IntroductionWe previously showed that erythropoietin (EPO) attenuates the morphological signs of spinal cord ischemia/reperfusion (I/R) injury in swine [1] without, however, improving neurological function. The clinical use of EPO has been cautioned most recently due to serious safety concerns arising from an increased mortality in acute stroke patients treated with EPO and simultaneously receiving systemic thrombolysis [2]. Carbamylated EPO (cEPO) is an EPO derivative without erythropoietic activity and devoid of the EPO side eff ects, but with apparently well maintained cytoprotective qualities [3]. We therefore tested the hypothesis whether cEPO may be equally effi cient as EPO in reducing morphological as well as functional aortic occlusion-induced spinal cord I/R injury. Methods In a randomized and blinded trial pigs received either vehicle (control, n = 9), EPO or cEPO, respectively (n = 9 each; 5,000 IU/kg over 30 minutes before and during the fi rst 4 hours of reperfusion). Animals underwent 30 minutes of thoracic aortic balloon occlusion with catheters placed immediately downstream of the A. subclavia and upstream of the aortic trifurcation. Spinal cord function was assessed by motor evoked potentials (MEP as percentage of the amplitude before aortic occlusion) and lower limb refl exes (assessed as the subjective strength of response) for a period of 10 hours after reperfusion. Tissue damage was evaluated using Nissl staining. Results Both EPO-treated and cEPO-treated animals presented with attenuated spinal cord injury in the Nissl staining (median (quartile) percentage of damaged neurons in the thoracic segments: control 27 (25,44), cEPO 8 (4,10), and EPO 5 (5,7), P <0.001 vs control group; in the lumbar segments: control 26 (19,32), cEPO 7 (5,13), EPO 8 (5,10), P <0.001 vs control group). However, while only cEPO treatment was associated with recovery of the MEP amplitude to pre-occlusion values when compared with the control group (P <0.05), lower limb refl ex response was comparably restored stronger in both treatment groups (P <0.05 vs control). Conclusions In a clinically relevant porcine model mimicking aortic crossclamping during vascular surgery repair of thoracic aortic aneurysm, cEPO protected spinal cord function and integrity as eff ective as EPO when applied at equipotent doses. Acknowledgements Supported by the Deutsche Forschungs gemeinschaft (SCHE 899/2-2). References Introduction Unfolded protein response (UPR)-mediated apoptosis plays a pivotal role in ischemia-reperfusion injury. Sodium 4-phenylbutyrate (PBA) has been reported to act as a chemical chaperone inhibiting UPR-mediated apoptosis triggered by ischemia in various organs other than the heart. Therefore we investigated whether PBA reduces UPR-mediated apoptosis and protects against myocardial ischemia-reperfusion injury in mice. Methods C57BL/6 mice were subjected to 30 minutes LAD ischemia followed by reperfusion. PBA (100 mg/kg) or PBS (control) was administrated intraperitoneally just before ischemia. Apoptosis, infarct ...
No abstract
Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II cells (A549). To study in vitro the direct influence of alveolar type II cells on mechanical stretch. Methods A549 were treated with different doses of lipopolysaccharide (LPS), 0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, and then A549 were lengthened 5%, 15%, 30% using a FLEXCELL tension unit 4000, a vacuum-driven device that applies strain to cells, which were cultured in six-well plates coated with collagen-I, and 12 cycles/min for 4 hours. Apoptosis was measured using the flow cytometry method that measures annexin V and propidium iodide (PI) staining. The morphological changes of apoptotic cells were observed by transmission electron microscope. Results Apoptosis could be induced in alveolar type II cells (A549) by mechanical stretch. The percentage of annexin V + PI cells increased after being treated with cyclic stretch for 4 hours by 5%, 15%, 30% in all groups. The morphological features of apoptotic cells demonstrated by transmission electron microscope were as follows: shrinkage of the cell, chromatin condensation and aggregation under the nuclear membrane as a crescent or lump, membrane-encapsulated nuclear fragment or cell organ formed by invagination of the cell membrane, and apoptotic body formation followed by vacuolization. Conclusion Apoptosis induced by mechanical stretch and LPS is dose dependent. Mechanical stretch aggravates apoptosis especially in cells treated with LPS. Annexin V and PI double staining is a specific, sensitive, and quantitative method for analyzing apoptotic cells. It is also helpful to clarify the protective mechanism of low-volume ventilation in ARDS. Acknowledgement The study was funded by the 'One Hundred People' project of Shanghai Sanitary Bureau (03-77-20). Introduction Although extrapulmonary ALI/ARDS is a common clinical entity, most animal models used to study this disease are induced by direct lung injuries. Our intention was therefore to investigate whether a condition resembling ALI/ARDS develops during the course of a fecal peritonitis in pigs; in that case experimental peritonitis would also prove as a clinically relevant ARDS model. Methods In 10 anesthetized, mechanically ventilated, and instrumented pigs fecal peritonitis was induced by inoculating autologue feces pellets suspended in saline. Mechanical ventilation was set with VT = 8 ml/kg, FiO 2 to reach a SaO 2 target of >90%, PEEP = 10 cmH 2 O if PaO 2 /FiO 2 > 300 and 12 cmH 2 O if PaO 2 /FiO 2 < 300, and respiratory rate to obtain a PaCO 2 of 35-45 mmHg. Before as well as 12 and 24 hours after peritonitis induction we measured the PaO 2 /FiO 2 ratio, the total compliance of the respiratory system (C), calculated as VT/(P plateau -PEEP) and inspiratory airway resistance (R i ) calculated as (P max -P plateau ) / mean inspiratory flow. Data are mean [range]. Results For data see Table 1. During the course of the 24-hour study period, six of 10 animals developed gas exchange deteriorations consistent w...
