• Title, Summary, Keyword: angiotensin II

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Attenuation of Reperfusion Injury with Angiotension $AT_1$ Receptor Blockade in Rat Myocardial Ischemic Model (백서 심근 허혈 모델에서 angiotension $AT_1$수용체 차단제의 재관류 손상 감소 효과)

  • Choi, Jun-Young;Choi, Dong-Ju;Ahn, Hyuk
    • The Korean Journal of Thoracic and Cardiovascular Surgery
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    • v.34 no.3
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    • pp.203-211
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    • 2001
  • 배경: AT$_1$수용체의 길항제가 세포 수준에서 심근을 재관류 손사으로부터 보호할수 있다는 것으로 알려져 있지만, 생체내에서의 효과나 그 기전은 아직 명확히 밝혀지지 않았다. 본 연구에서는 백서 심근 허혈 모델을 이용하여, AT$_1$ 수용체의 길항제들 중 하나인 irbesartan이 심근이 재관휴 손상에 미치는 효과를 알아보고, 재관류 손상을 매개하는 한 각지 기전으로서 세포자멸의 기여에 대하여 연구하고자 하였다. 대상 및 방법: Sprague-Dawley 백서에서 무작용 부형약(10% gum arabic: 1군, 개체수=14관) irbesartan(50mg/kg/day :II 군, 개체수=12)을 각각 3일 동안 24시간마다 경구로 투여하였다. 실험동물의 좌 관상 동맥을 45분간 결찰하였다가, 그 후 2시간 동안 재관류시킨 다음 심장을 적출 하였다. TTC(triphenyltetrazolium chloride) 염색법을 이용하여, 허혈 노출 부위에 대한 심근 경색 부위의 비율을 측정하였다. Agarose gel 전기영동상의 DNa 분절 양상과 TUNEL(TdT-mediated dUCP nick end labeling) 염색을 관찰하여 세포자멸이 일어난 정도를 평가하였다. 세포자멸을 조절하는데 관여하는 것으로 알려진 Bcl-2(B-cell lymphoma 2 gene), Bad 등의 단백과 ERK (extracellular signal-regulated kinase), p-38 등 신호전달체계에 작용하는 MAPKs(mitogen-activated protein kinases)의 발현을 측정하기 위하여 Western blot을 시행하였다. 결과: 허혈 노출부위에 대한 심근 경색부위의 비율은 II군(42$\pm$2.7%)이 I군( 64.1$\pm$4.65)에 비해 유의하게 작았다.(p< 0.05), Agarose gel 전기영동상의 DNA laddering 양상은 I군에서 보다 높게 발현되었다. Bad와 ERK2의 발현은 두 군간에 유의한 차이가 없었다. 결론: AT$_1$수용체 길항제인 irbesartan은 생체에서 심근의 재관류 손상을 줄이는 효과가 있었다. 이 효과는 적어도 부분적으로 나만 심근세포의 세포자멸이 감소한 것에 기인한 것으로 설명할 수 있으며, 이 항-세포 자멸 효과는 Bcl-2의 발현증가와 관련이 있는 것으로 추정되었다.

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Changes of Quality and Physiological Functionality during the Fermentation of Doenjangs Made by Isolated Nuruk Mold and Commercial Nuruk Mold (분리국균과 시판국균으로 제조한 된장의 숙성 중 품질과 생리기능성 변화)

