• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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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.

• Korean Journal of Veterinary Research
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• v.42 no.2
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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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• v.25 no.2
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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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• v.56 no.6
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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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• v.2 no.1
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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.

• The Korean Journal of Emergency Medical Services
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• v.20 no.2
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• pp.7-19
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• 2016

Purpose: To investigate the effect of early hypothermia on post-resuscitation myocardial recovery and survival time after cardiac arrest and resuscitation in a rat model of myocardial infarction(MI). Methods: Thoracotomies were performed in 10 male Sprague Dawley rats weighing 450-455g. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. Ninety minutes after arterial ligation, ventricular fibrillation was induced, cardiopulmonary resuscitation was subsequently performed before defibrillation was attempted. Animals were randomized to control group and experimental group(acute MI-normothermia)($32^{\circ}C$ for 4 hours). Duration of survival was recorded. Myocardial functions, including cardiac output, left ventricular ejection fraction, and myocardial performance index were measured using echocardiography. Results: Myocardial function was significantly better in hypothermia group than the control group during the first 4 hours post-resuscitation. The survival time of the experimental group was greater than that of the control group(p<.050). Conclusion: This study suggests that early hypothermia can attenuate post-resuscitation myocardial dysfunction after acute myocardial function, and may be a useful strategy in post-resuscitation care.

• Journal of Preventive Medicine and Public Health
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• v.28 no.2 s.50
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• pp.473-486
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• 1995

A hospital-based, matched case-control study was carried out to evaluate the relation ship of various suspected risk factors including snoring and serum level of cholesterol to cerebrovascular disease in Korea. A total of 127 incident cases of cerebrovascular disease(74 cases of cerebral infarction and 53 cases of intracerebral hemorrhage) admitted to. the department of neurology in a university hospital from December, 1993 to March, 1995 were compared with 127 matched controls admitted to same hospital in same period. A multivariate analysis suggested that ECG abnormality(left ventricular hypertrophy and atrial fibrillation), family history of cerebrovascular disease, fundoscopic abnormality, previous history of transient ischemic attack and hypercholesterolemia were risk factors of cerebrovascular disease, ECG abnormality, fundoscopic abnormality, smoking and hypercholesterolemia were also suggested as risk factors of cerebral infarction.

• Journal of Chest Surgery
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• v.31 no.12
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• pp.1172-1182
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• 1998

Background: Primary goal of anticoagulation treatment in patients with mechanical heart valve is the effective prevention of thromboembolism and safe avoidance of bleeding as well. Material and Method: Two-hundred and nine patients with the St. Jude Medical prosthesis operated on between 1984 and 1995, for mitral(MVR 122), aortic(AVR 39) and double mitral and aortic valve replacement(DVR 48) respectively, were studied on the practically achieved levels of anticoagulation and the clinical outcomes. Patients were on Coumadin and followed up by monthly visit to outpatient clinic for examination and prothrombin time measurement to adjust the International Normalized Ratios(INRs) within the low-intensity target range between 1.5 and 2.5. Result: A total anticoagulation follow-up period was 1082.0 patient- years(mean 62.1 months) and INRs of 10,205 measurements were available for evaluation. The accomplished INRs among the replacement groups were not significantly different and only 65% of INRs were within the target range. And, in individual patients, only 37% of patients had INRs included within the target range in more than 70% of tests during follow-up period. The levels of INRs in patients with atrial fibrillation, which was found in 57% of patients, were definitely higher than the ones measured in patients with regular rhythm(p<0.001). Thromboembolisms were experienced by 15 patients with the incidence of 1.265%/patient- year(MVR 1.412%, AVR 0.462% and DVR 1.531%/patient-year) and major bleeding by 4 patients with the incidence of 0.337%/patient-year(MVR 0.424%, AVR none and DVR 0.383%/patient-year). Frequent as well as prolonged missing of prothrombin time tests was the main risk factor strongly associated with the thromboembolic complications(odds ratio 1.99). The proportion of INRs within target range of less than 60% in individual patient was the highly significant risk factor of both thromboembolic and overall embolic and bleeding complications(p<0.004 and p<0.002 respectively). Conclusion: In conclusion, the low-intensity therapeutic target range of INRs was adequate in patients with AVR and in sinus rhythm. However, the patients with replacement of the mitral valve were more likely to require higher target range of INRs, especially in the presence of atrial fibrillation, to achieve the practical levels of anticoagulation enough to prevent thromboembolic complications effectively. For the higher therapeutic target range of INRs between 2.0∼3.0, further accumulation of clinical evidences are required. It is highly desirable to improve the patients' compliance under continuous instructions in visiting outpatient clinic and in taking daily Coumadin without omission and to keep INRs consistently within optimal range with tight control for minimization of chances and of periods of exposure to the risk of complications. And, particularly, patients with high risk of complications and with wide fluctuation of INRs should be better managed with frequent monitoring anticoagulation levels.

• Journal of Chest Surgery
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• v.19 no.1
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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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• v.37 no.6
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• pp.467-473
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• 2004

Background: The sinus conversion rate after the maze procedure in chronic atrial fibrillation using radiofrequency energy is lower than with either conventional 'cut and saw' technique or cryothermia. The creation of incomplete transmural lesions due to poor tissue-catheter contact is thought to be the main cause. To address this problem, the current study was aimed to evaluate the effectiveness of a specially constructed compression device designed to enhance tissue catheter contact during unipolar radiofrequency catheter ablation. Material and Method: Circum-ferential right auricular epicardial lesions were created with a linear radiofrequency catheter in 10 anesthetized pigs. A device specially designed to increase contact by compression of the catheter to the atrial wall was used in 5 pigs (study group). This device was not used in the control group (5 pigs). Conduction block across the right auricular lesion was assessed by pacing, and the transmurality of the lesions were confirmed by microscopic examination. Result: Conduction block was observed in a total of 8 pigs; 5 in study group and 3 in control group. Transmural injury was confirmed microscopically by the accumulation of acute inflammatory cells and loss of elastic fibers in the endocardium. In two pigs with failed conduction block, microscopic examination of the endocardium appeared normal. Conclusion: Failed radiofrequency ablation is strongly related to non-transmural energy delivery. The specially constructed compression device in the current study was successful in creating firm tissue-catheter contact and thereby generating transmural lesions during unipolar radiofrequency ablation.