Novel endothelin receptor antagonist attenuates endotoxin-induced lung injury in sheep.

Abstract:

OBJECTIVE:To evaluate the cardiopulmonary effects of the novel endothelin receptor antagonist tezosentan in endotoxin-induced lung injury in sheep and to assess the dose response to tezosentan and endothelin-1 in healthy sheep. DESIGN:Prospective, randomized, controlled experimental study. SETTING:University animal laboratory. SUBJECTS:Twenty-one yearling sheep. INTERVENTIONS:Seventeen awake, chronically instrumented sheep were subjected to intravenous infusion of Ringer's lactate for 24 hrs. The animals were randomly assigned to a sham-operated group (n = 3), a lipopolysaccharide group (n = 7) receiving an intravenous infusion of Escherichia coli lipopolysaccharide 15 ng x kg x min, and a tezosentan group (n = 7) subjected to lipopolysaccharide and, from 4 hrs, an intravenous injection of tezosentan 3 mg/kg followed by infusion of 1 mg x kg x hr. In addition, four healthy sheep, exposed to an intravenous infusion of endothelin-1 at 20 ng x kg x min, after 1 hr received tezosentan in stepwise increasing doses of 0.5, 1, and 2 mg x kg x hr that were maintained for 1 hr each. After a 4-hr recovery, the sheep received infusions of tezosentan at the same dose rates as a pretreatment to endothelin-1. MEASUREMENTS AND MAIN RESULTS:In the sham-operated sheep, all cardiopulmonary variables remained unchanged. Lipopolysaccharide caused pulmonary hypertension, increased extravascular lung water index, and induced arterial hypoxemia. Tezosentan decreased the increments in pulmonary vascular resistance and extravascular lung water index by as much as 60% and 70%, respectively. In parallel, tezosentan ameliorated arterial hypoxemia, increased cardiac index, attenuated the decrease in stroke volume index, and reduced systemic vascular resistance. Compared with the lipopolysaccharide group, tezosentan further increased plasma concentrations of endothelin-1. In healthy animals, the administration of endothelin-1 induced systemic and pulmonary hypertension, increased extravascular lung water index, and evoked bradycardia and a decrease in cardiac index. These changes were attenuated by tezosentan infused at 1 and 2 mg x kg x hr. CONCLUSIONS:In an ovine model of endotoxin-induced lung injury, tezosentan ameliorates pulmonary hypertension, lung edema, cardiac dysfunction, and arterial hypoxemia. Tezosentan counteracts the hemodynamic effects of endothelin-1 in a dose-dependent manner.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Kuklin VN,Kirov MY,Evgenov OV,Sovershaev MA,Sjöberg J,Kirova SS,Bjertnaes LJ

doi

10.1097/01.ccm.0000114575.08269.f6

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

766-73

issue

3

eissn

0090-3493

issn

1530-0293

pii

00003246-200403000-00023

journal_volume

32

pub_type

杂志文章
  • Complexity modeling: identify instability early.

    abstract::Biological systems are innately complex, display nonlinear behavior, and respond to both disease and its treatment in similar complex ways. Complex systems display self-organization and predictive behavior along a range of possible states, often referred to as chaotic behavior, and can be both characterized and quanti...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0b013e3181f24484

    authors: Pinsky MR

    更新日期:2010-10-01 00:00:00

  • Liver proteomics for therapeutic drug discovery: inhibition of the cyclophilin receptor CD147 attenuates sepsis-induced acute renal failure.

    abstract:OBJECTIVE:Sepsis-induced multi-organ failure continues to have a high mortality. The liver is an organ central to the disease pathogenesis. The objective of this study was to identify the liver proteins that change in abundance with sepsis and subsequently identify new drug targets. DESIGN:Proteomic discovery study an...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/01.ccm.0000281858.44387.a2

    authors: Dear JW,Leelahavanichkul A,Aponte A,Hu X,Constant SL,Hewitt SM,Yuen PS,Star RA

