摘要:

ObjectivesTo determine the possible role of enteric bacteria-derived endotoxin in the pathogenesis of the lung injury and mortality in rats following hemorrhagic shock and resuscitation.DesignProspective, randomized study.SettingAnimal laboratory of an institute for research in traumatology.SubjectsMale Sprague-Dawley rats, weighing 450 to 480 g.InterventionsAnesthetized rats were subjected to a prolonged hemorrhagic shock (mean arterial pressure of 30 to 35 mm Hg for 180 mins) followed by resuscitation. A murine monoclonal antibody to lipopolysaccharide from Escherichia coli and Salmonella, WN1 222-5, was administered at a total dose of 5 mg/kg iv, starting at the onset of shock (WN1 group). The control group was treated similarly to the WN1 group but received saline at the same volume as WN1 222-5.Measurements and Main ResultsThe 48-hr mortality rate was significantly reduced by WN1 222-5 treatment (28.6% in the treatment group vs. 78.6% in the control group; p = .0169). The characteristic lung injury in this model was significantly reduced in the WN1 group, as assessed by microscopic histopathologic examination increase in lung wet weight (7.60 +/- 0.47 g/kg in the control group vs. 5.14 +/- 0.31 g/kg in the WN1 group; p = .0002), and pulmonary neutrophilic infiltration (myeloperoxidase activity: 1835 +/- 567 mU/g wet weight in the control group vs. 891 +/- 212 mU/g wet weight in the WN1 group).ConclusionsThese data suggest that a) endotoxin derived from enteric bacteria might play an important role in the pathogenesis of lung injury; and b) antiendotoxin agents, such as WN1 222-5, appear to protect against endogenous bacterial endotoxin-related disorders in severe hemorrhagic shock in rats. (Crit Care Med 1997; 25:1030-1036)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveWe tested the hypothesis that the administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 2R,4R,5S-(2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid) (NPC 17742) or cis-4-(phosphonomethyl) piperidine-2-carboxylic acid (CGS 19755) or the noncompetitive NMDA receptor antagonist dizocilpine (MK-801), at the appropriate doses, would all have efficacy in decreasing early postischemic brain injury in a feline model of transient focal ischemia.DesignProspective, randomized, controlled animal trial.SettingUniversity research laboratory.SubjectsForty mixed-breed cats.InterventionsHalothane-anesthetized cats underwent 90 mins of left middle cerebral artery occlusion plus 4 hrs of reperfusion. At 75 mins of ischemia, control cats received intravenous saline (n = 10). Experimental cats (n = 10 in each group) were treated with NPC 17742 (5 mg/kg bolus and 2.5 mg/kg/hr throughout reperfusion), MK-801 (5 mg/kg intravenous bolus), or CGS 19755 (40 mg/kg intravenous bolus) in a randomized fashion.Measurements and Main ResultsMicrosphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia, and recovered to the same extent during early reperfusion, in the four groups. Triphenyltetrazolium-determined injury volume of the ipsilateral caudate nucleus in cats treated with NPC 17742 (105 +/- 25 [SEM] mm3), MK-801 (97 +/- 22 mm3), and CGS 19755 (97 +/- 13 mm3) was less than in control cats (198 +/- 21 mm3). Hemisphere injury volumes with NPC 17742 (1209 +/- 405 mm3) and MK-801 (1338 +/- 395 mm3) were less than that value in controls (2193 +/- 372 mm3), whereas injury volume with CGS 19755 (1553 +/- 519 mm3) treatment did not attain significance (p < .09).ConclusionsNMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions after 90 mins of transient focal ischemia in the cat. At the doses chosen, there appear to be no major differences in therapeutic efficacy for competitive and noncompetitive NMDA receptor antagonists. (Crit Care Med 1997; 25:1037-1043)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectivesTo determine if myocardial injury results from hepatoenteric ischemia-reperfusion. We also proposed to determine if this remote heart injury is mediated by a xanthine oxidase-dependent mechanism.DesignRandomized, controlled animal study.SettingUniversity-based