• 대한임상검사과학회지
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• 제43권4호
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• pp.179-187
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• 2011

Animal models are important tools in thrombosis research and preclinical drug development. In recent studies, ferric chloride ($FeCl_3$) has been widely used to induce arterial thrombosis in a variety of species. The purpose of this study was to find an optimal concentration of $FeCl_3$ and validate this model suited better for thrombosis research. A small piece of filter paper, soaked in $FeCl_3$ solution (10, 20 or 35%, v/v, in distilled water) was topically applied on the carotid artery of SD rats to measure the time to occlusion (TTO) and thrombus weight (TW) to ascertain 35%, as an optimal $FeCl_3$ concentration ($8.63{\pm}0.92min$; p =0.000, $0.79{\pm}0.03mg/mm$; p =0.000, respectively). To validate this experimental model, Ginkgo biloba special extract EGb761 (5, 10 or 30 mg/kg) as a reference agent administered by peritoneal route for 1h prior to the induction of thrombosis, showed significantly delayed TTO in a dose dependent manner ($18.50{\pm}2.17$, $29.17{\pm}1.83$, and $38.00{\pm}1.79min$, respectively) and significantly reduced TW and repaired collagen fibre in the injured vessel compare to vehicle group. Our results provide a simple, reproducible and well controlled in vivo screening system to induce thrombosis in rats by the topical application of 35% $FeCl_3$ to assess the efficacy of the new anti-thrombotic agents.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제16권3호
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• pp.397-418
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• 1994

Microvascular surgery has been widely used in the clinical field of replantation and reconstructive surgery. Since the last 20 years, microsurgical techniques and instruments have been rapidly developed and the success rate is remarkably increased. But thrombotic occlusion of vessels remains the major reason for clinical failure. The change of vessel wall is the most important factor in thrombus formation. If we can reduce the traumatic changes in the vessel walls during surgery, the success rate can be markedly increased. For this study, femoral arteries and veins of 36 Sprague-Dawley rats with average weights of 300gm were used. The author observed the histological changes and healing process in the anastomostic site after 1 hour, 24 hours, 1, 2, 3 and 4 weeks under light microscopy and scanning electron microscopy. The results were as follows : 1. The patency rate was 100% in femoral arteries and 85% in femoral vein. 2. At the early stages after microvascular anastomosis, the loss of endothelial cell in the vessel walls was observed in the wide area including anastomotic site. In scanning electron microscopic finding the anastomotic site was covered with much fibrin, many red blood cells and some platelets. 3. At 1st week, new endothelial cells were formed toward anastomotic site and at 3rd week, the anastomotic site was completely covered by new endothelial cells. At 4th week, the complete endothelialization over the threads was observed. 4. The media extended from the anastomotic site toward the end of the specimen. At later stages, the extent of media necrosis was markedly decreased. But the media necrosis of anastomotic site was not regenerated till 4th week. 5. Intimal hyperplasia appeared at 1st week and increased till 4th week. The layer consisted of endothelialization the most luminal layers and smooth muscle in the deeper layers. But in veins, the response was less pronounced than in arteries. 6. Foreign body granuloma remained during 4 weeks and aneurysm was observed at 3rd week in artery. In aneurismal wall, media necrosis, loss of elastic lamina and intimal hyperplasia were seen.

• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.59-68
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• 2021

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

• 대한한의학회지
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• 제34권2호
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• pp.51-58
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• 2013

