천식의 발병 기전

인광호,In, Kwang-Ho 한국생명보험의학회 2003 保險醫學會誌 Vol.22 No.-

폐결핵 환자에서의 발열의 빈도 및 화학치료에 대한 반응

인광호(Kwang Ho In),조재연(Jae Yon Cho),강경호(Kyung Ho Kang),유세화(Se Hwa Yoo) 대한내과학회 1991 대한내과학회지 Vol.40 No.2

N/A Fever is often used clinically to judge the severity of pulmonary tuberculosis and to evaluate its response to therapy. Sometimes fever persists for a long time even after starting chemotherapy. Records of 101 hospitalized patients with pulmonary tuberculosis were reviewed to investigate the incidence of fever, fever response to modern chemotherapy and analyzed possible factors affecting fever response in pulmonary tuberculosis. The results were as follows: 1) sixty-eight patients among 101 (69%) were febrile on admission. 2) There were no significant differences between febrile and afebrile groups in the extent of tuberculous lesion, presence of symptoms, and sputum smear positivity of acid-fast bacilli. 3) In febrile patients, the duration of fever after initiation of chemotherapy was short (mean, 5 days; range, 1 to 74 days). 4) In febrile patients there were no significant differences between early responders (<1 week) and the late responders (>1 week) in the extent of lesion, presence of symptoms, and smear positivity of acid-fast bacilli. In conclusion, the incidence of fever in pulmonary tuberculosis is high among admitted patients and fever subside after a few days of treatment in most cases, but sometimes it may persist much longer time.

기관내삽관과 기관절개술을 시행한 환자에서의 폐흡인에 관한 연구

인광호(Kwang Ho In),안태훈(Tae Hoon Ahn),유진목(Zin Moc Yu),강경호(Kyung Ho Kang),유세화(Se Hwa Yoo) 대한내과학회 1988 대한내과학회지 Vol.35 No.3

N/A Aspiration is a well recognized source of pulmonary infection. In most clinical situations, however, the actual incidence of aspiration has not been well documented, We investigated the incidence of pulmonary aspiration and the factors affecting aspiration in patients with intubation and tracheostomy. Aspiration was evaluated by applying Evans blue dye to the posterior tongue just after each formula tube feeding for 24 hours. Bluish discoloration and elevated glucose concentration of the material suctioned from the artificial airway were regarded as evidence of aspiration. The results obtained were as follows: 1) The incidence of pulmonary aspiration in patients with intubation or tracheostomy was high (69%), 2) Unconscious patients tended to aspirate frequently, but the presence or absence of ventilatory support, tracheostomy or intubation did not play a significant role in the development of aspiration. 3) There was only a weak correlation between the Evans blue dye test and the glucose oxidase reagent strip method in detecting pulnonary aspiration. In conclusion, the incidence of pulmonary aspiration in patients with intubation and tracheostomy is very high. These findings suggest that even in the case of intubation and tracheostomy, careful observation of pulmonary aspiration is necessary

실험견의 급성 저 산소성 폐고혈압중에서 내피세포 기원 확장인자 ( EDRF ) 의 역할

김인옥(In Ohk Kim),인광호(Kwang Ho In),조재연(Jae Yun Cho),이진구(Jin Goo Lee),심재정(Jae Jung Shim),강경호(Kyung Ho Kang),유세화(Se Hwa Yoo) 대한내과학회 1994 대한내과학회지 Vol.47 No.6

N/A Objectives : Hypoxic pulmonary vasoconstriction has been well documented in the pulmonary cirulation. However the mechanism and the modulating factors of the hypoxic pulmonary vasoconstriction remain unclarified. With the recent evidences that the endothelium-de- rived relaxing factor (EDRF) is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the results of studies on the role of EDRF during hypoxic pulmonary vasoconstriction have been inconsistent, and the studies in the intact animals are very rare. To investigate the role of EDRF during pulmonary hypertension induced by hypoxia, we measured changes of hemodynamic parameters after adding NO synthesis inhibitor and its substrate. Methods : Five dogs were anesthesized with thiopental sodium. After intubation with an endotracheal tube, the dogs were mechanically ventilated with a Harvard volume-cycled animal ventilator. Venous and arterial catheters were placed in the limb vein and femoral artery. Swan-Ganz catheter was inserted via right internal jugular vein for measuring pulmonary arterial pressure and pulmonary capillary wedge pressure, and cardiac output. We measured the changes of hemodynamic parameters in normoxia and hypoxia and the effects of L-NNA (30 mg/kg) and L-arginine (200 mg/kg). Results : 1) Hypoxia caused a significant increase in pulmonary arterial pressure. 2) The infusion of L-NNA in normoxic state did not change any of the hemodynamic variables. 3) With the infusion of L-NNA, the increase in pulmonary arterial pressure produced by hypoxia were significantly augmented. 4) With the infusion of L-arginine, hypoxic pulmonary hypertension augmented by L-NNA was significantly reversed, Conclusion : L-NNA did not affect the pulmonary arterial pressure in normoxic state, but augmented the pulmonary hypertension during hypoxia and L-arginine reversed the hypoxic pulmonary hypertension almost to control level. It is suggested that diminished EDRF formation contributes greatly to the pulmonary hypertension induced by hypoxia.