Purpose:To describe the epidemiology of the acute respiratory distress syndrome (ARDS) in a Brazilian ICU.Methods: This prospective observational, non-interventional study, included all consecutive patients with ARDS criteria [1] admitted in the ICU of a Brazilian tertiary hospital, between January 1997 and September 2001. Were collected in a prospective fashion the following variables: age, gender, APACHE II score at ICU admission and at ARDS diagnosis, cause of ARDS, presence of AIDS, cancer and immunosuppression, occurrence of barotrauma, performance of traqueostomy, mortality, duration of mechanical ventilation (MV), length of stay (LOS) in ICU and in hospital. The lung injury score (LIS) [2] was used to quantify the degree of pulmonary injury in the first week of ARDS. Results:There was 2182 patients (P) admitted in ICU during the study period, of whom 141 (6.46%) had ARDS criteria. Seventy-six (54%) were men, the mean age was 46 ± 18 years, APACHE II 18 ± 7 and 19 ± 7 at admission and at ARDS diagnosis, respectively. Septic shock accounted for 42% (60 P) of the ARDS causes, sepsis 22% (31 P), diffuse pulmonary infection 16% (23 P), aspiration pneumonia 11% (15 P), non-septic shock 5% (7 P) and others 4% (5 P). Ten percent (14 P) had AIDS, 30% (43 P) cancer and 25% (36 P) immunosuppression. All patients were mechanically ventilated with Tidal Volume between 4 and 8 ml/kg. Only 3.5% (5 P) had barotrauma and 10% (14 P) performed traqueostomy. Mortality rate was 79% in the ICU. The patients required 12 ± 10 days on MV, ranging from 1 to 55 days. The LOS in ICU and hospital was 14 ± 13 (1-69) days and 28 ± 32 (1-325) days, respectively. There was a time delay of 3.7 ± 4.5 days between admission in ICU and the onset of ARDS. The Murray score (mean ± SD) was 3.2 ± 0.4, 3 ± 0.5, 3 ± 0.5, 2.9 ± 0.6, 2.8 ± 0.7, 2.7 ± 0.7 and 2.6 ± 0.8 in the first 7 days, respectively.Conclusions: ARDS in our hospital has a similar incidence of reports in the USA and Europe. There was a higher mortality, which could be explained by a high incidence of infection causes of ARDS, mainly septic shock, and elevated combined occurrence of AIDS, cancer and immunosuppression, along the degree of LIS. The incidence of barotrauma was low, as a consequence of the current mechanical ventilation strategies. References:1. Bernard GR, Artigas A, Brigham KL, et al.: Am Respir Crit Care Med 1994 P2Role of multiple organ dysfunction syndrome in ARDS mortality FS Dias, N Almeida, IC Wawrzeniack, PB Nery Hospital São Lucas da PUCRS, Av. Ipiranga 6690, RS, Brazil Purpose: To correlate the occurrence and level of organ dysfunction in ARDS with mortality. Methods:This cohort study includes all consecutive patients with ARDS criteria [1] admitted in the ICU between January 1997 and September 2001. Were collected in a prospective fashion the following variables: age, gender, APACHE II score at the ARDS diagnosis, the occurrence of organ dysfunction determined by the multiple organ dysfunction syndrome (MODS) [2] in the first week, and mortality in ...
Purpose: To describe the epidemiology of the acute respiratory distress syndrome (ARDS) in a Brazilian ICU. Methods: This prospective observational, non-interventional study, included all consecutive patients with ARDS criteria [1] admitted in the ICU of a Brazilian tertiary hospital, between January 1997 and September 2001. Were collected in a prospective fashion the following variables: age, gender, APACHE II score at ICU admission and at ARDS diagnosis, cause of ARDS, presence of AIDS, cancer and immunosuppression, occurrence of barotrauma, performance of traqueostomy, mortality, duration of mechanical ventilation (MV), length of stay (LOS) in ICU and in hospital. The lung injury score (LIS) [2] was used to quantify the degree of pulmonary injury in the first week of ARDS. Results: There was 2182 patients (P) admitted in ICU during the study period, of whom 141 (6.46%) had ARDS criteria. Seventy-six (54%) were men, the mean age was 46 ± 18 years, APACHE II 18 ± 7 and 19 ± 7 at admission and at ARDS diagnosis, respectively. Septic shock accounted for 42% (60 P) of the ARDS causes, sepsis 22% (31 P), diffuse pulmonary infection 16% (23 P), aspiration pneumonia 11% (15 P), non-septic shock 5% (7 P) and others 4% (5 P). Ten percent (14 P) had AIDS, 30% (43 P) cancer and 25% (36 P) immunosuppression. All patients were mechanically ventilated with Tidal Volume between 4 and 8 ml/kg. Only 3.5% (5 P) had barotrauma and 10% (14 P) performed traqueostomy. Mortality rate was 79% in the ICU. The patients required 12 ± 10 days on MV, ranging from 1 to 55 days. The LOS in ICU and hospital was 14 ± 13 (1-69) days and 28 ± 32 (1-325) days, respectively. There was a time delay of 3.7 ± 4.5 days between admission in ICU and the onset of ARDS. The Murray score (mean ± SD) was 3.2 ± 0.4, 3 ± 0.5, 3 ± 0.5, 2.9 ± 0.6, 2.8 ± 0.7, 2.7 ± 0.7 and 2.6 ± 0.8 in the first 7 days, respectively. Conclusions: ARDS in our hospital has a similar incidence of reports in the USA and Europe. There was a higher mortality, which could be explained by a high incidence of infection causes of ARDS, mainly septic shock, and elevated combined occurrence of AIDS, cancer and immunosuppression, along the degree of LIS. The incidence of barotrauma was low, as a consequence of the current mechanical ventilation strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.