  • No, Jae-Duck;Lee, Dae-Hyung;Lee, Dae-Hyoung;Choi, Shin-Yang;Kim, Na-Mi;Lee, Jong-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.8
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    • pp.1025-1030
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    • 2006
  • In other to develop new functional doenjangs, two types of the isolated nuruk doenjangs were prepared with protease and amylase-producing Aspergillus oryzae D-2 and antihyperlipidemia Bacillus subtilis LK-12 and then changes of its quality and physiological functionalities were investigated during 2 months of fermentation and compared with those of the commercial nuruk doenjangs made by commercial Aspergillus oryzae and antihyperlipidemia Bacillus subtilis LK-12. ${\alpha}-Amylase$ activity of the isolated nuruk doenjangs during fermentation were decreased slightly, whereas proteases activities were increased significantly to $1.8{\sim}2.8$ Unit per mL after 1 month of fermentation. These ${\alpha}-amylase$ activities and proteases activities were similar with those of the commercial nuruk doenjangs. Amino-nitrogen content and reducing sugar content of the doenjangs after 2 months of fermentation were approximate $1.63{\sim}1.72\;mg%$ and $0.77{\sim}0.81%$, respectively. Antihypertensive angiotensin-Ⅰ converting enzyme inhibitory activities of the isolated nuruk doenjangs were slightly decreased from $85.6{\sim}87.2%$ to $84.0{\sim}85.1%$ after 2 months of fermentation and the commercial nuruk doenjangs were also significantly decreased from $85.7{\sim}88.0%$ to $69.1{\sim}79.7%$, lower than the isolated nuruk doenjangs. Fibrinolytic activity and HMG-CoA reductase inhibitory activity of the isolated nuruk doenjangs were very low and it were also similar with those of the commercial nuruk doenjangs. Antioxidant activity of the isolated nuruk doenjangs were showed $17{\sim}22%$, lower than that of the commercial nuruk doenjangs $(22{\sim}26%)$.

Clinicopathologic Changes of IgA Nephropathy in Children During Long-term (average 10.8 yrs) Follow-up (소아 IgA 신병증의 장기 추적(평균 10.8년)에 따른 임상 경과 및 병리학적 변화)

  • Moon, Chang-Min;Kim, Pyung-Kil;Lim, Beom-Jin;Song, Ji-Sun;Jeong, Hyeon-Joo
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.154-165
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    • 2010
  • Purpose : We know little about the natural course of IgA nephropathy (IgAN) in association with histologic changes especially in children. We investigated clinicopathologic features with long-term follow-up biopsy to clarify the outcomes and prognostic indicators for childhood IgAN. Methods : From our patients' medical records, we retrieved 20 patients with IgAN, to whom renal biopsies had been performed for the initial diagnosis and follow-up to find out any histologic changes. Initial and follow-up biopsies were classified by Haas classification. The changes of these parameters were compared with the evolution of clinical features. Results : Patients were treated with angiotensin-converting enzyme inhibitors in combination with angiotensin receptor blockers (in subclass II or above) and short-term cyclosporine A(in patients showing nephrotic syndrome). Histologic improvement in 7 cases and deterioration in 3 cases were observed. At the time of last biopsy, 10 cases (50%) showed clinical remission and the others showed improved clinical features. These clinical outcomes did not correlate with initial Haas classifications. Hypertension at onset observed in 5 cases (25%) revealed significant correlation with clinical outcome (P =0.01) and last Haas classification (P =0.007). None of the cases showed progression to CRF or ESRD. Conclusion : During a mean follow-up of $10.8{\pm}3.4$ years, childhood IgAN showed good clinicopathologic outcome. Hypertension at onset was only a strong predictor of clinicopathologic outcomes, but initial Haas classification cannot predict outcomes in children. Histologic change of IgAN in long term follow-up period cannot be completely predicted by clinical data and vice versa. Therefore, a renal biopsy should be considered as a part of follow-up plan.

The Relation between Obesity and Glomerular Filtration Rate in Children and Adolescents (소아 및 청소년에서 비만과 사구체여과율과의 관계)

