• 동의생리병리학회지
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• 제17권4호
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• pp.930-938
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• 2003

The purpose of the present study was to investigate the effects of Hyunhosaiksan (HHS) on antithrombotic actions which include blood activation, thrombus removal, warming of circulating blood, and the control of pain on abdomen and lower and upper burning spaces. HHS significantly inhibited platelet aggregation induced by ADP and epinephrine in a HHS dose-dependent manner when analyzed by the Sigmoid Emax model in WinNonlin. EC50 values of HHS were 1.71 ㎍/ml and 0.004 ㎍/ml for ADP and epinephrine respectively. In the vivo study, HHS inhibited pulmonary embolism induced by collagen and epinephrine, which was however statistically insignificant. HHS increased number of platelets, APTT and volume of fibrinogen significantly as compared with the control group in dextran-induced thrombus model. Furthermore, HHS stimulated levels of blood flow in vivo though its effect was not observed in vitro. These results suggest that Hyunhosaiksan (HHS) can be used for treating numerous diseases related with blood aggregation and circulation problems. Further systematic investigations on the synergic effects among drugs used in the oriental medicine as well as in the western medicine in relation to thrombosis therapy would provide an important insight into the potential therapeutic applications.

• 생약학회지
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• 제52권1호
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• pp.26-33
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• 2021

During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.

• Journal of Chest Surgery
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• 제54권6호
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• pp.543-546
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• 2021

A 55-year-old woman who had received an implantable left ventricular assist device 3 months earlier presented with dyspnea and a low-flow alarm of the device. Computed tomography and log-file analysis of the device system suggested inflow cannula obstruction. Since the patient had cardiogenic shock due to pump failure, venoarterial extracorporeal membrane oxygenation (ECMO) was initiated. With ECMO, surgical exchange of the pump was considered. However, the obstruction spontaneously resolved without surgical intervention. It turned out that an obstructive thrombus was washed out by rebooting the pump. Moreover, the thrombus was embolized in the patient's left subclavian artery. The patient underwent heart transplantation 4 months after the pump obstruction accident and continued to do well.

• 한국임상수의학회지
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• 제39권5호
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• pp.253-257
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• 2022

A 5-year-old castrated male Golden Retriever dog weighing 15 kg presented with evidence of intestinal intussusception. The patient had cachexia and severe dehydration before being referred to our department. Ultrasound imaging revealed a target sign indicative of intestinal intussusception. Emergency surgery was performed shortly after diagnosis. After a successful surgery, the patient was hospitalised for postoperative care. Initial treatment was aimed at the reversion of dehydration and the provision of adequate nutrition. Fluid therapy and central parenteral nutrition were administered via the peripheral and central venous catheters, respectively. Ten days postoperatively, swelling and edema were observed in the head and neck. Ultrasound and computed tomography confirmed complete blockage of the cranial vena cava due to thrombosis, which consequently obstructed both the left and right jugular veins. For treatment, dalteparin and tissue plasminogen activator were administered. However, the patient lost all of its vital function on the daybreak of postoperative day 11. Venous thrombus formation secondary to central parenteral nutrition application via the central line is a rare but possible complication. Veterinarians who are concerned about taking care of patients receiving CPN through the central line should keep the possibility of venous thrombus formation in mind.

• Journal of Yeungnam Medical Science
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• 제40권3호
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• pp.276-282
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• 2023

Background: Bleeding and thrombosis are major complications associated with high mortality in extracorporeal membrane oxygenation (ECMO) management. Anticoagulant therapy should be adequate to reduce thrombosis. However, related studies are limited. Methods: We retrospectively reviewed all patients supported with ECMO at a single institution between January 2014 and July 2022 and included those on all types of ECMO using the Permanent Life Support System. Patients were classified into two groups according to their measured mean activated partial thromboplastin time (aPTT) during ECMO management: a high-anticoagulation (AC) group (aPTT, ≥55 seconds; n=52) and a low-AC group (aPTT, <55 seconds; n=79). The primary outcome was thrombotic or bleeding events during ECMO. Results: We identified 10 patients with bleeding; significantly more of these patients were in the high-AC group (n=8) than in the low-AC group (15.4% vs. 2.5%, p=0.01). However, thrombus events and oxygenator change-free times were not significantly different between the two groups. Four patients in the high-AC group died of bleeding complications (brain hemorrhage, two; hemopericardium, one; and gastrointestinal bleeding, one). One patient in the low-AC group developed a thrombus and died of ECMO dysfunction due to circuit thrombosis. Conclusion: Heparin did not significantly improve thrombotic outcomes. However, maintaining an aPTT of ≥55 seconds was a significant risk factor for bleeding events, especially those associated with mortality.

