摘要:

Background and MethodsIn the present study, we evaluated the effect of N-acetylcysteine treatment in a nonseptic shock model induced by zymosan in the rat.Animals were randomly divided into eight groups (ten animals in each group).The first group was treated with ip administration of saline solution (0.9% NaCl) and served as the sham group. The second group was treated with ip administration of zymosan (500 mg/kg suspended in saline solution). In the third and fourth groups, rats received ip administration of N-acetylcysteine (40 mg/kg; 1 and 6 hrs after administration of zymosan or saline). In the fifth and sixth groups, rats received ip administration of N-acetylcysteine (20 mg/kg; 1 and 6 hrs after zymosan or saline administration). In the seventh and eighth groups, rats received ip administration of N-acetylcysteine (10 mg/kg; 1 and 6 hrs after zymosan or saline administration).After zymosan or saline injection, animals were monitored for the evaluation of systemic toxicity (conjunctivitis, ruffled fur, diarrhea, and lethargy), loss of body weight, and mortality for 72 hrs.Exudate formation, leukocyte infiltration, nitrate/nitrite production, lung and intestine myeloperoxidase activity and lipid peroxidation, and histologic examination were evaluated at 18 hrs after zymosan administration.ResultsAdministration of zymosan in the rat induced acute peritonitis, as assessed by a marked increase in the leukocyte count in the exudate, as well as by an increase in the exudate nitrate/nitrite concentration. Lung and intestine myeloperoxidase activity and lipid peroxidation was significantly increased in zymosan-treated rats. This inflammatory process coincided with the damage of lung and small intestine.Peritoneal administration of zymosan in the rat also induced a significant increase in the plasma levels of nitrite and nitrate and stable metabolites of nitric oxide and in levels of peroxynitrite, as measured by the oxidation of the fluorescent dihydrorhodamine 123 at 18 hrs after zymosan challenge.Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, a specific "footprint" of peroxynitrite, in the lung of zymosan-shocked rats. Pretreatment of zymosan-shocked rats with ip administration of N-acetylcysteine (40, 20, and 10 mg/kg, 1 and 6 hrs after zymosan) prevented the development of peritonitis and reduced peroxynitrite formation in a dose-dependent manner. In addition, ip administration of N-acetylcysteine (40 mg/kg, 1 and 6 hrs after zymosan) was effective in preventing the development of lung and intestine injury and neutrophil infiltration, as determined by myeloperoxidase evaluation.ConclusionsTaken together, the present results demonstrate that N-acetylcysteine exerts potent anti-inflammatory effects. (Crit Care Med 1999; 27:1524-1532)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo study the relative contributions of mean airway pressure (mPaw) and tidal excursion (VT) to ventilator-induced lung injury under constant perfusion conditions.DesignProspective, randomized study.SettingExperimental animal laboratory.SubjectsFifteen sets of isolated rabbit lungs.InterventionsRabbit lungs were perfused (constant flow, 500 mL/min; capillary pressure, 10 mm Hg) and randomized to be ventilated at identical peak transpulmonary pressure (pressure control ventilation [30 cm H2O and frequency of 20/min]) with three different ventilatory patterns that differed from each other by either mPaw or VT: group A (low mPaw [13.4 +/- 0.2 cm H2O]/large VT[55 +/- 8 mL], n = 5); group B (high mPaw [21.2 +/- 0.2 cm H2O]/small VT[18 +/- 1 mL], n = 5); and group C (high mPaw [21.8 +/- 0.5 cm H2O]/large VT[53 +/- 5 mL], n = 5).Measurements and Main ResultsContinuous weight gain (edema formation), change in ultrafiltration coefficient (Delta Kf, vascular permeability index), and histology (lung hemorrhage) were examined. In group A, Delta Kf(0.08 +/- 0.08 g/min/cm H2O/100 g) was less than in group B (0.28 +/- 0.19 g/min/cm H2O/100 g) or group C (0.41 +/- 0.29 g/min/cm H2O/100 g) (p = .05). Group A experienced significantly less hemorrhage (histologic score, 5.4 +/- 2.2) than groups B (10.3 +/- 2.1) and C (11.1 +/- 3.0) (p < .05). A similar trend was observed for weight gain. In contrast to tidal excursion, mPaw was found to be a significant factor for lung hemorrhage and increased Kf(two-way analysis of variance; p < .05). Weight gain (r2= .54, p = .04) and lung hemorrhage (r2= .65, p = .01) correlated with the mean pulmonary artery pressure changes that resulted from the implementation of the ventilatory strategies. The difference between the changes in mPaw and mean pulmonary artery pressure linearly predicted Delta Kf(p = .005 and .05, respectively, r2= 0.73).ConclusionsUnder these experimental conditions, mPaw contributes more than tidal excursion to lung hemorrhage and permeability alterations induced by mechanical ventilation. (Crit Care Med 1999; 27:1533-1541)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveVentricular fibrillation (VF) is known to increase myocardial oxygen requirements and to alter coronary vascular physiology. However, the significance of these effects during cardiac arrest and resuscitation is not well understood. A model was developed in the isolated rat heart to investigate the myocardial effects of VF during a simulated episode of cardiac arrest and resuscitation. We hypothesized that VF would intensify the severity of myocardial ischemia and consequently accentuate postischemic myocardial dysfunction.DesignProspective and randomized.SettingResearch laboratory.SubjectsTwenty Sprague-Dawley rats.InterventionsHearts were harvested and perfused at a constant flow rate of 10 mL/min using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. In five hearts, VF was induced by a 0.05-mA current delivered to the right ventricular endocardium. The perfusate flow was then stopped for a 10-min interval and resumed at 20% of baseline flow for another 10 mins. After 20 mins of VF, the perfusate flow was returned to baseline and a sinus rhythm reestablished by epicardial electrical shocks. The studies were randomized and included three additional groups to control for the effects of ischemia without VF (n = 5), the effects of VF without ischemia (n = 5), and the stability of the preparation (n = 5).Measurements and Main ResultsIsovolumic indices of left ventricular function were obtained using a latex balloon advanced through the mitral valve and distended to an end-diastolic pressure of 10 mm Hg. The coronary effluent was collected from the right ventricular cavity. VF during myocardial ischemia was associated with a higher coronary effluent PCO2, increased coronary vascular resistance, and development of ischemic contracture as indicated by increases in left ventricular pressure from 9 +/- 3 to 33 +/- 6 mm Hg (p < .05). After defibrillation, contractility and relaxation rapidly returned to baseline values, whereas the isovolumic end-diastolic pressure remained elevated for 20 mins. These changes were much less prominent when ischemia was not accompanied by VF.ConclusionsThese findings indicate that VF may adversely affect myocardial ischemia by hastening the development of ischemic contracture, increasing coronary vascular resistance, and favoring the development of diastolic pump failure early after resuscitation from cardiac arrest. (Crit Care Med 1999; 27: 1542-1550)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesIntraparenchymal airways are involved in air flow regulation. Relaxation of intraparenchymal airways to volatile anesthetics varied by topographic location. This study was conducted to determine whether other bronchodilators (terbutaline, diltiazem, and aminophylline) relax bronchiolus to a greater degree than bronchus, as seen with volatile anesthetics.DesignIn vitro, controlled, randomized study.SettingAnimal research laboratory.SubjectsAdult dogs (n = 9).InterventionsProximal (outer diameter, 4-6 mm) and distal (outer diameter, 0.8-1.5 mm) airway rings of dogs were contracted in tissue baths with the effective concentration of acetylcholine that produces half the maximum response. Airway relaxant dose-response curves were constructed to measure isometric tension after administration of terbutaline (concentration range, 10-8to 10-4M), diltiazem (concentration range, 3 x 10-7to 1 x 10-4M), and aminophylline (concentration range, 10-7to 10-4M).Measurements and Main Results.05. At the concentrations tested, they were equally efficacious. No significant differences in relaxation between proximal and distal airways were noted with diltiazem or aminophylline in the entire dose range. However, terbutaline relaxed the distal airway more than the proximal airway in the entire dose range.ConclusionsThe results demonstrate that only terbutaline showed a differential airway relaxant effect between proximal and distal airways, as seen