• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.484-492
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• 1996

To detect ischemic tissue in experimental model of cerebral ischemia made by middle cerebral artery(MCA)-occlusion, we acquired triple image of $^{99m}Tc$-glucarate, [$^{18}F$]fluoro-deoxyglucose (FDG), and 2,3,5- triphenyltetrazolium (TTC) staining. We made cerebral infarction either with reperfusion (after occlusion of 2 hours) or without reperfusion in 10 Sprague-Dawley rats by inserting thread to MCA through internal carotid artery. After 22 hours, we injected 740 MBq of $^{99m}Tc$-glucarate and 55.5 MBq of [$^{18}F$]FDG through tail vein. Each 1 mm slice of rat brains was frozen and exposed to imaging plate for 20 minutes in freezer to get an [$^{18}F$]FDG image. After 20 hours enough to fade radioactivity of [$^{18}F$]FDG, the slices were again imaged by BAS1500 for $^{99m}Tc$-glucarate uptake. Finally, these brain tissues were stained with TTC. Semi-quantitative visual analysis was done by grading 0 to 3 points according to the degree of uptakes($^{99m}Tc$-glucarate) and decreased uptakes([$^{18}F$]FDG and TTC). Ten rats survived with neurologic symptoms. TTC staining confirmed the development of infarction. The size of the infarction was relatively larger in the group without reperfusion. [$^{18}F$]FDG images were similar to TTC-stained images. However, we found regions with intermediate uptake which were not stained with TTC. We found regions with intermediate [$^{18}F$]FDG uptake where TTC staining was normal. $^{99m}Tc$-glucarate uptake was round only in TTC non-stained region. In the TTC stained regions, there were no uptake of $^{99m}Tc$-glucarate. We could not find clear relation between $^{99m}Tc$-glucarate uptake with [$^{18}F$]FDG uptake. This was partly because percent uptake of $^{99m}Tc$-glucarate was so small (less than 1 percent of injected dose) and because there were quite heterogeneity of patterns of [$^{18}F$]FDG uptake and TTC. With these findings, we could conclude that $^{99m}Tc$-glucarate were taken up only in part of ischemic tissues which were proven to be nonviable. The establishment of MCA-occluded rat model with or without reperfusion and triple imaging for $^{99m}Tc,\;^{18}F$ and TTC helped the characterization of $^{99m}Tc$-glucarate uptakes. Further work is needed to clarify the meaning or diversities or [$^{18}F$]FDG and TTC and their relation with $^{99m}Tc$-glucarate.

• Korean Journal of Oriental Medicine
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• v.6 no.1
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• pp.81-87
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• 2000

Chungpesagan-Tang (CST), a Korean traditional prescription composed of oriental medical herbs, has been used successfully to improve human health and regimen. This study was designed to examine the inhibitory effects of CST against in vitro ischemia/reperfusion-induced inflammatory response. We have characterized the production of prostaglandin $E_2$ and arachidonic acid during ischemia/reperfusion in the human neuroblastoma SK-N-MC and human monocytic macrophage U937 cells and the inhibitory effect of CST on these inflammation-related substance formation has been found out in this study. This result suggested that CST used in this experiment reinforced antiinflammatory potentials and protected cells against ischemia/reperfusion-induced inflammatory resopnse.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.67-72
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• 1997

Myocardial scintigraphy is a widely used noninvasive procedure with high sensitivity for the detection of patients with suspected coronary artery disease. The purpose of this study was to determine the prognostic value of a normal myocardial scintigraphy in 292 patients (150 males, 142 females, mean age $53{\pm}12$ years) with chest pain who were followed from 7 to 58 (mean 25) months. Myocardial SPECT was performed with Tc-99m MIBI in 173 patients, with Tc-99m tetrofosmin in 74 patients and with T1-201 in 45 patients. During the follow-up period, there were 2 cardiac deaths and 2 nonfatal myocardial infarctions resulting in cardiac event rate of 1.37% (0.66% Per Year). The cardiac event rate was not different in patients with angiographically normal coronary arteries (1/30, 3.3%) and in those who had significant coronary artery disease (2/27, 7.4%) (p=0.60). In conclusion, patients with chest pain and normal myocardial scintigraphy have a low cardiac event rate, and there was no significant difference of. cardiac event rates between patients with normal and abnormal coronary angiograms.

