Abstract:
OBJECTIVES:Mechanical ventilation can cause ventilator-induced brain injury via afferent vagal signaling and hippocampal neurotransmitter imbalances. The triggering mechanisms for vagal signaling during mechanical ventilation are unknown. The objective of this study was to assess whether pulmonary transient receptor potential vanilloid type-4 (TRPV4) mechanoreceptors and vagal afferent purinergic receptors (P2X) act as triggers of ventilator-induced brain injury. DESIGN:Controlled, human in vitro and ex vivo studies, as well as murine in vivo laboratory studies. SETTING:Research laboratory. SUBJECTS:Wild-type, TRPV4-deficient C57BL/6J mice, 8-10 weeks old. Human postmortem lung tissue and human lung epithelial cell line BEAS-2B. INTERVENTION:Mice subjected to mechanical ventilation were studied using functional MRI to assess hippocampal activity. The effects of lidocaine (a nonselective ion-channel inhibitor), P2X-purinoceptor antagonist (iso-PPADS), or genetic TRPV4 deficiency on hippocampal dopamine-dependent pro-apoptotic signaling were studied in mechanically ventilated mice. Human lung epithelial cells (BEAS-2B) were used to study the effects of mechanical stretch on TRPV4 and P2X expression and activation. TRPV4 levels were measured in postmortem lung tissue from ventilated and nonventilated patients. MEASUREMENTS AND MAIN RESULTS:Hippocampus functional MRI analysis revealed considerable changes in response to the increase in tidal volume during mechanical ventilation. Intratracheal lidocaine, iso-PPADS, and TRPV4 genetic deficiency protected mice against ventilationinduced hippocampal pro-apoptotic signaling. Mechanical stretch in both, BEAS-2B cells and ventilated wild-type mice, resulted in TRPV4 activation and reduced Trpv4 and P2x expression. Intratracheal replenishment of adenosine triphosphate in Trpv4 mice abrogated the protective effect of TRPV4 deficiency. Autopsy lung tissue from ventilated patients showed decreased lung TRPV4 levels compared with nonventilated CONCLUSIONS:: TRPV4 mechanosensors and purinergic receptors are involved in the mechanisms of ventilator-induced brain injury. Inhibition of this neural signaling, either using nonspecific or specific inhibitors targeting the TRPV4/adenosine triphosphate/P2X signaling axis, may represent a novel strategy to prevent or treat ventilator-induced brain injury.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
González-López A,López-Alonso I,Pickerodt PA,von Haefen C,Amado-Rodríguez L,Reimann H,Niendorf T,Kuebler W,Albaiceta GM,Francis RCE,Spies CDdoi
10.1097/CCM.0000000000003977subject
Has Abstractpub_date
2019-11-01 00:00:00pages
e911-e918issue
11eissn
0090-3493issn
1530-0293journal_volume
47pub_type
杂志文章abstract:OBJECTIVES:To examine perceptions of nurses and physicians in regard to ethical decision-making climate in the ICU and to test the hypothesis that the worse the ethical decision-making climate, the greater the discordance between nurses' and physicians' rating of ethical decision-making climate with physicians hypothes...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/CCM.0000000000004017
更新日期:2019-12-01 00:00:00
abstract:OBJECTIVE:Inotropic and vasopressor drugs are routinely used in critically ill patients to maintain adequate blood pressure and cardiac output in patients with cardiogenic shock although potentially at the expense of increasing myocardial oxygen demand. Pacing optimization has been demonstrated as effective in reducing...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001655
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVES:To determine the outcome of oxygen consumption (VO2) and energy expenditure after cessation of sedation in severe head-injured patients and to assess its usefulness as a predictor of neurologic severity. DESIGN:Prospective, descriptive study. SETTING:Neurosurgical intensive care unit (ICU) in a university ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199407000-00011
更新日期:1994-07-01 00:00:00
abstract:OBJECTIVES:With the exception of a few single-center descriptive reports, data on critical care organizations are relatively sparse. The objectives of our study were to determine the structure, governance, and experience to date of established critical care organizations in North American academic medical centers. DES...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001200
更新日期:2015-10-01 00:00:00
abstract:OBJECTIVE:To determine whether neutrophil depletion could eradicate intestinal bacterial translocation in bum-injured rats. DESIGN:Prospective, randomized, controlled study. SETTING:University research laboratory. SUBJECTS:Adult male Sprague-Dawley rats. INTERVENTIONS:The rats were intravenously administered a rabb...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200005000-00048
