• Korean Journal of Radiology
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• v.20 no.5
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• pp.830-843
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• 2019

Objective: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. Materials and Methods: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2^*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D^*), perfusion fraction (f) were calculated. Results: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D^* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2^* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2^* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. Conclusion: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.

• Korean Journal of Radiology
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• v.21 no.6
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• pp.647-659
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• 2020

Objective: The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphohydrolase-1, can hydrolyze extracellular nucleotides to attenuate their prothrombotic and proinflammatory effects. The purpose of this study was to temporally evaluate the therapeutic effect of APT102 on IRI in rats and to elucidate the evolution of IRI in the acute stage using cardiovascular magnetic resonance imaging (CMRI). Materials and Methods: Fifty-four rats with MI, induced by ligation of the origin of the left anterior descending coronary artery for 60 minutes, were randomly divided into the APT102 (n = 27) or control (n = 27) group. Intravenous infusion of APT102 (0.3 mg/kg) or placebo was administered 15 minutes before reperfusion, and then 24 hours, 48 hours, 72 hours, and on day 4 after reperfusion. CMRI was performed at 24 hours, 48 hours, 72 hours, and on day 5 post-reperfusion using a 7T system and the hearts were collected for histopathological examination. Cardiac function was quantified using cine imaging and IMH/edema using T2 mapping, and infarct/MVO using late gadolinium enhancement. Results: The extent of infarction (p < 0.001), edema (p < 0.001), IMH (p = 0.013), and MVO (p = 0.049) was less severe in the APT102 group than in the control group. IMH size at 48 hours was significantly greater than that at 24 hours, 72 hours, and 5 days after reperfusion (all p < 0.001). The left ventricular ejection fraction (LVEF) was significantly greater in the APT102 group than in the control group (p = 0.006). There was a negative correlation between LVEF and IMH (r = -0.294, p = 0.010) and a positive correlation between IMH and MVO (r = 0.392, p < 0.001). Conclusion: APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI.

• The Korean Journal of Pharmacology
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• v.7 no.1
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• pp.53-65
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• 1971

It is well known that diabetes mellitus is associated with metabolic derangements, such as hyper-glycemia, ketosis, glycosuria, and also widespread alterations in the blood vessels, kidneys, eyes, peripheral nerves and heart. It is also recognized that healing of skin wound is delayed in diabetics. In bone, according to Aegerter, osteopenia develops in diabetes mellitus and it is chiefly ascribed to overutilization of protein. Shim claims that total blood flow to the entire skeletal system is approximately 4 to 8 percent of resting cardiac output and blood supply to the skeletal system would be decreased on account of secondary arteriosclerotic changes in the diabetics. An adequate blood supply is an essential factor in the healing process of fracture, and disturbed blood flow, either local or systemic, will invariably delay union of the fragments or the fragments from being fused. As the author has encountered several cases of diabetics in whom healing of fracture was delayed or incomplete, this experimental study was undertaken to elucidate the effects of hyperglycemia and diabetes mellitus on the healing process of fracture. In this experiment adult albino rabbits, weighing about 2 kg. were used and divided into 6 groups. The femur of each animal was fractured surgically, and then the healing process of fracture was periodically checked by radiography at an interval of one week for a period of 6 weeks. Thereafter, all the rabbits were killed to obtain tissue preparation of the femur. The experimental groups were as follows; 1) Control group: Six rabbits sustained a surgical fracture to the femur, without being given any other treatment or drug. 2) Alloxan-treated group: For inducing diabetes, alloxan was given intravenously to 17 rabbits in various dose as follows; to 7 of them 40 mg/kg, to 6 rabbits 80 mg/kg and to 4 rabbits 120 mg/kg of body weight, respectively. 3) Insulin-treated group: Protamine-zinc insulin was injected subcutaneously to each of 6 rabbits in a daily dose of 1 unit per kilogram of body weight. 4) Group treated with insulin after alloxan: Four rabbits were given 80 mg of alloxan once and than 1 unit of insulin per kilogram of body weight daily. Another 5 rabbits were injected 1 unit of insulin per kg of body weight daily following administration of alloxan in a dose of 120 mg/kg. 5) Homotransplantation group: Following intravenous injection of alloxan in a dose of 120 mg/kg, 10 rabbits underwent homotransplantation of a short bone segment to the femur. Five of them were subsequently given 1 unit/kg of insulin daily. 6) Sugar-treated group: six rabbits were fed $15{\sim}20$ gm of sugar daily throughout the period of experiment. The results obtained are summarized as follows; 1. Blood sugar level and damage to the pancreatic islet increased proportionately when alloxan was given to the rabbits in various doses. No appreciable change could be observed in the islets when the blood sugar level was altered by either oral administration of sugar or subcutaneous injection of insulin. 2. Comparing with the control group, healing of fracture was delayed in the alloxan-treated group, while callus formation and periosteal reaction were shown to be more prominent in this group and subsequently, the ultimate osseous tissue formed at the fracture site was significantly smaller in amount and less compact. These findings were more marked as the amount of alloxan increased. 3. Administration of insulin prevented the delay in healing process of fracture in the rabbits with alloxan-induced hyperglycemia. In this case, the course and progression of fracture healing were almost similar to those of control group. 4. Union between the host bone and the fragment transplanted from other rabbit of the same species was more delayed in the group treated with alloxan alone than in the group to which insulin was administered after development of alloxan-induced diabetes. In both groups periosteal new bone developed from the ends of the host bone, above and below the transplanted fragment, and directly fused with failure of periosteal callus to bridge the adjacent ends of the host bone and the transplanted fragment. 5. The healing process of fracture was not inhibited by alteration in blood sugar level when the blood sugar was abnormally increased by excessive sugar intake or lowered by administration of insulin alone. The healing of fracture in these groups progressed similarly as in the control group. In brief summary, it appears that the healing process of fracture would be definitely disturbed in diabetic state brought about by damage to the pancreatic islet. As such an inhibition could be overcome with insulin, it seems that insulin plays an important role in healing of fracture, but alteration in blood sugar level alone does not modify healing process of fracture to significant degree.