  • Jung, Youngsu;Kim, Dongwoon;Lim, Inseok
    • Clinical and Experimental Pediatrics
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    • v.48 no.11
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    • pp.1219-1224
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    • 2005
  • Purpose : The prevalence of obesity in children and adolescents has been rising rapidly in Korea because of changes of diet and lifestyle. As with adults, obesity in children and adolescents can cause diabetes mellitus, hyperlipidemia, cardiovascular diseases and renal diseases. The aim of the present study is to examine the relation of obesity, glomerular filtration rate(GFR) and serum cystatin C concentration in children and adolescents. Methods : Data of 115 children and adolescents aged between 6 years and 20 years without clinical evidence of renal diseases were included in the study. From May 2004 to December 2004, blood samples were collected from children and adolescents who were seen at the Department of Pediatrics at Chungang University Yongsan Hospital. Obesity degrees and body mass indices(BMI) were measured, and GFRs were estimated from Schwartz's formula. Serum cystatin C was measured by particle enhanced nephelometric immunoassay using Behring Nephelometer II. Results : GFRs were significantly different between the obese group(BMI >95 percentile, $145.79{\pm}23.10mL/min$) and the non-obese group(BMI <95 percentile, $134.61{\pm}26.19mL/min$) divided by BMI (P=0.031). GFRs were not significantly different between the obese group(obesity degree >120 percent, $144.29{\pm}23.08mL/min$) and the non-obese group(obesity degree <120 percent, $134.54{\pm}26.57mL/min$) divided by obesity degree(P=0.051), but were significantly different between severe obese group (obesity degree >150 percent, $155.55{\pm}20.40mL/min$) and the non-obese group(P=0.004). GFRs were correlated positively with BMI($r^2=0.037$, P=0.039), but were not correlated significantly with obesity degree($r^2=0.030$, P=0.066). Serum cystatin C concentrations were not significantly different between the obese group and the non-obese group, divided by BMI as well as by obesity degree(P>0.05). Conclusion : Obesity may lead to an alteration of renal hemodynamics such as hyperfiltration, appropriate control and management for obesity is necessary.

Telmisartan increases hepatic glucose production via protein kinase C ζ-dependent insulin receptor substrate-1 phosphorylation in HepG2 cells and mouse liver

  • Cho, Kae Won;Cho, Du-Hyong
    • Yeungnam University Journal of Medicine
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    • v.36 no.1
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    • pp.26-35
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    • 2019
  • Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

$Na^{+}/Ca^{2+}$ Exchange System in Atrial Trabeculae and Vascular Smooth Muscle of the Rabbit (토끼 심방근 및 혈관 평활근에서의 $Na^{+}/Ca^{2+}$ 교환기전에 관한 연구)

  • Kim, Hee-Ju;Moon, Hyung-Ro;Earm, Yung-E;Ho, Won-Kyung
    • The Korean journal of physiology & pharmacology
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    • v.22 no.1
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    • pp.13-29
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    • 1988
  • In order to elucidate the regulatory mechanism of intracellular calcium ion concentrations, contractions or contractures induced by $Na^{+}-removal$, calcium-application or ouabain-treatment as an index of $Na^+/Ca^{2+}$ exchange activity were studied in atrial muscle or vascular smooth muscle (aorta and renal artery) of the rabbit. The magnitude of low sodium contractures in atrial trabeculae increased with sigmoid shape when external sodium concentrations were reduced to sodium-free condition, whereas that of calcium contracture intensified in a parabolic pattern when external calcium concentrations were elevated to 8 mM. $Na^{+}-removal$ contractures were induced in a duration-dependent manner to $K^{+}-free$ exposure and same findings were observed with ouabain treatment. $Na^{+}-free$ contractures were not affected by verapamil treatment, but stimulated by $100{\mu}M\;Mn^{2+}$ and inhibited by high concentrations of $Mn^{2+}\;(2{\sim}8mM)$ in a dose-dependent manner. Ryanodine which is known to suppress the release of calcium from internal store abolished spontaneous twitch contractions induced by $K^{+}-free$ solution, but had no effect on the development $Na^{+}-free$ contractures. Na-free contractures were not always induced in vascular smooth muscle preparations. Contractures by $O\;mM\;Na^+$ were usually seen in aorta, but not often in renal artery.$50\;mM\;K^+$, noradrenaline (NA) and angiotensin II (AII) always evoked very large contraction in all preparations of vascular smooth muscle. Contractures developed by $O\;mM\;Na^+$ were not sensitive to verapamil treatment as in atrial trabeculae, but were abolished by $100{\mu}M\;Mn^{2+}$. In contrast to $Na^{+}-free$ contractures, $Mn^{2+}(100{\mu}M)$ had no effect on the contractures induced by NA or 50 mM$K^+$. Caffeine in the concentration of 10 mM evoked transient contracture in the distal renal artery. The rate of spontaneous relaxation in caffeine contracture was dependent upon the concentrations of external sodium, and had double component of relaxation when the rate of relaxation was plotted in the semilogarithmic scale of relative tension versus time. Especially late components of relaxation had more direct relation to $Na^+$ concentrations. It could be concluded that $Na^+/Ca^{2+}$ exchange mechanism in the heart has a large capacity, inhibited by $Mn^{2+}$ but not by verapamil and ryanodine, while $Na^+/Ca^{2+}$ exchange system in vascular smooth muscle has a very low capacity especially in small artery, inhibited by low concentration of $Mn^{2+}\;(100{\mu}M)$ but not affected by verapamil and ryanodine.

