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Pericyte Contractile Responses to Endothelin-1 and Aβ Peptides: Assessment by Electrical Impedance Assay.

ABSTRACT: Pericytes are vascular mural cells that contract and relax in response to vasoactive stimuli to regulate neurovascular coupling and cerebral blood flow. Pericytes are damaged and degenerate in Alzheimer's disease (AD). We previously showed that the level of the regulatory vasoconstrictor, endothelin-1 (EDN1), is elevated in AD cerebral cortex and upregulated by amyloid-beta (Aβ). We have used electrical impedance analysis to monitor the contractile and proliferative response of cultured human fetal and adult brain-derived pericytes to EDN1 in real-time. EDN1 caused transient, dose-dependent contraction of fetal and adult brain pericytes that was mediated by EDN1 type A receptors and increased the subsequent proliferation of fetal but not adult cells. The contractile responses to EDN1 were weaker in the adult pericytes. The EDN1-mediated contractile response of fetal pericytes was unchanged after exposure to Aβ₁ _- ₄₀ or Aβ₁ _- ₄₂ (0.1-10 μM) for 1 h but both contraction and subsequent relaxation were significantly impaired upon exposure to Aβ for 24 h. These data suggest that chronic exposure to Aβ interferes with EDN1-mediated pericyte contractility, potentially contributing to neurovascular uncoupling and reduced cerebral blood flow in AD.

SUBMITTER: Hibbs E

PROVIDER: S-EPMC8417582 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPendelluft, defined as asynchronous alveolar ventilation, is caused by different regional time constants or dynamic pleural pressure variations. The aim of the present study was to propose a simple method to evaluate pendelluft based on electrical impedance tomography (EIT). The efficacy of this method was demonstrated in well-known pendelluft scenarios in 6 patients.MethodsTwo patients with flail chest after accidents, two patients with acute respiratory distress syndrome (ARDS) and two patients with acutely exacerbated obstructive lung disease were prospectively included. EIT measurements were performed before and after surgery (in patients with flail chest, who had video-assisted thoracoscopic surgery with ribs fixation), or at two different levels of positive end-expiratory pressure (PEEP; ARDS patients), or two different time points (obstructive lung disease). Pendelluft was assessed by regional phase shift (defined as time difference between global and regional impedance-time curves) and amplitude differences (defined as the impedance difference between sum of all regional tidal variation and the global tidal variation).ResultsIn patients with flail chest, pendelluft diminished several days after surgery (pendelluft amplitude normalized to tidal impedance variation reduced from 88% to 2% in one patient, 12% to 2% in the other). Increased PEEP reduced the amplitude of pendelluft (from 3% to 0% in one patient, 20% to 2% in the other) but not necessarily the phase shifts (average time differences were <0.1 second for both patients for both ins- and expiration) in ARDS patients. Pendelluft assessment in obstructive lung diseases reflected the change in airway resistance (from 5% to 1% in one patient after broncholytic medication administration, as airway resistance fell from 15 to 11 cmH2O/L/s; from 9% to 35% in the other patient with acute exacerbation, the corresponding airway resistance increased from 15 to 22 cmH2O/L/s).ConclusionsThe proposed EIT-based method can be used to evaluate the degree of pendelluft in dimension of phase shift and amplitude difference.

Project description:BackgroundNoninvasive monitoring of maximal inspiratory and expiratory flows (MIF and MEF, respectively) by electrical impedance tomography (EIT) might enable early recognition of changes in the mechanical properties of the respiratory system due to new conditions or in response to treatments. We aimed to validate EIT-based measures of MIF and MEF against spirometry in intubated hypoxemic patients during controlled ventilation and spontaneous breathing. Moreover, regional distribution of maximal airflows might interact with lung pathology and increase the risk of additional ventilation injury. Thus, we also aimed to describe the effects of mechanical ventilation settings on regional MIF and MEF.MethodsWe performed a new analysis of data from two prospective, randomized, crossover studies. We included intubated patients admitted to the intensive care unit with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) undergoing pressure support ventilation (PSV, n?=?10) and volume-controlled ventilation (VCV, n?=?20). We measured MIF and MEF by spirometry and EIT during six different combinations of ventilation settings: higher vs. lower support during PSV and higher vs. lower positive end-expiratory pressure (PEEP) during both PSV and VCV. Regional airflows were assessed by EIT in dependent and non-dependent lung regions, too.ResultsMIF and MEF measured by EIT were tightly correlated with those measured by spirometry during all conditions (range of R2 0.629-0.776 and R2 0.606-0.772, respectively, p?<?0.05 for all), with clinically acceptable limits of agreement. Higher PEEP significantly improved homogeneity in the regional distribution of MIF and MEF during volume-controlled ventilation, by increasing airflows in the dependent lung regions and lowering them in the non-dependent ones.ConclusionsEIT provides accurate noninvasive monitoring of MIF and MEF. The present study also generates the hypothesis that EIT could guide PSV and PEEP settings aimed to increase homogeneity of distending and deflating regional airflows.

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Pericyte Contractile Responses to Endothelin-1 and Aβ Peptides: Assessment by Electrical Impedance Assay.

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