animal research facility.SubjectsThirty-six New Zealand white male rabbits, weighing 1.8 to 3 kg.InterventionsAnesthetized rabbits were randomly assigned to one of four groups (n = 9 per group): a) a sham-operated group; b) a sham-operated group pretreated with sodium tungstate (xanthine oxidase inactivator); c) an aorta occlusion group; and d) an aorta occlusion group pretreated with sodium tungstate. Descending thoracic aorta occlusion was maintained for 40 mins with a 4-Fr Fogarty embolectomy catheter, followed by 2 hrs of reperfusion.Measurements and Main ResultsMyocardial injury, manifested by increased circulating creatine kinase-MB fraction activity, was significantly associated with aortic occlusion and reperfusion (p < .05). Sodium tungstate pretreatment significantly (p < .05) reduced circulating and myocardial xanthine oxidase activity. Xanthine oxidase inactivation by sodium tungstate significantly decreased circulating creatine kinase-MB fraction activity after hepatoenteric ischemia-reperfusion (p < .05). Finally, circulating creatine kinase-MB fraction activity was significantly associated with circulating xanthine oxidase activity (r2=.85; p < .001).ConclusionsWe conclude that remote myocardial injury is caused by hepatoenteric ischemia-reperfusion. The pathoetiology of this myocardial injury involves a xanthine oxidase-dependent mechanism. (Crit Care Med 1997; 25:1044-1050)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine if inhibition of nitric oxide synthase with NG-nitro-L-arginine-methyl-ester (L-NAME) potentiates endotoxin-induced cardiopulmonary dysfunction and release of cyclooxygenase products in a porcine model of endotoxemia.DesignProspective, multiple group, controlled experimental study.SettingPhysiologic research laboratory at a veterinary medicine college.SubjectsFifty-seven domestic pigs (mean 28.7 +/- 0.8 [SEM] kg).InterventionsPentobarbital-anesthetized pigs were intubated and mechanically ventilated to normocapnia with room air. A thermodilution cardiac output catheter was advanced into the pulmonary artery. Additional catheters were inserted into the jugular and femoral veins and femoral artery. The pigs received the following infusions: saline (control, n = 5); L-NAME (0.1, 0.5, 2.2, or 5.5 mg/kg/hr, from -0.5 to 2 hrs, n = 16); Escherichia coli endotoxin (5 micro g/kg from 0 to 1 hr followed by 2 micro g/kg from 1 to 2 hrs, iv, n = 14); L-NAME plus endotoxin (n = 9); indomethacin plus endotoxin (n = 6); or L-NAME plus indomethacin plus endotoxin (n = 7).Measurements and Main ResultsL-NAME significantly (p < .05) worsened endotoxin-induced hypoxemia and enhanced the increases in pulmonary vascular resistance index and systemic vascular resistance index at 30 to 60 mins. Endotoxin increased (p < .05) plasma concentrations of thromboxane B2by seven- to eight-fold at 30 to 120 mins and 6-keto-prostaglandin F1alpha by 16- to 24-fold at 60 to 120 mins. L-NAME enhanced (additive effect) endotoxin-induced increases in plasma concentrations of thromboxane B2(60 mins) and significantly (p < .05) potentiated the increases in 6-keto-prostaglandin F1alpha (120 mins). At 120 mins of endotoxemia, indomethacin (cyclooxygenase inhibitor) plus L-NAME markedly increased (p < .05, synergistic effect) systemic vascular resistance index compared with endotoxemic pigs pretreated with either L-NAME or indomethacin.ConclusionsDuring endotoxemia, inhibition of nitric oxide synthase with L-NAME may be deleterious to cardiopulmonary function, as evidenced by potentiation of endotoxin-induced systemic and pulmonary vasoconstriction, impairment of gas exchange, and enhanced biosynthesis of cyclooxygenase products. Moreover, during endotoxemia, the concomitant inhibition of two important vasodilators (i.e., nitric oxide and prostacyclin) is associated with a potentiated (p < .05) increase in systemic vascular resistance index. (Crit Care Med 1997; 25:1051-1058)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine the influence of positive end-expiratory pressure (PEEP) on intracranial pressure and cerebral perfusion