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Does extracorporeal membrane oxygenation attenuate hypoxic pulmonary vasoconstriction in a porcine model of global alveolar hypoxia?


  • 影响因子:1.85
  • DOI:10.1111/aas.13588
  • 作者列表:"Holzgraefe B","Larsson A","Eksborg S","Kalzén H
  • 发表时间:2020-03-31

BACKGROUND:During severe respiratory failure, hypoxic pulmonary vasoconstriction (HPV) is partly suppressed but may still play a role in increasing pulmonary vascular resistance (PVR). Experimental studies suggest that the degree of HPV during severe respiratory failure is dependent on pulmonary oxygen tension (PvO2 ). Therefore, it has been suggested that increasing PvO2 by veno-venous extracorporeal membrane oxygenation (V-V ECMO) would adequately reduce PVR in V-V ECMO patients. OBJECTIVE:Whether increased PvO2 by V-V ECMO decreases PVR in global alveolar hypoxia. METHODS:Nine landrace pigs were ventilated with a mixture of oxygen and nitrogen. After 15 minutes of stable ventilation and hemodynamics, the animals were cannulated for V-V ECMO. Starting with alveolar normoxia, the fraction of inspiratory oxygen (FI O2 ) was stepwise reduced to establish different degrees of alveolar hypoxia. PvO2 was increased by V-V ECMO. RESULTS:V-V ECMO decreased PVR (from 5.5 [4.5 - 7.1] to 3.4 [2.6 - 3.9] mmHg l-1 min, p=0.006) (median (interquartile range),) during ventilation with FI O2 of 0.15. At lower FI O2 , PVR increased; at FI O2 0.10 to 4.9 [4.2 - 7.0], p=0.036, at FI O2 0.05 to 6.0 [4.3 - 8.6], p=0.002, and at FI O2 0 to 5.4 [3.5 - 7.0] mmHg l-1 min , p=0.05. CONCLUSIONS:The effect of increased PvO2 by V-V ECMO on PVR depended highly on the degree of alveolar hypoxia. Our results partly explain why V-V ECMO does not always reduce right ventricular afterload at severe alveolar hypoxia.


背景: 在严重呼吸衰竭时,缺氧性肺血管收缩 (HPV) 被部分抑制,但仍可能在增加肺血管阻力 (PVR) 中起作用。实验研究表明,严重呼吸衰竭时 HPV 的程度依赖于肺氧分压 (PvO2)。因此,静脉-静脉体外膜肺氧合 (V-V ECMO) 增加 PvO2 可充分降低 V-V ECMO 患者的 PVR。 目的: V-V ECMO 升高的 PvO2 是否降低全肺泡缺氧时的 PVR。 方法: 9 头长白猪用氧氮混合气通气。15 分钟稳定通气和血流动力学后,动物插管 V-V ECMO。从肺泡常氧开始,逐步降低吸气氧分数 (FI O2),建立不同程度的肺泡缺氧。V-V ECMO 使 PvO2 增加。 结果: V-V ECMO 使 PVR 降低 (从 5.5 [4.5 - 7.1] 降至 3.4 [2.6 - 3.9] mmHg l-1-1 · min,p = 0.006) (中位数 (四分位数间距),) 在 FI O2 为 0.15 的通风过程中。在较低的 FI O2 时,PVR 增加; 在 FI O2 0.10 至 4.9 [4.2 - 7.0] 时,p = 0.036,在 FI O2 0.05 至 6.0 [4.3 - 8.6] 时,p = 0.002,并且在 FI O2 0 到 5.4 [3.5 - 7.0] mmHg l-1 min,p = 0.05。 结论: V-V ECMO 增加 PVR 的 PVR 效应高度依赖于肺泡缺氧程度。我们的结果部分解释了为什么 V-V ECMO 在严重肺泡缺氧时并不总是降低右心室后负荷。



作者列表:["De Cunto G","Brancaleone V","Riemma MA","Cerqua I","Vellecco V","Spaziano G","Cavarra E","Bartalesi B","D'Agostino B","Lungarella G","Cirino G","Lucattelli M","Roviezzo F"]

METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.

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作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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作者列表:["Zaragosi LE","Deprez M","Barbry P"]

METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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