Abstract:
OBJECTIVE:Vascular dysfunction plays a central role in sepsis, and it is characterized by hypotension and hyporesponsiveness to vasoconstrictors. Nitric oxide is regarded as a central element of sepsis vascular dysfunction. The high amounts of nitric oxide produced during sepsis are mainly derived from the inducible isoform of nitric oxide synthase 2. We have previously shown that nitric oxide synthase 2 levels decrease in later stages of sepsis, whereas levels and activity of soluble guanylate cyclase increase. Therefore, we studied the putative role of other relevant nitric oxide sources, namely, the neuronal (nitric oxide synthase 1) isoform, in sepsis and its relationship with soluble guanylate cyclase. We also studied the consequences of nitric oxide synthase 1 blockade in the hyporesponsiveness to vasoconstrictors. DESIGN:Randomized controlled prospective experimental study. SETTING:Academic research laboratory. SUBJECTS:Female Wistar rats submitted to cecal ligation and puncture method. INTERVENTIONS:1) Six, 12, and 24 hours after cecal ligation and puncture, vascular reactivity to phenylephrine (3 and 30 nmol/kg) before and after 7-nitroindazole (45 μmol/kg, s.c.) or aminoguanidine (30 μmol/kg, s.c.) administration was evaluated. 2) Protein levels and interaction between nitric oxide synthase 1 and soluble guanylate cyclase were determined. 3) Six, 12, and 24 hours after cecal ligation and puncture, thoracic aorta segments were stimulated with phenylephrine in the presence or absence of 7-nitroindazole and cyclic guanosine monophosphate accumulation was determined. 4) After 24 hours of cecal ligation and puncture, norepinephrine was infused (10 μg/kg/min) in the presence or absence of 7-nitroindazole or S-methyl-L-thiocitrulline (1 μmol/kg, IV) and mean arterial pressure was registered. MEASUREMENTS AND MAIN RESULTS:1) Both nitric oxide synthase 1 and soluble guanylate cyclase are expressed in higher levels in vascular tissues during sepsis; 2) both proteins physically interact and nitric oxide synthase 1 blockade inhibits cyclic guanosine monophosphate production; 3) pharmacological blockade of nitric oxide synthase 1 using 7-nitroindazole or S-methyl-L-thiocitrulline reverts the hyporesponsiveness to phenylephrine and increases the vasoconstrictor effect of norepinephrine and phenylephrine. CONCLUSIONS:Sepsis induces increased expression and physical association of nitric oxide synthase 1/soluble guanylate cyclase and a higher production of cyclic guanosine monophosphate that together may help explain sepsis-induced vascular dysfunction. In addition, selective inhibition of nitric oxide synthase 1 restores the responsiveness to vasoconstrictors. Therefore, inhibition of nitric oxide synthase 1 (and possibly soluble guanylate cyclase) may represent a valuable alternative to restore the effectiveness of vasopressor agents during late sepsis.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Nardi GM,Scheschowitsch K,Ammar D,de Oliveira SK,Arruda TB,Assreuy Jdoi
10.1097/CCM.0000000000000301subject
Has Abstractpub_date
2014-06-01 00:00:00pages
e391-400issue
6eissn
0090-3493issn
1530-0293journal_volume
42pub_type
杂志文章,随机对照试验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
doi:10.1097/CCM.0b013e31819541f8
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVE:To test the hypotheses that, for uncontrolled hemorrhagic shock (UHS) in rats, mild hypothermia, compared with normothermia, would increase long-term survival as well as moderate hypothermia, oxygen breathing would increase survival further, and hypothermia and oxygen would mitigate visceral ischemia (dysoxia...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200007000-00047
更新日期:2000-07-01 00:00:00
abstract:OBJECTIVE:To investigate the effect of norepinephrine on static (right atrial pressure, pulmonary artery occlusion pressure ) and dynamic (pulse pressure variation and arterial systolic pressure variation) preload indicators in experimental hemorrhagic shock. DESIGN:Prospective controlled experimental study. SETTING:...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000182801.48137.13
更新日期:2005-10-01 00:00:00
abstract::High-risk patients who survived general (noncardiac) surgery were observed to have cardiac index (CI) values averaging 4.5 L/min.m2, oxygen delivery (DO2) greater than 600 ml/min.m2, and oxygen consumption (VO2) 170 ml/min.m2 during the first 2 or three days postoperatively. Patients who subsequently died maintained r...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:To examine the effects of hypertonic (7.5%) saline-6% dextran 70 (HSD) and isotonic (0.9%) saline-6% dextran 70 (ISD) on cardiovascular function and intestinal perfusion in experimental endotoxin shock. DESIGN:Experimental, randomized, unblinded, interventional study. SETTING:University experimental animal ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200008000-00027
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:To compare the effects of continuous negative extrathoracic pressure (CNEP) and positive end-expiratory pressure (PEEP) at the same level of transpulmonary pressure. DESIGN:Prospective analysis. SETTING:Medical intensive care unit of a university hospital. PATIENTS:Nine consecutive acute lung injury patien...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199806000-00021
更新日期:1998-06-01 00:00:00
abstract:OBJECTIVE:We aim to describe current clinical practice, the past decade of experience and factors related to improved outcomes for pediatric patients receiving high-frequency oscillatory ventilation. We have also modeled predictive factors that could help stratify mortality risk and guide future high-frequency oscillat...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1097/CCM.0000000000001278
更新日期:2015-12-01 00:00:00
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
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:To determine prevalence, risk factors, and outcome of thrombocytopenia in medical intensive care patients. DESIGN:Prospective observational study. SETTING:The 12-bed medical intensive care unit of a university hospital. PATIENTS:All consecutively admitted patients with normal platelet count at admission an...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200208000-00015
更新日期:2002-08-01 00:00:00
abstract:OBJECTIVES:Extracorporeal cardiopulmonary resuscitation has shown survival benefit in select patients with refractory cardiac arrest but there is insufficient data on the frequency of different types of brain injury. We aimed to systematically review the prevalence, predictors of and survival from neurologic complicati...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004377
更新日期:2020-07-01 00:00:00
abstract:OBJECTIVE:To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. DESIGN:Prospective, single-center, observational study. SETTING:Univ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200012000-00012
更新日期:2000-12-01 00:00:00
abstract:OBJECTIVES:Radiographic criteria for acute respiratory distress syndrome have been criticized for poor reliability. Our objective was to test an educational intervention to improve the radiographic identification of acute respiratory distress syndrome by participants in the Large Observational Study to Understand the G...
