. Tissue blood flow is proportional to local metabolic demand and can vary widely without any change in arterial pressure. Furthermore, changes in arterial pressure within physiologic limits do not alter tissue blood flow. The reason for these apparent incongruities derive from the determinants of organ blood flow. Tissues autoregulate their levels of delivered oxygen to meet their metabolic demand. As tissue metabolic demand increases, as occurs in the gut during digestion, the brain with cognition or muscle with exercise, local O₂ consumption increases to sustain adequate ATP flux. This stimulates the local capillary endothelia in a retrograde fashion to decrease upstream vasomotor tone [1]. These metabolism-induced changes in local vasomotor tone are complimented by local and global sympathetic tone changes mediated through α-adrenergic receptor stimulation and systemic catecholamine release [2].

Central to the control of local blood flow is flow through vessels with tone [3]. Mean arterial pressure (MAP) remains nearly constant from aorta to peripheral arteries because most of the arterial circuit functions more as a capacitor storing blood under pressure than a conduit losing energy through flow-based resistance. Hence, radial arterial catheterization reports the same MAP as sensed in the aorta. However, as blood flows down the arterial tree to the terminal arteries and arterioles, relative flow velocity increases and vessel diameter decreases. This leads to rapid drop in arterial pressure within these small arterioles as a function of resistance. The circumferential arterial vascular smooth muscle tone opposes the expansive forces of the intralumenal vascular pressure. By Laplace’s Law vascular wall tension is a function of the ratio intralumenal pressure times the radius of curvature to wall thickness. As vessel diameter decreases for the same vasomotor tone, its active tension promoting constriction relative to intralumenal pressure increases. Once vasomotor tone exceeds local arterial pressure the vessel collapses limiting flow. The intraluminal pressure at which vessels collapse is their critical closing pressure (Pcc). Pcc is the effective back pressure to arterial flow independent of further downstream capillary and venous pressures. Starling used a pressurized external chamber through which a collapsible arterial outflow circuit flowed from his isolated heart preparations to sustain coronary perfusion; hence these collapsable vascular segments are called a “Starling resistors” [4]. Pcc is usually greater than mean systemic filling pressure (Fig. 1)[5]. The Pcc to mean circulatory filling pressure difference is called the “vascular waterfall” as flow over the edge is independent of how far it subsequently falls. Tissue perfusion pressure (TPP) is MAP minus Pcc. Accordingly, there is both arterial resistance in the small arteries that define a given arterial pressure-flow relation and a Pcc which defines the effective back pressure to that flow.

Arterial resistance and the collapsible segment are linked but reflect different vascular loci.. Arteriolar resistance is controlled by local and global sympathetic tone, whereas the downstream collapsible segments are influenced more by local metabolic demand. Every vascular bed has its own specific arterial resistance and Pcc. Although a lumped parameter global arterial resistance and Pcc can be defined for the arterial circuit by observing the instantaneous cardiac output to arterial pressure relation as flow is rapidly decreased, this relation may not reflect regional blood flow. Regional tissue Pcc values will vary to sustain adequate organ perfusion relative to varying local metabolic activity. If, however, there is a generalized loss of peripheral vasomotor tone, as is often seen in sepsis and post-cardiac surgery vasoplegia, global Pcc will decrease. Although this may seem like a good thing for increasing tissue perfusion, it also causes MAP to proportionally fall and any ability to autoregulate blood flow to tissues relative to their metabolic demand is profoundly blunted.

The implications of Pcc are protean to understanding cardiovascular homeostasis, regional blood flow distribution, micro-circulatory blood flow and the effect of hypotension, sepsis and vasoactive drug therapy on tissue perfusion.

First, because different vascular beds can have different resistances and Pcc, step decreases in MAP will redistribute blood flow among organs as a function of their local vascular resistances and Pcc. This explains why the kidney is vulnerable to hypotension-induced ischemia whereas the gut and the liver less so [2].

Second, both exogenous α-adrenergic agonist infusions and pathologic vasoplegia as seen in sepsis [6] will inhibit local blood flow redistribution by overriding or blocking local sympathetic feedback loops, respectively, potentially promoting tissue ischemia independent of arterial pressure.

