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| 3. |
- Berg, Sören, et al.
(författare)
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Proinflammatory cytokines increase the rate of glycolysis and adenosine-5'-triphosphate turnover in cultured rat enterocytes
- 2003
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 31:4, s. 1203-1212
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Measurements of steady-state adenosine-5'-triphosphate (ATP) levels in tissue samples from patients or experimental animals with sepsis or endotoxemia provide little information about the rate of ATP production and consumption in these conditions. Accordingly, we sought to use an in vitro "reductionist" model of sepsis to test the hypothesis that proinflammatory cytokines modulate ATP turnover rate. Design: In vitro "reductionist" model of sepsis. Setting: University laboratory. Subjects: Cultured rat enterocyte-like cells. Interventions: IEC-6 nontransformed rat enterocytes were studied under control conditions or following incubation for 24 or 48 hrs with cytomix, a mixture of tumor necrosis factor-a (10 ng/mL), interleukin-1ß (1 ng/mL), and interferon-? (1000 units/mL). To measure ATP turnover rate, ATP synthesis was acutely blocked by adding to the cells a mixture of 2-deoxyglucose (10 mM), potassium cyanide (8 mM), and antimycin A (1 µM). ATP content was measured at baseline (before metabolic inhibition) and 0.5, 1, 2, 5, and 10 mins later. Log-linear ATP decay curves were generated and the kinetics of ATP utilization thereby calculated. Measurements and Main Results: ATP consumption rate was higher in cytomix-stimulated compared with control cells (3.11 ± 1.39 vs. 1.25 ± 0.66 nmol/min, respectively, p < .01). Similarly, the half-time for ATP disappearance was shorter in cytomix-stimulated compared with control cells (2.63 ± 1.00 vs. 6.21 ± 3.49, p < .05). In contrast to these findings, the rate of ATP disappearance was similar in cytokine-naïve and immunostimulated IEC-6 cells when protein and nucleic acid synthesis were inhibited by adding 50 µg/mL cycloheximide and 5 µg/mL actinomycin D to cultures for 4 hrs. The rates of glucose consumption and lactate production were significantly greater in cytomix-stimulated compared with controls cells. Conclusions: Incubation of IEC-6 cells with cytomix significantly increased ATP turnover. Increased ATP turnover rate was supported by increases in the rate of anaerobic glycolysis. These findings support the view that proinflammatory mediators impose a metabolic demand on visceral cells. In sepsis, cells may be more susceptible to dysfunction on the basis of diminished oxygen delivery and/or mitochondrial dysfunction.
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| 4. |
- Chew, Michelle, et al.
(författare)
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Pediatric cardiac output measurement using surface integration of velocity vectors : an in vivo validation study
- 2000
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Ingår i: Critical Care Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0090-3493 .- 1530-0293. ; 28:11, s. 3664-3671
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test the accuracy and reproducibility of systemic cardiac output (CO) measurements using surface integration of velocity vectors (SIVV) in a pediatric animal model with hemodynamic instability and to compare SIVV with traditional pulsed-wave Doppler measurements.Design: Prospective, comparative study.Setting: Animal research laboratory at a university medical center.Subjects: Eight piglets weighing 10-15 kg.Interventions: Hemodynamic instability was induced by using inhalation of isoflurane and infusions of colloid and dobutamine.Measurements: SIVV CO was measured at the left ventricular outflow tract, the aortic valve, and ascending aorta. Transit time CO was used as the reference standard.Results: There was good agreement between SIVV and transit time CO. At high frame rates, the mean difference ± 2 sd between the two methods was 0.01 ± 0.27 L/min for measurements at the left ventricular outflow tract, 0.08 ± 0.26 L/min for the ascending aorta, and 0.06 ± 0.25 L/min for the aortic valve. At low frame rates, measurements were 0.06 ± 0.25, 0.19 ± 0.32, and 0.14 ± 0.30 L/min for the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. There were no differences between the three sites at high frame rates. Agreement between pulsed-wave Doppler and transit time CO was poorer, with a mean difference ± 2 sd of 0.09 ± 0.93 L/min. Repeated SIVV measurements taken at a period of relative hemodynamic stability differed by a mean difference ±2 sd of 0.01 ± 0.22 L/min, with a coefficient of variation = 7.6%. Intraobserver coefficients of variation were 5.7%, 4.9%, and 4.1% at the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. Interobserver variability was also small, with a coefficient of variation = 8.5%.Conclusions: SIVV is an accurate and reproducible flow measurement technique. It is a considerable improvement over currently used methods and is applicable to pediatric critical care.
