New Thrombolytic Infusion Application of Dissolving Renal Artery Embolic Thrombosis: Low-Dose Slow-Infusion Thrombolytic Therapy.
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ABSTRACT:
SUBMITTER: Karakurt A
PROVIDER: S-EPMC5954957 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPercutaneous closure of patent foramen ovale (PFO) is used in selected individuals to eliminate the risk of recurrent cerebral embolism due to paradoxical embolization. Although device thrombosis is rare, it can cause serious complications. Herein, we report a 40-year-old woman who developed acute PFO closure device-associated thrombus and was subsequently treated with slow infusion of low-dose tissue plasminogen activator (t-PA) (25 mg/6 h).Case summaryA 40-year-old woman was admitted to the hospital because of an cerebrovascular accident (CVA). Computed tomography and magnetic resonance imaging of the brain demonstrated the presence of an ischaemic lesion in the right cerebellar infarct. Since no pathological finding was detected that could cause CVA, it was considered that there might be paradoxical embolism due to PFO. Percutaneous PFO closure was decided by the heart and brain team. The occluder was implanted under transoesophageal echocardiography (TEE) and fluoroscopy guidance. Although activated clotting time was 250 s, hypermobile acute thrombus measuring 11 × 5 mm was seen on the left atrial side of the PFO device. Slow infusion of low-dose t-PA treatment was given. As soon as after a single-dose t-PA, control TEE was performed and it was seen that almost the entire thrombus was lysed. The patient did not have any complications during the treatment period.DiscussionAcute PFO device thrombosis is a rare but important complication. If there is no contraindication for lytic treatment in acutely developing large PFO device thrombosis, slow infusion of low-dose t-PA may be useful.
| S-EPMC11362546 | biostudies-literature
Project description:Combination therapy with focused ultrasound (FUS) and a neuroprotective agent, BNG-1, was examined in an acute carotid thrombotic occlusion model using LED irradiation in rat to improve the thrombolytic effect of rt-PA. Seven treatment groups included (A) intravenous bolus injection of 0.45 mg/kg rt-PA, (B) intravenous bolus injection of 0.9 mg/kg, (C) sonothrombolysis with FUS alone, (D) oral administration of 2 g/kg BNG-1 for 7 days alone, (E) A + D, (F) A + C, and (G) A + C + D. Four comparison groups were made including (H) 0.45 mg/kg rt-PA 20% bolus +80% IV fusion + FUS, (I) 0.9 mg/kg rt-PA with 10% bolus + 90% intravenous fusion, (J) B + C, (K) B + D. At 7 days after carotid occlusion, small-animal carotid ultrasound and 7 T MR angiography showed the recanalization rate of ≤50% stenosis was 50% in group B and 83% in group I, but 0% in groups A and C and 17% in group D. Combination therapy improved recanalization rate to 50-63% in groups E and F, to 67-83% in groups J and K, and to 100% in groups G and H. Our study demonstrated combination therapy with different remedies can be a feasible strategy to improve the thrombolytic effect of rt-PA.
| S-EPMC5431649 | biostudies-literature
Project description:We report a case of bilateral renal infarction following thrombolytic and anticoagulant therapy for left ventricular embolism-induced lower leg artery ischemia. Imaging demonstrated thrombi from the left ventricle leading to bilateral renal arterial occlusion. Catheter embolectomy and long-term oral anticoagulant therapy were initiated, and the patient recovered with no residual complications. (Level of Difficulty: Intermediate.).
| S-EPMC9666748 | biostudies-literature
Project description:BackgroundAn increase in transvalvular pressure gradient of prosthetic valve should always raise suspicion for obstructive valve thrombosis. A multimodality diagnostic approach including transthoracic echocardiography, transoesophageal echocardiography (TOE), cinefluoroscopy, or computed tomography (CT) is necessary for a prompt diagnosis. The management of mechanical prosthetic valve thrombosis (PVT) is high risk in any therapeutic option taken. Emergency valve replacement is recommended for critically ill patients. Fibrinolysis is an alternative for patients with contraindication to surgery or if surgery is not immediately available.Case summaryA 52-year-old woman presented with symptoms and signs of cardiac congestion. On laboratory, brain natriuretic peptide was elevated and international normalized ratio (INR) was in subtherapeutic range. She underwent a mitral valve replacement with mechanical prosthesis 7 months before, because of a significant residual regurgitation after repair on the same year. TOE revealed severe stenosis of the prosthesis with immobile anterior disc but there was no mass present. CT revealed a minor lesion at the hinge points of the prosthesis without involvement of the ring, suggestive for thrombus. The initial fruitless management with intravenous (i.v) heparin in high therapeutic range was followed by a successful 'low-dose, ultra-slow' fibrinolysis.DiscussionCT may help differentiate thrombus vs. pannus. The acute onset of symptoms, inadequate anticoagulation, and restricted leaflet motion increased the suspicion for PVT. The current European guidelines propose normal dose fibrinolysis. We performed 'low-dose, ultra-slow' fibrinolysis due to lower bleeding risk with successful results. Low dose should be considered as alternative to normal dose fibrinolysis or urgent surgery.
