The oral thrombolysis for venous thrombosis (clinical trial)

2019 ◽  
Author(s):  
С.В. Мишенина ◽  
П.Г. Мадонов ◽  
Г.И. Байкалов ◽  
С.Г. Леонтьев ◽  
С.П. Зотов
Keyword(s):  
Clinical Trial ◽  
Blood Flow ◽  
Oral Administration ◽  
Venous Thrombosis ◽  
Target Therapy ◽  
Severe Bleeding ◽  
Thrombolytic Action ◽  
Complex Therapy ◽  
Thrombolytic Effect ◽  
Higher Doses

Введение. Таргетная терапия тромбозов заключается в тромболитической терапии. В настоящий момент в подавляющем большинстве случаев терапия тромбозов у пациента сводится к назначению антикоагулянтов в расчете на механизм собственного фибринолиза/тромболизиса. Применение активаторов плазминогена эффективно, но сопряжено с опасностью тяжелых кровотечений и проводится только в условиях стационара. Очень перспективно для лечения тромбозов выглядит применение лекарственных препаратов на основе иммобилизированных субтилизинов, которые имеют прямое тромболитическое действие при пероральном приеме. В России зарегистрирован лекарственный препарат на основе иммобилизированных субтилизинов Тромбовазим, который имеет показание лечение хронической венозной недостаточности. Основой фармакодинамики препарата является тромболитическое действие. Цель исследования: показать, что включение лекарственного препарата Тромбовазим в комплексную терапию тромбозов венозного русла нижних конечностей улучшает результаты лечения. Материалы и методы. Проведено многоцентровое рандомизированное плацебоконтролируемое двойное слепое клиническое исследование. В настоящий момент лекарственный препарат Тромбовазим зарегистрирован к медицинскому применению в дозе 1600 ЕД/сут. Клиническое исследование было проведено по двум протоколам: Протокол 1 включение Тромбовазима в комплексную терапию тромбоза в суточной дозе 1600 ЕД Протокол 2 включение Тромбовазима в комплексную терапию тромбоза в более высоких дозах 3200 и 4800 ЕД/сут. Результаты. У пациентов, принимающих лекарственный препарат Тромбовазим в дозе 1600 3200 ЕД/сут, увеличение кровотока либо реканализацию вены наблюдали в 1,6 раза чаще (на 60 больше), чем среди пациентов, получающих плацебо. Эффективная тромболитическая доза препарата Тромбовазим 1600 3200 ЕД/сут. Заключение. Лекарственный препарат на основе иммобилизированных субтилизинов Тромбовазим обладает тромболитическим действием при пероральном применении. Тромбовазим в составе комплексной терапии больных с тромбозом венозных сосудов быстро восстанавливает кровоток в зоне скомпрометированного кровообращения. Introduction. The target therapy of thrombosis consists of thrombolytic therapy. At present in most of cases, the therapy of thromboses in patient is reduced to the prescribing of anticoagulants based on mechanism of own fibrinolysis/thrombolysis. The use of plasminogen activators is effective, but is associated with the risk of severe bleeding and is carried out only in hospital. The administration of drugs that based on immobilized subtilisins looks very promising for thromboses treatment. The immobilized subtilisins have a direct thrombolytic effect under oral administration. The drug Trombovazim is based on immobilized subtilisins and has been registered in Russia. Trombovazim has an indication treatment of chronic venous insufficiency thrombolytic action is the basis of its pharmacodynamics. Aim: to show that Trombovazim in complex therapy of venous thromboses of the lower extremities improves the treatment outcomes. Materials and methods. A multicenter randomized doubleblind placebocontrolled clinical trial was carried out. At present Trombovazim is registered for medical use at a dose of 1600 U/day. The clinical study was undertaken according to 2 protocols: Рrotocol 1 Trombovazim inclusion in complex therapy of thrombosis at a dose of 1600 U/day Рrotocol 2 Trombovazim inclusion in complex therapy of thrombosis in higher doses 3200 and 4800 U/day. Results. In patients taking Trombovazim at a dose of 1600 3200 U/day increased blood flow or vein recanalization was observed 1.6 times more often (60 more) than in patients receiving placebo. The effective thrombolytic dose of Trombovazim is 1600 3200 U/day. Conclusion. Trombovazim has a thrombolytic action under oral administration. Thrombovazim in complex therapy of patients with venous thrombosis quickly restores the blood flow in a zone of compromised blood circulation.