Objectives: The aim of this study was to examine the antithrombotic effects of the four herbal ingredients (Mume Fructus, MF; Santali Albi Lignum, SAL; Amomi Tsao-Ko Fructus, ATF; and Amomi Fructus, AF) of modified Jeho-tang (MJHT) in a ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis model. Methods: Thirty minutes prior to a 35% $FeCl_3$ application, Sprague-Dawley (SD) rats were injected with saline, MF, SAL, ATF or AF (100 mg/kg, intraperitoneal injection), respectively. The effect of the MJHT ingredients was examined for time to occlusion (TTO) and thrombus weight (TW) in a $FeCl_3$-induced thrombosis model. Histological analysis was performed to examine the effect of the MJHT ingredients on collagen fiber damage using hematoxylin & eosin and Masson's trichrome staining. Results: Compared with vehicle treatment, MF, SAL and ATF treatment delayed TTO (vehicle, $8.11{\pm}0.60$ min; MF, $16.67{\pm}1.03$ min; SAL, $17.50{\pm}1.52$ min and ATF, $13.33{\pm}1.21$ min; P < 0.001) and inhibited thrombus formation (vehicle, $0.79{\pm}0.03$ mg/mm; MF, $0.61{\pm}0.07$ mg/mm; SAL, $0.57{\pm}0.03$ mg/mm and ATF, $0.72{\pm}0.02$ mg/mm; P < 0.001). In addition, each herbal ingredient of MJHT except for AF prevented the collagen fiber damage induced by a 35% $FeCl_3$ application. These results indicate that the MJHT ingredients MF ${\geq}$ SAL ${\geq}$ ATF ${\geq}$ AF possess antithrombotic activity in a $FeCl_3$-induced carotid arterial thrombosis. Conclusions: Altogether, these results are the first evidence that the MJHT ingredients MF, SAL and ATF have the ability to prevent vascular damage and thrombus formation in $FeCl_3$-induced carotid arterial thrombosis.

• Journal of Trauma and Injury
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• 제26권3호
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• pp.243-247
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• 2013

Introduction: Surgical treatment of subclavian artery (SA) injury is challenging because approaching the lesion directly and clamping the proximal artery is difficult. This can be overcome by using an endovascular technique. Case 1: A 37-year-old male was drawn into the concrete mixer truck. He had a right SA injury with multiple traumatic injuries: an open fracture of the right leg with posterior tibial artery (PTA) injury, a right hemothorax, and fractures of the clavicle, scapula, ribs, cervical spine and nasal bone. The injury severity score (ISS) was 27. Computed tomography (CT) showed a 30-mm-length thrombotic occlusion in the right SA, which was 15 mm distal to the vertebral artery (VA). A self-expandable stent($8mm{\times}40mm$ in size) was deployed through the right femoral artery while preserving VA flow, and the radial pulse was palpable after deployment. Other operations were performed sequentially. He had a viable right arm during a 13-month follow-up period. Case 2: A 25-year-old male was admitted to our hospital due to a motorcycle accident. The ISS was 34 because of a hemothorax and open fractures of the mandible and the left hand. Intraoperative angiography was done through a right femoral artery puncture. Contrast extravasation of the SA was detected just outside the left rib cage. After balloon catheter had been inflated just proximal to the bleeding site, direct surgical exploration was performed through infraclavicular skin incision. The transected SA was identified, and an interposition graft was performed using a saphenous vein graft. Other operations were performed sequentially. He had a viable left arm during a 15-month follow-up period. Conclusion: The challenge of repairing an SA injury can be overcome by using an endovascular approach.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제13권1호
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• pp.16-29
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• 1991

미세혈관봉합술에서의 가장 큰 문제점은 봉합부에서의 내피손상과 혈전형성이라고 볼 수 있다. 이 연구의 목적은 봉합시 일어날 수 있는 내피손상부에서의 치유과정을 관찰코져 각각 다른 문합술인 혈관함입문합술과 혈관단단문합술을 백서 대퇴부동맥에 적용하여 개존율및 전자현미경적 관찰을 통하여 비교하였고 아울러 임상에의 적용 가능성을 검토코져 하였다. 저자는 미세현미경시야에서 혈관함입문합술 20례와 단단문합술 20례를 시행한후 1일, 3일, 1주, 2주, 3주에 각각 4마리씩 희생후 문합혈관부를 육안관찰후 주사전자현미경으로 조직변화를 관찰하여 다음의 결과를 얻었다. 1. 혈관 함입문합술 시술시 문합후 개존율은 90%였고 혈관 단단문합술은 85%였다. 2. 혈관 함입문합시 술후 3일째는 문합부에서의 혈소판 응집물이 기질화되었으며 함입으로 좁아져 있던 혈관내경이 약 1주째 혈관 합입부의 중막 위축현상으로 다소 넓어졌다. 3. 혈관 내피재생과정을 혈관 함입문합술에서는 7일에서 14일경에, 혈관 단단문합술에서는 14일에서 21일째 완성되었다.