기관지 천식 환자에서 천식 증상의 정도에 따른 $\beta_2$ 교감신경 수용체의 유전자 다형성

심재정,김제형,이승룡,권영환,이소라,이상엽,강세용,강용구,조재연,인광호,원남희,유세화,강경호,Shim, Jae-Jeong,Kim, Jei-Hyung,Lee, Seung-Yong,Kwan, Young-Hwan,Lee, So-Ra,Lee, Sang-Youb,Kang, Se-Yong,Kang, Yong-Koo,Cho, Jae-Youn,In, Kwang-Ho,Wo 대한결핵및호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.1

서 론: $\beta_2$ 교감신경 수용체 유전자에는 여러 종류의 다형성(polymorphism)가 존재하며, 천식 환자에서 $\beta_2$ 교감신경 수용체의 대표적인 변이는 $\beta_2$ 교감신경 수용체의 아미노산이 대치된 부분으로 Arg16-Gly, Gln27-Glu, Val34-Met 및 Thr164-Ile 등인 것으로 알려져 있다. 지속적인 $\beta_2$ 교감신경 유도체의 자극에 대하여 세포표면으로 부터 세포내의 전달과정이 둔화되어 점차 세포전달이 없어질 수도 있는 desensitization 또는 수용체와 수가 감소하는 downregulation이 존재하는 것으로 알려져 있다. 천식환자에서 $\beta_2$ 교감신경 수용체의 desensitization 또는 downregulation 뿐만 아니라 천식 표현형과 $\beta_2$ 교감신경 수용체 유전자 다형성의 상관 관계에 대한 연구가 이루어지고 있으나 논란이 많다. 이에 본 연구는 기관지 천식환자에서 $\beta_2$ 교감신경 수용체의 가장 흔한 16, 27, 34 및 164 의 아미노산에 해당하는 유전자의 다형성을 MASA (Mutated Allele Specific Amplification)법으로 시행하여 각각의 다형성의 발생 빈도와 천식의 심한 정도와 연관이 있는 가를 확인하였다. 대상 및 방법: 대상 환자는 천식 환자 103명이었으며, 이중 남자는 54명, 여자는 49명으로 평균 연령은 46.6세 (19~80세)였고 이환 기간은 4.7년이었다. 대상 환자는 경미하고 간헐적 증상을 보인 30명, 지속적인 경미한 천식 환자는 32명으로 경미한 천식은 모두 62명이었으며, 중등증의 천식 증상은 17명 및 중종의 천식증상을 보인 환자는 24명이었다. 이중 1년 중에 6개월 이상 전신적 스테로이드를 투여하는 환자는 39명이었으며, 투약 중에도 야간 발작이나 야간 기침이 발생되었던 환자는 44명이었다. 대상 환자로부터 10cc의 전혈구를 체취 하여 분리된 림파구에서 분리된 DNA를 이용하여 MASA 방법으로 $\beta_2$ 교감신경 수용체 16번, 27번, 34번 및 164번째 아미노산의 다형성을 검색하였고, 천식의 심한 정도 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포와 야간 천식의 발작이나 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포를 확인하였다. 결 과: 16 번째 Arginine이 Glycine으로 변이는 heterozygous 변이가 67명, homozygous 변이가 13명으로 heterozygous 변이가 65.1%로 가장 많았다. 27번째 Glutamine이 Glutamate로 변이는 heterozygous만 11명으로 10.7%였으며, 34번째 Valine이 Methionine으로 변이를 일으키는 100번째 핵산의 경우도 heterozygous만 6명으로 5.8%였다. 27 번째와 34번째 아미노산의 변이를 일으키는 homozygous 변이와 164번째 아미노산의 변이는 대상 환자 중에는 없었다. 천식 증상의 심한 정도를 경종 및 중등증, 중중으로 2 구분하여 $\beta_2$ 교감신경 수용체 다형성의 발생빈도를 관찰한 결과 중증의 천식환자에서 16번째 아미노산의 변이의 빈도는 많았으나 (p=0.015), 27번, 34번 및 164번째의 아미노산의 변이는 천식 증상의 정도와는 연관성이 없었다. 야간 천식 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 다형성은 16, 27, 34 및 164번째 아미노산의 핵산의 변이와 연관성이 없었다. 결 론: 이상의 결과로 기관지 천식 환자에서 $\beta_2$ 교감신경 수용체 다형성은 Arg 16, Gln 27 및 Val 34의 변이가 존재하고, Arg 16이 가장 많았으며, Thr 164는 없었다. 기관지 천식 환자에서 증상이 심한 중증 천식은 $\beta_2$ 교감 신경 수용체의 다형성중 Arg 16의 변이는 중증 천 Background: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of $\beta_2$-Adrenergic Receptor ($\beta_2$AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the $\beta_2$AR has recently been seguenced. The $\beta_2$AR genotype at the polymorphic loci of codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the $\beta_2$AR and its functions are being elucidated. Purpose : The gene encoding the $\beta_2$AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. Methods: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the $\beta_2$AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16,27,34, and 164. Results: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of $\beta_2$AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of $\beta_2$AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1 %,10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the $\beta_2$AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. Conclusion: The arginine 16 to glycine polymorphism of the $\beta_2$AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the $\beta_2$AR gene and nocturnal asthma.