更新日期:2000-05-01 00:00:00
abstract:OBJECTIVE:The efficacy of noninvasive mechanical ventilation (NIMV) in improving breathing pattern and arterial blood gases (ABG) in hypercapnic patients has been well documented; however, little attention has been given to the choice of the interface and the ventilatory mode. We evaluated the effects of three types of...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-200006000-00015
更新日期:2000-06-01 00:00:00
abstract:OBJECTIVE:To determine the role of toll-like receptor 2 in cardiac dysfunction during polymicrobial sepsis. DESIGN:Controlled animal study. SETTING:University hospital research laboratory. SUBJECTS:Male C57BL/6, wild-type, toll-like receptor 2-/-. INTERVENTION:Polymicrobial peritonitis, a clinically relevant model ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181d99e67
更新日期:2010-05-01 00:00:00
abstract:OBJECTIVES:Clinical providers have access to a number of pharmacologic agents during in-hospital cardiac arrest. Few studies have explored medication administration patterns during in-hospital cardiac arrest. Herein, we examine trends in use of pharmacologic interventions during in-hospital cardiac arrest both over tim...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003506
更新日期:2019-02-01 00:00:00
abstract:OBJECTIVE:The mortality of critically ill patients associated with intestinal ischemia/reperfusion remains very high, which results from multiorgan dysfunction or failure due to intestinal injury induced by intestinal ischemia/reperfusion. This study was carried out to investigate whether intestinal ischemia/reperfusio...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3182546855
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVES:The primary objective of this study was to identify which patient demographic, patient health, and hospital characteristics were associated with in-hospital mortality. A secondary objective was to determine the relative influence of these characteristics on mortality. DESIGN AND SETTING:Public-use data for ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31825bc92f
更新日期:2012-11-01 00:00:00
abstract::The effect of positive end-expiratory pressure (PEEP) on PaO2 during collapse of a single pulmonary lobe was investigated in seven dogs. Increasing PEEP to the ventilated region of lung increased the proportion of cardiac output flowing to the collapsed lobe and decreased PaO2 and pH. PaCO2 increased at the onset of l...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198505000-00004
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVE:The purpose of this study is to: 1) describe a newly mechanism of blood flow to the brain during cardiopulmonary resuscitation using the impedance threshold device in a piglet model of cardiac arrest, and 2) describe the survival benefits in humans of applying all of the highly recommended changes in the 2005...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/ccm.0b013e31818a7e56
更新日期:2008-11-01 00:00:00
abstract:OBJECTIVE:To compare urea nitrogen removal by continuous hemodiafiltration vs. functional native kidneys in critically ill, septic patients receiving > 2 g of amino acids/kg body weight per day. DESIGN:Prospective, comparative, unblinded study. SETTING:Trauma critical care units of a Level I adult trauma hospital. P...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199403000-00009
更新日期:1994-03-01 00:00:00
abstract:OBJECTIVE:To determine which of a series of disposable or interchangeable positive end-expiratory pressure (PEEP) devices functions with the least imposition of inspiratory and expiratory work during continuous positive airway pressure. DESIGN:Prospective laboratory evaluation performed on a lung model. SETTING:Resea...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199408000-00004
更新日期:1994-08-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to analyze the effect of the International Nosocomial Infection Control Consortium's multidimensional approach on the reduction of ventilator-associated pneumonia in patients hospitalized in intensive care units. DESIGN:A prospective active surveillance before-after study. The stud...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3182657916
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVES:Our understanding of the acute respiratory distress syndrome in children is limited, and literature is dominated by investigations in adult patients. Recent preclinical studies suggest that the susceptibility to and severity of acute respiratory distress syndrome in children could differ from that in adults....