Effect of acetylcholine infusion on adrenal vasculature and catecholamine secretion

1993 ◽  
Vol 265 (3) ◽  
pp. H966-H972 ◽  
Author(s):  
J. R. Tobin ◽  
M. J. Breslow ◽  
R. J. Traystman
Keyword(s):  
Blood Flow ◽  
Muscarinic Receptor ◽  
Cholinergic Receptor ◽  
Catecholamine Secretion ◽  
Receptor Stimulation ◽  
Similar Dose ◽  
Adrenal Vasculature ◽  
Higher Doses

To evaluate effects of cholinergic receptor stimulation on regional adrenal blood flow (Q, radiolabeled microspheres) and catecholamine secretion, acetylcholine (ACh) was infused into pentobarbital-anesthetized, ventilated dogs. Unilateral adrenal denervation and placement of lumboadrenal catheters preceded intra-aortic infusion of 1) ACh alone (n = 6), 2) ACh plus hexamethonium (Hex) 20 mg/kg (n = 6), or 3) ACh plus atropine (Atr) (0.5 mg/kg) and Hex. ACh alone and in combination with Hex elicited similar dose-related (2, 20, and 100 mumol/min) increases in catecholamine secretion (181 +/- 61 to 1,055 +/- 229, 31,644 +/- 9,411, and 179,181 +/- 69,659 ng.min-1 x g medulla-1), whereas Hex and Atr together inhibited ACh-induced secretion by 95%. ACh caused marked medullary vasodilation (0.71 +/- 0.05 to 0.14 +/- 0.03 mmHg.ml-1 x min.100 g) in all three groups. To determine whether medullary vasodilation was due to incomplete muscarinic blockade, Hex-pretreated animals (n = 4) received ACh (100 mumol/min) and three increasing doses of Atr (0.5, 5, and 25 mg/kg). Catecholamine secretion was inhibited by all doses of Atr; however, vasodilation was blocked only by the two higher doses of Atr. These data suggest possible different mechanisms of muscarinic receptor-mediated catecholamine secretion and vasodilation.

The Immediate And Long-Term Effects of Shexiang Tongxin Dropping Pill On Coronary Slow Flow: Study Protocol For A Randomized Double-Blind Placebo-Controlled Trial

2021 ◽  
Author(s):  
Birong Liu ◽  
Yong Liu ◽  
Liyong Ma ◽  
Jia Liu ◽  
Jingen Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Blood Flow ◽  
Blood Stasis ◽  
Blood Stasis Syndrome ◽  
Controlled Study ◽  
Slow Flow ◽  
Long Term Effects ◽  
Coagulation Function ◽  
Coronary Slow Flow

Abstract Background: Coronary slow flow (CSF) is a phenomenon characterized by delayed contrast medium progression in angiography in the absence of obstructive coronary epicardial disease. However, there is currently no definite effective therapy. A small sample self-controlled study had suggested an immediate improvement in coronary slow blood flow by Shexiang Tongxin Dropping Pills (STDP). But high-quality evidences on drug dosage, medication cycle and long-term effects are still lacking while the mechanism of STDP remains unclear. Methods: This study is a randomized, double-blinded, and placebo-controlled clinical trial. A total of 64 CSF patients diagnosed by coronary angiography will be randomly allocated into the test group, using STDP, and the control group, using placebo. The main efficacy indicators for immediate effects include thrombolysis in myocardial infarction (TIMI) blood flow grading and corrected TIMI frame count. Long-term effects will be evaluated by the comparison of cardiac radionuclide score, and patient condition such as angina readmission rate and angina scale. The safety indicators include a routine complete blood count, liver and renal function test, cardiac markers (including TnI, CK-MB, Myo), NT-proBNP, coagulation function, 12-lead electrocardiogram, and echocardiography. All adverse events during the trial will be recorded. Moreover, endothelial factors (including ET-1, NO, eNOS, iNOS), inflammatory factors (including adropin, IL-6, IL-1, IL-18, TNF-α, Lp-PLA2, hs-CRP) will be observed. Blood stasis syndrome (including platelet activation factors such as CD62 and CD63, coagulation function and blood stasis syndrome score) will be evaluated.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000035167. Registered on August 2, 2020. http://www.chictr.org.cn/showproj.aspx?proj=57349