| S-EPMC7319841 | biostudies-literature
Project description:The mechanisms underlying hyperarousal, the key symptom of insomnia, have remained elusive, hampering cause-targeted treatment. Recently, restless rapid-eye-movement (REM) sleep emerged as a robust signature of sleep in insomnia. Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal. Participants (n = 1,199) completed questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thought-like nocturnal mentation that was validated to be a specific proxy for restless REM sleep (selective fragmentation: R = 0.57, P < 0.001; eye movement density: R = 0.46, P < 0.01) in 32 polysomnographically assessed participants. The experience of distress lasting overnight increased with insomnia severity (? = 0.29, P < 10(-23)), whereas short-lasting distress did not (? = -0.02, P = 0.41). Insomnia severity was associated with hyperarousal (? = 0.47, P < 10(-63)) and with the thought-like nocturnal mentation that is specifically associated with restless REM sleep (? = 0.31, P < 10(-26)). Structural equation modeling showed that 62.4% of the association between these key characteristics of insomnia was mediated specifically by reduced overnight resolution of emotional distress. The model outperformed all alternative mediation pathways. The findings suggest that restless REM sleep reflects a process that interferes with the overnight resolution of distress. Its accumulation may promote the development of chronic hyperarousal, giving clinical relevance to the role of REM sleep in emotion regulation in insomnia, depression, and posttraumatic stress disorder.
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Project description:Background: Hemorrhagic transformation, neurotoxicity, short treatment time windows, and other defects are considered as the major limitations for the thrombolytic therapy. This study is devoted to figure out whether Danhong injection (DHI) combined with tissue-plasminogen activator (t-PA) could extend the treatment time windows and ameliorate brain injury, hemorrhagic complication and BBB disruption after focal embolic stroke. Methods:In vitro, the combined concentrations of DHI and t-PA were added to wells reacted with plasminogen and D-Val-Leu-Lys-AMC. The optimum ratio of the combination of DHI plus t-PA was explored by detecting relative fluorescent. In vivo experiments, we firstly investigated the optimal dose of t-PA and Danhong injection for focal embolic stroke. The neurological deficit score, infarct volume and brain edema were assessed. Secondly, we proved that the combination group extended the thrombolytic window for treatment of focal embolic stroke. The neurological deficit score, infarct volume, brain edema and hemorrhagic complication were assessed, while levels of BAX, Bcl-2 and caspase-3 in brain tissue were analyzed by real-time polymerase chain reaction. Finally, to ask whether combination therapy with DHI plus t-PA protected the blood-brain barrier in a rat model of focal embolic stroke, neurological deficit score, ELISA, RT-PCR, western blot and fluorescence were used to detect the indicators of blood-brain barrier, such as tight junction protein, blood-brain barrier permeability and related gene expression. Results:In vitro, plasmin activity assays showed that the combination of t-PA with DHI at about 1:1.6 w/v ratio increased by almost 1.4-fold the plasmin-generating capability of t-PA. In vivo experiments, the results showed that the combination of Danhong injection (4 mL/kg) and t-PA (2.5 mg/kg) could extend the t-PA treatment time windows to 4.5 h. And the combination t-PA (2.5 mg/kg) with DHI (4 mL/kg) ameliorated neurological score, cerebral infarction, brain edema, brain hemorrhage, and BBB disruption. Conclusion: Combination therapy with Danhong injection (4 mL/kg) plus t-PA (2.5 mg/kg) could extend the t-PA treatment time windows to 4.5 h, ameliorate BBB disruption, reduce infarction, brain swelling and hemorrhage after ischemic stroke.
| S-EPMC5897498 | biostudies-literature
Project description:Our previous study showed that PI3Kγ inhibition with AS605240 plus a standard rat-dose tPA (10 mg/kg) combination attenuates delayed tPA-induced brain hemorrhage and ameliorates acute stroke injury 3 days after ischemic stroke in rats. The purpose of this study was to investigate whether combining AS605240 with tPA can enhance thrombolytic efficacy, so that lower doses of tPA can be applied to improve long-term outcome after ischemic stroke. The results showed that AS605240 plus low-dose tPA (5 mg/kg) combination therapy at 4 h after stroke onset significantly reduced infarct volume and neurological deficits at 24 h after stroke compared with saline, AS605240 or low-dose tPA alone group. Importantly, the combination therapy significantly reduced the delayed tPA-associated brain hemorrhage. Moreover, the combination therapy significantly decreased the size of the residual embolus within the middle cerebral artery, which was associated with a decrease in plasma plasminogen activator inhibitor-1 (PAI-1) activity compared with saline and tPA alone. Finally, AS605240 plus low-dose tPA combination improved long-term outcome for at least 35 days after stroke compared with the saline-treated group. Taken together, these findings suggest that PI3Kγ inhibition with AS605240 might act as an adjunct approach for enhancing tPA thrombolytic efficacy in acute ischemic stroke.