• Journal of Chest Surgery
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• v.37 no.1
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• pp.27-34
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• 2004

Background: Infective endocarditis shows higher operative morbidity and mortality rates than other cardiac diseases. The vast majority of studies on infective endocarditis have been made on aortic endocarditis, with little attention having been paid to infective endocarditis on the mitral valve. This study attempts to investigate the clinical aspects and operative results of infective endocarditis on the mitral valve. Meterial and Method: The subjects of this study consist of 23 patients who underwent operations for infective endocariditis on the mitral valve from June 1995 to May 2003. Among them, 2 patients suffered from prosthetic valvular endocarditis and the other 21 from native valvular endocarditis. The subjects were evenly distributed age-wise with an average age of 44.8$\pm$15.7 (11∼66) years. Emergency operations were performed on seventeen patients (73.9%) due to large vegetation or instable hemodynamic status. In preoperative examinations, twelve patients exhibited congestive heart failure, four patients renal failure, two patients spleen and renal infarction, and two patients temporary neurological defects, while one patient had a brain abscess. Based on the NYHA functional classification, seven patients were determined to be at Grade II, 9 patients at Grade III, and 6 patients at Grade IV. Vegetations were detected in 20 patients while mitral regurgitation was dominant in 19 patients with 4 patients showing up as mitral stenosis dominant on the preoperative echocardiogram. Blood cultures for causative organisms were performed on all patients, and positive results were obtained from ten patients, with five cases of Streptococcus viridance, two cases of methicillin-sensitive Staphylococcus aureus, and one case each of Corynebacteriurn, Haemophillis, and Gernella. Operations were decided according to the AA/AHA guidelines (1988). The mean follow-up period was 27.6 $\pm$23.3 (1 ∼ 97) months. Result: Mitral valve replacements were performed on 43 patients, with mechanical valves being used on 9 patients and tissue valves on the other 4. Several kinds of mitral valve repair or mitral valvuloplasty were carried out on the remaining 10 patients. Associated procedures included six aortic valve replacements, two tricuspid annuloplasty, one modified Maze operation, and one direct closure of a ventricular septal defect. Postoperative complications included two cases of bleeding and one case each of mediastinitis, low cardiac output syndrome, and pneumonia. There were no cases of early deaths, or death within 30 days following the operation. No patient died in the hospital or experienced valve related complications. One patient, however, underwent mitral valvuloplasty 3 months after the operation. Another patient died from intra-cranial hemorrhage in the 31st month after the operation. Therefore, the valve-related death rate was 4.3%, and the valve-related complication rate 8.6% on mid-term follow-up. 1, 3-, and 5-year valve- related event free rates were 90.8%, 79.5%, and 79.5%, respectively, while 1, follow-up. 1, 3-, and 5-year valve- related event free rates were 90.8%, 79.5%, and 79.5%, respectively, while 1, 3-, and 5-year survival rates were 100%, 88.8%, and 88.8%, respectively. Conclusion: The findings suggest that a complete removal of infected tissues is essential in the operative treatment of infectious endocarditis of the mitral valve. It is also suggested that when infected tissues are completely removed, neither type of material nor method of operation has a significant effect on the operation result. The postoperative results also suggest the need for a close follow-up observation of the patients suspected of having brain damage, which is caused by preoperative blood contamination or emboli from vegetation, for a possible cerebral vascular injury such as mycotic aneurysm.

