1.Comparison of Factors Associated With Direct Versus Transferred-in Admission to Government-Designated Regional Centers Between Acute Ischemic Stroke and Myocardial Infarction in Korea
Dae-Hyun KIM ; Seok-Joo MOON ; Juneyoung LEE ; Jae-Kwan CHA ; Moo Hyun KIM ; Jong-Sung PARK ; Byeolnim BAN ; Jihoon KANG ; Beom Joon KIM ; Won-Seok KIM ; Chang-Hwan YOON ; Heeyoung LEE ; Seongheon KIM ; Eun Kyoung KANG ; Ae-Young HER ; Cindy W YOON ; Joung-Ho RHA ; Seong-Ill WOO ; Won Kyung LEE ; Han-Young JUNG ; Jang Hoon LEE ; Hun Sik PARK ; Yang-Ha HWANG ; Keonyeop KIM ; Rock Bum KIM ; Nack-Cheon CHOI ; Jinyong HWANG ; Hyun-Woong PARK ; Ki Soo PARK ; SangHak YI ; Jae Young CHO ; Nam-Ho KIM ; Kang-Ho CHOI ; Juhan KIM ; Jae-Young HAN ; Jay Chol CHOI ; Song-Yi KIM ; Joon-Hyouk CHOI ; Jei KIM ; Min Kyun SOHN ; Si Wan CHOI ; Dong-Ick SHIN ; Sang Yeub LEE ; Jang-Whan BAE ; Kun Sei LEE ; Hee-Joon BAE
Journal of Korean Medical Science 2022;37(42):e305-
Background:
There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI.
Methods:
Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed.
Results:
Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI.
Conclusions
Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.
2.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
3.Percutaneous Left Atrial Appendage Occlusion Yields Favorable Neurological Outcomes in Patients with Non-Valvular Atrial Fibrillation
Oh-Hyun LEE ; Young Dae KIM ; Jung-Sun KIM ; Nak-Hoon SON ; Hui-Nam PAK ; Boyoung JOUNG ; Cheol-Woong YU ; Hyun-Jong LEE ; Woong-Chol KANG ; Eun-Seok SHIN ; Rak-kyeong CHOI ; Do-Sun LIM ; Yo Han JUNG ; Hye-Yeon CHOI ; Kyung-Yul LEE ; Bang-Hoon CHO ; Sang Won HAN ; Joong Hyun PARK ; Han-Jin CHO ; Hyung Jong PARK ; Hyo Suk NAM ; Ji Hoe HEO ; Chak-yu SO ; Gary Shing-Him CHEUNG ; Yat-yin LAM ; Xavier FREIXA ; Apostolos TZIKAS ; Yangsoo JANG ; Jai-Wun PARK
Korean Circulation Journal 2021;51(7):626-638
Background and Objectives:
Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy.
Methods:
Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke.
Results:
mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01).
Conclusions
Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.
4.Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia: The Fimasartan-Based Blood Pressure Control after Acute Cerebral Ischemia Study
Keun-Sik HONG ; Sun Uck KWON ; Jong-Ho PARK ; Jae-Kwan CHA ; Jin-Man JUNG ; Yong-Jae KIM ; Kyung Bok LEE ; Sung Il SOHN ; Yong-Seok LEE ; Joung-Ho RHA ; Jee-Hyun KWON ; Sang Won HAN ; Bum Joon KIM ; Jaseong KOO ; Jay Chol CHOI ; Sang Min SUNG ; Soo Joo LEE ; Man-Seok PARK ; Seong Hwan AHN ; Oh Young BANG ; Yang-Ha HWANG ; Hyo Suk NAM ; Jong-Moo PARK ; Hee-Joon BAE ; Eung Gyu KIM ; Kyung-Yul LEE ; Mi Sun OH
Journal of Clinical Neurology 2021;17(3):344-353
Background:
and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia.
Methods:
This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293).
Results:
Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event.
Conclusions
Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.
5.Percutaneous Left Atrial Appendage Occlusion Yields Favorable Neurological Outcomes in Patients with Non-Valvular Atrial Fibrillation
Oh-Hyun LEE ; Young Dae KIM ; Jung-Sun KIM ; Nak-Hoon SON ; Hui-Nam PAK ; Boyoung JOUNG ; Cheol-Woong YU ; Hyun-Jong LEE ; Woong-Chol KANG ; Eun-Seok SHIN ; Rak-kyeong CHOI ; Do-Sun LIM ; Yo Han JUNG ; Hye-Yeon CHOI ; Kyung-Yul LEE ; Bang-Hoon CHO ; Sang Won HAN ; Joong Hyun PARK ; Han-Jin CHO ; Hyung Jong PARK ; Hyo Suk NAM ; Ji Hoe HEO ; Chak-yu SO ; Gary Shing-Him CHEUNG ; Yat-yin LAM ; Xavier FREIXA ; Apostolos TZIKAS ; Yangsoo JANG ; Jai-Wun PARK
Korean Circulation Journal 2021;51(7):626-638
Background and Objectives:
Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy.