산화질소 ( Nitric Oxide ) 의 기도내 신경성 염증 조절에 관한 연구

심재정(Jae Jeong Shim),박상면(Sang Myun Park),이진구(Jin Goo Lee),조재연(Jae Yeun Cho),인광호(Kwang Ho In),유세화(Se Hwa Yoo),강경호(Kyung Ho Kang),김철환(Chul Hwan Kim) 대한내과학회 1994 대한내과학회지 Vol.47 No.4

N/A Baekground: Asthma is classified as an inflammatory disease because there are inflammatory changes in the asthmatic airways. There are many evidences that sensory neuropeptides are involved in these inflammatory responses. Neurogenic inflammation is caused by the antidromic nonadrenergic noncholinergic (NANC) release of neuropeptides from vagal nerves. Recently nitric oxide (NO) has received considerable attention as a messenger molecule in the peripheral nervous system and relaxes airway smooth muscle. Also NO is a potent vasodilator and involved in plasma exudation from airway vessels, To investigate the role of nitric oxide in neurogenic inflammation, neurogenic inflammatory responses in rat airways according to duration of NANC stimuation and effects of NO were evaluated, Method: Neurogenic inflammation was produced in rat airways of 2 experimental groups of 1 min and 2 min stimulation with 5V, 1mSec, 5Hz after cholinergic and adrenergic blockade and compared with sham NANC, The magnitude of airway microvascular leakages was checked in the trachea, main bronchus, peripheral bronchus, and lung parenchyme and the leakeage was measured by Evans blue dye extravasation. NW-nitro-L-arginine (L-NNA, 5 mg/kg iv), L-NNA and L-arginine (50 mg/kg iv) were given 15 min before 2 min stimulation on 3 separate groups for evaluation of NO effects, and microvascular leakage was compared with 2 min NANC stimulation group. Results: 1) Vascular permeability of 1 min NANC stimulation group was increased trachea (208.2%, p<0.05), main bronchus (169.4%, p<0.05), and peripheral bronchus (123.6, p=0.18) compared with sham NANC group. 2) There was about l.5 times increase of vascular permeability in 2 min stimulation group compared with 1 min stimulation group (p<0,05), but not significantly increased permeability of lung parenchyme in both groups. 3) In L-NNA pretreated stimulation oup, there was increased vascular permeability of the trachea (133.3%, p<0.05), main bronchus (167.4%, p<0.05), and peripheral bronchus (197.1%, p<0.05) compared with 2 min stimulation group. 4) L-NNA and L-arginine pretreated stimulation group revealed suppressed vascular permeability com- pared with L-NNA pretreated stimulation group. Conclusion: These results revealed that neurogenic inflammation in the rat airway increases inflammatory responses according to duration of stimulation and blocking of NO synthetase increases neurogenic inflammation. These results provide that nitric oxide modulates inflammatory response of NANC stimulation of the vagal nerves in the rat airways.