• Journal of Chest Surgery
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• v.31 no.8
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• pp.739-748
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• 1998

Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

• Journal of Chest Surgery
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• v.30 no.10
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• pp.966-972
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• 1997

Between June 1994 to August 1996, 13 patients underwent emergency coronary artery bypass operations. There were 3 males and 10 females and ages ranged from 56 to 80 years with the mean of 65.5 years. The indications for emergency operations were cardiogenic shock in 12 cases and intractable polymorphic VT(ve'ntricular tachycardia) in 1 case. The causes of cardiogenic shock were acute evolving infarction in 6 cases, PTCA failure in 4 cases, acute myocardial infarction in 1 case, and post-AMI VSR(ventricular septal rupture) in 1 case. Pive out of 13 patients could go to operating room within 2 hours. However, the operations were delayed from 3 to 10 hours in 8 patients due to non-medical causes. In 12 patients, 37 distal anastomoses were constructed with only 3 LITA's(left internal thoracic arteries) and 34 saphenous veins. In a patient with post-AMI VSR, VSR repair was added. In a patient with intractable VT and critical sten sis limited to left main coronary artery, left main coronary angioplasty was performed. Pive patients died after operation with the operative mortality of 38.5%. Three patients died in the operating room due to LV pump failure, one patient died due to intractable ventricular tachycardia on postoperative second day, and one patient died on postoperative 7th day due to multi-organ failure with complications of mediastinal bleeding, low cardiac output syndrome, ARF, and lower extremity ischemia due to IABP. In 8 survived patients, 3 major complications (mediastinitis, PMI, UGI bleeding) developed but eventually recovered. We think that the aggressive approach to critically ill patients will salvage some of such patients and the most important factor for patient salvage is early surgical intervention before irreversible damage occurs.

• Journal of Chest Surgery
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• v.41 no.5
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• pp.550-562
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• 2008

Background: We attempted to reproduce a previously reported method that is known to be effective for decellularization, and we sought to find the optimal condition for decellularization by introducing some modifications to this method. Material and Method: Porcine semilunar valves, arterial walls and pericardium were processed for decellularization with using a variety of combinations and concentrations of decellularizing agents under different conditions of temperature, osmolarity and incubation time. The degree of decellularization and the preservation of the extracellular matrix were evaluated by staining with hematoxylin and eosin and with alpha-Gal and DAPI in some of the decellularized tissues. Result: Decellularization was achieved in the specimens that were treated with sodium deoxycholate, sodium dodesyl sulfate, Triton X-100 and sodium dodesyl sulfate with Triton X-100 as single-step methods, and this was also achieved in the specimens that were treated with hypotonic solution ${\rightarrow}$ Triton X-100 ${\rightarrow}$ sodium dodesyl sulfate, sodium deoxycholate ${\rightarrow}$ hypotonic solution ${\rightarrow}$ sodium dodesyl sulfate, and hypotonic solution sodium dodesyl sulfate as multi-step methods. Conclusion: Considering the number and the amount of the chemicals that were used, the incubation time and the degree of damage to the extracellular matrix, a single-step method with sodium dodesyl sulfate and Triton X-100 and a multi-step method with hypotonic solution followed by sodium dodesyl sulfate were both relatively optimal methods for decellularization in this study.