Third, microcirculatory flow, as a direct measure of tissue blood flow, should vary independent of global changes in cardiac output and arterial pressure, as those changes are proportional changes in local metabolic demand [7]. This dissociation between measures of regional and global flow changes during sepsis and shock resuscitation may also reflect such metabolic demand imbalance as manifest by local Pcc not being responsive to local control. Increasing MAP with norepinephrine from 65 to 85 mm Hg can improve or worsen microcirculatory perfusion depending on the basal state of microcirculation [8].

In adequately fluid-resuscitated patients, evidence of tissue hypoperfusion, such as prolonged refill capillary time and oliguria with intra-abdominal hypertension, can be managed by titrating norepinephrine to higher MAP levels. Beneficial or detrimental effects of vasopressors on tissue perfusion can occur depending on their relative actions on MAP and Pcc.Monitoring TPP may offer an advantage for blood pressure optimization in circulatory shock patients [9]. In a retrospective study, lower TPP was associated with higher mortality, longer hospital stay, and higher blood lactate levels than patients with higher TPP for the same MAP [10.

Clearly, global blood flow and MAP are important hemodynamic parameters to monitor and use as initial targets for resuscitation. However, preserving arterial pressure above the population-based autoregulatory range does not insure adequate organ perfusion in the setting of vasoplegia or excess catecholamine infusions. Thus, assessment of end-organ perfusion-based function is an essential aspect in the assessment of circulatory sufficiency to define end-points of resuscitation.

No datasets were generated or analysed during the current study.

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Authors and Affiliations

Department of Critical Care, University of Pittsburgh, 1215.4 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA
Michael R. Pinsky
Unidad de Cuidados Intensivos, Hospital Universitario SAS Jerez, Jerez de La Frontera, Spain
M. Ignacio Monge García
Facultad de Ciencias Médicas‬, Universidad Nacional de La Plata‬, La Plata, Argentina
Arnaldo Dubin

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Contributions

MRP conceived the mission of the comment and recruited the coauthors to add clinical relevance. He wrote the initial and final draft of the manuscript. IMG reviewed the initial draft and added clinical comment and approved the final draft of the manuscript. AD reviewed the initial draft and added clinical comment and approved the final draft of the manuscript.

Corresponding author

Correspondence to Michael R. Pinsky.

Competing interests

MRP is a member of the editorial board of Critical Care

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Pinsky, M.R., García, M.I.M. & Dubin, A. Significance of critical closing pressures (starling resistors) in arterial circulation. Crit Care 28, 127 (2024). https://doi.org/10.1186/s13054-024-04912-4

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Received: 08 April 2024
Accepted: 13 April 2024
Published: 18 April 2024
DOI: https://doi.org/10.1186/s13054-024-04912-4

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中文翻译：

动脉循环中临界闭合压力（Starling 电阻）的意义

动脉压是驱动组织血流的输入压力。然而，在大多数情况下，器官血流量与动脉压无关。组织血流量与局部代谢需求成正比，并且可以在动脉压没有任何变化的情况下变化很大。此外，生理限度内动脉压的变化不会改变组织血流。这些明显不协调的原因源于器官血流的决定因素。组织自动调节输送的氧气水平以满足代谢需求。随着组织代谢需求的增加，如消化过程中肠道、具有认知功能的大脑或运动时的肌肉，局部 O ₂消耗增加以维持足够的 ATP 通量。这以逆行方式刺激局部毛细血管内皮细胞，以降低上游血管舒缩张力[1]。这些代谢引起的局部血管舒缩张力的变化得到α-肾上腺素能受体刺激和全身儿茶酚胺释放介导的局部和整体交感神经张力变化的补充[2]。

局部血流控制的核心是通过有张力的血管的血流[3]。从主动脉到外周动脉，平均动脉压 (MAP) 几乎保持恒定，因为大多数动脉回路的功能更像是在压力下存储血液的电容器，而不是通过基于流动的阻力损失能量的导管。因此，桡动脉导管插入术报告的 MAP 与主动脉中感测到的 MAP 相同。然而，当血液沿着动脉树流向终末动脉和小动脉时，相对流速增加，血管直径减小。这导致这些小动脉内的动脉压作为阻力的函数迅速下降。周围动脉血管平滑肌张力抵抗腔内血管压力的扩张力。根据拉普拉斯定律，血管壁张力是管腔内压力乘以曲率半径与管壁厚度之比的函数。当血管舒缩张力相同时，血管直径减小，其主动张力促进相对于腔内压力的收缩增加。一旦血管舒缩张力超过局部动脉压，血管就会塌陷，限制血流。血管塌陷时的管腔内压力是其临界闭合压力（Pcc）。 Pcc 是动脉血流的有效背压，与下游毛细血管和静脉压力无关。 Starling 使用了一个加压的外部腔室，通过该外部腔室，可折叠的动脉流出回路从他的离体心脏制剂中流出，以维持冠状动脉灌注。因此，这些可塌陷的血管段被称为“Starling 电阻器”[4]。 Pcc 通常大于平均全身充盈压（图 1）[5]。 Pcc 表示循环充盈压差，称为“血管瀑布”，因为边缘上的流量与其随后下降的距离无关。组织灌注压 (TPP) 是 MAP 减去 Pcc。因此，小动脉中存在定义给定动脉压力-流量关系的动脉阻力和定义该流量的有效背压的 Pcc。