    更新日期:2007-10-01 00:00:00

  • Endothelium as an organ system.

    abstract::The endothelium is a highly dynamic cell layer that is involved in a multitude of physiologic functions, including the control of vasomotor tone, the trafficking of cells and nutrients, the maintenance of blood fluidity, and the growth of new blood vessels. Over the past several decades, advances in basic research of ...

    journal_title:Critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1097/01.ccm.0000129669.21649.40

    authors: Aird WC

    更新日期:2004-05-01 00:00:00

  • Lessons learned: critical care management of patients with Ebola in the United States.

    abstract:OBJECTIVE:This report will describe the preparations for and the provision of care of two patients with Ebola virus disease in the biocontainment unit at the University of Nebraska Medical Center. DATA SOURCES:Patient medical records. STUDY SELECTION:Not applicable. DATA EXTRACTION:Not applicable. DATA SYNTHESIS:No...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0000000000000935

    authors: Johnson DW,Sullivan JN,Piquette CA,Hewlett AL,Bailey KL,Smith PW,Kalil AC,Lisco SJ

    更新日期:2015-06-01 00:00:00

  • International study on microcirculatory shock occurrence in acutely ill patients.

    abstract:OBJECTIVES:Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and it...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0000000000000553

    authors: Vellinga NA,Boerma EC,Koopmans M,Donati A,Dubin A,Shapiro NI,Pearse RM,Machado FR,Fries M,Akarsu-Ayazoglu T,Pranskunas A,Hollenberg S,Balestra G,van Iterson M,van der Voort PH,Sadaka F,Minto G,Aypar U,Hurtado FJ,Mar

    更新日期:2015-01-01 00:00:00

  • Heparin-binding protein: a diagnostic marker of acute bacterial meningitis.

    abstract:BACKGROUND:The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis. OBJECTIVE:In this study we investigated whether heparin-binding protein levels in cerebrospina...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0b013e318206c396

    authors: Linder A,Akesson P,Brink M,Studahl M,Björck L,Christensson B

    更新日期:2011-04-01 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

    doi:10.1097/01.CCM.0000084857.87446.DD

    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

  • Noninvasive continuous positive airway pressure in neutropenic patients with acute respiratory failure requiring intensive care unit admission.

    abstract:OBJECTIVE:To evaluate the tolerance and the efficacy of noninvasive continuous positive airway pressure (CPAP) in severe acute respiratory failure occurring in intensive care unit (ICU) neutropenic patients with hematologic malignancies, and to establish predictive variables of efficacy of this method. DESIGN:Prospect...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-200009000-00012

    authors: Hilbert G,Gruson D,Vargas F,Valentino R,Chene G,Boiron JM,Pigneux A,Reiffers J,Gbikpi-Benissan G,Cardinaud JP

    更新日期:2000-09-01 00:00:00

  • Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin.

    abstract:OBJECTIVE:Phenylephrine is often used for management of cerebral perfusion pressure after traumatic brain injury, but can have undesirable actions. Few studies have evaluated alternatives. The hypothesis was that arginine vasopressin was as effective as phenylephrine for maintaining tissue oxygenation during cerebral p...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0b013e3181847af3

    authors: Dudkiewicz M,Proctor KG

    更新日期:2008-09-01 00:00:00

  • Reversible increase in maximal cortisol secretion rate in septic shock.

    abstract:OBJECTIVE:Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modelin...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0000000000000721

    authors: Dorin RI,Qualls CR,Torpy DJ,Schrader RM,Urban FK 3rd

    更新日期:2015-03-01 00:00:00

  • Selective decontamination of the digestive tract in multiple trauma patients--is there a role? Results of a prospective, double-blind, randomized trial.

    abstract:OBJECTIVE:To evaluate the efficacy of the technique of selective decontamination of the digestive tract in preventing the development of secondary infection and its influence on morbidity and mortality rates in multiple trauma patients with chest injuries requiring intermittent positive-pressure ventilation. DESIGN:Pr...

