Angiotensin-(1-7) protects from experimental acute lung injury.


OBJECTIVES:Recently, recombinant angiotensin-converting enzyme 2 was shown to protect mice from acute lung injury, an effect attributed to reduced bioavailability of angiotensin II. Since angiotensin-converting enzyme 2 metabolizes angiotensin II to angiotensin-(1-7), we hypothesized that this effect is alternatively mediated by angiotensin-(1-7) and activation of its receptor(s). DESIGN:To test this hypothesis, we investigated the effects of intravenously infused angiotensin-(1-7) in three experimental models of acute lung injury. SETTING:Animal research laboratory. SUBJECTS:Male Sprague-Dawley rats, Balb/c mice, and C57Bl6/J mice. INTERVENTIONS:Angiotensin-(1-7) was administered with ventilator- or acid aspiration-induced lung injury in mice or 30 minutes after oleic acid infusion in rats. In vitro, the effect of angiotensin-(1-7) on transendothelial electrical resistance of human pulmonary microvascular endothelial cells was analyzed. MEASUREMENTS AND MAIN RESULTS:Infusion of angiotensin-(1-7) starting 30 minutes after oleic acid administration protected rats from acute lung injury as evident by reduced lung edema, myeloperoxidase activity, histological lung injury score, and pulmonary vascular resistance while systemic arterial pressure was stabilized. Such effects were largely reproduced by the nonpeptidic angiotensin-(1-7) analog AVE0991. Infusion of angiotensin-(1-7) was equally protective in murine models of ventilator- or acid aspiration-induced lung injury. In the oleic acid model, the two distinct angiotensin-(1-7) receptor blockers A779 and D-Pro-angiotensin-(1-7) reversed the normalizing effects of angiotensin-(1-7) on systemic and pulmonary hemodynamics, but only D-Pro-angiotensin-(1-7) blocked the protection from lung edema and protein leak, whereas A779 restored the infiltration of neutrophils. Rats were also protected from acute lung injury by the AT1 antagonist irbesartan; however, this effect was again blocked by A779 and D-Pro-angiotensin-(1-7). In vitro, angiotensin-(1-7) protected pulmonary microvascular endothelial cells from thrombin-induced barrier failure, yet D-Pro-angiotensin-(1-7) or NO synthase inhibition blocked this effect. CONCLUSIONS:Angiotensin-(1-7) or its analogs attenuate the key features of acute lung injury and may present a promising therapeutic strategy for the treatment of this disease.


Crit Care Med


Critical care medicine


Klein N,Gembardt F,Supé S,Kaestle SM,Nickles H,Erfinanda L,Lei X,Yin J,Wang L,Mertens M,Szaszi K,Walther T,Kuebler WM




Has Abstract


2013-11-01 00:00:00












  • Exogenous interleukin-10 fails to decrease the mortality or morbidity of sepsis.

    abstract:OBJECTIVE:To determine if exogenous interleukin (IL)-10 will decrease the morbidity or mortality of sepsis induced by cecal ligation and puncture. DESIGN:Prospective, randomized, controlled study. SETTING:University research laboratory. SUBJECTS:Adult, female, Balb¿c mice. INTERVENTIONS:Balb¿c mice were subjected t...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Remick DG,Garg SJ,Newcomb DE,Wollenberg G,Huie TK,Bolgos GL

    更新日期:1998-05-01 00:00:00

  • The Period 2 Enhancer Nobiletin as Novel Therapy in Murine Models of Circadian Disruption Resembling Delirium.

    abstract:OBJECTIVES:Delirium occurs in approximately 30% of critically ill patients, and the risk of dying during admission doubles in those patients. Molecular mechanisms causing delirium are largely unknown. However, critical illness and the ICU environment consistently disrupt circadian rhythms, and circadian disruptions are...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Gile J,Scott B,Eckle T

    更新日期:2018-06-01 00:00:00

  • Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections.

    abstract:OBJECTIVE:To determine whether the absence or presence of clinical pharmacists in intensive care units (ICUs) results in differences in mortality rates, length of ICU stay, and ICU charges for Medicare patients with nosocomial-acquired infections, community-acquired infections, and sepsis. DESIGN, SETTING, AND PATIENT...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: MacLaren R,Bond CA,Martin SJ,Fike D

    更新日期:2008-12-01 00:00:00

  • A National Emergency Airway Registry for children: landscape of tracheal intubation in 15 PICUs.

    abstract:OBJECTIVES:To characterize the landscape of process of care and safety outcomes for tracheal intubation across pediatric intensive care units BACKGROUND:Procedural process of care and safety outcomes of tracheal intubation across pediatric intensive care units has not been described. We hypothesize that the novel Nati...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Nishisaki A,Turner DA,Brown CA 3rd,Walls RM,Nadkarni VM,National Emergency Airway Registry for Children (NEAR4KIDS).,Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network.