• 대한의생명과학회지
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• 제29권3호
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• pp.184-189
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• 2023

Normal activation of platelets and their aggregation are crucial during hemostasis process. It appears excessive or abnormal aggregation of platelets may bring about cardiovascular diseases like stroke, atherosclerosis, and thrombosis. For this reason, finding a substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. This study examined the effect of artemisinin on regulation of U46619-induced platelet aggregation, granule secretion. In addition, the effects of artemisinin on phosphorylation of PI3K/Akt and MAPK pathway involved in platelet aggregation was studied. As a result, artemisinin significantly downregulated of PI3K/Akt and MAPK pathway. In addition, artemisinin significantly reduced granule secretion, and platelet aggregation was inhibited by artemisinin. Therefore, we suggest that artemisinin is an anti-platelet substance that regulates PI3K/Akt and MAPK pathway and is valuable as a therapeutic and preventive agent for platelet-derived cardiovascular disease.

• 대한영상의학회지
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• 제83권2호
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• pp.444-449
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• 2022

심장에서 발생하는 종양의 대부분은 원격 전이이며 일차성 심장 종양은 드물다. 그중에서도 심장의 일차성 신경내분비 종양은 더 드물게 보고되고 있다. 우리는 기저질환이 없는 환자에서 발생한 좌심방이 종괴에 대해 보고하고자 한다. 종괴의 위치, 초음파에서의 움직임, 환자의 뇌경색 발생으로 혈전을 의심하였다. 그 후 종괴에 대한 수술적 절제를 시행하였고, 신경 내분비 종양으로 진단받았다.

• 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 Applied Biological Chemistry
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• 제65권4호
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• pp.239-245
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• 2022

지혈이 일어나는 과정에서 혈소판의 정상적인 활성화가 중요하지만, 혈소판의 과도하거나 비정상적인 활성화는 뇌졸중, 죽상동맥 경화증 및 혈전증과 같은 심혈관 질환을 유발할 수 있다. 따라서, 혈소판 활성화를 조절하거나 억제할 수 있는 새로운 물질의 발견은 심혈관 질환의 예방 및 치료에 도움이 될 수 있다. Artemether는 Artemisia annua의 유효성분으로 알려진 artemisinin의 유도체로서 말라리아 치료에 효과적이라고 보고된 바 있고, 항산화 및 대사 효소 억제를 통해 기능하는 것으로 알려져 있다. 그런데, 혈소판 활성화 및 응집에 있어서의 artemether의 역할과 collagen으로 유도한 사람 혈소판에서 artemether의 작용기전은 현재까지 알려진 바가 없다. 본 연구는 artemether가 collagen에 의해 유도된 혈소판 활성화와 혈전 형성에 어떤 영향을 미치는 지 연구하였다. 그 결과, cAMP level이 artemether에 의해 유의하게 증가되었고, cAMP-의존성 kinase의 기질인 VASP 및 IP₃R이 인산화되었다. Artemether에 의한 IP₃R 인산화는 세포질 내로의 Ca²⁺ 동원을 억제하였고, 인산화된 VASP는 혈소판 막에 위치한 αIIb/β₃ 불활성화를 일으켜 fibrinogen 결합을 억제하였다. 결과적으로, artemether는 thrombin으로 유도한 fibrin clot의 형성을 억제하였다. 따라서, 우리는 artemether가 과도한 혈소판 활성화 및 혈전 형성으로 인한 심혈관 질환의 효과적인 예방 및 치료제로 작용할 수 있음을 제안한다.

• Annals of Clinical Neurophysiology
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• 제13권1호
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• pp.68-70
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• 2011