• Journal of Applied Biological Chemistry
• /
• v.66
• /
• pp.402-407
• /
• 2023

The regulation of platelet aggregation is crucial for maintaining normal hemostasis, but abnormal or excessive platelet aggregation can contribute to cardiovascular disorders such as stroke, atherosclerosis, and thrombosis. Therefore, identifying substances that can control or suppress platelet aggregation is a promising approach for the prevention and treatment of these conditions. 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. As a result, cAMP production were increased significantly by artemisinin, as well as phosphorylated VASP and IP₃R which are substrates to cAMP-dependent kinase by artemisinin in a significant manner. The Ca²⁺ normally mobilized from the dense tubular system was inhibited due to IP₃R phosphorylation from artemisinin, and phosphorylated VASP by artemisinin aided in inhibiting platelet activity via αIIb/β3 platelet membrane inactivation and inhibiting fibrinogen binding. Finally, artemisinin inhibited thrombin-induced thrombus formation. Therefore, we suggest that artemisinin has importance with cardiovascular diseases stemming from the abnormal platelets activation and thrombus formation by acting as an effective prophylactic and therapeutic agent.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.29 no.4
• /
• pp.232-238
• /
• 2003

This study was performed to evaluate the effect of topical and intravenous heparin on thrombosis and patency in the microvascular anastomosis of the traumatized veins. Nine white rabbits weighing about 2 kg were used. After exposure of both femoral veins, the veins were crushed by the jaws of smooth needle holder in order to create a thrombosis model. Transectional incision was made in the vein. The animals were then divided into 3 groups based on the administration method of heparin: 1) Experimental Group I, topical irrigation of lumen with heparin saline solution (n=6); 2) Experimental Group 2, topical irrigation of lumen with heparin saline solution and intravenous injection of heparin (0.75 mg/kg) via the marginal ear vein for 3 days; 3) Control Group, topical irrigation of lumen with saline solution (n=6). The patency was evaluated with empty-and-refill test and thrombus formation was judged by surgical microscope. The results were as follows: 1. Thirty minutes after microvascular anastomosis, the patency of all Experimental Groups was better than Control group. However, there was no significant difference among groups. 2. Three days after anastomosis, the patency of all Experimental Groups was much more improved than that of Control Group (P<0.05). There was no significant difference between Experimental Group 1 and 2. 3. Three days after anastomosis, the amount of thrombus in all Experimental Groups was much less than that of Control Group (P<0.05). 4. In histologic findings a lot of luminal thrombus were observed around sutured area in Control Groups. Few luminal thrombus was observed in all Experimental Groups. Mild necrosis in the vessel wall was observed around sutured area in all specimens. These results indicate that topical irrigation of heparin may improve the patency and inhibit the formation thrombus in the microvascular anastomosis of the traumatized veins.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.31 no.4
• /
• pp.300-305
• /
• 2005

Purpose: For the reconstruction of maxillofacial defect created by trauma, infection, or tumor etc, the role of microvascular anastomosis or vessel graft has been increased. Many methods has been tried to increase the success rate of microvascular anastomosis. Various anticoagulants and thrombolytic agents have been used to reduce the failure rate of microvascular anastomosis and avoid re-operation. Many drugs, however, have been used in the limited cases because most of these drugs may cause complications, such as allergy, fever or systemic bleeding. This study was performed to evaluate the influence of the Argatroban on patency and thrombosis in microvascular anastomosis when it is used for local irrigation or general administration. Materials & methods: Eight mature rabbits, weighing 2kg, were used. After exposing both femoral veins, the artificial thrombotic model was made by crushing injury using a smooth needle holder, and the transverse incision were made on femoral vein. The animals were divided into 4 groups according to Argatroban administration methods; control group (n=4), topical irrigation of lumen with saline solution; experimental group 1 (n=4), topical irrigation of lumen with Argatroban saline solution; experimental group 2 (n=4), topical irrigation of lumen with heparin followed by intravenous injection of Argatroban; experimental group 3 (n=4), topical irrigation of lumen with Argatroban followed by IV of Argatroban. Microvascular anastomosis was done with 10-0 Ethilon. The patency was evaluated by empty-and-refill test 30 minutes and 3 days after microanastomosis. The thrombus formation was examined 3 days after microanastomosis by surgical microscope. The histologic findings were also examined. Results: 1. Thirty minutes after microvascular anastomosis, the patency of all experimental groups was better than that of control group, but there was no significant difference among groups. 2. Three days after microvascular anastomosis, the patency of all experimental groups was more improved than that of control group (p<0.05). There was no significant difference among experimental groups. 3. Three days after microvascular anastomosis, the amount of thrombus in all experimental groups was less than that of control group (p<0.05). There was no significant difference among experimental groups. 4. Histologically, a lot of luminal thrombus was observed around sutured area in control group. Few luminal thrombus was observed in all experimental groups. The necrotic changes were observed on the sutured vein wall in all specimens. Conclusion: These results indicate that topical irrigation and/or intravenous administration of Argatroban is effective in improving patency and preventing thrombus formation after microvascular anastomosis.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.35 no.5
• /
• pp.284-293
• /
• 2013