    更新日期:2013-03-01 00:00:00

  • Detrimental hemodynamic effects of assisted ventilation in hemorrhagic states.

    abstract:OBJECTIVE:Our goal was to demonstrate explicitly that lower-frequency positive-pressure ventilation not only preserves adequate oxygenation and acid-base status in hemorrhagic states, but also that "normal" or higher respiratory rates significantly compromise hemodynamics, even with moderate degrees of hemorrhage. DES...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Pepe PE,Lurie KG,Wigginton JG,Raedler C,Idris AH

    更新日期:2004-09-01 00:00:00

  • Neutrophil depletion in rats reduces burn-injury induced intestinal bacterial translocation.

    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


    authors: Fazal N,Shamim M,Khan SS,Gamelli RL,Sayeed MM

    更新日期:2000-05-01 00:00:00

  • Influence of political power, medical provincialism, and economic incentives on the rationing of surgical intensive care unit beds.

    abstract:OBJECTIVE:To determine factors influencing rationing decisions in a surgical ICU during a temporary nursing shortage when two to six of the unit's 16 beds were closed. DESIGN:Blinded, concurrent data collection, retrospective chart review. SETTING:Surgical ICU. PATIENTS:All patients (n = 308) for whom a surgical ICU...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Marshall MF,Schwenzer KJ,Orsina M,Fletcher JC,Durbin CG Jr

    更新日期:1992-03-01 00:00:00

  • Sucralfate does not reduce the risk of acid aspiration pneumonitis.

    abstract:OBJECTIVE:To study the pulmonary effects of aspirating a mixture of sucralfate in water and sucralfate in hydrochloric acid in an animal model of aspiration pneumonia. DESIGN:Prospective, randomized, controlled study with repeated measures. SETTING:University research laboratory. SUBJECTS:Thirty-two in situ, isolate...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Toung TJ,Rosenfeld BA,Yoshiki A,Grayson RF,Traystman RJ

    更新日期:1993-09-01 00:00:00

  • Inhaled prostacyclin for the treatment of pulmonary hypertension after cardiac surgery.

    abstract:OBJECTIVE:To describe the effects of inhaled prostacyclin administered after cardiopulmonary bypass (CPB) to a patient with severe pulmonary hypertension. DESIGN:Case report and literature review. SETTING:Cardiac surgical operating rooms and postoperative recovery unit. PATIENTS:A 63-yr-old female who had undergone ...

    journal_title:Critical care medicine

    pub_type: 杂志文章,评审


    authors: Lowson SM,Doctor A,Walsh BK,Doorley PA

    更新日期:2002-12-01 00:00:00

  • Acute respiratory failure neuropathy: a variant of critical illness polyneuropathy.

    abstract:OBJECTIVE:To describe a severe axonal polyneuropathy that follows acute respiratory failure and, in turn, causes continued ventilator dependence and paralysis after resolution of the primary illness. DESIGN:Retrospective chart review of three patients and prospective analysis of two patients. SETTING:Respiratory and ...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Gorson KC,Ropper AH

    更新日期:1993-02-01 00:00:00

  • Hypophosphatemia induced by mechanical ventilation in patients with chronic obstructive pulmonary disease.

    abstract::The aim of this study was to assess prospectively the variations of serum phosphorus concentration (P) after onset of mechanical ventilation (MV) in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory acidosis. In 14 COPD patients, we measured P, PaCO2, and pH, immediately before MV (H0), ...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Laaban JP,Grateau G,Psychoyos I,Laromiguière M,Vuong TK,Rochemaure J

    更新日期:1989-11-01 00:00:00

  • Surfactant protein-B polymorphisms and mortality in the acute respiratory distress syndrome.

    abstract:OBJECTIVE:To determine whether polymorphisms of the surfactant protein B gene may be associated with increased mortality in patients with the acute respiratory distress syndrome. DESIGN:A prospective cohort study. SETTING:Four adult intensive care units at a tertiary academic medical center. PATIENTS:Two hundred fou...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Currier PF,Gong MN,Zhai R,Pothier LJ,Boyce PD,Xu L,Yu CL,Thompson BT,Christiani DC

    更新日期:2008-09-01 00:00:00

  • Trendelenburg position and passive leg raising do not significantly improve cardiopulmonary performance in the anesthetized patient with coronary artery disease.

    abstract::The effects of the Trendelenburg (TREND) position and passive straight leg raising (PLR) on cardiopulmonary performance in 18 anesthetized patients undergoing myocardial revascularization were studied with a two-dimensional transesophageal echocardiography probe and a thermodilution right ventricular ejection fraction...

