Abstract:
OBJECTIVE:Several studies report calcium mishandling, sarcomere disarray, and caspase activation during heart failure. Although active caspases have been shown to cleave myofibrillar proteins, little is known regarding their effects on calcium handling proteins. Therefore, we aimed to explore how endotoxin-induced caspase activation disrupts intracellular calcium regulation. DESIGN:Randomized controlled trial. SETTING:Small animal research laboratory. SUBJECTS:Adult male Sprague-Dawley rats. INTERVENTIONS:Sepsis was induced by injection of endotoxin (10 mg/kg, intravenously). Caspase inhibition was achieved by coinjection with zVAD.fmk (3 mg/kg, intravenously). We first isolated adult rat ventricular myocytes from control, endotoxin, and (endotoxin + zVAD)-treated rats to characterize contractile parameters and cellular calcium homeostasis. Underlying molecular mechanisms responsible for calcium mishandling were explored on sarcoplasmic reticulum vesicles and mitochondria prepared from treated animals. All experiments were performed 4 hrs postendotoxin treatment. MEASUREMENTS AND MAIN RESULTS:zVAD normalized reductions in fractional cell shortening and relaxation rate triggered by endotoxin treatment. Both sarco-/endoplasmic reticulum Ca-ATPase and mitochondria-dependent calcium uptakes were impaired after endotoxin treatment and prevented when myocytes were isolated from zVAD-treated endotoxinic rat hearts. zVAD blocked endotoxin-induced phospholamban dephosphorylation, protein phosphatase 2A activation, and mitochondrial calcium retention capacity reduction. To strengthen these results, control sarcoplasmic reticulum vesicles and mitochondria were incubated with active recombinant caspase-3. Although no effects were observed on mitochondria, caspase-3 directly exerts detrimental effects on sarcoplasmic reticulum calcium uptake capacity by activating protein phosphatase 2A, leading to phospholamban dephosphorylation. CONCLUSIONS:Caspase inhibition protects from endotoxin-induced sarcoplasmic reticulum calcium uptake capacity reduction and mitochondrial dysfunction.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Neviere R,Hassoun SM,Decoster B,Bouazza Y,Montaigne D,Maréchal X,Marciniak C,Marchetti P,Lancel Sdoi
10.1097/CCM.0b013e3181eedafbsubject
Has Abstractpub_date
2010-10-01 00:00:00pages
2031-6issue
10eissn
0090-3493issn
1530-0293journal_volume
38pub_type
杂志文章abstract:OBJECTIVE:To assess the effects of step-changes in tidal volume on work of breathing during lung-protective ventilation in patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). DESIGN:Prospective, nonconsecutive patients with ALI/ARDS. SETTING:Adult surgical, trauma, and medical int...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000194538.32158.af
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:To evaluate if the up-regulation of vascular endothelial growth factor strengthens the protective effect of amniotic fluid stem cells in a renal ischemia-reperfusion injury model. DESIGN:Randomized animal study. SETTINGS:University research laboratory. SUBJECTS:A total of 40 males 12-week-old Wistar rats w...
journal_title:Critical care medicine
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doi:10.1097/CCM.0000000000002020
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journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198512000-00016
更新日期:1985-12-01 00:00:00
abstract:OBJECTIVES:To understand when the use of high-frequency ventilation would be advantageous, we formulated the problem of achieving adequate alveolar ventilation at minimal pressure cost by dividing it into two simpler problems: a) the pressure cost per unit of convective oscillatory flow; and b) the convective flow cost...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-199422091-00004
更新日期:1994-09-01 00:00:00
abstract:OBJECTIVE:To describe a case of intentional ingestion of hand sanitizer in our hospital and to review published cases and those reported to the American Association of Poison Control Centers' National Poison Data System. DESIGN:A case report, a literature review of published cases, and a query of the National Poison D...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/CCM.0b013e31822f09c0
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVE:To evaluate whether current criteria for the diagnosis of brain death fulfill the requirement for the "irreversible cessation of all functions of the entire brain, including the brainstem." DATA SOURCES:Clinical, philosophical, legal, and public policy literature on the subject of brain death. DATA EXTRACTI...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-199212000-00018
更新日期:1992-12-01 00:00:00
abstract:OBJECTIVES:To investigate whether admission B-type natriuretic peptide levels predict the development of acute kidney injury in acute coronary syndromes. DESIGN:Prospective study. SETTING:Single-center study, 13-bed intensive cardiac care unit at a University Cardiological Center. PATIENTS:Six-hundred thirty-nine ac...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000025
更新日期:2014-03-01 00:00:00
abstract:OBJECTIVES:To establish Department of Veterans Affairs' intensive care unit (ICU) costs from a database and to use this information to validate the Russell equation, the most commonly used method of calculating ICU costs. To compare and trend Department of Veterans Affairs' and nationwide (USA) ICU and healthcare costs...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
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journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198207000-00001
更新日期:1982-07-01 00:00:00
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更新日期:2008-08-01 00:00:00
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journal_title:Critical care medicine
pub_type: 杂志文章,随机对照试验
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更新日期:2008-02-01 00:00:00
abstract:OBJECTIVES:To measure total serum nitrite and nitrate concentrations in children with the sepsis syndrome as an indicator of endogenous nitric oxide production. To determine if there is an association between total serum nitrite and nitrate concentrations and vascular responsiveness to norepinephrine. DESIGN:A prospec...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199505000-00010
更新日期:1995-05-01 00:00:00
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journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31818b3477
更新日期:2008-11-01 00:00:00
abstract::Critically ill patients who fear impending death may die suddenly. We studied prospectively the incidence of death in critically ill surgical patients who articulated the fear that they were about to die. Physiologic, environmental, and behavioral correlates which might influence perceptions of impending death were ex...