기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할

김제형 ( Je Hyeong Kim ),윤대위 ( Dae Wui Yoon ),허규영 ( Gyu Young Hur ),정기환 ( Ki Hwan Jung ),이승룡 ( Sung Yong Lee ),이상엽 ( Sang Yeub Lee ),신철 ( Chol Shin ),심재정 ( Jae Jeong Shim ),인광호 ( Kwang Ho In ),유세화 ( Se H 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.60 No.4

연구배경: 활성산소종은 기계환기로 인한 폐손상 (ventilator-induced lung injury, VILI)에서 주요한 역할을 한다. Poly (ADP-ribose) polymerase-1 (PARP1)은 DNA 손상 감시 기능을 하는 단백질로서, DNA 파열을 신호하고 복구에 관여한다. 그러나 활성 산소종에 의한 것과 같은 심한 유전자 손상을 받게 되면, 과활성화되어-nicotinamide adenine dinucleotide (NAD(+))의 결핍을 통한 세포의 사멸을 초래하여, 염증 반응을 일으킨다. 본 연구에서는 VILI의 기전에 있어서 PARP1의 역할 및 그 억제제의 효과를 고찰하고자 하였다. 방법: 48마리의 수컷 C57BL/6 생쥐를 겉보기 수술군 (Sham군), 폐보호적 환기군(lung protective ventilation group, LPV군), 기계환기기로 인한 폐손상군 (ventilator-induced lung injury group, VILI군) 및 PARP1 억제제인 PJ34 전처치 후 기계환기로 인한 폐손상군 (PJ34+VILI군)으로 나누어 실험하였다. LPV군에 대한 기계환기는 PIP 15 cmH2O+PEEP 3 cmH2O+RR 90/min. 조건으로, VILI 및 PJ34+VILI군에 대해서는 PIP 40 cmH2O+PEEP 0 cmH2O+RR 90/min.의 조건으로 2시간 동안 시행하였다. PJ34+VILI군에서 PARP1 억제제로는, PJ34 20 mg/Kg을 기계환기 2시간 전에 복강 내로 주사하였다. VILI의 정도는 습건중량비 및 급성폐손상 지수로 측정하였고, PARP1의 활성은 biotinylated NAD를 이용한 면역조직화학적 방법을 이용하였다. 또한 기관지폐포세척액 (bronchoalveolar lavage fluid, BALF) 내에서 myeloperoxidase (MPO) 활성 및 tumor necrosis factor- (TNF- ), interleukin-1 (IL-1), IL-6 등의 염증성 시토카인의 농도를 측정하였다. 결과: PJ34+VILI군에서 VILI군과 비교하여, PJ34 전처치로 인하여 폐손상의 정도가 현저히 감소 하였다(p<0.05). 5개의 고배율 시야에서 관찰한 PARP1의 활성을 보이는 세포의 수는 VILI군에서 유의하게 증가하였고, PJ34+VILI군에서 현저히 감소하였다(p=0.001). BALF 내에서 측정한 MPO 활성 및 TNF-, IL-1, IL-6의 농도 역시 PJ34+VILI군에서 의미 있게 감소하였다(p<0.05). 결론: VILI의 기전에 있어서 PARP1의 과활성이 주요한 역할을 하고, PARP1 억제제가 MPO 활성 및 염증성 시토카인의 감소와 함께 VILI의 발생을 억제한다. Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through-nicotinamide adenine dinucleotide (NAD(+)) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was PIP 15 cmH2O+PEEP 3 cmH2O+RR 90/min+2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of PIP 40 cmH2O+PEEP 0 cmH2O+RR 90/min+2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor (TNF)-, interleukin (IL)-1, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, TNF-, IL-1, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines. (Tuberc Respir Dis 2006; 60: 451-463)

고립성 폐결절의 감별진단에서 결핵균에 대한 Nested PCR 의 유용성

심재정(Jae Jeong Shim),이소라(So Ra Lee),이상엽(Sang Youb Lee),이상화(Sang Hwa Lee),서정경(Jung Kyung Suh),정희진(Hee Jin Cheong),조재연(Jae Yun Cho),김우주(Woo Joo Kim),강은영(Eun Young Kang),인광호(Kwang Ho In),유세화(Se Hwa Yoo),강 대한내과학회 1997 대한내과학회지 Vol.52 No.6