动脉阻力和可塌陷段相关，但反映不同的血管位点。小动脉阻力受局部和整体交感神经张力控制，而下游可塌陷段更多地受局部代谢需求的影响。每个血管床都有其特定的动脉阻力和 Pcc。尽管可以通过观察流量快速下降时的瞬时心输出量与动脉压的关系来定义动脉回路的集中参数全局动脉阻力和 Pcc，但这种关系可能无法反映局部血流。区域组织 Pcc 值会有所不同，以维持相对于不同的局部代谢活动的足够的器官灌注。然而，如果周围血管舒缩张力普遍丧失，如败血症和心脏手术后血管麻痹中常见的情况，则整体 Pcc 将下降。虽然这对于增加组织灌注来说似乎是一件好事，但它也会导致 MAP 成比例下降，并且任何相对于代谢需求自动调节组织血流的能力都被严重削弱。

Pcc 对于理解心血管稳态、局部血流分布、微循环血流以及低血压、脓毒症和血管活性药物治疗对组织灌注的影响具有丰富的意义。

首先，由于不同的血管床可能具有不同的阻力和 Pcc，因此 MAP 的逐步降低将根据其局部血管阻力和 Pcc 重新分配器官之间的血流。这解释了为什么肾脏容易受到低血压引起的缺血的影响，而肠道和肝脏则不易发生[2]。

其次，外源性α-肾上腺素能激动剂输注和脓毒症中所见的病理性血管麻痹[6]将分别通过超越或阻断局部交感神经反馈回路来抑制局部血流重新分布，从而可能促进独立于动脉压的组织缺血。

第三，微循环流量作为组织血流量的直接测量，其变化应独立于心输出量和动脉压的整体变化，因为这些变化与局部代谢需求成比例的变化[7]。脓毒症和休克复苏期间区域和全球流量变化测量值之间的这种分离也可能反映了这种代谢需求不平衡，如局部 Pcc 对局部控制不敏感所表明的那样。使用去甲肾上腺素将 MAP 从 65 毫米汞柱增加到 85 毫米汞柱可以改善或恶化微循环灌注，具体取决于微循环的基础状态 [8]。

在充分液体复苏的患者中，组织灌注不足的证据，例如毛细血管再充盈时间延长和少尿伴腹内高压，可以通过滴定去甲肾上腺素至更高的 MAP 水平来控制。血管升压药对组织灌注的有益或有害影响可能取决于它们对 MAP 和 Pcc 的相对作用。监测 TPP 可能有利于循环休克患者的血压优化 [9]。在一项回顾性研究中，在相同 MAP 下，与 TPP 较高的患者相比，较低的 TPP 与较高的死亡率、较长的住院时间和较高的血乳酸水平相关[10。

显然，整体血流和平均动脉压是重要的血流动力学参数，需要监测并用作复苏的初始目标。然而，将动脉压保持在基于人群的自动调节范围之上并不能确保在血管麻痹或过量儿茶酚胺输注的情况下有足够的器官灌注。因此，基于终末器官灌注的功能评估是评估循环充足性以定义复苏终点的一个重要方面。

当前研究期间没有生成或分析数据集。

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匹兹堡大学重症监护系，1215.4 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA
迈克尔·平斯基
Unidad de Cuidados Intensivos，Hospital Universitario SAS Jerez，赫雷斯-德拉弗龙特拉，西班牙
M.伊格纳西奥·蒙赫·加西亚
拉普拉塔国立大学医学科学学院，拉普拉塔，阿根廷
阿纳尔多·杜宾

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