journal_title:Critical care medicine
pub_type: 杂志文章,meta分析,评审
doi:10.1097/CCM.0000000000001388
更新日期:2016-04-01 00:00:00
abstract:OBJECTIVE:To discuss the potential therapeutic value of intraluminal oxygenation of the gut in critical illness. DATA SOURCES:Relevant articles published in the English language literature. STUDY SELECTION:No special study has been carried out for the present presentation. DATA EXTRACTION:Information from the litera...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-199302001-00012
更新日期:1993-02-01 00:00:00
abstract::A polarographic conjunctival oxygen sensor was used to measure oxygen tension in a tissue bed supplied by the internal carotid artery. The shared vascular source of the conjunctiva and brain suggests that conjunctival PO2 monitoring may provide an index of cerebral perfusion. We studied the effects of hyperventilation...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198601000-00003
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVES:Recently, the definition of sepsis has changed from a physiologic derangement (Sepsis-1 and -2) to organ dysfunction (Sepsis-3) based. We sought to determine the concordance between the different sepsis phenotypes and how that affected mortality. DESIGN:Retrospective, multicenter study. SETTING:Three acade...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004449
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVE:Artery puncture and hematoma formation are the most common immediate complications during internal jugular vein catheterization. This study was performed to assess whether the bevel-down approach of the puncture needle decreases the incidence of posterior venous wall damage and hematoma formation during inter...
journal_title:Critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1097/CCM.0b013e318232da48
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:When a patient is incompetent, the family is often considered to be a natural surrogate. The doctors' responsiveness to family wishes may vary. We explored if doctors' personal characteristics were associated with responsiveness to the relatives' wishes when admission to the intensive care unit (ICU) is consi...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181958409
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVES:Survivors of critical illness in early life are at risk of long-term-memory and attention impairments. However, their neurobiologic substrates remain largely unknown. DESIGN:A prospective follow-up study. SETTING:Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands. PATIENTS:Thirty-eight scho...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002553
更新日期:2017-10-01 00:00:00
abstract:OBJECTIVE:To determine whether a correlation exists between concentrations of intracellular and extracellular potassium and to determine the frequency of ventricular ectopy in patients after cardiac operations. DESIGN:Prospective, observational clinical evaluation. SETTING:Surgical-respiratory intensive care unit of ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199911000-00018
更新日期:1999-11-01 00:00:00
abstract:OBJECTIVE:To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections. DESIGN:Prospective, nonblind, randomized trial. SETTING:Multicenter trial conducted at 22 centers. PATIENTS:T...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00003246-199710000-00015
更新日期:1997-10-01 00:00:00
abstract::The educational objectives in use in our Pediatric ICU are described. These have importance for educational programs in critical care medicine, in particular, where patient care needs can easily overwhelm educational needs. It is important not to overlook our role as teachers in the development of proper attitudes and...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-197705000-00008
更新日期:1977-05-01 00:00:00
abstract:OBJECTIVE:To investigate a role of the opiate system during acute hypoxic hypoxia, the effects of naloxone and morphine on hypoxic survival rate were investigated in awake adult mice. DESIGN:Prospective, randomized, animal trial. SETTING:University research laboratory. SUBJECTS:Male dd-Y mice (n = 864 in experiment ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199909000-00035
更新日期:1999-09-01 00:00:00
abstract::Hypophosphatemia may occur in Reye's syndrome. We retrospectively studied 42 patients with Reye's syndrome to determine the frequency and degree of hypophosphatemia, to identify possible causes, and to determine whether hypophosphatemia was related to the severity of disease or mortality. Nineteen (46%) patients were ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198506000-00008
更新日期:1985-06-01 00:00:00
abstract:OBJECTIVE:We studied the in-hospital course, long-term prognosis, and functional status of elderly patients with life-threatening cardiogenic pulmonary edema requiring mechanical ventilation. DESIGN:Semiprospective evaluation. SETTING:Twelve intensive care units and one emergency prehospital medical department in uni...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200104000-00042
更新日期:2001-04-01 00:00:00
abstract:OBJECTIVE:This article analyzes, from a legal perspective, a recent phenomenon involving a clash between the values of attending medical personnel and the instructions of surrogate decision-makers acting on behalf of incompetent patients. Some hospitals have gone to court to challenge decisions by surrogates to continu...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-199605000-00026
更新日期:1996-05-01 00:00:00
abstract::The intensive care unit (ICU) represents a hospital setting in which death and discussion about end-of-life care are common, yet these conversations are often difficult. Such difficulties arise, in part, because a family may be facing an unexpected poor prognosis associated with an acute illness or exacerbation and, i...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-200102001-00006
更新日期:2001-02-01 00:00:00