    journal_title:Critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Reich DL,Konstadt SN,Raissi S,Hubbard M,Thys DM

    更新日期:1989-04-01 00:00:00

  • Sustained endotoxemia leads to marked down-regulation of early steps in the insulin-signaling cascade.

    abstract:OBJECTIVES:To determine the effects of sustained, 3-day endotoxin infusion on early steps of the insulin-signaling pathway in rat liver and skeletal muscle in vivo; to examine insulin signaling in well-established acute endotoxin models of insulin resistance. DESIGN:Prospective, controlled animal study. SETTING:Unive...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: McCowen KC,Ling PR,Ciccarone A,Mao Y,Chow JC,Bistrian BR,Smith RJ

    更新日期:2001-04-01 00:00:00

  • Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group.

    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


    authors: Sieger B,Berman SJ,Geckler RW,Farkas SA

    更新日期:1997-10-01 00:00:00

  • Difficulties in predicting outcome in cardiac surgery patients.

    abstract:OBJECTIVE:To evaluate a novel combination of preoperative, intraoperative, and postoperative variables (including the Parsonnet, and the Acute Physiology and Chronic Health Evaluation II and III [APACHE II and III] scores) in cardiac surgery patients in order to predict hospital outcome, complications, and length of st...

    journal_title:Critical care medicine

    pub_type: 临床试验,杂志文章


    authors: Turner JS,Morgan CJ,Thakrar B,Pepper JR

    更新日期:1995-11-01 00:00:00

  • Insulin inhibits tumor necrosis factor-alpha induction in myocardial ischemia/reperfusion: role of Akt and endothelial nitric oxide synthase phosphorylation.

    abstract:OBJECTIVES:Intensive insulin therapy with tight glucose control is known to result in reduced morbidity and mortality in inflammation-related critical illness. Tumor necrosis factor (TNF)-alpha induction in myocardial infarction may trigger inflammation and have detrimental effects on cardiomyocytes. This study was des...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Li J,Zhang H,Wu F,Nan Y,Ma H,Guo W,Wang H,Ren J,Das UN,Gao F

    更新日期:2008-05-01 00:00:00

  • Sedation, analgesia, and neuromuscular blockade for high-frequency oscillatory ventilation.

    abstract:OBJECTIVE:To provide a comprehensive review of the issue related to the administration of sedative, analgesic, and neuromuscular blocking agents (NMBA) to patients who are receiving ventilatory support for acute respiratory distress syndrome (ARDS) with high-frequency oscillatory ventilation. RESULTS:Sedative, analges...

    journal_title:Critical care medicine

    pub_type: 杂志文章,评审


    authors: Sessler CN

    更新日期:2005-03-01 00:00:00

  • Coping Strategies and Posttraumatic Stress Symptoms in Post-ICU Family Decision Makers.

    abstract:OBJECTIVE:To assess the coping strategies used by family decision makers of adult critical care patients during and after the critical care experience and the relationship of coping strategies to posttraumatic stress symptoms experienced 60 days after hospitalization. DESIGN:A single-group descriptive longitudinal cor...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Petrinec AB,Mazanec PM,Burant CJ,Hoffer A,Daly BJ

    更新日期:2015-06-01 00:00:00

  • Sensitivity of routine intensive care unit surveillance for detecting myocardial ischemia.

    abstract:OBJECTIVE:To assess the effectiveness of routine intensive care unit surveillance compared with frequent 12-lead electrocardiogram monitoring for detecting electrocardiogram evidence suggestive of prolonged myocardial ischemia in vascular surgery patients. DESIGN:Prospective cohort trial. SETTING:Intensive care unit....

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Martinez EA,Kim LJ,Faraday N,Rosenfeld B,Bass EB,Perler BA,Williams GM,Dorman T,Pronovost PJ

    更新日期:2003-09-01 00:00:00

  • Critical care checklists, the Keystone Project, and the Office for Human Research Protections: a case for streamlining the approval process in quality-improvement research.

    abstract::Checklists have been recently promulgated as a method to enhance patient safety and improve outcomes for critically ill patients. Specifically, recent work performed by researchers from the Johns Hopkins Medical Institutions has demonstrated that the addition of checklists to usual care in the intensive care unit is a...

    journal_title:Critical care medicine

    pub_type: 杂志文章,评审


    authors: Savel RH,Goldstein EB,Gropper MA

    更新日期:2009-02-01 00:00:00

  • The Very Elderly Admitted to ICU: A Quality Finish?

    abstract:OBJECTIVE:Very elderly persons admitted to ICUs are at high risk of death. To document life-sustaining interventions (mechanical ventilation, vasopressors, renal replacement therapy) provided in the ICU and outcomes of care. DESIGN:Multicenter, prospective cohort study. SETTING:ICUs of 24 Canadian hospitals. PARTICI...

    journal_title:Critical care medicine

    pub_type: 杂志文章,多中心研究


    authors: Heyland D,Cook D,Bagshaw SM,Garland A,Stelfox HT,Mehta S,Dodek P,Kutsogiannis J,Burns K,Muscedere J,Turgeon AF,Fowler R,Jiang X,Day AG,Canadian Critical Care Trials Group.,Canadian Researchers at the End of Life Network.