• Journal of Chest Surgery
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• 제40권1호
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• pp.1-7
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• 2007

배경: 심장판막 및 그 주변의 큰 혈관들의 내피세포는 다른 부위와 달리 훨씬 완화된 면역 반응을 보이는 것에 착안하여, 고정액이나 면역학적 처치를 거치지 않은 이종 판막의 대동맥 판막의 임상적 유용성을 돼지-염소 간 이종 폐동맥 판막도관 이식 실험을 통해 알아보고자 하였다. 대상 및 방법: 돼지 폐동맥 판막도관은 특별한 면역학적 처치를 거치지 않은 채 준비하여 인공심폐기 가동 하에 염소의 우심실 유출로에 이식하였다. 염소들은 군당 2마리씩 배정하여 이식 후 하루, 1주, 3개월, 6개월, 12개월 동안 각각 관찰하였다. 실험동물을 희생하기 전 심초음파검사를 시행하여 판막의 움직임을 관찰하였고, 이종 장기를 적출한 후 판막도관의 조직학적 변화를 관찰하였다. 결과: 총 12마리 중 10마리에서 정해진 기간 동안 생존하였다. 이식된 폐동맥의 전벽의 동맥류가 12개월과 3개월 관찰한 각각 한 마리의 염소에서 발견되었다. 심초음파 검사에서는 다양한 정도의 폐동맥 판막 폐쇄부전의 소견을 보였으나 판막의 협착이나 혈전형성, 증식증은 관찰되지 않았다. 조직학적 관찰에서 이식 세포의 핵은 핵농축 및 핵융해를 통해 없어졌지만, 이식된 이종 판막도관의 세 구역(폐동맥, 폐동맥 판막, 누두부)은 구조가 보존되면서 점차적으로 시간에 따라 숙주 세포로 대체되었다. 결론: 면역학적 처리를 거치지 않은 이종 폐동맥 판막도관이 돼지-염소 간 이종 이식실험에서 다소의 문제점이 발견되기는 하였지만 성공적으로 숙주 세포로 대체되어 기존의 조직판막의 대안이 될 가능성을 제시하였다.

• Journal of Chest Surgery
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• 제37권3호
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• pp.245-251
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• 2004

심폐바이패스하 관상동맥우회술과 달리 심폐바이패스 없이 시행하는 관상동맥우회술의 경우 수술 후 혈액응고 기능이 항진되어 이식편의 혈전과 같은 문제가 발생되는 것이 우려된다. 비교연구를 통하여 심폐바이패스 없이 시행하는 관상동맥우회술 후 혈액응고기능이 항진되는지를 규명하고자 하였다. 2001년 11월부터 2002년 5월까지 관상동맥우회술을 시행받은 환자 중 심폐바이패스 없이 시행하는 관상동맥우회술을 시행받은 11명(I군, 연구군)과 같은 기간에 좌심실 심첨부와 중격의 무운동성으로 관상동맥우회술과 Dor 술식을 시행받은 11명의 환자들을(II군, 대조군)비교하였다. 술후 혈액응고기능이 항진되는지를 알아보기 위해 thromboelastography 검사를 수술 전, 술 후 1, 2, 3, 5일째 시행하여 r time, k time, $\alpha$ angle, MA값을 측정하였고 동시에 혈액응고기능검사, fibrinogen, D-dimer, protein S, protein C, antithrombin III, plasminogen, 혈소판 수 등을 시행하여 비교하였다. TEG검사의 각각의 변수값과 혈액응고기능검사 중 MA값, $\alpha$ angle, 혈소판수가 양 군 간 의미있는 차이를 보였다. MA값이 I군의 경우 술 후 3일과 5일째 140$\pm$72%와 153$\pm$98%로 증가하였으나 II군의 경우 87$\pm$27%와 78$\pm$28%로 감소하였다(p<0.05). $\alpha$ angle은 술후 3일째 I군이 122$\pm$92%로 증가하였고 II군이 69$\pm$23%로 감소하였다(p=0.09). 혈소판수는 술 후 3일째 I군이 63$\pm$55%였으며 II군이 33$\pm$13%였다(p<0.05). 심폐바이패스하 관상동맥우회술과 비교하여 심폐바이패스 없이 시행하는 관상동맥우회술의 경우 혈액응고기능이 항진되며 따라서 보다 적극적인 항응고치료의 필요성이 제기된다고 할 수 있다.