N/A Objectives: The evaluation and management of a patient with solitary pulmonary nodule(SPN) are guided by principles that were derived from earlier surgical studies. SPN has a relatively good prognosis even if it is a malignant lesion. In Korea, where there is a high incidence of pulmonary tuberculosis, approximately 40% to 70% of clinically encountered solitary pulmonary nodules are tuberculous lesions. SPNs can be diagnosed by clinical findings and chest imaging techniques, but confirmed only by pathologic or cytologic studies. Transthoracic needle aspiration biopsy(TNAB) or cytology will be diagnostic in 80% to 95% of malignant nodules, but will identify the benign nature in 50% to 90% of benign nodules; such results imply lower accuracy of TNBA or cytology in diagnosing benign nodules. Differential diagnosis of SPNs can be difficult in tuberculosis endemic areas, such as in Korea, Nested polymerase chain reaction(PCB) is the widely used method to test very small amount of pathogene and to detect M, tuberculosis in fine needle aspirates. Methods: 33 patients with SPN found on chest radiographs were evaluated by chest CT, mycobacteriologic and cytologic studies from sputum, bronchial washing fluids, and transthoracic fine needle aspirates, 17 cases were malignant SPNs(51.5%), consisting af 14 primary lung cancers and 3 metastatic SPNs, 18 cases were benign SPNs(48.5%), consisting of 8 tuberculous, 4 localized pneumonia, 1 pulmonary sequestration, and 3 radiologically suspected tuberculous lesions without response to anti-TB drugs. Nested PCR for detecting M. tuberculosis using TB-1, TB-2, TB-28, and TB-29C was carried out on fine needle aspirates from 33 patients with SPN. Results: Among the pathologically proven 17 malignant SFNs, 15(88.5%) cases were detected as cancer on chest CT. 15(88.5%) cases were confirmed by transthoracic needle aspiration cytology, among which 3(17.7%) cases showed positive on sputum cytology, and other 3(17.7%) cases yielded positive on bronchial washing cytology as well. Two cases of malignant nodules were confirmed by open resection. In 8 tuberculous SPNs, Neither AFB stain of sputum, bronchial washings, nor transthoracic needle aspirates showed positive. However, mycobacterium was cultured in 1 (9.l%) case from sputum, in 3 (27.3%) cases from bronchial washing fluids, and in 2 (18.2%) cases from transthoracic needle aspirates. Thus, five cases were confirmed bacteriologically; one case had positive culture results on both bronchial washing and transthoracic needle aspirates. Three out of 8 tuberculous cases were radiologically suspected and showed response to anti-TB drugs, but were not bacteriologically confirmed. Chest CT could detect 72.7% of tuberculous nodules. Aspirates from malignancy, pneumonia, and sequestration were negative on nested PCR for tuberculosis, One of the 3 radiologically suspected tuberculous nadules with- out response to anti-TB drugs yielded positive results on nested PCR for M, tuberculosis. In contrast, 7 out of 8(87.5%) aspirates from proven tuberculous nodules showed positive results on nested PCR for M. tuberculous, which included 4 bacteriologically proven tuberculous nodules and 3 radiologically suspected tuberculous nodules with response to anti-TB drugs. Conclusion: Nested PCR could be used to detect M. tuberculosis in fine needle aspirates from tuberculous SPN with good sensitivity (87.5%) and specificity(96.0%). Therefore, nested PCR for detecting M. tuberculosis in fine needle aspirates may be useful in the differential diagnosis of solitary pulmonary nodules.

저산소성 폐질환에서 폐동맥압의 비관혈적 측정에 관한 연구

이진구(Jin Goo Lee),인광호(Kwang Ho In),박상면(Sang Myun Park),조재연(Jae Yeon Jho),심재정(Jae Jeong Shim),강경호(Kyung Ho Kang),심완주(Wan Joo Shim),유세화(Se Hwa Yoo) 대한내과학회 1995 대한내과학회지 Vol.49 No.4