Does blood flow restriction training increase the diameter of forearm vessels in chronic kidney disease patients? A randomized clinical trial

2018 ◽  
Vol 19 (6) ◽  
pp. 626-633 ◽  
Author(s):  
Jefferson BN Barbosa ◽  
Tuíra O Maia ◽  
Priscila S Alves ◽  
Shirley D Bezerra ◽  
Elaine CSC Moura ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Chronic Kidney Disease ◽  
Blood Flow ◽  
Kidney Disease ◽  
Radial Artery ◽  
Handgrip Strength ◽  
Cephalic Vein ◽  
Blood Flow Restriction ◽  
Control Group ◽  
Flow Restriction

Introduction: Blood flow restriction training can be used as an alternative to conventional exercise in chronic kidney disease patients with indication of arteriovenous fistula. Objective: Evaluating the efficacy of blood flow restriction training in the diameter and distensibility change of the cephalic vein and the diameter and flow of the radial artery, muscle strength and forearm circumference in chronic kidney disease patients with arteriovenous fistula pre-creation. Methods: A blind randomized clinical trial consisting of 26 chronic kidney disease patients allocated into a blood flow restriction training group (blood flow restriction; n = 12) and a group without blood flow restriction training (control group; n = 14). Blood flow restriction was performed at 50% of systolic blood pressure and using 40% of handgrip strength as load for the isometric exercises in both groups. Results: An increase in the diameter of the cephalic vein in the 2 cm (p = 0.008) and 10 cm segments (p = 0.001) was observed in the control group. The diameter of the radial artery increased in all segments in the blood flow restriction group (2, 10 and 20 cm; p = 0.005, p = 0.021 and p = 0.018, respectively) and in the 10 and 20 cm segments (p = 0.017 and p = 0.026) in the control group. Handgrip strength only increased in the control group (p = 0.003). Conclusion: Physical training associated with blood flow restriction increased cephalic vein diameters in both groups and was effective in increasing the diameter of the radial artery; however, it did not demonstrate superiority over the exercise group protocol without blood flow restriction.

scholarly journals The Glucosamine Controversy; A Pharmacokinetic Issue

2011 ◽  
Vol 14 (2) ◽  
pp. 264 ◽  
Author(s):  
Ali Aghazadeh-Habashi ◽  
Fakhreddin Jamali
Keyword(s):  
Clinical Trial ◽  
Animal Studies ◽  
The Other ◽  
Naturally Occurring ◽  
Assessment Metrics ◽  
Disease Modifying ◽  
Clinical Trial Results ◽  
Higher Doses ◽  
Positive Results ◽  
Rule Out

Glucosamine (GlcN) is a naturally occurring aminosugar that is widely used to treat osteoarthritis despite controversial clinical trial results. Animal studies, on the other hand, unequivocally suggest anti-inflammatory and disease modifying effects for GlcN. Many explanations have been offered as to the root of the controversy. They include superiority of a crystalline sulphate salt over HCl, industry bias, insensitive assessment metrics and poor methodology. Herein, we rule out a difference in bioequivalence between GlcN salts and that of chemically equivalent doses and suggest additional factors; i.e., inconsistency in the chemical potency of some products used, under-dosing of patients as well as variable and erratic bioavailability indices for the lack of GlcN efficacy observed in some studies. Clinical trials using higher doses of pharmaceutical grade GlcN or formulations with greater bioavailability should yield positive results. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

P4-305: IMPACT OF SIMVASTATIN ON CEREBRAL BLOOD FLOW, PULSATILITY INDEX, AND ALZHEIMER'S DISEASE BIOMARKERS: A CLINICAL TRIAL

2006 ◽  
Vol 14 (7S_Part_30) ◽  
pp. P1571-P1571
Author(s):  
Natanya S. Russek ◽  
Sara Elizabeth Berman ◽  
Karen K. Lazar ◽  
Yue Ma ◽  
Carson A. Hoffman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Pulsatility Index ◽  
Disease Biomarkers ◽  
Flow Pulsatility

scholarly journals Verapamil improves the outcome after cadaver renal transplantation.