• Korean Journal of Head & Neck Oncology
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• v.9 no.1
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• pp.3-9
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• 1993

The benficial effects for perfusion in the preservation of free flaps have been controversial in the clinical and experimental field until now. This study was undertaken to observe the effect of UW solution. a recently developed. high molecular weight. organ perfusion solution. for protection of ischemic injury in normothermic free myocutaneous flaps. Forty rabbits were used in this sutdy. A 1x2x1cm sized gastrocnemius myocutaneous flap based on the feeding vessel from common femoral artery was made. The author set up the ischemic time for 12 hours in these flaps. The flap was washed out with normal saline(control grop, n=10), urokinase(comparative group I, n=10), UW solution before ischemic time(comparative group II, n=10) and UW solution before ischemic time and pentoxifylline before reperfusion(comparative group III, n=10). Afterthen, reperfusion was made for 12 hours. After this procedure, we checked the degree of ischemia and necrosis of myocutaneous flap by gross finding, electrical stimulation test of muscle, triphenyltetrazolium chloride staining and wet/dry weight ratio. The degree of necrosis of comparative group II and III were lesser than control and urokinase group in gross finding(p<0.05). In the electrical stimulation test of muscle, there was no statistical difference between control($1.76{\pm}1.01$) and urokinase($2.36{\pm}\1.02$) group however the muscular power of comparative group II($3.54{\pm}0.93$) and III($3.49{\pm}1.37gm/mm^2$) demonstrated significantly higher than control group(p<0.05). The ischemic findings were found in seven cases of control group and three cases of urokinase group but there were no ischemic findings in comparative group II and III in TIC stain(p<0.05). In the wet/dry weight ratio of flaps in order to evaluate the tissue edema. there was no statistical difference between control($4.55{\pm}0.29$) and III($3.75{\pm}0.48$) were scored significantly lesser than control and urokinase group (p<0.05). These results suggest that perfusion washout with UW solution improves the viability of normothermic free myocutaneous flap by inhibition of cellular swelling.

• Journal of Chest Surgery
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• v.35 no.1
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• pp.11-19
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• 2002

Background: Ischemia-reperfusion myocardial injury is an important factor to determine the early and the late mortality of transplanted patients. Recently, modulation of the cytosolic NADH/NAD+ ratio by Pyruvate and aspartate was tested to Protect the heart from ischemia-reperfusion injury. Material and Method: We added pyruvate and aspartate to the University of Wisconsin solution, and evaluated their effect on myocardial protection. We used 16 piglet(age 1 to 3 days) hearts. Eight hearts were arrested with and stored in the University of Wisconsin solution(UW solution) for 24 hours(control group), and the other eight hearts were arrested with and stored in the modified UW solution added pyruvate(3mmol/L) and aspartate(2 mmol/L)(test group). All hearts underwent modified reperfusion with blood cardioplegic solution followed by conversion to a left-sided working model with perfusion from a support pig. And then, we measured stroke work index(SWI), high-energy phosphate stores, and myocardial water content of the hearts. SWI was calculated at left ventricular end-diastolic pressures of 3, 6, 9, and 12 mmHg after 60 and 120 minutes reperfusion, respectively, Result: At 60 minutes and 120 minutes after reperfusion, SWI was higher in the test group than in the control group significantly. The levels of AMP, ADP, ATP of the test group were also higher. But, the creatine phosphate level and myocardial water content were similar in the two groups. Conclusion: From these results, we could Prove that pyruvate and aspartate enhance cardiac contractility and high-energy phosphate stores after ischemia.