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Determinants of Erythropoietin Hyporesponsiveness in Management of Anemia in Hemodialysis Patients (혈액투석 환자의 빈혈관리에서 Erythropoietin 반응에 영향을 미치는 인자)

  • Shin, Seung-Hee;Ji, Eun-Hee;Lee, Young-Sook;Oh, Jung-Mi
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.122-130
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    • 2011
  • Objective: Although recombinant human erythropoietin (rhEPO) has revolutionized the treatment of anemia in chronic kidney disease (CKD) receiving hemodialysis (HD) with no need of blood transfusion, some patients have a blunted or appear to be resistant to rhEPO. There is a controversy in the causes of rhEPO resistance in maintenance HD patients with anemia. This study is to examine current anemia treatment outcomes and the factors influencing the rhEPO responsiveness in HD patient with CKD. Methods: The clinical parameters or factors relating to erythrompoietin treatment outcomes and erythropoietin responsiveness were collected from the HD patients in two large dialysis centers for three months. The collected paramenters included serum iron, total iron biding capacity (TIBC), transferrin saturation rate, ferritin, albumin, intact PTH, C-reactive protein (CRP), nPCR and medications such as an angiotensin converting enzyme inhbitor, an angiotension II receptor blocker and an HMG-CoA reductase inhibitor (HMG-CoA RI). The data were analyzed to examine the degree of acheiveing the anemia treatment goal and factors relating to ERI. Results: Among total 111 patients, 42 (42.3%) and 47 (37.8%) patients achieved the target Hct and Hb based on the Health Insurance Review and Assessment Services (HIRA) reimbursement criteria. In the higher ERI group (upper quartile), the patients had higher CRP levels (0.5 mg/dl) (p=0.0096), and lower TIBC score (<$240{\mu}g/dl$) (p=0.0027), and less patients were taking HMG-CoA RI (p=0.0019). Male patients (p=0.0204), patients with high TIBC score ($R^2$=0.084, p=0.0021) and patients taking HMG-CoA RI (p=0.0052) required to administer less dose of rhEPO meaning higher erythropoietin responsiveness. Conclusion: Less than 50% of CKD patients were achieving the goals of anemia by erythropoietin administration in large hospitals in Korea even though the goals were lower than those of NKF-K/DOQI practice guideline. The factors influencing ERI were sex, TIBC and HMG-CoA RI administration status, and neither an ACEI nor an ARB did not influence ERI.

Bioequivalence of Losata Tablet to Cozaar Tablet (Losartan Potassium 50 mg) using HPLC with Fluorescence Detector (고속액체크로마토그래피-형광검출기를 이용한 코자 정(로자탄칼륨 50 mg)에 대한 로사타 정의 생물학적동등성)

  • Kang, Hyun-Ah;Kim, Se-Mi;Yoo, Dong-Jin;Kang, Seung-Rae;Lee, Sang-No;Kim, Yong-Hee;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.40 no.1
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    • pp.51-57
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    • 2010
  • Losartan potassium, 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol mono-potassium salt, is a new class of antihypertensive agents, and is an antagonist in angiotensin receptor. The purpose of the present study was to evaluate the bioequivalence of two Losartan potassium tablets, Cozaar tablet (MSD Pharmaceutical Co., Ltd.) and Losata tablet (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of losartan from the two losartan potassium formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male subjects, $23.86{\pm}1.80$ years in age and $67.27{\pm}6.60\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 50 mg as losartan potassium was orally administered, blood samples were taken at predetermined time intervals, and the concentrations of losartan in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and Equiv Test/K-BE Test 2002 was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Cozaar, were -2.70%, 1.45% and 2.31% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.8852~log 1.0655 and log 0.8319~log 1.2342 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Losata tablet was bioequivalent to Cozaar tablet.