journal_title:Critical care medicine
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doi:10.1097/00003246-198607000-00005
更新日期:1986-07-01 00:00:00
abstract:OBJECTIVE:To evaluate the role of cholesterol and lipoproteins in children with severe meningococcal sepsis. DESIGN:Retrospective observational study. SETTING:A university-affiliated pediatric intensive care unit. PATIENTS:Fifty-seven patients admitted to the pediatric intensive care unit with meningococcal sepsis o...
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pub_type: 杂志文章
doi:10.1097/01.ccm.0000171272.50888.ad
更新日期:2005-07-01 00:00:00
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doi:10.1097/CCM.0b013e31822e9fab
更新日期:2012-01-01 00:00:00
abstract:OBJECTIVES:Extracellular mitochondrial DNA and N-formyl peptides released following tissue damage may contribute to systemic inflammation through stimulation of the innate immune system. In this review, we evaluate existing in vivo human data regarding a role for mitochondrial DNA and N-formyl peptides in producing sys...
journal_title:Critical care medicine
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doi:10.1097/CCM.0000000000003381
更新日期:2018-12-01 00:00:00
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...
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doi:10.1097/00003246-197909000-00013
更新日期:1979-09-01 00:00:00
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更新日期:2013-05-01 00:00:00
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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:2000-02-01 00:00:00
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更新日期:1980-02-01 00:00:00
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journal_title:Critical care medicine
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doi:10.1097/CCM.0000000000003670
更新日期:2019-05-01 00:00:00
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journal_title:Critical care medicine
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doi:10.1097/CCM.0b013e3182656ae5
更新日期:2012-12-01 00:00:00
abstract::Several variables may account for the response of electrochemical skin surface PO2 sensors to anesthetic gases: cathode material and size, pH of the electrolyte and membrane material. These variables cannot be chosen arbitrarily and their influence has been tested with two types of sensors. In one type (LSC), a large ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198110000-00010
更新日期:1981-10-01 00:00:00
abstract:OBJECTIVE:To compare the effects of cardiac surgery with and without extracorporeal circulation on the mechanics of the respiratory system, lung, and chest wall. We also determined the time course of those effects. DESIGN:Prospective, controlled study. SETTING:An eight-bed, cardiac-surgical intensive care unit at a u...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1097/00003246-200211000-00005
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVES:The absence of N20 somatosensory evoked potential after cardiac arrest is related to poor outcome. However, discrimination between the low-amplitude and the absence of N20 is challenging. P25 and P30 are short-latency positive peaks with latencies between 25 and 30 ms following N20 (P25/30). P25/30 is eviden...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003083
更新日期:2018-06-01 00:00:00
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doi:10.1097/01.CCM.0000295586.83787.7E
更新日期:2008-01-01 00:00:00
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journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001864
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVE:To determine the effect that acute physiologic derangements have on outcome after subarachnoid hemorrhage (SAH) and to design a composite score summarizing these abnormalities. DESIGN:Prospective observational study. SETTING:Neuroscience intensive care unit in a tertiary care academic center. PATIENTS:Cons...
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pub_type: 杂志文章
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更新日期:2004-03-01 00:00:00