    更新日期:2015-07-01 00:00:00

  • A prospective, randomized, controlled evaluation of peripheral nerve stimulation versus standard clinical dosing of neuromuscular blocking agents in critically ill patients.

    abstract:OBJECTIVES:To determine if vecuronium doses individualized by peripheral nerve stimulation are lower than those doses chosen by standard clinical techniques; and to determine whether patients monitored by peripheral nerve stimulation exhibit shorter recovery times and less prolonged neuromuscular blockade after discont...

    journal_title:Critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Rudis MI,Sikora CA,Angus E,Peterson E,Popovich J Jr,Hyzy R,Zarowitz BJ

    更新日期:1997-04-01 00:00:00

  • Hyperkalemia during cardiac arrest and resuscitation in the canine model.

    abstract::Although recent clinical reports have noted hypokalemia after resuscitation from cardiac arrest, extensive animal work indicates that potassium is released from cells during ischemia. This study was undertaken to define the changes that occur in serum potassium ion during cardiac arrest and resuscitation in a canine m...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Martin GB,Carden DL,Nowak RM,Foreback C,Tomlanovich MC

    更新日期:1986-04-01 00:00:00

  • Severe acute respiratory syndrome and critical care medicine: the Toronto experience.

    abstract:BACKGROUND:The 2003 global outbreak of severe acute respiratory syndrome (SARS) provided numerous challenges to the delivery of critical care. The Toronto critical care community has learned important lessons from SARS, which will help in preparation for future disease outbreaks. OBJECTIVES:The objectives of this stud...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Booth CM,Stewart TE

    更新日期:2005-01-01 00:00:00

  • Systemic and muscle oxygen uptake/delivery after dopexamine infusion in endotoxic dogs.

    abstract:BACKGROUND AND METHODS:This study was designed to test whether dopexamine, a dopaminergic and beta 2-adrenergic agonist, would a) increase systemic oxygen delivery (DO2) in endotoxic dogs, and b) interfere with the ability of resting skeletal muscle to extract oxygen. There were three treatment groups (n = 6 in each gr...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Bredle DL,Cain SM

    更新日期:1991-02-01 00:00:00

  • Constructing the illness narrative: a grounded theory exploring patients' and relatives' use of intensive care diaries.

    abstract:OBJECTIVE:After a stay in the intensive care unit, patients risk experiencing delusional memories, memory loss, and symptoms of posttraumatic stress. Since the 1990s, diaries have been kept for intensive care unit patients to help fill in memory gaps, aid psychosocial recovery, and improve health-related quality of lif...

    journal_title:Critical care medicine

    pub_type: 杂志文章,多中心研究


    authors: Egerod I,Christensen D,Schwartz-Nielsen KH,Agård AS

    更新日期:2011-08-01 00:00:00

  • Prophylactic Seizure Medication and Health-Related Quality of Life After Intracerebral Hemorrhage.

    abstract:OBJECTIVES:Prophylactic levetiracetam is currently used in ~40% of patients with intracerebral hemorrhage, and the potential impact of levetircetam on health-related quality of life is unknown. We tested the hypothesis that prophylactic levetiracetam is independently associated with differences in cognitive function he...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Naidech AM,Beaumont J,Muldoon K,Liotta EM,Maas MB,Potts MB,Jahromi BS,Cella D,Prabhakaran S,Holl JL

    更新日期:2018-09-01 00:00:00

  • Thermodilution and Fick cardiac index determinations following cardiac surgery.

    abstract::With the thermodilution technique, repeated determination of cardiac index (CI) has become a rapid, easily accomplished, safe procedure. We paired 77 CI determinations measured by direct Fick and thermodilution techniques in 21 patients who underwent myocardial revascularization. Commercially available thermistor-tipp...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Hodges M,Downs JB,Mitchell LA

    更新日期:1975-09-01 00:00:00

  • Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

    abstract:OBJECTIVE:Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. DESIGN:Single-center prospective study. SETTING:Univ...

    journal_title:Critical care medicine

    pub_type: 杂志文章


    authors: Amour J,Birenbaum A,Langeron O,Le Manach Y,Bertrand M,Coriat P,Riou B,Bernard M,Hausfater P

    更新日期:2008-04-01 00:00:00