Purpose: For reconstruction of craniomaxillofacial defects caused by tumor, trauma, infection etc, free flap transplantation with microvascular surgery is a very useful method. Thrombus formation at the anastomosis site is the major cause of graft failure. 4-Hexylresorcinol (4-HR) is generally known as an antiseptic and antiparasitic agent. This study was conducted in order to evaluate the effect of 4-HR on blood coagulation in vitro. In addition, we investigated thrombus formation and endothelial repair of an injured vessel in an animal model. Methods: In the in vitro experiment, we compared blood coagulation time between the 4-HR treated group and normal blood. Thirty rats were used for in vivo animal experiments. After exposure of the right femoral vein, a micro vessel clamp was placed and the femoral vein was intentionally cut. Microvascular anastomosis was performed on all rats using 10-0 nylon under microscopy. The animals were divided into two groups. In the experimental group (n=15), 4-HR (250 mg/kg) mixed with olive oil (10 mL/kg) was administered per os daily. Animals in the control group (n=15) were given olive oil only. The animals were sacrificed at three days, seven days, and fourteen days after surgery and rat femoral vein samples were taken. Vascular patency and thrombus formation were investigated just before sacrifice. Histologic analysis was performed under a microscope. Results: Results of an in vitro blood coagulation test showed that coagulation time was delayed in the 4-HR treated group. The results obtained from an in vivo 4-HR administered rat model showed that the patency of all experimental groups was better at thirty minutes, seven days, and fourteen days after microvascular anastomosis than that of the control group at seven and fourteen days after anastomosis, and the amount of thrombus in the experimental groups was much less than that of the control group. Endothelial repair was observed in the histologic analysis. Conclusion: Findings of this study demonstrated that blood coagulation was delayed in the vitro 4-HR treated group. In addition, good vascular patency, anti-thrombotic effect, and repair of venous endothelial cells were observed in the vivo 4-HR administered rat group.

• Biomedical Science Letters
• /
• v.27 no.4
• /
• pp.270-276
• /
• 2021

Physiological agents trigger a signaling process called "inside-out signaling" and activated platelets promote adhesion, granule release, and conformational changes of glycoprotein IIb/IIIa (αIIb/β₃). Activated αIIb/β₃ interacts with fibrinogen and initiates a second signaling step called "external signaling". These two signaling pathways can cause hemostasis or thrombosis, and thrombosis is a possible medical problem in arterial and venous vessels, and platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, modulating platelet activity is important for platelet-mediated thrombosis and cardiovascular disease. Esculetin is a coumarin-based physiologically active 6,7-dihydroxy derivative known to have pharmacological activity against obesity, diabetes, renal failure and CVD. Although some studies have confirmed the effects of esculetin in human platelet activation and experimental mouse models, it is not clear how esculetin has antiplatelet and antithrombotic effects. We confirmed the effect and mechanism of action of escultein on human platelets induced by collagen. As a result, esculetin decreased Ca²⁺ recruitment through upregulation of inositol 1, 4, 5-triphosphate receptor. In addition, esculetin upregulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)-dependent pathways and inhibits fibrinogen binding and thrombus contraction. Our results demonstrate the antiplatelet effect and antithrombotic effect of esculetin in human platelets. Therefore, we suggest that esculetin could be a potential phytochemical for the prevention of thrombus-mediated CVD.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.23 no.2
• /
• pp.137-143
• /
• 2001

The effect of topical heparin application and vascular freezing on thrombosis was evaluated in the femoral vein of rabbits. The femoral veins were crushed, incised transversely and treated by 4 different ways; 1) group 1, heparin treated only, 2) group 2, frozen only, 3) group 3, heparin treated and frozen, 4) group 4, treated with saline as control. The patency was evaluated by empty-and-refill test and thrombus formation was judged by stereoscopic and SEM observation. The results obtained were as follows: 1. Thirty minutes after suture, the patency was more improved in the three groups than the control, but there was no significant difference among groups. 2. Three days after suture, the patency was more improved in the three groups than the control, and was prominent in group 1 and group 3 (P<0.05). 3. Significantly reduced thrombus could be seen in most case of group 3. These results suggest that topical application of heparin and vascular freezing is effective in reducing thrombus formation in microsurgery of vein.