    journal_title:Critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00003246-199401000-00010

    authors: Hammond JM,Potgieter PD,Saunders GL

    更新日期:1994-01-01 00:00:00

  • The Stability and Workload Index for Transfer score predicts unplanned intensive care unit patient readmission: initial development and validation.

    abstract:OBJECTIVE:Unplanned readmission of hospitalized patients to an intensive care unit (ICU) is associated with a worse outcome, but our ability to identify who is likely to deteriorate after ICU dismissal is limited. The objective of this study is to develop and validate a numerical index, named the Stability and Workload...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0B013E318164E3B0

    authors: Gajic O,Malinchoc M,Comfere TB,Harris MR,Achouiti A,Yilmaz M,Schultz MJ,Hubmayr RD,Afessa B,Farmer JC

    更新日期:2008-03-01 00:00:00

  • Dysphagia in Mechanically Ventilated ICU Patients (DYnAMICS): A Prospective Observational Trial.

    abstract:OBJECTIVES:Swallowing disorders may be associated with adverse clinical outcomes in patients following invasive mechanical ventilation. We investigated the incidence of dysphagia, its time course, and association with clinically relevant outcomes in extubated critically ill patients. DESIGN:Prospective observational t...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0000000000002765

    authors: Schefold JC,Berger D,Zürcher P,Lensch M,Perren A,Jakob SM,Parviainen I,Takala J

    更新日期:2017-12-01 00:00:00

  • Efficacy of silver-coating central venous catheters in reducing bacterial colonization.

    abstract:OBJECTIVE:To compare silver-coated and uncoated central venous catheters regarding bacterial colonization. To assess the relative contribution of catheter hub and skin colonization to catheter tip colonization. DESIGN:Prospective, randomized clinical trial. SETTING:Intensive care unit in a university hospital. PATIE...

    journal_title:Critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00003246-199903000-00028

    authors: Bach A,Eberhardt H,Frick A,Schmidt H,Böttiger BW,Martin E

    更新日期:1999-03-01 00:00:00

  • Emergency preservation and delayed resuscitation allows normal recovery after exsanguination cardiac arrest in rats: a feasibility trial.

    abstract:OBJECTIVE:Emergency preservation and resuscitation (EPR) comprise a novel approach for resuscitation of exsanguination cardiac arrest victims. EPR uses a cold aortic flush to induce deep hypothermic preservation, followed by resuscitation with cardiopulmonary bypass. Development of a rat EPR model would enable study of...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/01.CCM.0000253398.61666.0D

    authors: Drabek T,Stezoski J,Garman RH,Wu X,Tisherman SA,Stezoski SW,Fisk JA,Jenkins L,Kochanek PM

    更新日期:2007-02-01 00:00:00

  • Endothelial cell apoptosis in sepsis.

    abstract:OBJECTIVE:To discuss a potential role for endothelial cell apoptosis in the pathogenesis of sepsis. DATA SOURCES:Studies published in biomedical journals and studies from the authors' laboratory. STUDY SELECTION:In vitro and in vivo studies of endothelial cell apoptosis in endotoxin and sepsis models. DATA EXTRACTIO...

    journal_title:Critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1097/00003246-200205001-00009

    authors: Hotchkiss RS,Tinsley KW,Swanson PE,Karl IE

    更新日期:2002-05-01 00:00:00

  • Bedside calculation of body surface area for infants and children.

    abstract::In 179 healthy boys and girls, the relationship between body surface area (S) in dm2 and body weight (bw) in kg was investigated. The body surface was calculated from the DuBois and DuBois formula. For infants below 20 kg, the relationship followed the regression equation S=3.6kg + 9; r=0.996. For infants with bw betw...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-198111000-00005

    authors: Lindahl S,Okmian L

    更新日期:1981-11-01 00:00:00

  • Interprofessional Shared Decision-Making in the ICU: A Systematic Review and Recommendations From an Expert Panel.