• Journal of Chest Surgery
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• v.43 no.3
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• pp.235-245
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• 2010

Background: Our goal was to evaluate anti-calcification effects of decellularization and diverse fixing methods including preincubation of the bovine pericardium with ethanol. We also assessed changes in mechanical properties. Material and Method: Harvested bovine pericardium was decellularized with 0.25% sodim dodecysulfate and then treated with 5 methods of fixation: (1) 0.5% glutaraldehyde (GA) for 14 days, (2) 0.5% GA for 5 days, 2% GA for 2 days and 0.25% GA for 7 days, (3) 0.5% GA for 5 days, 2% GA for 2 days, 0.25% GA for 7 days, and then 70% ethanol for 2 days, (4) 0.5% GA for 5 days, a mixture of 2% GA and 70% ethanol for 2 days, and 0.25% GA for 7 days, (5) 0.5% GA for 5 days, a mixture of 2% GA, 65% ethanol, and 5% octanediol for 2 days and then 0.25% GA for 7 days. All treated bovine pericardia were tested for histological variables, lipid content, and mechanical properties including tensile strength and thermal stability. A total 10 kinds of differently treated bovine pericardia were implanted into rat subdermis and harvested 8 weeks later. Harvested pericardia were evaluated for calcium content. Result: No protein denaturation was observed microscopically after decellularization. There was a 32% mean decrease in tensile strength index after decellularization in the bovine pericardium group fixed. Octanediol preincubation attenuated the decrease in tensile strength and maintained thermal stability. TG and cholesterol were not affected by decellularization but were decreased by organic solvent. Calcium content was decreased after decellularization, and organic solvent preincubation decreased calcification in the non-decellularized bovine pericardium group. Conclusion: Decellularization and organic solvent preincubation have anti-calcification effects but decellularization may cause mechanical instability. A method of decellularization and fixation that does not cause damage to matrices will be needed for evaluation of the next step in using tissue-engineering for replacement of cardiac valves.

• Journal of Chest Surgery
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• v.29 no.6
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• pp.593-598
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• 1996

The large number of past investigation on extended myocardial protection clearly indicates that cold potassium cardioplegia and topical cooling have limited capabilities. Accordingly, more recent experimen- tal approaches have focused on the modalities of reperfusion and their implication on postischemic myo- cardial recovery. Oxygen may play a crucial role in the development of ischemic and reperfusion injury. Reactive oxygen radicals may be produced during ischemia or reperfusion after incomplete reduction of molecular oxygen or from other pathway and then induce fatal injury of the heart. The important obser- vation of oxygen-induced myocardial damage during reperfusion has led to the concept of applying oxy- gen free radical scavengers. So, this study is on dietary vitamin C supplementation as antioxidant in rats to determine whether or not they have a higher tolerance against cardiac ischemia-reperf'usion injury under Langendorff system. Male or female Sprague-Dawley rats (190-33Og) were randomly separated into two groups. Group A was not treated(n=10). Group B received vitamin C supplement (n=10). Experiment was performed 24 hours after vitamin C 200mg fed orally as injectable ascorbic acid. There were significant differences in contractile parameters between control and vitamin C-treated group. The RLVP (r te of post/preischemic left ventricular pressure) and Rdp/dt (rate of post/preischemic dp/dt) were significant statistically between two groups (p<0.05). But, RHR (rate of post/preischemic heart rate), time to first beat and sta'utilization were not significant. In conclusion, pretreatment with the antioxidant, ascorbic acid, was found to preserve left ventricular contractile function. But the precise mechanism of action of ascorbic acid has not as yet been determined, so further study will be required.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.130-138
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• 1996

Bone scan is known to be an effective tool for observing the state of soft tissues and bones of electric burn patients. It is also used for observing the progress of patients after debridement or skin graft as well as deforming to amputate specific body parts. To evaluate bone scan's role in electric burn, we analyzed bone scan 37 patients with electric burn. Among the 37 patients, 8 of 37 were injured in low voltage and 29 of them in high voltage. 27 patients received the electrical input through the hand, 6 through the scalp, 2 through the shoulder, 1 through the left chest wall and 1 through the left inguinal area. Among 29 patients received high voltage, 22 patients had the electrical output through the foot, 3 through the hand, 2 through the shoulder, 1 through the buttock and 1 through the left chest wall. Bone scans revealed cellulitis in 37 patients with 47 sites, osteomyelitis in 15 patients with 15 sites & bone defects in 4 patients with 4 sites. In 4 patients with skin graft or skin flap, follow up bone scan showed improvements of bony uptake in preoperatively bony defect area and all of them were healed without complication. There were 2 cases in which uptake increased in the myocardium, 1 in the liver and 6 in the kidney, however, serum calcium level, EKG, cardiac enzyme, liver and renal function tests were normal. In conclusion, bone scans are helpful in the assessment of injury sites after electrical insult and in differential diagnosis of cellulitis and osteomyelitis. It is also useful tool of assessment after skin graft or skin flap, however, it should be further evaluated about internal organ damage.