1991 ◽  
Vol 2 (5) ◽  
pp. 983-990
Author(s):  
I Dawidson ◽  
P Rooth ◽  
C Lu ◽  
A Sagalowsky ◽  
K Diller ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Transplantation ◽  
Renal Transplant ◽  
Oral Administration ◽  
Renal Artery ◽  
Graft Survival ◽  
Antilymphocyte Globulin ◽  
Acute Renal Dysfunction ◽  
Transplant Patients ◽  
Blood Flow Velocities

Because of their favorable effects on renal hemodynamics, calcium antagonists may have a major role in the prevention and management of certain types of acute renal dysfunction. In fact, verapamil (VP) was shown to prevent cyclosporin A (CsA)-induced decreases in RBF in mice and in cadaver renal transplant (CRT) recipients. The study presented here of 59 cadaver renal transplant patients evaluates the outcome from perioperative treatment with VP (N = 30) administered intraoperatively into the renal artery (10 mg) followed by oral administration of 120 mg every 8 to 12 h for 14 days versus no drug (N = 29). Early immunosuppression included azathioprine, corticosteroids, and antilymphocyte globulin with subsequent overlapping with CsA on days 5 and 6. Actuarial graft survival at 1 yr was different when the two groups were compared (P less than 0.05). Estimated graft survival at 1 yr for VP patients was 93.3 compared with 72.4% in control patients. The improved graft survival was most striking in repeat transplants with 90% graft survival at 1 yr for VP recipients versus 37.5% for controls. Compared with controls, VP recipients had significantly improved renal parenchymal diastolic blood flow velocities on the first day after surgery (7.8 versus 5.8 cm/s). By day 7, GFR were greater with VP (44 +/- 29 mL/min) versus controls (28 +/- 22 mL/min). Of VP patients, 67% (18 of 24) had GFR greater than 30 mL/min versus 33% (9 of 26) for control patients. Similarly, on the seventh day, 77% (21 of 30) of VP patients had serum creatinines less than 2.0 mg% versus 34% (10 of 29) for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract 196: Sanguinate (PEGylated-carboxyhemoglobin-bovine) Improves Cerebral Blood Flow and Oxygen Extraction to Vulnerable Brain Regions in Patients at Risk for Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rajat Dhar ◽  
Hemant Misra ◽  
Michael Diringer
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Brain Regions ◽  
Oxygen Extraction ◽  
Patients At Risk ◽  
Higher Doses

Introduction: Sanguinate is a dual-action oxygen transfer and carbon monoxide-releasing agent with efficacy in animal models of focal brain ischemia and established safety in health volunteers. We performed a dose-escalation study in subarachnoid hemorrhage (SAH) patients at risk for delayed cerebral ischemia (DCI) to evaluate tolerability and explore efficacy in improving cerebral blood flow (CBF) and flow-metabolism balance to vulnerable brain regions. Methods: 12 subjects were studied over three dose tiers: 160mg/kg, 240 mg/kg, and 320 mg/kg, with close safety evaluation prior to proceeding to higher doses. After baseline 15 O-PET measurement of global and regional CBF and oxygen extraction fraction (OEF), Sanguinate was infused over two hours; PET was repeated immediately after and again at 24-hours. Vulnerable brain regions were defined as those with baseline OEF ≥ 0.5. Results: Sanguinate infusion resulted in a significant but transient rise in mean arterial pressure (115±15 to 127±13 mm Hg) that was not dose-dependent. No adverse physiologic or clinical effects were observed with infusion at any dose. Global CBF did not rise significantly after Sanguinate (42.6±7 to 45.9±9 ml/100g/min, p=0.18). However, in the 28% of regions classified as vulnerable, Sanguinate resulted in a significant rise in CBF (42.2±11 to 51.2±18) and reduction in OEF (0.6±0.1 to 0.5±0.11, both p<0.001). The increase in regional CBF was only seen with the two higher doses but OEF improved in all tiers. However, response was attenuated at 24-hours. Conclusions: We safely administered a novel oxygen transport and vasodilating agent to a cohort of patients with SAH. Sanguinate infusion appeared to improve CBF and flow-metabolism balance in vulnerable brain regions and warrants further study in those at-risk for DCI. Higher or repeat dosing may be required for sustained efficacy.

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