• Journal of Life Science
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• v.19 no.6
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• pp.818-824
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• 2009

The mechanisms responsible for ischemia/reperfusion (I/R) injury have direct or indirect relevance to clinical lung injury after severe shock, cardiopulmonary bypass, and transplantation. This study investigated the effects of aspirin on intestinal I/R-induced acute lung injury (ALI) in rats. Lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression in A549 and RAW264.7 cells. RAW264.7 macrophages had shown greater expression of COX-2 than A549 cells. In addition, the NADPH oxidase inhibitor apocynin and p38 MAPK inhibitor SB203580 attenuated LPS-stimulated COX-2 expression. To induce ALI, intestinal ischemia was performed for 60 min prior to the 4 hr reperfusion by clamping the superior mesenteric artery in Sprague-Dawley rats. In order to test and compare the effect of non-specific COX inhibitor aspirin with the effect of mepacrine, a well known phospholipase$A_{2}$ inhibitor, rats were divided into 4 groups: Sham, I/R, Mepa+I/R (mepacrine, 60 mg/kg, i.p.), ASA+I/R (aspirin, 10 mg/kg, i.p.). In the present investigation, myeloperoxidase activities in the lung and intestinal tissues were increased by I/R. These changes were reduced by single pretreatment of mepacrine (60 mg/kg, i.p.) or aspirin (10 mg/kg, i.p.) 30 min before I/R. Structural studies demonstrated that the tissue injuries in the lung and intestine after I/R were also attenuated by the pretreatment of mepacrine or aspirin. These results suggest that I/R-induced ALI is mediated, in part, by the activation of COX. In addition, pretreatment of aspirin might be helpful for the prevention of ALI in ARDS-prone patients. In addition, the p38 MAPK inhibitor and apocynin also might be helpful to ALI through the inhibition of COX-2 expression.

• Journal of Chest Surgery
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• v.32 no.5
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• pp.413-421
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• 1999

Background: Ischemia reperfusion injury is known to contribute to the major causes of the early graft failure in lung transplantation. Triiodothyronine (T3) has been suggested to ameliorate ischemia reperfusion injury from both in vivo and in vitro experiments of various organs. Prospecting its beneficial effect for pulmonary allograft preservation, we made a new solution by adding T3 into the extracellular type dextran solution. Material and Method: Twelve adult mongrel dogs underwent left lung allotransplantation. Six donor dogs were flushed with the new solution(Group 1, n=6), and the remaining six were flushed with Euro-Collins solution to serve as controls(Group 2, n=6). Allografts were stored in each preservation solution for 20 hours at 4$^{\circ}C$. Left single lung transplantations were performed. The right pulmonary artery and the right main bronchus were clamped at 15 minutes after the reperfusion and maintained throughout the experiment to evaluate the transplanted left lung function. Result: Arterial carbon dioxide tension was better in group 1 than in group 2 throughout the experiment period and the difference was statistically significant at 2 hours after reperfusion(28.0${\pm}$3.0 mmHg and 53.1${\pm}$17.4 mmHg, p<0.05). The differences of arterial oxygen partial pressure, peak airway pressure and pulmonary vascular resistance showed no statistical significance. The malondialdehyde(MDA) level, measured from tissue obtained at 120 minutes after reperfusion showed no statistically significant difference. The tissue wet/dry ratio of group 1(649${\pm}$27 %) was significantly lower than that of group 2(686${\pm}$71 %, p<0.05). The microscopic examination revealed varying degrees of injury represented mainly by findings such as perivascular neutrophil infiltration, capillary hemorrhage and interstitial congestion. These findings were less severe in group 1 than those in group 2. Conclusion: The new solution demonstrated superior allograft preservation after 20 hour ischemia compared to Euro-Collins solution in canine single left lung transplantation model, these results suggest that T3 might be a promising agent for pulmonary allograft preservation.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.560-567
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• 2002