pressure.DesignNeurosurgical intensive care patients requiring intracranial pressure monitoring and mechanical ventilation were studied in a randomized, controlled study.SettingTertiary care, neurosurgical intensive care unit.PatientsEighteen patients were enrolled in the study. Patients had posttraumatic head injuries (n = 9), subarachnoid hemorrhage (n = 7), obstructive hydrocephalus (n = 1), and intracerebral hemorrhage of unknown cause (n =1).InterventionsPatients had PEEP levels of 5, 10, and 15 cm H2O applied to their lungs.Measurements and Main Results15 mm Hg). PEEP at 5 cm H2O had no effect on intracranial pressure in the group with normal intracranial pressure. However, PEEP at 10 and 15 cm H2O produced a significant (p < .05) increase in intracranial pressure (1.9 and 1.5 mm Hg, respectively). In the group with increased intracranial pressure, no significant change in intracranial pressure occurred at any of the PEEP levels used. In both groups, cerebral perfusion pressure was unchanged throughout.ConclusionsIn patients with normal intracranial pressure, PEEP at 5 cm H sub 2 O did not significantly alter intracranial pressure. The clinical relevance of the intracranial pressure increase at PEEP levels of 10 and 15 cm H260 mm Hg. In patients with increased intracranial pressure, higher levels of PEEP did not significantly change intracranial pressure or cerebral perfusion pressure. (Crit Care Med 1997; 25:1059-1062)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectivesTo examine whether preoperative heart failure and cardiac surgery influence nitric oxide production and atrial natriuretic peptide (ANP) biological activity in infants and whether nitric oxide and ANP participate in the control of postoperative pulmonary vascular tone.DesignProspective, clinical study.SettingTertiary pediatric cardiac intensive care unit in a referral cardiosurgical center.PatientsNineteen infants (median age 4 months) undergoing cardiac surgery: 13 infants with ventricular or atrioventricular septal defect associated with heart failure and pulmonary hypertension (group 1); and six infants with tetralogy of Fallot, without heart failure (group 2).InterventionsBlood samples obtained from indwelling catheters or bypass circuit outlets.Measurements and Main ResultsNitrite and nitrate blood concentrations (as a marker for nitric oxide synthesis) and the molar ratio of cyclic guanosine 3 prime,5 prime-monophosphate (cGMP) to ANP (as a marker for ANP biological activity) were determined before, during, and up to 24 hrs after cardiopulmonary bypass (CPB). In group 1 patients, these biological parameters were related to postoperative pulmonary arterial pressure.Preoperative nitrite and nitrate concentrations were higher in group 1 patients than in group 2 patients (p < .02), and this difference persisted during CPB. Nitrite and nitrate concentrations 24 hrs postoperatively were lower than preoperative values in group 1 patients (p < .05) and were unchanged in group 2 patients. An inverse correlation was observed postoperatively between nitrite and nitrate concentrations and systolic pulmonary arterial pressure (r2= 0.4, p < .05). Group 1 patients had a lower preoperative cGMP/ANP ratio than group 2 patients (p < .05), despite higher ANP levels (p < .005). The cGMP/ANP ratio decreased during CPB in both groups (p < .0001), and in group 2 patients, cGMP and ANP values remained below preoperative values <or=to24 hrs postoperatively. A correlation was observed between ANP levels and systolic pulmonary arterial pressure 2 and 4 hrs postoperatively (r2= .4, p < .05, respectively), but no correlation was observed between ANP biological activity and postoperative pulmonary arterial pressure.ConclusionsInfants with heart failure and pulmonary hypertension have increased nitric oxide synthesis and decreased ANP biological activity; both phenomena may be involved in the pathophysiology of this clinical condition. CPB has no detectable effect on nitric oxide production but does decrease ANP biological activity. In patients with preoperative heart failure and pulmonary