Methods:
Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke.
Results:
mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01).
Conclusions
Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.
6.Executive Summary of Stroke Statistics in Korea 2018: A Report from the Epidemiology Research Council of the Korean Stroke Society
Jun Yup KIM ; Kyusik KANG ; Jihoon KANG ; Jaseong KOO ; Dae Hyun KIM ; Beom Joon KIM ; Wook Joo KIM ; Eung Gyu KIM ; Jae Guk KIM ; Jeong Min KIM ; Joon Tae KIM ; Chulho KIM ; Hyun Wook NAH ; Kwang Yeol PARK ; Moo Seok PARK ; Jong Moo PARK ; Jong Ho PARK ; Tai Hwan PARK ; Hong Kyun PARK ; Woo Keun SEO ; Jung Hwa SEO ; Tae Jin SONG ; Seong Hwan AHN ; Mi Sun OH ; Hyung Geun OH ; Sungwook YU ; Keon Joo LEE ; Kyung Bok LEE ; Kijeong LEE ; Sang Hwa LEE ; Soo Joo LEE ; Min Uk JANG ; Jong Won CHUNG ; Yong Jin CHO ; Kang Ho CHOI ; Jay Chol CHOI ; Keun Sik HONG ; Yang Ha HWANG ; Seong Eun KIM ; Ji Sung LEE ; Jimi CHOI ; Min Sun KIM ; Ye Jin KIM ; Jinmi SEOK ; Sujung JANG ; Seokwan HAN ; Hee Won HAN ; Jin Hyuk HONG ; Hyori YUN ; Juneyoung LEE ; Hee Joon BAE
Journal of Stroke 2019;21(1):42-59
Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the “Stroke Statistics in Korea” project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.
Adult
;
Aged
;
Alcohol Drinking
;
Ambulances
;
Atrial Fibrillation
;
Cerebral Hemorrhage
;
Emergency Medical Services
;
Emergency Service, Hospital
;
Epidemiology
;
Female
;
Hemorrhage
;
Hope
;
Humans
;
Hypertension
;
Incidence
;
Korea
;
Male
;
Mortality
;
Prevalence
;
Reperfusion
;
Risk Factors
;
Smoke
;
Smoking
;
Stroke
;
Subarachnoid Hemorrhage
;
Writing
7.Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment.
Yongsik JUNG ; Soo Jung LEE ; Juneyoung LEE ; Woo Chul NOH ; Seok Jin NAM ; Byeong Woo PARK ; Young Tae BAE ; Sung Soo KANG ; Heung Kyu PARK ; Jung Han YOON ; Je Ryong KIM ; Se Hun CHO ; Lee Su KIM ; Byung In MOON ; Sung Hoo JUNG ; Chol Wan LIM ; Sung Yong KIM ; Ho Yong PARK ; Jeongyoon SONG ; Kwang Man LEE ; Sung Hwan PARK ; Joon JEONG ; Hae Lin PARK ; Sung Won KIM ; Beom Seok KWAK ; Sun Hee KANG ; Young Up CHO ; Geum Hee GWAK ; Yong Lae PARK ; Sang Wook KIM ; Sehwan HAN
Journal of Breast Cancer 2018;21(2):182-189
PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.
Aromatase
;
Asian Continental Ancestry Group
;
Bone Density
;
Breast Neoplasms*
;
Breast*
;
Chemotherapy, Adjuvant
;
Cholesterol
;
Consent Forms
;
Female
;
Humans
;
Observational Study
;
Quality of Life*
8.MRI-based Algorithm for Acute Ischemic Stroke Subtype Classification.
Youngchai KO ; Soojoo LEE ; Jong Won CHUNG ; Moon Ku HAN ; Jong Moo PARK ; Kyusik KANG ; Tai Hwan PARK ; Sang Soon PARK ; Yong Jin CHO ; Keun Sik HONG ; Kyung Bok LEE ; Jun LEE ; Dong Eog KIM ; Dae Hyun KIM ; Jae Kwan CHA ; Joon Tae KIM ; Jay Chol CHOI ; Dong Ick SHIN ; Ji Sung LEE ; Juneyoung LEE ; Kyung Ho YU ; Byung Chul LEE ; Hee Joon BAE
Journal of Stroke 2014;16(3):161-172
BACKGROUND AND PURPOSE: In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC). METHODS: We enrolled patients who experienced an acute ischemic stroke, were hospitalized in the 14 participating centers within 7 days of onset, and had relevant lesions on MR-diffusion weighted imaging (DWI). MAGIC was designed to reflect recent advances in stroke imaging and thrombolytic therapy. The inter-rater reliability was compared with and without MAGIC to classify the Trial of Org 10172 in Acute Stroke Treatment (TOAST) of each stroke patient. MAGIC was then applied to all stroke patients hospitalized since July 2011, and information about stroke subtypes, other clinical characteristics, and stroke recurrence was collected via a web-based registry database. RESULTS: The overall intra-class correlation coefficient (ICC) value was 0.43 (95% CI, 0.31-0.57) for MAGIC and 0.28 (95% CI, 0.18-0.42) for TOAST. Large artery atherosclerosis (LAA) was the most common cause of acute ischemic stroke (38.3%), followed by cardioembolism (CE, 22.8%), undetermined cause (UD, 22.2%), and small-vessel occlusion (SVO, 14.6%). One-year stroke recurrence rates were the highest for two or more UDs (11.80%), followed by LAA (7.30%), CE (5.60%), and SVO (2.50%). CONCLUSIONS: Despite several limitations, this study shows that the MAGIC system is feasible and may be helpful to classify stroke subtype in the clinic.