N/A Objectives: The presence of pulmonary hypertension in patients with hypoxic lung disease is associated with poor prognosis. Right heart catheterization is the reference method for the diagnosis of pulmonary arterial hypertension but this invasive technique is not always well tolerated in all patients with hypoxic lung disease. There is a need for noninvasive method to allow the accurate estimation of pulmonary arterial pressure in these patients. To find reliable noninvasive methods of measuring pulmonary artery pressure, we evaluated the reliability of continuous wave Doppler echocardiography and gated cardiac blood pool scintigraphy in patents with hypoxic lung disease. Methods: Noninvasive measurements of systolic pulmonary artery pressure by continuous wave Doppler echocardiography and right ventricular ejection fraction by gated cardiac blood pool scintigraphy were compared with systolic pulmonary atery pressure measured by cardiac catheterization in 12 patients with hypoxic lung disease. Results: 1) The systolic pulmonary artery pressures estimated by continuous wave Doppler echocardiography correlated closely with those measured by cardiac catheterization (r=0.88, p<0.01) 2) The right ventricular ejection fraction estimated by gated cardiac blood pool scintigraphy was also correlated well with the systolic pulmonary artery pressure measured by cardiac catheterization (r=0.85, p<0.01). Conclusion: Continuous wave Doppler echocar-diographic estimation of systolic pulmonary artery pressure and gated car diac blood pool scintigraphic estimation of right ventricular ejection pressure are reliable and feasible noninvasive assessment of pulmonary hypertension in patients with hypoxic lung disease.

실험견의 급성 저산소성 폐고혈압증에서 K+ Channel 의 역할

조재연(Jae Youn Cho),박상면(Sang Myun Park),박희남(Hee Nam Park),이진구(Jin Goo Lee),심재정(Jae Jeong Shim),인광호(Kwang Ho In),강경호(Kyung Ho Kang),유세화(Se Hwa Yoo) 대한내과학회 1996 대한내과학회지 Vol.50 No.3

N/A Objectives: Numerous studies about mediators in acute hypoxic process have been done. These studies revealed that endothelium derived relaxing factor(EDRF, known as nitric oxide) contributed greatly to the pathogenesis of hypoxic pulmonary hypertension and endothelium derived hyperpolarizing factor(EDHF) regulated the tone of vascular smooth muscle. EDHE is known to open K+ channel, hyperpolarizes vascular smooth muscle cells, closes voltage-dependent Ca++ channel and finally relaxes vascular smooth muscle. Some studies revealed that acute hypoxic pulmonary hypertension was developed by inhibition of EDRF &EDHF. To investigate the role of K+ channel in pulmonary hypertension during acute hypoxia, we measured changes of hemodynamic parameters in experimental dogs after adding glibenclamide(K+ channel blocker), methylene blue(S-guanylate cyclase inhibitor), L-NNA(NO synthase inhibitor) and nicorandil(K+ channel opener and S-guanylate cyclase activator). Methods: Six dogs were anesthetized with thiopental sodium and mechanically ventilated with Harvard volume-cycled animal ventilator. Venous and arterial catheters were placed in the limb vein for infusion and femora} artery to measure systemic arterial pressure. Swan-Ganz catheter was inserted via right internal jugular vein for measuring pulmonary arterial pressure, pulmonary capillary wedge pressure asnd cardiac output. We measured the influence of glibenclamide (3mg/kg). methylene blue(lmg/kg), L-NNA (30mg/kg) and nicorandil(300μg/kg) on the changes of hemodynamic parameters during normoxia and hypoxia. Results: The infusion of nicorandil did not affect mean pulmonary arterial pressure during normoxia and significantly inhibited the increase of mean pulmonary arterial pressure during hypoxia. Glibenclamide did not change mean pulmonary arterial pressure during normoxia, but significantly augmented the increase of mean pulmonary arterial pressure during hypoxia. Methylene blue infusion did not affect mean pulmonary arterial pressure during normoxia, but moderately augmented the increase of mean pulmonary arterial pressure during hypoxia. The infusion of L-NNA did not affect mean pulmonary arterial pressure during normoxia and augmented the increase of mean pulmonary arterial pressure singnificantly during hypoxia, The increase of pulmonary arterial pressure induced by glibenclamide, methylene blue, and L-NNA, under hypoxic state was inhibited by nicorandil. Conclusion: Glibenclamide (K channel blocker) did not affect the mean pulmonary arterial pressure in normoxic state, but augmented the pulmonary hypertension during hypoxia and this effect was inhibited by nicorandil. It is suggested that K+ channel contributes to pulmonary hypertension developed during hypoxia, and the depressive effect of nicorandil seems to be attributable to its dual actions as a K' channel opener and an activator of S-guanylate cyclase.