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 Medjournal_title
Critical care medicineauthors
Kuklin VN,Kirov MY,Evgenov OV,Sovershaev MA,Sjöberg J,Kirova SS,Bjertnaes LJdoi
10.1097/01.ccm.0000114575.08269.f6subject
Has Abstractpub_date
2004-03-01 00:00:00pages
766-73issue
3eissn
0090-3493issn
1530-0293pii
00003246-200403000-00023journal_volume
32pub_type
杂志文章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
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journal_title:Critical care medicine
pub_type: 杂志文章,评审
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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...
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1994-01-01 00:00:00
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doi:10.1097/00003246-198111000-00005
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journal_title:Critical care medicine
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doi:10.1097/00003246-200104000-00009
更新日期:2001-04-01 00:00:00
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更新日期:1992-04-01 00:00:00
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更新日期:1988-12-01 00:00:00
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更新日期:2018-09-01 00:00:00
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journal_title:Critical care medicine
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更新日期:1979-09-01 00:00:00
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