    abstract:OBJECTIVES:There is growing recognition that high-quality care for patients and families in the ICU requires exemplary interprofessional collaboration and communication. One important aspect is how the ICU team makes complex decisions. However, no recommendations have been published on interprofessional shared decision...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0000000000003870

    authors: Michalsen A,Long AC,DeKeyser Ganz F,White DB,Jensen HI,Metaxa V,Hartog CS,Latour JM,Truog RD,Kesecioglu J,Mahn AR,Curtis JR

    更新日期:2019-09-01 00:00:00

  • Evaluation of Institutional Review Board review and informed consent in publications of human research in critical care medicine.

    abstract:OBJECTIVE:To examine the frequency of obtaining Institutional Review Board (IRB) approval and informed consent in critical care research. DATA SOURCES AND DATA EXTRACTION:One-year retrospective review of original critical care research in humans published in seven journals, including American Journal of Respiratory an...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-199809000-00035

    authors: Matot I,Pizov R,Sprung CL

    更新日期:1998-09-01 00:00:00

  • Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials.

    abstract:OBJECTIVES:Randomized trials have suggested that hypertonic saline solutions may be superior to mannitol for the treatment of elevated intracranial pressure, but their impact on clinical practice has been limited, partly by their small size. We therefore combined their findings in a meta-analysis. DATA SOURCES:We sear...

    journal_title:Critical care medicine

    pub_type: 杂志文章,meta分析

    doi:10.1097/CCM.0b013e318206b9be

    authors: Kamel H,Navi BB,Nakagawa K,Hemphill JC 3rd,Ko NU

    更新日期:2011-03-01 00:00:00

  • Detection of false lumen perfusion at the beginning of cardiopulmonary bypass in patients undergoing repair of aortic dissection.

    abstract:OBJECTIVE:In patients undergoing surgical repair of aortic dissection, false lumen perfusion during cardiopulmonary bypass may produce central nervous system damage, myocardial ischemia, aortic rupture, and death. We describe a method to detect false lumen perfusion at the beginning of retrograde aortic perfusion that ...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-200006000-00026

    authors: Voci P,Testa G,Tritapepe L,Menichetti A,Caretta Q

    更新日期:2000-06-01 00:00:00

  • Changes in biochemical and biophysical surfactant properties with cardiopulmonary bypass in children.

    abstract:OBJECTIVE:The aim of the present study was to characterize pulmonary surfactant properties in children undergoing cardiovascular surgery with cardiopulmonary bypass. DESIGN:Prospective clinical trial. SETTING:University hospital pediatric intensive care unit. PATIENTS:Fifty pediatric patients with congenital cardiac...

    journal_title:Critical care medicine

    pub_type: 临床试验,杂志文章

    doi:10.1097/00003246-200301000-00045

    authors: Friedrich B,Schmidt R,Reiss I,Günther A,Seeger W,Müller M,Thul J,Schranz D,Gortner L

    更新日期:2003-01-01 00:00:00

  • Blunted erythropoietic response to anemia in multiply traumatized patients.

    abstract:OBJECTIVES:To assess the relations between anemia, serum erythropoietin (EPO), iron status, and inflammatory mediators in multiply traumatized patients. DESIGN:Prospective observational study. SETTING:Intensive care unit. PATIENTS:Twenty-three patients suffering from severe trauma (injury severity score > or =30). ...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-200104000-00009

    authors: Hobisch-Hagen P,Wiedermann F,Mayr A,Fries D,Jelkmann W,Fuchs D,Hasibeder W,Mutz N,Klingler A,Schobersberger W

    更新日期:2001-04-01 00:00:00

  • Endotoxemia reduces cerebral perfusion but enhances dynamic cerebrovascular autoregulation at reduced arterial carbon dioxide tension.