journal_title:Critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/CCM.0000000000003000
更新日期:2018-05-01 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:OBJECTIVES:Glucose is the primary substrate for the energy requirements of the nervous system. Nevertheless, administration of glucose to critically ill patients with central nervous system trauma may have adverse effects on their neurologic recovery. The purpose of this study was to evaluate the effects of other sourc...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::A patient with brainstem infarction met the clinical criteria for brain death but had persistent EEG activity, complicating our decision to withdraw life support. We evaluated cerebral blood flow with xenon-enhanced computed tomography (Xe/CT), which documented the absence of posterior circulation flow and persistent,...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198705000-00014
更新日期:1987-05-01 00:00:00
abstract:OBJECTIVES:To study the relation between nitrite, nitrate, nitrotyrosine, and nitrosothiols as NO indices in human septic shock. DESIGN:A prospective clinical study. SETTING:Intensive care units in a university hospital and a central county hospital. PATIENTS:Sixteen patients admitted for septic shock. Nine healthy ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200008000-00017
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:To examine the effect of hypertonic saline on bacterial translocation and the number and function of natural killer and T cells in controlled hemorrhagic shock. DESIGN:Randomized controlled study. Duration of follow-up was 24 hrs. SETTING:University research laboratory. SUBJECTS:Adult male Sprague-Dawley r...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-200204000-00025
更新日期:2002-04-01 00:00:00
abstract:OBJECTIVE:Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. PATIENTS:We represent three cases of intractable high-vol...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002310
更新日期:2017-06-01 00:00:00
abstract::Critical care clinicians no longer consider family members as visitors in the intensive care unit. Family-centered care has emerged from the results of qualitative and quantitative studies evaluating the specific needs of families of patients dying in the intensive care unit. In addition, interventional studies have e...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000237049.44246.8C
更新日期:2006-11-01 00:00:00
abstract::There is an increasing evidence that survivors of critical illness suffer from impaired health-related quality of life. There are relatively few studies that have evaluated the effect of interventions in clinical trials to improve these long-term outcomes. Studies to improve long-term outcomes after critical illness f...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3181922bb7
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE:To determine the impact of adding a month of critical care training in the postgraduate year (PGY)-2 on the critical care skills of PGY-3 residents. DESIGN:Prospective, nonrandomized. SETTING:The internal medicine (IM) residency program of a tertiary care medical center. STUDY SUBJECTS:The study subjects i...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e31819cc170
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVES:Despite the universal proliferation of emergency medical services programs throughout the United States since 1970, only a few have ever documented a valid lifesaving effect, particularly in large, urban centers. The purpose of this study was to demonstrate the effect of specialized physician supervision on ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199309000-00009
更新日期:1993-09-01 00:00:00
abstract:OBJECTIVES:The electronic health record is a primary source of information for all professional groups participating in ICU rounds. We previously demonstrated that, individually, all professional groups involved in rounds have significant blind spots in recognition of patient safety issues in the electronic health reco...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000003302
更新日期:2018-10-01 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::Three patients under observation in ICUs developed mechanical upper airway obstruction requiring surgical intervention for airway control. One patient was treated by tracheotomy placed through a vertical midline incision and 2 patients were treated by cricothyroidotomy followed by elective tracheostomy and closure of ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198108000-00004
更新日期:1981-08-01 00:00:00
abstract:OBJECTIVE:To assess whether paralysis alters pulmonary deposition of albuterol delivered by metered dose inhaler and spacer to small animals. DESIGN:A parallel group study of intubated and ventilated rabbits. INTERVENTIONS:Animals in group 1 (n = 7) were paralyzed with intravenous pancuronium, and ventilated at a rat...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199701000-00026
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVES:Anxiety results from the anticipation of a threat and might be associated with poor outcome in the critically ill. This study aims at showing that anxiety at admission in critically ill patients is associated with new organ failure over the first 7 days of ICU hospitalization independently of baseline organ ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004495
更新日期:2020-10-01 00:00:00
abstract:OBJECTIVES:Extracorporeal membrane oxygenation is used to stabilize severe cardiocirculatory and/or respiratory failure. However, extracorporeal membrane oxygenation is associated with a coagulopathy characterized by thromboembolic and hemorrhagic complications. This study aimed to characterize the pathomechanism of th...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004286
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:The mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway is an essential component of innate immunity necessary for mediating proinflammatory responses in the setting of sepsis. We previously demonstrated that the mitogen-activated protein kinase 1/2 inhibitor trametinib pr...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001672
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVES:To outline both the preclinical and clinical data demonstrating surfactant alterations in acute lung injury, which provide the rationale for testing exogenous surfactant administration in this setting. We also review the results of the randomized, controlled clinical trials conducted to date that have evalua...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/01.CCM.0000057911.19145.9F
更新日期:2003-04-01 00:00:00