hypertension, endogenous nitric oxide appears to play a role in the control of postoperative pulmonary vascular tone. (Crit Care Med 1997; 25:1063-1070)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectivesThe systemic inflammatory response syndrome (SIRS) is typified by the presence of fever, hemodynamic changes, and end organ dysfunction. Endothelial cell activation leads to overproduction of nitric oxide, which results in sustained vasodilation and hypotension. This study was undertaken to determine the sensitivity, specificity, and positive and negative predictive values of plasma nitrite/nitrate measurements in identifying patients with clinical characteristics of SIRS, as defined by criteria based on physician diagnosis.DesignProspective cohort study with consecutive sampling of patients.SettingTertiary, multidisciplinary, pediatric intensive care unit (ICU) at Children's Hospital of Wisconsin.PatientsPatients were divided into five groups. There were 16 pediatric controls undergoing elective surgery and 177 pediatric ICU patients without and 46 pediatric ICU patients with physician-diagnosed sepsis, septic shock, SIRS, or sepsis syndrome documented in the medical record (all considered physician-diagnosed sepsis). The 223 pediatric ICU patients included 195 pediatric ICU patients not meeting and 28 pediatric ICU patients meeting predetermined physiologic criteria for SIRS (considered criteria-based sepsis).InterventionsBlood samples were obtained for quantitative nitrite/nitrate analysis at the time of admission to the pediatric ICU and daily until discharge.Measurements and Main Results54 micro M to identify patients with criteria-based sepsis is characterized as follows: 61% sensitivity, 68% specificity, 21% positive predictive value, and 92% negative predictive value.ConclusionsClinical diagnosis of SIRS is strongly associated with increased total plasma nitrite/nitrate concentrations in pediatric patients in the pediatric ICU. Many patients with increased nitrite/nitrate concentrations have inflammation without having a clinical diagnosis of SIRS. Our data suggest that increased plasma nitrite/nitrate concentrations are the standard for identifying patients with inflammation in the pediatric ICU. (Crit Care Med 1997; 25:1071-1078)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo investigate whether an infusion of recombinant tissue plasminogen activator would dissolve microvascular thromboses and improve organ perfusion in a patient with fulminant meningococcemia.DesignDescriptive case report.SettingFifteen-bed pediatric intensive care unit (ICU) in a university hospital.PatientA 4-month-old male with fulminant meningococcemia, refractory shock, and multiple organ failure.InterventionsIn addition to standard aggressive ICU care, the patient received a recombinant tissue plasminogen activator infusion at a total dose of 1.25 mg/kg over 4 hrs.Measurements and Main ResultsHeart rate, arterial blood pressure, urine output, and base deficit (as a reflection of severity of metabolic acidosis) were recorded immediately before the recombinant tissue plasminogen activator infusion and 4 hrs later, after completion of the recombinant tissue plasminogen activator infusion. The amount of exogenous vasopressor and inotropic support required to maintain the patient's hemodynamic status before and after recombinant tissue plasminogen activator infusion were also compared. Subjective observations regarding the patient's peripheral perfusion status were also noted. The patient showed a dramatic improvement in hemodynamics, urine output, and metabolic acidosis, as well as a perceived increase in skin perfusion after recombinant tissue plasminogen activator infusion.ConclusionsIn this patient, recombinant tissue plasminogen activator infusion resulted in improved organ perfusion and cardiac performance. Selective use of recombinant tissue plasminogen activator in the treatment of fulminant meningococcemia merits further investigation. (Crit Care Med 1997; 25:1079-1082)

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1997

数据来源: OVID