    abstract:OBJECTIVE:The administration of endotoxin to healthy humans reduces cerebral blood flow but its influence on dynamic cerebral autoregulation remains unknown. We considered that a reduction in arterial carbon dioxide tension would attenuate cerebral perfusion and improve dynamic cerebral autoregulation in healthy subjec...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0b013e3182474ca7

    authors: Brassard P,Kim YS,van Lieshout J,Secher NH,Rosenmeier JB

    更新日期:2012-06-01 00:00:00

  • Ventilation/perfusion indices do not correlate with the difference between oxygen consumption measured by the Fick principle and metabolic monitoring systems in critically ill patients.

    abstract:OBJECTIVE:To determine whether the difference between oxygen consumption (VO2) measured by metabolic gas monitoring systems and by the Fick principle is related to venous admixture, deadspace/tidal volume ratio, or alveolar-arterial oxygen tension gradient in critically ill patients. DESIGN:A prospective study. SETTI...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-199204000-00008

    authors: Myburgh JA,Webb RK,Worthley LI

    更新日期:1992-04-01 00:00:00

  • Continuous monitoring of tissue oxygen tension during hyperoxia and hypoxia: relation of subcutaneous, transcutaneous, and conjunctival oxygen tension to hemodynamic variables.

    abstract::Subcutaneous, transcutaneous, and conjunctival oxygen tensions (PscO2, PtcO2, and PcjO2, respectively) were measured in anesthetized dogs subjected sequentially to normoxia, hyperoxia, and hypoxia. Intravascular pressure, hemodynamic and oxygen transport variables were measured simultaneously. PtcO2 and PcjO2 closely ...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-198812000-00011

    authors: Gottrup F,Gellett S,Kirkegaard L,Hansen ES,Johannsen G

    更新日期:1988-12-01 00:00:00

  • Features of Adult Hyperammonemia Not Due to Liver Failure in the ICU.

    abstract:OBJECTIVES:To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. DESIGN:Retrospective case series. SETTING:Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical I...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0000000000003278

    authors: Sakusic A,Sabov M,McCambridge AJ,Rabinstein AA,Singh TD,Mukesh K,Kashani KB,Cook D,Gajic O

    更新日期:2018-09-01 00:00:00

  • Association of hypomagnesemia and mortality in acutely ill medical patients.

    abstract:OBJECTIVE:To test the hypothesis that the mortality rate of acutely ill patients admitted to a medical ward or medical ICU is higher for those patients who present with hypomagnesemia than for those patients who do not present with hypomagnesemia. DESIGN:Prospective, observational study. SETTING:Emergency Department ...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-199302000-00010

    authors: Rubeiz GJ,Thill-Baharozian M,Hardie D,Carlson RW

    更新日期:1993-02-01 00:00:00

  • Clinical implications of the oxyhemoglobin dissociation curve in the neonatal period.

    abstract::Factors responsible for determining the position of the oxyhemoglobin equilibrium curve during the neonatal period are briefly reviewed and the clinical implications of these changes are examined. Two clinical trials employing exchange transfusions as an adjunct to conventional therapy of the severe respiratory distre...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/00003246-197909000-00013

    authors: Oski FA

    更新日期:1979-09-01 00:00:00

  • Development and validation of a printed information brochure for families of chronically critically ill patients.

    abstract:OBJECTIVE:Families and other surrogate decisionmakers for chronically critically ill patients often lack information about patient prognosis or options for care. This study describes an approach to develop and validate a printed information brochure about chronic critical illness aimed at improving comprehension of the...

    journal_title:Critical care medicine

    pub_type: 杂志文章

    doi:10.1097/CCM.0b013e31822d7901

    authors: Carson SS,Vu M,Danis M,Camhi SL,Scheunemann LP,Cox CE,Hanson LC,Nelson JE

    更新日期:2012-01-01 00:00:00