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Project description:Coronavirus disease 2019 (COVID-19) has been extensively associated with microvascular and macrovascular thrombosis. Several reports have demonstrated a link between COVID-19 and pulmonary embolism, deep vein thrombosis, myocardial infarction, stroke, and aortic thrombosis. Renal artery thrombosis is of special interest because of its life-threatening consequences, such as acute kidney injury and renal infarction. We present a case of left renal artery thrombosis as a long-term complication of COVID-19. Moreover, we demonstrate the effectiveness of interventional radiology to regain vascularization of the affected kidney.
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Project description:To construct a stable rat portal vein thrombosis (PVT) model and explore the time window of urokinase thrombolytic therapy on this basis. Constructing a rat PVT model by combining anhydrous ethanol disruption of portal endothelium with stasis of blood flow. Forty-eight rats after PVT modeling were divided into control group and experimental group, with 24 rats in each group. The experimental and control groups were given urokinase treatment and saline tail vein injection, respectively. The two groups of rats were observed and compared for PVT formation at 1, 3 and 5 days after modeling, respectively. A stable rat PVT model was successfully constructed. No significant differences were found in PVT length, portal vein wet weight, and percentage of luminal occlusion area in the control rats at 1, 3, and 5 days after successful modeling (P > 0.05). Compared with control rats 1 day after modeling, the percentage of non-organized thrombus luminal area was significantly decreased (P < 0.0001), and the percentage of organized thrombus luminal area was significantly increased (P < 0.0001) in the PVTs of control rats at 3 and 5 days after modeling. After thrombolytic treatment with urokinase, plasma fibrinogen (FBG) levels were significantly decreased in the experimental group of rats compared with the control group (P < 0.0001), and plasma D-dimer (D2D) levels were significantly increased in the experimental group of rats compared with the control group (P < 0.0001). In addition, we observed prolongation of prothrombin time (PT) in the experimental group at 1, 3 and 5 days after modeling compared to the control group (P = 0.0001). Compared with the control group, portal vein wet weight and PVT length were significantly decreased in the experimental group of rats at 1 day after modeling (P < 0.05), whereas these differences were not found in the two groups of rats at 3 and 5 days after modeling (P > 0.05). The percentage of non-organized thrombus area in the experimental group was significantly decreased compared with that in the control group at 1, 3, and 5 days after modeling (P < 0.05), whereas there was no significant difference in the percentage of lumen area of organized thrombus between the two groups (P > 0.05). The method of producing a rat PVT model by destroying the endothelium of the portal vein by anhydrous ethanol combined with blood flow stasis is feasible and reproducible. In addition, the optimal time window for thrombolysis in the treatment of PVT in rats using urokinase is the early stage of thrombosis, when the fibrin content is highest.
| S-EPMC11296622 | biostudies-literature
Project description:SMTP-7 (Stachybotrys microspora triprenyl phenol-7) is a small molecule that promotes thrombolysis and suppresses inflammation possibly through plasminogen modulation and soluble epoxide hydrolase (sEH) inhibition, respectively. Here, we demonstrate an efficacy of SMTP-7 in a severe embolic stroke model in monkeys. The middle cerebral artery was embolized by an autologous blood clot. Saline, SMTP-7, or tissue-type plasminogen activator (t-PA) (n = 5 in each group) was given after 3 hours, and neurologic deficit scoring and infarct characterization were performed after 24 hours. Hemorrhagic infarct-accompanied premature death was observed for two animals in t-PA group. SMTP-7 treatment significantly reduced the sizes of infarct by 65%, edema by 37%, and clot by 55% compared to saline treatment. Plasma levels of the products of plasminogen activation (plasmin-α2-antiplasmin complex) and sEH reaction (dihydroxyeicosatrienoic acid) in SMTP-7 group were 794% (P < 0.05) and 60% (P = 0.085) compared to saline group, respectively. No significant changes in the plasma levels of MMP-9, CRP, MCP-1, and S100B were found. There was an inverse correlation between plasmin-α2-antiplasmin complex level and infarct volume (r = 0.93, P < 0.05), suggesting a role of thrombolysis in the SMTP-7 action to limit infarct development. In conclusion, SMTP-7 is effective in treating severe embolic stroke in monkeys under conditions where t-PA treatment tends to cause hemorrhagic infarct-associated premature death.
| S-EPMC6282002 | biostudies-literature