Arteries
;
Atherosclerosis
;
Classification*
;
Diagnosis
;
Humans
;
Magic
;
Magnetic Resonance Imaging
;
Recurrence
;
Stroke*
;
Thrombolytic Therapy
9.Intralobar Pulmonary Sequestration Receiving Its Blood Supply from the Celiac Artery.
Ki Hwan JUNG ; Seung Hwa LEE ; Ju Han LEE ; Won Min JO ; Chol SHIN ; Je Hyeong KIM
Tuberculosis and Respiratory Diseases 2010;68(6):358-362
Intralobar pulmonary sequestration is a rare congenital lung anomaly. It is defined as a portion of nonfunctioning lung parenchyma that receives its blood supply from an anomalous systemic artery. Patients often present with chronic or recurrent pneumonia. A chest radiograph may show a cystic lesion with air-fluid levels in the lung base. A high index of suspicion is needed for a diagnosis. Surgical removal of a symptomatic intralobar pulmonary sequestration is generally the treatment of choice. Identifying the aberrant artery is a difficult problem when resecting a pulmonary sequestration. The thoracic and abdominal aortas are the most common origins for the abnormal blood supply. However, arterial supply from the celiac artery is quite rare. We present a case of intralobar pulmonary sequestration with the blood supply originating from the celiac artery.
Aorta, Abdominal
;
Arteries
;
Bronchopulmonary Sequestration
;
Celiac Artery
;
Humans
;
Lung
;
Pneumonia
;
Respiratory System Abnormalities
;
Thorax
10.Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Augments Acute Lung Injury via Its Neutrophil Priming Effects.
Jae Chol CHOI ; Jae Woo JUNG ; Hee Won KWAK ; Ju Han SONG ; Eun Ju JEON ; Jong Wook SHIN ; In Won PARK ; Byoung Whui CHOI ; Jae Yeol KIM
Journal of Korean Medical Science 2008;23(2):288-295
Granulocyte macrophage-colony stimulating factor (GM-CSF) has immuno-stimulatory effects. We hypothesized that GM-CSF plays an important role both in lipopolysaccharide (LPS)- and hemorrhage-induced acute lung injury (ALI). We also postulated that GM-CSF augments LPS-induced inflammation by priming neutrophils. ALI was induced in GM-CSF-/- or control C57BL mice either by LPS injection or by hemorrhage. Lung inflammation (by lung expression for tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin-1beta (IL-1beta), interleukin- 6 (IL-6), and keratinocyte-derived chemokine) and lung injury (by myeloperoxidase and evans blue dye assay) were evaluated after ALI. Incremental doses of LPS (0, 1, 10, and 100 ng/mL) and GM-CSF (0, 1, 10, and 100 ng/mL) were added to bone marrow neutrophils. The expression of TNF-alpha, MIP-2, and IL-1beta was evaluated with enzyme linked immunosorbent assay. The mRNA expression of three cytokines, and the nuclear translocation of nuclear factor kappa B (NF kappa-B) were evaluated by reverse transcriptase-polymerase chain reaction and electropnoretic mobility shift assay, respectively. GM-CSF -/- mice showed decreased neutrophil infiltration, less leakage, and lower expression of cytokines in the lung after LPS or hemorrhage. GM-CSF augmented LPS-induced protein and mRNA expression of TNF-alpha, MIP-2 and IL-1beta, which was mediated by increased intra-nuclear translocation of NF-kappa B. GM-CSF plays an important role in high-dose LPS and hemorrhage-induced ALI, which appears to be mediated by its priming effect on neutrophils.
Animals
;
Bone Marrow Cells/cytology
;
Chemokine CXCL2/metabolism
;
Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/*physiology
;
Interleukin-1beta/metabolism
;
Lipopolysaccharides/metabolism
;
Lung/metabolism/pathology
;
*Lung Injury
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Neutrophils/*cytology/metabolism
;
Peroxidase/metabolism
;
Tumor Necrosis Factor-alpha/metabolism

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