주산기 뇌손상은 주로 급격한 저산소-허혈 손상에 의하는데 급격한 산소 공급의 차단은 oxidative phosphorylation을 정지 시켜서 뇌대사를 위한 에너지 공급이 차단되게 된다. 에너지 공급이 차단된 뇌세포는 뇌세포막에서 세포 내외의 이온 농도 차를 유지시키던 ATP-dependent $Na^{+}-K^{+}$ pump의 기능이 정지 되고, 세포 내외의 농도 차에 따라 $Na^{+}$, $Cl^{+}$, $Ca^{{+}{+}}$의 대규모 세포 내로 이동이 일어난다. 세포 내로 calcium 이온의 이동은 glutamate 수용체의 활성화에 의해서도 일나는데, 세포 내 calcium 이온의 증가는 protease, lipase, nuclease 등을 활성화 시켜 세포를 사망에 이르게 하는 연속적이고 다양한 생화학적 반응을 일으키게 된다. Glutamate는 대표적인 신경 전달 물질인데 저산소-허혈 손상 시 glutamate 수용체의 지나친 흥분은 미성숙 뇌에 뇌손상을 유발하는데, NMDA 또는 non-NMDA 수용체와 복합체를 형성하고 있는 calcium 이동 통로를 활성화 시켜 세포 내 calcium 이온을 증가시키고, 그 외에 metabotropic recetor는 G-protein의 활성화 등을 통해 뇌손상을 유발하는 다양한 생화학적 반응을 매개한다. 저산소-허혈 손상 후 재산소화와 재관류가 일어나면서 뇌세포의 지연성 사망(secondary neuronal death)이 일어나는데 이는 초기 손상 후 뒤이어 일어나는 다양한 생화학적 반응에 의하는데 다량의 산소 자유기 발생, nitric oxide의 생성, 염증 반응과 싸이토카인, 신경전도 물질의 과흥분 등이 관여하며, 신경 세포 사망은 세포괴사(necrosis)뿐 아니라 일부는 세포 사멸(apoptosis)로 알려진 의도된 세포 사망(programmed cell death)에 의한 것으로 생각되고 있다(Fig. 2).

• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. Numerous studies on safe long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

• Journal of Chest Surgery
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• v.36 no.3
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• pp.123-130
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• 2003

Background: In order to develop the acute heart failure model for the animal experiment of the pneumatic ventricular assist device, we decided to use young pig whose coronary artery distribution is almost the same as humans and also very cheap in price. The purpose of this study is to develop stable, reproducible acute ischemic heart failure model in swine using coronary artery ligation method. Material and Method: Five young pigs whose weights are the same as adult humans are under experiment. Each pig was under endotracheal intubation and connected to a mechanical ventilator. Through left lateral thoracotomy, we exposed the heart and induced ischemic heart failure by coronary artery ligation. The ligation began at the distal part of the left anterior descending coronary artery. After 5 minutes of initial ligation we reperfused the artery and then re-ligated. Before and after each ligation-reperfusion procedure we assessed the left ventricular end-diastolic pressure, arterial pressure, and cardiac index. We also measured left ventricular end-diastolic dimension, end-systolic dimension, fractional shortening, ejection fraction using intraoperative epicardial echocardiography. After appropriate heart failure was established with sequential (from distal part of LAD to proximal location) ligation-reperfusion-ligation procedure, we inserted the ventricular assist device and operated. Result: We established stable acute ischemic heart failure in 3 of 5 young pigs with this sequential ligation-reperfusion-ligation procedure, and could maintained 50% less ejection fraction before the procedure according to intraoperative epicardial echocardiography. We also observed no ventricular arrhythmia usually associated with simple coronary artery ligation in large animals and no cardiac arrest associated with ventricular arrhythmia or myocardial stunning. In pathologic specimen, we observed scattered ischemic myocardium in all around the ischemic field induced by coronary artery ligation. Conclusion: Under the concept of ischemic preconditioning, we developed safe and reproducible acute ischemic heart failure model in swine using sequential coronary artery ligation-reperfusion-ligation method.