• Archives of Reconstructive Microsurgery
• /
• v.9 no.2
• /
• pp.179-185
• /
• 2000

In the field of microsurgery, the vascular obstruction of the microvascular anastomosis by thrombus is one of the most important complication. The purpose of this study is to compare the effect between aspirin and prostaglandin $E_1$($PGE_1$) which act as the peripheral vasodilatation and platelet disaggregation. We have used total 48 white male rats and divided them into three gruoups(A, B and C group). Each group consists of 16 rats respectively. A group is as control, B group is medicated with aspirin(3.0mg/kg/day) and C group with $PGE_1(1.2{\mu}g/kg/day)$. The gross and histopathologic findings at anastomosed site were observed on 3, 5, 10 and 15 days after vascular anastomosis and the results were obtained as the followings. 1. The microvascular patency rate is 81.2% in control group, 93.8% in aspirin group and 100% in $PGE_1$ group. 2. On the histologic examination, the formation of mural thrombus is decreased both in the aspirin and $PGE_1$ group as comparing with the control group and also the hypertrophy of the intima forming from media is less formed in $PGE_1$ group than aspirin group and the degree of thickeness is also less. 3. The fibrosis of media is less observed in $PGE_1$ group than aspirin group. According to the above results, the application of $PGE_1$ to the microsurgery is considered to be effective on the prevention of the thrombus formation and on providing high patency rate.

• Journal of Chest Surgery
• /
• v.23 no.3
• /
• pp.438-451
• /
• 1990

Pneumatic total artificial heart[TAH] has been clinically applied for the purpose of permanent or temporary use followed by cardiac transplantation in the patients with end stage heart diseases. In spite of the good durability of the pneumatic TAH, thrombus formation, bleeding and infection resulted in death. The Tomasu heart, which is a type of pneumatic TAH, was used in this study. This model is a modified Jarvik heart and consists of atrial cuffs, outflow vascular grafts and thin-layer seamless diaphragm type of ventricles. Cardiac outputs of the left artificial heart were measured by Donovan`s mock circulation under variable conditions of driving parameters, and an experimental artificial heart implantation was performed in 4 calves to observe the changes of hemodynamic parameters in early postoperative period and hematologic and bio-chemical changes in a long-term survival case. In the mock circulation test, cardiac output of the heart was increased with the increase of the left atrial pressure and left driving pressure. Maximum cardiac output was obtained at the heart rate of 120 to 130/min and percent systole of 40 to 45Zo under the condition of a constant left driving pressure of 180mmHg and left atrial pressure of 10mmHg. During the first 24 hours of TAH pumping, driving pressure ranged from 178$\pm$5mmHg to 187$\pm$8mmHg for the left heart and from 58$\pm$6mmHg to 78$\pm$28mmHg for the right heart. The Mean arterial pressure significantly increased between 2 and 8 hours after the start of pumping. The survival time ranged from 27 hours to 46 days. The causes of death were respiratory failure in 2 cases, mechanical valve failure in one, and left ventricular outflow obstruction due to thrombus in a 46-day survival case. This study demonstrated that Tomasu artificial heart operated effectively during the first 24 hours of artificial heart pumping, but thrombus formation around the valve holding area was the main problem in long-term survival case.

• Journal of Mechanical Science and Technology
• /
• v.19 no.9
• /
• pp.1761-1772
• /
• 2005

In blood flow passing through the mechanical heart valve (MHV) and elastic blood vessel, hemolysis and platelet activation causing thrombus formation can be seen owing to the shear stress in the blood. Also, fracture and deformation of leaflets can be observed depending on the shape and material properties of the leaflets which is opened and closed in a cycle. Hence, comprehensive study is needed on the hemodynamics which is associated with the motion of leaflet and elastic blood vessel in terms of fluid-structure interaction. In this paper, a numerical analysis has been performed for a three-dimensional pulsatile blood flow associated with the elastic blood vessel and curved bileaflet for multiple cycles in light of fluid-structure interaction. From this analysis fluttering phenomenon and rebound of the leaflet have been observed and recirculation and regurgitation have been found in the flow fields of the blood. Also, the pressure distribution and the radial displacement of the elastic blood vessel have been obtained. The motion of the leaflet and flow fields of the blood have shown similar tendency compared with the previous experiments carried out in other studies. The present study can contribute to the design methodology for the curved bileaflet mechanical heart valve. Furthermore, the proposed fluid-structure interaction method will be effectively used in various fields where the interaction between fluid flow and structure are involved.

• Journal of Veterinary Clinics
• /
• v.39 no.5
• /
• pp.253-257
• /
• 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.