with volatile anesthetics. (Crit Care Med 1999; 27:1551-1556)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo test the hypotheses that during lethal uncontrolled hemorrhagic shock (UHS) in rats compared with normothermia and room air breathing: a) mild hypothermia would prolong survival time as well as moderate hypothermia; b) oxygen breathing would prolong survival further; and c) hypothermia and oxygen would mitigate visceral ischemia (dysoxia) during UHS.DesignProspective, randomized, controlled laboratory animal study.SettingAnimal research facility.SubjectsMale Sprague-Dawley rats.InterventionFifty-four rats were lightly anesthetized with halothane during spontaneous breathing. UHS was induced by blood withdrawal of 3 mL/100 g over 15 mins, followed by 75% tail amputation with topical application of heparin. Five minutes after tail cut, rats were randomly divided into nine groups (6 rats each) with three rectal temperature levels (38[degree sign]C [100.4[degree sign]F; normothermia] vs. 34[degree sign]C [93.2[degree sign]F; mild hypothermia] vs. 30[degree sign]C [86[degree sign]F; moderate hypothermia]) by surface cooling; each with 3 FIO2levels (0.25 vs. 0.5 vs. 1.0). Rats were observed without fluid resuscitation until death (apnea and pulselessness). Visceral ischemia was monitored by observing liver and gut surface PCO2.Measurements and Main ResultsMean survival time, which was 51 mins in the control group with normothermia and FIO2of 0.25, was more than doubled with hypothermia, to 119 mins in the combined mild hypothermia groups (p < .05) and to 132 mins in the combined moderate hypothermia groups (p < .05; NS for moderate vs. mild hypothermia). FIO2had no statistically significant effect on survival time. Increases in visceral surface PCO2correlated with hypotension (r2= .22 for intestine and .40 for liver). Transiently, increased FIO2, not hypothermia, mitigated visceral ischemia.ConclusionsBoth mild and moderate hypothermia prolonged survival time during untreated, lethal UHS in rats. Increased FIO2had no effect on survival. The effects of hypothermia and increased FIO2during UHS on viscera, the ability to be resuscitated, and outcome should be explored further. (Crit Care Med 1999; 27:1557-1564)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveIntravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) may be more effective than optimal doses of epinephrine. The main purpose of this study was to determine whether intraosseous vasopressin achieves serum drug levels comparable with intravenous doses during CPR and, additionally, to evaluate the effects of intraosseous vasopressin during CPR.DesignProspective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, blood gases, and return of spontaneous circulation.SettingUniversity hospital laboratory.SubjectsTwelve domestic pigs.InterventionsAfter 4 mins of untreated ventricular fibrillation and 3 mins of CPR, 12 pigs were randomized to be treated with intravenous administration of vasopressin (0.8 unit/kg vasopressin; n = 6) or intraosseous vasopressin (0.8 unit/kg vasopressin; n = 6). Defibrillation was performed 5 mins after drug administration to attempt the return of spontaneous circulation.Measurements and Main ResultsAt both 90 secs and 5 mins after drug administration, intravenous and intraosseous administration of vasopressin resulted in comparable mean (+/- SEM) coronary perfusion pressure (43 +/- 4 vs. 44 +/- 3 and 30 +/- 2 vs. 37 +/- 2 mm Hg, respectively) and vasopressin plasma concentrations (13,706 +/- 1,857 vs. 16,166 +/- 3,114 pg/mL and 10,372 +/- 883 vs. 8246 +/- 2211 pg/mL, respectively). All animals in both groups were successfully resuscitated; pigs that received intraosseous vasopressin had a significantly higher (p < .05) mean arterial (92 +/- 6 vs. 129 +/- 12 mm Hg) and coronary perfusion pressure (84 +/- 11 vs. 119 +/- 11 mm Hg) at 5 mins of return of spontaneous circulation.ConclusionsIntraosseous vasopressin resulted in comparable vasopressin plasma levels, hemodynamic variables, and return of spontaneous circulation rates as did intravenous vasopressin. Intraosseous vasopressin may be an alternative for vasopressor administration during CPR, when intravenous access is delayed or not available. (Crit Care Med 1999; 27:1565-1569)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine the plasma elimination of methohexitone in patients with critically elevated intracranial pressure (ICP) who received the drug in high doses for several days.DesignDrug-monitoring study.SettingIntensive care unit at a university hospital.PatientsTwelve intensive care unit patients with brain injuries who received methohexitone as a final therapeutic approach after routine therapy had proved to be insufficient in controlling critically elevated ICP.Measurements and Main ResultsPlasma samples were taken during methohexitone infusion, before cessation, and in distinct, short increments after discontinuation of the infusion. Methohexitone was determined in plasma by reverse-phase high-pressure liquid chromatography and photometric detection. The median duration of infusion of methohexitone was 137 hrs (minimum, 27 hrs; maximum, 445 hrs), with a median infusion rate of 62.5 [micro sign]g/kg/min (minimum, 22.5 [micro sign]g/kg/min; maximum, 116.2 [micro sign]g/kg/min). Plasma concentrations of methohexitone at burst suppression under concomitant analgesic sedation ranged from 1.6 to 17.3 [micro sign]g/mL (median, 4.7 [micro sign]g/mL). After cessation of methohexitone infusion, the decline of plasma concentrations followed a biexponential function. Clearance rates, volume of distribution at steady state, context-sensitive half-time, and initial and terminal elimination half-times were calculated. Pharmacokinetic data showed remarkable interindividual variability that could not be correlated to the infusion rate, to the duration of the infusion, or to obvious differences in physiology or the disease states of these patients. Even in patients with high plasma concentrations who received the drug for a considerable length of time, the initial decline in plasma concentration was exponential, indicating redistribution.ConclusionsWe conclude that the elimination kinetics of methohexitone after long-term, high-dose infusion in critically ill patients with brain injuries may favor the use of methohexitone over thiopentone for controlling critically elevated ICP by allowing for a more timely neurologic examination after cessation. (Crit Care Med 1999; 27:1570-1576)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesThis study was undertaken to compare three methods for the identification of unmeasured anions in pediatric patients with critical illness. We compared the base excess (BE) and anion gap (AG) methods with the less commonly used Fencl-Stewart strong ion method of calculating BE caused by unmeasured anions (BEua). We measured the relationship of unmeasured anions identified by the three methods to serum lactate concentrations and to mortality.DesignRetrospective cohort study.SettingTertiary care pediatric intensive care unit in an academic pediatric hospital.PatientsThe study population included 255 patients in the pediatric intensive care unit who had simultaneous measurements of arterial blood gases, electrolytes, and albumin during the period of July 1995 to December 1996. Sixty-six of the 255 patients had a simultaneous measurement of serum lactate.Measurements and Main Resultsor=to45 mg/dL was defined as being abnormally elevated for this study. The presence of unmeasured anions identified by significantly abnormal BEua was poorly identified by BE or AG. Of the 255 patients included in the study, 67 (26%) had a different interpretation of acid base balance when the Fencl method was used compared with when BE and AG were used. Plasma lactate concentration correlated better with BEua (r2= .55; p = .0001) than with AG (r2= .41; p = .0005) or BE (r2or=to45 mg/dL (relative risk of death = 2.35; p = .04). In logistic regression analysis, mortality was more strongly associated with BEua (area under the receiver operating characteristic curve = 0.79; p = .0002) than lactate (receiver operating characteristic curve area = 0.63; p = .05), BE (receiver operating characteristic curve area = 0.53; p = .32), or AG (receiver operating characteristic curve area = 0.64; p = .08) in this patient sample.ConclusionsCritically ill patients with normal BE and normal AG frequently have elevated unmeasured anions detectable by BEua. The Fencl-Stewart method is better than BE and similar to AG in identifying patients with high lactate levels. Elevated unmeasured anions identified by the Fencl-Stewart method were more strongly associated with mortality than with BE, AG, or lactate in this patient sample. (Crit Care Med 1999; 27:1577-1581)

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID