• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.112-112
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• 2003

Voltage-gated $K^{+}$ (Kv) channels represent a structurally and functionally diverse group of membrane proteins. These channels play an important role in determining the length of the cardiac action potential and are the targets for antiarrhythmic drugs. Many $K^{+}$ channel genes have been cloned from human myocardium and functionally contribute to its electrical activity. One of these channels, Kv1.5, is one of the more cardiovascular-specific $K^{+}$ channel isoforms identified to date and forms the molecular basis for an ultra-rapid delayed rectifier $K^{＋}$ current found in human atrium. Thus, the blocker of hKv1.5 is expected to be an ideal antiarrhythmic drug for atrial fibrillation. Chelidonine was isolated from Chelidonium majus L. We examined the effect of chelidonine on the hKv1.5 current expressed in Ltk-cells using whole cell mode of patch clamp techniques. Chelidonine selectively inhibited the hKv1.5 current expressed in Ltk-cells in a concentration-dependent manner, whereas did not affect the HERG current expressed in HEK-293 cells. Additionally, chelidonine reduced the tail current amplitude recorded at -50 mV after 250 ms depolarizing pulses to +60 mV, and slowed the deactivation time course resulting in a 'crossover' phenomenon when the tail currents recorded under control conditions and in the presence of chelidonine were superimposed. We found that chelidonine also inhibited the $K^{+}$ current in isolated human atrial myocytes where hKv1.5 channels were predominantly expressed. Furthermore, we examined the effects of chelidonine on the action potentials in rabbit hearts using conventional microelectrode technique. Chelidonine prolonged the action potential durations (APD) of atrial, ventricular myocytes and Purkinje fibers in a dose-dependent manner. However, the effect of chelidonine on atrial APD was frequency-dependent whereas the effect of chelidonine on the APDs of ventricular myocytes and Purkinje fibers was not frequency- dependent. Also, the selective action of chelidonine on heart was more potent than dofetilide, $K^{+}$ channel blocker.

• 대한수의학회지
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• 제42권2호
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• pp.153-162
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• 2002

For the induction of arthropathy, 5% hydrogen peroxide($H_2O_2$) was injected for 5 weeks into the intraarticular space of the New Zealand white rabbits to damage articular cartilage. Alginic acid of low molecular weight (2%) made from macromolecular alginate treated with enzyme was administered into articular space at the dose of 5 mg/kg twice a week for 3 and 6 weeks using 1 ml syringe and 26 G needle. Saline was injected for the control. Tissues surrounding the articulation were obtained for the measurements of superoxide dismutase(SOD) activity as a major antioxidant enzyme and malondialdehyde (MDA) as a lipid peroxidation level. Histopathologic examination on the surface of articular cartilage was carried out. Data showed that injection of hydrogen peroxide for 5 weeks had led to the induction of free radical damage and of articular cartilage change as confirmed by microscopic observation. The application of hydrogen peroxide caused a gradual increase in the SODs and MDA. These patterns were similar after 3 and 6 weeks of alginate treatment. Furthermore, microscopic examinations revealed that hydrogen peroxide caused flaking, fibrillation, fissuring, denudation, and hypocellularity in the articular surfaces. In conclusion, lipid peroxidation was demonstrated in the articular cartilage by the administration of hydrogen peroxide in the rabbit model. This lipid peroxidation could be caused by oxygen free radicals. The histologic and enzymatic correlations on lipid peroxidation in the articulation have provided a better understanding of arthropathy. It is possible to take advantage of these findings to evaluate effective alginate dosage more efficiently.

• Journal of Chest Surgery
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• 제25권2호
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• pp.125-130
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• 1992

To evaluate the effect of oxygenation[95% O2+5% CO2] of St. Thomas Hospital No.2 cardioplegic solution[Plegisol], 20 isolated perfused rat hearts were studied under hyp-othermic[20oC] ischemic arrest for 2 hours with infusion of cardioplegic solution every 30 minutes throughout the ischemic period. Ten isolated hearts were studied with the oxygenated cardioplegic solution and 10 another isolated hearts with the nonoxygenated one. Mean oxygen tensions of the nonoxygenated and oxygenated cardioplegic solutions were 150mmHg and 470mmHg, respectively. Two in 10 hearts infused with the nonaxygenated cardioplegic solution were not recovered from nonworking heart due to persistent ventricular fibrillation. In comparing hem-odynamic parameters between both groups, the mean postischemic recovery[expressed as a percentage of its preischemic control value] was significantly greater with the oxygenated solution[in 10 recovered hearts] than the nonoxygenated solution[in 8 recovered hearts] [95.9$\pm$1.8% compared with 88.5$\pm$2.9% in peak aortic pressure, p<0.05, 75.7$\pm$5.2% compared with 43.5$\pm$6.5% in aortic flow, p<0.01, 75.5$\pm$4.6% compared with 54.1$\pm$5.6% in cardiac output, p<0.01, 78.3$\pm$4.6% compared with 60.3$\pm$4.6% compared with 60.3$\pm$6.2% in stroke volume, p<0.05, and 80.4$\pm$5.3% compared with 58.6$\pm$7.0% in dP/dT, p<0.05]. It is concluded that oxygenation of St. Thomas Hospital No.2 cardioplegic solution improves cardiac electrical stability and postischemic hemodynamic recovery after ischemic arrest in the isolated perfused rat heart.

• Journal of Chest Surgery
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• 제56권6호
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• pp.374-386
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• 2023

Background: The heightened morbidity and mortality associated with repeat cardiac surgery are well documented. Redo median sternotomy (MS) and minimally invasive valve surgery are options for patients with prior cardiac surgery who require mitral valve surgery (MVS). We conducted a systematic review and meta-analysis comparing the outcomes of redo MS and minimally invasive MVS (MIMVS) in this population. Methods: We searched PubMed, EMBASE, and Scopus for studies comparing outcomes of redo MS and MIMVS for MVS. To calculate risk ratios (RRs) for binary outcomes and weighted mean differences (MDs) for continuous data, we employed a random-effects model. Results: We included 12 retrospective observational studies, comprising 4157 participants (675 for MIMVS; 3482 for redo MS). Reductions in mortality (RR, 0.54; 95% confidence interval [CI], 0.37-0.80), length of hospital stay (MD, -4.23; 95% CI, -5.77 to -2.68), length of intensive care unit (ICU) stay (MD, -2.02; 95% CI, -3.17 to -0.88), and new-onset acute kidney injury (AKI) risk (odds ratio, 0.34; 95% CI, 0.19 to 0.61) were statistically significant and favored MIMVS (p<0.05). No significant differences were observed in aortic cross-clamp time, cardiopulmonary bypass time, or risk of perioperative stroke, new-onset atrial fibrillation, surgical site infection, or reoperation for bleeding (p>0.05). Conclusion: The current literature, which primarily consists of retrospective comparisons, underscores certain benefits of MIMVS over redo MS. These include decreased mortality, shorter hospital and ICU stays, and reduced AKI risk. Given the lack of high-quality evidence, prospective randomized control trials with adequate power are necessary to investigate long-term outcomes.

• The Korean Journal of Physiology
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• 제2권1호
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• pp.47-52
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• 1968

Twenty white rabbits anesthetized with nembutal (30 mg/kg) were employed in this experiment. Five of them served as controls; the remaining rabbits as experimental group were subjected to irreversible hemorrhagic shock. Shock was induced by bleeding the animals until mean blood pressure decreased to a level of 50-40 mmHg. This level of pressure was maintained for 3-4 hours, after which the drawn blood was reinfused. The reinfusion of blood caused the elevation of arterial pressure almost the control level for some minutes, after which a gradual and progressive decline of blood pressure became evident. This decline was thought to be the result from irreversible hemorrhagic shock. When mean blood pressure declined to less than 50 mmHg, chest was opened and samples of arterial blood and left ventricular muscle were taken. Left ventricular muscle and blood plasma were analyzed for potassium, sodium, chloride and water content. Blood glucose concentration was determined by Somogyi-Nelson's method. Extracellular and intracellular myocardial water and electrolyte content were calculated on the basis that electrolytes are distributed between plasma water and interstitial water according to Gibbs-Donnan equilibrium. In this calculation extracellular water was substituted for Na space. The findings obtained were as follows: 1. The concentration of blood glucose was 87mg% in the controls and it rose to 222 mg% in shock (P<0.01). 2. Plasma potassium elevated significantly from 3.3 mEq/l in controls to 8.0 mEq/l in shock (P<0.01), while small decreases in sodium (151-146 mEq/l) and chloride (102-96 mEq/l) were observed (P<0.3, P<0.1), 3. The changes of blood water content (83.1-84.3%) and cardiac water content (77.5-78.3 gm/100gm WT) were observed. 4. In control animals myocardial potassium levels which averaged 30.2 mEq/100 gmDT rose significantly to 40.3 mEq/100 gmDT in shock (P<0.01), while moderate decreases in sodium(16.3-14.3 mEq/100 gmDT) were observed in shock. 5. The calculated transmembrane resting potential of left ventricular muscle of control animals averaged 95 mV, while rabbits in shock averaged 77 mV. (P <0.01). The findings of this experiment do not correspond with the conclusions that myocardial depression seems to be the cause of irreversible hemorrhagic shock, because the excitability of heart muscle is elevated. From the point of view that the lowered transmembrane resting potential, the cause of death in terminal stage of irreversible hemorrhagic shock may be ventricular fibrillation. It can't be said, however, that the lowered transmembrane resting potential is responsible for the transition from reversible to irreversible hemorrhagic shock. The marked increase in blood glucose suggested that glycogenolysis in the liver is favorably active in shock.

• 한국응급구조학회지
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• 제20권2호
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• pp.7-19
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• 2016

연구 목적: 본 연구에서는 심근경색 쥐 모델에서 심장정지를 유발시킨 후 심폐소생술을 수행하는 과정에서 조기 저체온 치료를 적용하여 심장근육의 기능회복과 생존율에 미치는 효과를 조사하고자 하였다. 연구 방법: 본 연구를 위하여 체중 450-550g의 수컷 Sprague Dawley 쥐 10 마리에 개흉을 실시하였다. 왼내림심장동맥을 묶어서 심근경색을 유발시켰다. 왼내림심장동맥을 묶은 후 90분 동안 심실세동을 유도하고, 심폐소생술과 제세동을 실시하였다. 대조군(정상체온군)은 회복과정에 정상체온으로 유지한 군이며, 실험군(저체온군)은 회복과정에 $32^{\circ}C$ 4시간 저체온을 유지한 군이다. 연구 결과: 심박출량, 좌심실박출률, 심근수행지수는 심폐소생술 후 첫 4시간 동안 대조군보다 실험군에서 더 양호하게 나타났다. 실험군의 생존시간은 대조군보다 더 길게 나타났다(p<.050). 결 론: 본 연구를 통하여 조기 저체온 치료의 적용이 급성심근경색의 심폐소생술 후 심장 기능을 개선하는 데 탁월한 효과가 있으며, 치료법의 새로운 기준이 될 것이다.

• Journal of Preventive Medicine and Public Health
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• 제28권2호
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• pp.473-486
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• 1995