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- Cucchiara, BL, et al.
(författare)
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Early impairment in consciousness predicts mortality after hemispheric ischemic stroke
- 2004
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 32:1, s. 241-245
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Early predictors of poor outcome after acute ischemic stroke may be useful in selecting patients for potentially beneficial but high-risk interventions. Design. Cohort study of patients given placebo in a randomized clinical trial. Setting. Multicenter trial at 139 U.S. and 14 Canadian hospitals. Patients. A cohort of 564 placebo-treated patients with major anterior circulation ischemic stroke enrolled in the Clomethiazole in Acute Stroke Study-Ischemic Stroke (CLASS-I) trial. Patients did not have significant impairment in consciousness at baseline and were enrolled within 12 hrs of symptom onset. Interventions: Prospective data collection of a number of clinical variables including use of a 6-point level of consciousness scale (1 = awake, 6 = no reaction to pain) to measure patients' level of consciousness at enrollment and 12 additional times during the first 24 hrs after enrollment. The ability of level of consciousness score and additional clinical data to predict 30-day mortality was assessed. Measurements and Main Results., At 1 month, 114 of 564 patients (20%) had died. In univariate analysis, factors significantly associated with mortality included older age, white race, higher National Institutes of Health Stroke Scale score, higher serum glucose, atrial fibrillation, and any impairment in level of consciousness (p < .05). After controlling for these factors, increasing level of consciousness score at 3 hrs after enrollment and at all but one subsequent time point was significantly associated with increased mortality (odds ratio, 1.8 per point, 95% confidence interval, 1.2-2.6, p = .003 at 3-hr time point). Maximum level of consciousness score during the initial 24 hrs of monitoring also predicted mortality (odds ratio, 1.9 per point, 95% confidence interval, 1.4-2.5, p < .001). Conclusion: The development of a decreased level of consciousness within the initial hours after stroke onset, as evaluated by a simple six-point scale, is a powerful independent predictor of mortality after major anterior circulation ischemic stroke.
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- Elf, Kristin, et al.
(författare)
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Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care
- 2002
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 30:9, s. 2129-2134
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate today's refined neurosurgical intensive care of patients with traumatic brain injury after implementation of an organized secondary insult program focused on the importance of avoiding secondary brain damage together with a standardized treatment protocol system.DESIGN: Clinical observational patient study.PATIENTS: A total of 154 patients 16-79 yrs of age with acute head trauma and pathologic computed tomographic findings treated between 1996 and 1997.SETTING: Neurointensive care unit.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Good recovery was obtained in 44% of the patients, moderate disability in 35%, severe disability in 16%, and no patient remained in a vegetative state. Six percent of the patients died, but only two of these patients (1.3%) died as direct result of their head injury. When the results for patients with Glasgow Coma Scale motor scores of >or=4 were compared with the periods 1980-1981 (preneurosurgical intensive care) and 1987-1988 (basic neurosurgical intensive care), mortality had decreased from 40% in the first period to 27% in the second period and to 2.8% in the present series. Favorable outcome in the same group of patients had increased steadily from 40% in the first period, to 68% in the second period, and finally, to 84% in the present series.CONCLUSIONS: The main observation in this hospital series of traumatic brain injury patients was a low rate of death directly caused by head injury and a high rate of favorable outcome. The comparison of patients with Glasgow Coma Scale motor scores of >or=4 with the previously reported results from the same unit indicate that substantial improvement in outcome has been achieved.
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| 7. |
- Gedeborg, Rolf, et al.
(författare)
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Adverse effects of high-dose epinephrine on cerebral blood flow during experimental cardiopulmonary resuscitation
- 2000
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 28:5, s. 1423-1430
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To study the effects of high-dose epinephrine, compared with standard-dose epinephrine, on the dynamics of superficial cortical cerebral blood flow as well as global cerebral oxygenation during experimental cardiopulmonary resuscitation. We hypothesized that high-dose epinephrine might be unable to improve cerebral blood flow during cardiopulmonary resuscitation as compared with standard-dose epinephrine.DESIGN:Randomized controlled study.SETTING:University hospital research laboratory.SUBJECTS:A total of 20 male anesthetized piglets.INTERVENTIONS:Ventricular fibrillation was induced. A nonintervention interval of 8 mins was followed by open-chest cardiopulmonary resuscitation. The animals were randomized to receive repeated bolus injections of either 20 microg/kg (standard-dose group, n = 10) or 200 microg/kg (high-dose group, n = 10) of epinephrine.MEASUREMENTS AND MAIN RESULTS:Focal cortical cerebral blood flow was measured continuously by using laser Doppler flowmetry. The duration of blood flow increase was significantly shorter in the high-dose group after the second dose of epinephrine. In the high-dose group there was also a consistent tendency for lower peak levels and shorter duration of flow increase in response to repeated bolus doses of epinephrine. Cerebral oxygen extraction ratio was significantly lower in the high-dose group after administration of epinephrine.CONCLUSIONS:Repeated bolus doses of epinephrine 200 microg/kg, as compared with 20 microg/kg, do not improve superficial cortical cerebral blood flow during experimental open-chest cardiopulmonary resuscitation. High-dose epinephrine appears to induce vasoconstriction of cortical cerebral blood vessels resulting in redistribution of blood flow from superficial cortex. This might be one explanation for the failure of high-dose epinephrine to improve overall outcome in clinical trials.