Physicochemical and Functional Properties of Kochujang with Broccoli Leaf Powder (브로콜리잎 분말 첨가 재래식 고추장의 이화학적 및 기능적 특성)

  • Oh, You-Sung;Baek, Jin-Woo;Park, Kyeong-Yeol;Hwang, Joon-Ho;Lim, Sang-Bin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.5
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    • pp.675-681
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    • 2013
  • Home-made broccoli Kochujang (HMBK) was prepared with the addition of 5% broccoli leaf powder. Its physicochemical and functional properties were measured in extracts (80% methanol, 80% ethanol, and distilled water) and compared with home-made Kochujang (HMK) and factory-produced Kochujang (FPK). Total phenolic content (TPC) was 22% higher in methanol extract from HMBK (524.2 GAE/100 g) compared to HMK (431.0 GAE/100 g). TPC was 8% higher in ethanol extract from HMBK (541.9 GAE/100 g) compared to HMK (499.9 GAE/100 g). DPPH radical scavenging activity was 1.6 times higher in the methanol extracts from HMBK than HMK. In contrast there was no difference in DPPH radical scavenging activity between HMBK and HMK. Oxygen radical absorbance capacities in methanol and ethanol extracts from HMBK were similar to HMK, but both were higher than extracts from FPK (55% and 23% higher, respectively). Inhibition of angiotensin I converting enzyme activity in methanol extracts from HMBK was similar to HMK, but it was 2.6 times higher than inhibition activities from FPK. Interestingly, only ethanol extract from HMBK showed a 10.7% and 18.3% inhibition on cell growth of the human colon adenocarcinoma grade II cell line (HT-29) and human lung carcinoma cell line (NCI-H1229), respectively. These results indicate home-made Kochujang with broccoli leaf powder contains high total phenolics, antioxidant activities, and cancer cell growth inhibition activities.

Bronchial Responsiveness in Patients with Mitral Valvular Heart Disease (승모판 심장질환 환자에서 기관지 반응성에 대한 연구)

  • Kim, Ho-Cheol;Kim, Min-Gu;Hwang, Young-Sil
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.752-759
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    • 1995
  • Background: Bronchial asthma is characterized by noctunal dyspnea, cough and wheezing because of airway hyperresponsiveness to nonspecific stimuli. These symptoms and signs are also observed in patients with congestive heart failure. Therefore, this is so called "cardiac asthma". There are lots of experimental and clinical datas to suggest that airway dysfunctions occur in acute and chronic congestive heart failure. However, it is still controversial whether bronchial hyperresponsiveness is present in patients with congestive heart failure. To assess whether bronchial hyperresponsiveness is present in patients with congestive heart failure and to demonstrate the relationship between bronchial responsiveness and vascular pressure, we performed methacholine provocation test in 11 patients with mitral valvular heart disease. Methods: All patients were in the New York Heart Association functional class II and treated continuously with digoxin and/or dichlozid and/or angiotensin converting enzyme inhibitor except one patient. All patients were undergone right and left side heart catheterization for hemodynamic measurements. A 20 percent fall of peak expiratory flow rate were considered as positive response to methacholine provocation test. Results: 1) Only one patient who has normal pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index was positive in methacholine provocation test. 2) Their mean pulmonary artery pressure, pulmonary capillary wedge pressure were $21.72{\pm}9.70mmHg$, $15.45{\pm}8.69mmHg$ respectively which were significantly higher. Conclusion: It is speculated that in stable congestive heart failure patients, bronchial responsiveness as assessed by methacholine provocation test may not be increased.

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