본 연구는 뇌혈관질환의 위험요인을 규명하고, 특히 혈청 콜레스테롤 값 및 코골음과 뇌혈관질환과의 관련성을 검정하기 위하여 시도된 짝지은 병원 환자-대조군 연구이다. 환자군인 뇌혈관질환군은 1993년 12월부터 1995년 3월까지(16개월간) 경상대학교 병원 신경과에 처음 입원하는 환자로 뇌전산화 단층촬영으로 확진되는 뇌경색 74명, 뇌출혈 53명 총 127명으로 하였다. 대조군은 환자군과 비슷한 시기에 입원하는 경상대학교 병원의 신경과 이외 병동의 입원 환자중 환자군과 성(性)이 같고 연령이 5세 이내인 대상자를 환자군과 1:1 개별 짝짓기(individual matching)하여 127명을 선정하였다. 대조군은 과거에 뇌혈관질환의 병력이 없고 원칙적으로 뇌혈관질환의 잠재적 위험요인과 관계없는 질병으로 입원한 경우로만 하였다. 본 연구결과 논란이 있는 코골음과 저콜레스테롤혈증이 뇌혈관질환의 위험요인이라고 할 수 없었다. 유의한 위험요인은 심전도의 이상(좌심실비대 및 심방세동)이 가장 중요하였고, 그 외에도 뇌혈관질환의 가족력, 안저검사의 이상소견, 과거 일과성 허혈성 발작의 경험 및 혈청 콜레스테롤치의 상승이었다. 뇌경색의 위험요인은 역시 심전도의 이상이 가장 중요하였고, 그외에도 안저검사의 이상소견, 흡연 및 혈청 콜레스테롤치의 상승이었다. 이상의 위험요인을 고려할 때 뇌혈관질환을 예방하기 위해서는 고혈압의 치료가 중요하며, 특히 안저검사와 심전도 검사에서 이상소견이 나타나지 않도록 철저히 관리해야 한다. 가족력이 있는 사람들과 과거 일과성 허혈성 발작 경험자는 특히 고위험군으로서 다른 위험요인을 가지지 않도록 교육해야 한다. 또한 흡연과 고콜레스테롤 혈증의 건강에 대한 위해성도 다시 한번 강조되어야 한다. 이렇게 함으로써 보건당국은 단일 사망원인으로 우리나라에서 제1의 사망원인인 뇌혈관질환을 예방하기 위하여 더욱 노력해야 할 것이다.

• Journal of Chest Surgery
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• 제31권12호
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• pp.1172-1182
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• 1998

배경: 기계적 보철판막을 사용한 환자에서의 항응혈제 치료의 목표는 혈전전색의 효과적 예방과 출혈의 안전한 방지에 있다. 대상 및 방법: 1984년부터 1995년까지 쎈트쥬드판막으로 심장판막을 치환한 209례(승모판치환 122, 대동맥판치환 48, 중복판막치환 48)의 환자에서 실제로 수행된 항응혈제 수준과 임상적 결과를 분석하였다. 쿠마딘으로 항응혈제 치료를 개시하고 원칙적으로 월 1회의 외래 내원하여 검사와 프로트롬빈시간 측정으로 국제정상화비(International Normalized Ratio : INR)를 낮은 강도의 치료적 목표범위 1.5∼2.5 내에 조정하였다. 결과: 총 항응혈제 추적기간은 1082.0환자년(평균 62.1개월)이고 프로트롬빈시간 검사는 총 10,205회였다. 치환판막군간에 유의한 차이없이 총 측정수의 65%에서의 INR값만이 목표범위이내에 있었다. 각 환자에서 추적기간중 시행한 프로트롬빈시간 측정의 70%이상이 목표범위에 포함되었던 환자는 77례(37%)에 불과하였다. 환자의 57%에서 본 심방세동이 있던 환자에서의 INR수준은 정상동률이던 환자에서의 수준보다 분명하게 높았다(p<0.001). 혈전전색증은 15례가 경험하여 연간빈도가 1.265%/환자년(승모판치환 1.412%/환자년, 대동맥판치환 0.462%/환자년, 중복판막치환 1.531%/환자년)이고 출혈은 4례로 0.337%/환자년의 연간빈도를 보였다(승모판치환 0.424%/환자년, 대동맥판치환은 없고, 중복판막치환 0.383%/환자년). 빈번하거나 장기간의 프로트롬빈시간 측정의 탈락은 혈전전색합병증에 크게 연관된 주요 위험요소였다(대응비 1.99). 각 환자에서의 INR값이 목표범위내에 포함된 비율이 60%에 미달하였던 환자에서는 혈전전색합병증과 전색과 출혈의 종합합병증의 발생률이 높아 명확하게 큰 위험요소였다(각각 p<0.004 및 p<0.002). 결론: 낮은 강도의 치료적 목표범위가 대동맥판치환이고 정상동률인 환자에서는 적절한 수준인 듯 하다. 그러나 승모판을 치환한 환자에서 특히 심방세동을 동반할 때에는 혈전전색합병증을 효과적으로 예방하기에 충분한 실제적 항응혈제 수준을 성취하려면 보다 높은 INR의 목표범위가 필요할 듯 하며 INR 2.0∼3.0을 치료적 목표범위로 하는 임상적 결과의 축적이 필요하다. 환자가 합병증에 노출되는 기회와 기간을 최소화하려면 주기적 외래방문을 지키고 쿠마딘 복용을 빼지 않도록 계속 지도하여 환자의 순응도를 높이는 동시에 INR값을 엄격하게 적정범위 내에 일관되게 유지하여야 한다. 특히 합병증의 위험요소가 있는 환자와 INR값의 변동폭이 지나치게 넓은 환자에서는 빈번한 항응혈제 수준의 감시가 필요하다.