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| 8. |
- Johansson, Mats, 1958-, et al.
(författare)
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Positive end-expiratory pressure affects regional redistribution of ventilation differently in prone and supine sheep
- 2004
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 32:10, s. 2039-2044
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine interactions between positive end-expiratory pressure (PEEP) and posture on regional distribution of ventilation and to compare measurements of regional ventilation with two aerosols: a wet fluorescent microsphere aerosol (FMS, median mass aerodynamic diameter 1.1 μm) and a dry 99mTc-labeled carbon particle aerosol (Technegas, TG, median mass aerodynamic diameter ≈0.1 μm). Design: Experimental study. Setting. Academic laboratory. Subjects: Anesthetized and mechanically ventilated sheep (n = 16). Interventions: Four conditions were studied: prone or supine posture with of without 10 cm H2O PEEP. Measurements and Main results: Comparisons of FMS and TG were made in five animals. The median correlation coefficient of the two ventilation tracers was .95 (range, .91-.96). The mean ventilation per unit weight of dry lung for horizontal planes was almost identical whether measured with TG or FMS. The distribution of ventilation was assessed by analyzing deposition of aerosol in about 1,000 lung regions per animal. Distribution of ventilation down the vertical axis was linear in prone (the slope indicated a dorsal-to-ventral three-fold difference in ventilation) but unimodal in supine animals with the mode in the center of the lung. Redistribution of ventilation with 10 PEEP differed between posture, shifting the mode in supine toward dependent lung regions while eliminating the dorsal-to-ventral gradient in prone. The regional heterogeneity in ventilation was greater in supine sheep at both levels of PEEP, and this was due mostly to greater isogravitational heterogeneity in supine than in prone position. Conclusions: The wet fluorescent microsphere aerosol was as reliable as Technegas for high-resolution measurements of regional ventilation. The markedly different effects of 10 PEEP in supine and prone sheep may have important implications for gas exchange both in noninjured and injured lungs.
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| 9. |
- Mutschler, Diana K., et al.
(författare)
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Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early circulatory depression in porcine endotoxemia
- 2003
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 31:6, s. 1780-1785
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the early myocardial biochemical inflammatory response with the microdialysis technique during porcine endotoxemia and to simultaneously monitor systemic hemodynamics. DESIGN: Prospective, randomized, placebo-controlled trial with parallel groups. SETTING: Animal research laboratory at the University Hospital of Uppsala, Sweden. SUBJECTS: Thirteen piglets aged 12-14 wks receiving general anesthesia. INTERVENTIONS: After thoracotomy and the insertion of microdialysis probes in standardized locations in the left ventricle of the heart and in the quadriceps muscle, seven pigs received a continuous infusion of endotoxin, initiating a severe endotoxemic shock. Six pigs received saline instead of endotoxin. MEASUREMENTS AND MAIN RESULTS: Endotoxemia caused a rapid and pronounced elevation of a metabolite obtained from prostaglandin degradation, 15-keto-dihydro-PGF(2alpha), in myocardial microdialysate fluid being specific of cyclooxygenase (COX)-mediated inflammation (p <.001 vs. saline-infused controls). Simultaneously, we observed a decrease in left ventricular stroke work index in the endotoxemic pigs (p <.01 vs. saline-infused controls). Endotoxemia did not alter 15-keto-dihydro-PGF(2alpha) levels in quadriceps muscle. Endotoxemia caused increases in taurine, hypoxanthine, and magnesium in myocardial microdialysate (p <.05 vs. saline-infused controls), whereas the contents of pyruvate, lactate, inosine, adenosine, and calcium were not significantly changed. CONCLUSION: Endotoxemia induced a myocardial COX-mediated inflammation without signs of ischemia. In parallel, a depletion of myocardial energy substrates and a deterioration in myocardial performance were seen.
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