• Journal of Chest Surgery
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• 제19권1호
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• pp.35-42
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• 1986

Prevention of thrombombolism after rosthetic cardiac valve replacement is essential for the patients. About 90% of patients are free of major and minor thromboembolic complications 5 year after replacement of cardiac valves with prosthetic devices when they are under control of anticoagulant therapy. Ticlopidine is a drug that alter platelet function to have an antithrombotic effect. It is an antiaggregating agent which inhibits primary platelet function to have an antithrombotic effect. It is an antiaggregating agent which inhibits primary platelet aggregation induced by ADP and increases the production of prostaglandin $D_{2}$. Aspirin in small doses inhibits platelet synthesis of prostaglandins by irreversibly blocking the enzyme cyclo-oxygenase. Platelet secretion and aggregation are impaired with Ticlopidine and Aspirin. the thromboembolic event sof 54 patient s who were treated with Ticlopidine and Aspirin after cardiac valve replacement were evaluated and compared with that of 79 patients who were treated with Wafarin and Aspirin after the same type of operation. The follow-up period ranged from 4 to 110 months (mean of 48 months). there were 11 major thromboembolic episodes including three deaths in the warfarin goup during mean follow-up period of 56 months. two cases of CVA and one hemoarthrosis were noted due to overdose of Warfarin. Inticlopidine group, there was only one fatal thromboembolic epdisode three month after mitral valve replacement during mean follow-up period of 18 months. Two episodes of hypermenorrhea resulting anemia ere noted in the ticlopidine group. We measured the parameters of platelet function in aggreagation curve of platelet with platelet aggregometer (chrono-log Aggregometer, Model No. 430) Aggregation test was performed with three final concentrations of epinephrine in 10 uM/L, ADP in 5uM/L. 28 patients with prosthetic cardiac valves and 35 healthy volunteers were subgrouped as follows to analyze the effect of antithrombotic drugs used. Group I ; 11 patients treated with 250-500 mg of ticlopidine and 0.5gm of Aspirin as a daily single dose after cardiac valve replacement (14 St. Jude Medical and 1 Carpentier-Edwards, 9 patients with atrial fibrillation among them) Group II ; 10 patients treated with 3-5 mg of Warfarin and 0.75 gm of Aspirin daily to prolong prothrombin time around 20 seconds for more than 6 months and single Aspirin dose was maintained afterward as a life-long regimes(3 St. Jude Medical, 1 Hall-Kaster and 7 Carpentier-Edwards valve, 9 patients in atrial fibrilation). Group III ; 7 patients who quit anticoagulant treatment (Warfarin + Aspirin) 6-12 months after the regime as group II (3 St. Jude Medical. 1 bjork-Shiley, 1 Hall-Kaster, 3 Carpentier-Edwards valve, 2 of them are with atrial fibrillation). Group IV ; 35 healthy vounteers (28 males and 7 females). The following results were obtained. 1. The mean maximal platelet aggregability in Group I induced by 10uM/L epinephrine was 15.6%, and 17.5 and 18.7% in BM in proportion to the induction by 5 and 10 uM/L ADP. 2. The mean maximal platelet aggregability in Group II induced by 10uM/L epinephrine was 16.5%, and 27.4 and 44.7% in BM in proportion to the induction by 5 and 10uM/L ADP. 3. The mean maximal platelet aggregability in group III induced by 10uM/L epinephrine was 65%, and 56.5 and 51.8% in BM in proportion to the induction by 5 and 10 uM/L ADP. 4. The mean maximal platelet aggregability in the normal subjects induced by 10 uM/L epinephrine was 64%, and 65 and 69% in Bm inproportion to the induction by 5 and 10 uM/L ADP. 5. Reversible change of platelet aggregation curve induced by 5 and 10uM/L was noted all of the patients in Group I. conclusion : Ticlopidine is an antiaggregating agent which inhibits primary platelet aggregation induced by ADP, and increases the production of prostaglandin $D_{2}$. Ticlopidine and Aspirin produced a significant inhibition of platelet in the presence of ADP and epinephrine in our study. Acccording to our brief experience, 250 mg of ticlopidine and low dose of Aspirin resulted synergistic superior effect to each drug alone in prevention of thromboembolism after prosthetic cardiac valve replacement.

• Journal of Chest Surgery
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• 제37권6호
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• pp.467-473
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• 2004

배경: 심방세동의 수술적 치료 방법인 미로술식에 있어 고주파에너지를 이용한 절제술은 전통적인 절개 및 봉합술 (cut and saw) 또는 냉동절제술(cyroablation)에 비해 술 후 동율동의로의 전환율이 낮은 것으로 알려져 있다. 이는 절제술 시 심방벽 (atrial wall)과 도자 간의 접촉이 원활하지 않아 심방의 전층에 걸쳐 고주파 에너지가 전달되지 않기 때문인 것으로 생각된다. 이에 고주파 절제시 심방과 도자간의 접촉을 원활하게 하기 위한 기구를 개발하였으며 동물실험을 통하여 그 임상적인 효과를 관찰하고자 하였다. 대상 및 방법: 60 kg 내외의 돼지 10 마리를 대상으로 하였다. 우심방이 첨부로부터 3∼4 cm 하방의 심방외벽에 고주파에너지를 가하여 우심방이가 우심방에서 완전히 분리되도록 원형의 병변 (circumferential lesions)을 만들었다. 이때 실험군(n=5)에서는 새로 고안한 기구를 이용하여 도자를 심방벽에 완전히 밀착시킨 후 고주파 에너지를 가하였으며, 대조군(n=5)에서는 이러한 기구의 사용 없이 통상적인 방법으로 에너지를 가하였다. 고주파절제술이 끝난 후 우심방이 첨부에 인공심장박동 전극을 설치하고 심박동을 유발하여 고주파 절제부위 이하로 심박동이 전달되는지를 관찰하여 절제술의 성공 여부를 판단하였다. 또한 심방조직에 대해 조직학적 검사를 시행하여 심외막, 심근, 그리고 심내막층에 고주파에너지에 의한 열손상의 생성 유무를 관찰하였다. 결과: 실험군에서 5예, 대조군에서 3예 등 총 8예에서 심박동의 전달 차단 (conduction block)이 관찰되었으며 조직학적 검사 소견상 심내막(endocardium)에서 탄성섬유(elastic fiber)의 소실과 급성 염증세포의 축적 등 급성 열손상의 소견이 관찰되었다. 한편 심박동의 전달 차단이 관찰되지 않았던 대조군의 2예에서는 심내막이 정상으로 나타났다. 또한 기관 및 식도에 대한 조직학적 검사에서 열손상에 의한 병변은 관찰되지않았다. 결론: 고주파에너지에 의한 절제술 시 심방의 전층에 병변을 만들기 위해서는 심장과 도자간의 접촉이 가장 중요한 인자로 생각된다. 본 연구에서 새로 개발한 기구는 고주파에너지를 이용한 도자절제술 시 심장과 도자 간의 확고한 접촉을 유도하여 심방 전층에 병변을 만드는 데 매우 효과적이었으며 이러한 기구의 사용은 향후 고주파에너지를 이용한 미로술식의 성적향상에 도움이 될 것으로 사료된다.