cardiovascular-agents and Edema

The use of a venoactive drug is considered an important component of medical treatment of chronic venous disease (CVD), although the efficacy of certain venoactive drugs (VADs) on one or more individual leg symptoms or signs may have not been extensively studied to justify a strong recommendation in guidelines on CVD. The aim of this systematic review and meta-analysis was to study the effectiveness of the micronized purified flavonoid fraction (MPFF, Daflon®) across the spectrum of defined venous symptoms, signs, quality of life (QoL) and treatment assessment by the physician.. On September 9, 2017, a systematic review of the databases MEDLINE, Scopus and Cochrane Central was performed, supplemented by hand searching, to identify randomized double-blind placebo-controlled trials on MPFF in patients with CVD.. The main outcome measures were the individual and global symptoms, leg edema and redness, skin changes, QoL and evaluation of the overall effectiveness of the treatment by the physician. The effectiveness of MPFF compared with placebo was expressed as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). Trial quality of evidence was graded using the GRADE system.. We identified 7 trials, mostly with low risk of bias, involving 1,692 patients. On qualitative analysis, MPFF significantly improved nine defined leg symptoms, including pain, heaviness, feeling of swelling, cramps, paresthesia, burning sensation, and pruritus (itching), but also functional discomfort compared with placebo, leg redness, skin changes and QoL. On quantitative analysis, MPFF compared with placebo, assessed as a categorical variable, reduced leg pain (RR 0.53, P=0.0001, NNT=4.2), heaviness (RR 0.35, P<0.00001, NNT=2.0), feeling of swelling (RR 0.39, P<0.00001, NNT=3.1), cramps (RR 0.51, P=0.02, NNT=4.8), paresthesia (RR 0.45, P=0.03, NNT=3.5), and functional discomfort (RR 0.41, P=0.0004, NNT=3.0). Similarly, MPFF compared with placebo, assessed as a continuous variable reduced pain (SMD -0.25, 95% CI -0.38 to -0.11), heaviness (SMD -0.80, 95% CI -1.05 to -0.54), feeling of swelling (SMD -0.99, 95% CI -1.25 to -0.73), burning sensation (SMD -0.46, 95% CI -0.78 to -0.14), cramps (SMD -0.46, 95% CI -0.78 to -0.14), and functional discomfort (SMD -0.87, 95% CI -1.13 to -0.61). Regarding objective assessments of leg edema, the use of MPFF compared with placebo reduced ankle circumference (SMD -0.59, 95% CI -1.15 to -0.02), and leg redness (SMD -0.32, 95% CI -0.56 to -0.07, RR 0.50, P=0.03, NNT=3.6), improved skin changes (RR 0.18, P=0.0003, NNT=1.6) and quality of life (SMD -0.21, 95% CI -0.37 to -0.04) and was associated with clinical improvement as assessed by the physician (RR 0.28, P<0.00001, NNT=2.5). Heterogeneity was mostly minimal. The existing evidence where sufficient was mostly of high quality.. Based on high quality evidence, MPFF is highly effective in improving leg symptoms, edema and quality of life in patients with CVD.

Topics: Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Diosmin; Double-Blind Method; Edema; Humans; Odds Ratio; Quality of Life; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Treatment Outcome; Varicose Veins; Venous Insufficiency

Approximately 90% of German adults show alterations of their lower limb veins; about every fifth suffers from symptoms of chronic venous insufficiency (CVI). With compression therapy showing low compliance, CVI oedemas and accompanying subjective symptoms are frequently treated with anti-oedematous drugs of herbal origin. A guideline outlines the requirements for clinical studies with CVI drugs. Water displacement plethysmometry (volumetry) is the gold standard for determining the reduction ofoedemas. Besides reducing oedemas, drugs should also demonstrate effects on accompanying symptoms influencing quality of life. Despite assistance provided by the guideline, clinical studies in CVI are complex and subject to multiple error sources in planning and execution. The corroboration of successful studies in further confirmatory studies is good practice and demanded by regulatory authorities. This practice reduces the risk of drugs being accepted as effective just based on the play of chance. As an example, placebo controlled studies with an extract from red vine leaves show that a careful definition of patients as well as meticulous study planning and execution can reproducibly verify significant and clinically relevant treatment effects. When evaluating clinical studies it is recommended to refer to the CONSORT statement. Publications missing certain minimum information make interpretation difficult and may result in a biased judgment of the effects of therapy.

Topics: Biomedical Research; Cardiovascular Agents; Clinical Trials as Topic; Edema; Guidelines as Topic; Humans; Plant Extracts; Plethysmography; Venous Insufficiency

The aim of this study was to compare the reduction of venous ankle edema in randomized controlled trials of the main venoactive drugs versus a placebo or versus another venoactive drug and thereby to confirm or invalidate the existing recommendations on the pharmacological treatment of venous edema.. Publications of randomized controlled trials of venoactive drugs versus either a placebo or another venoactive drug on the reduction of ankle circumferences (AC) were searched through Medline and selected according to the Jadad and the Cucherat evaluation grids.. Ten publications dated between 1975 and 2009 including a total of 1010 patients were identified for the meta-analysis. Included were the following venoactive drugs: micronised purified flavonoid fraction (MPFF), hydroxyethylrutoside, ruscus extracts and diosmin. The mean reduction in AC was -0.80 ± 0.53 cm with MPFF , -0.58 ± 0.47 cm with ruscus extract, -0.58 ± 0.31 cm with hydroxyethylrutoside, -0.20 ± 0.5 cm with single diosmin, and -0.11 ± 0.42 cm with placebo. The reduction in AC was significantly superior to that of placebo whatever the drug concerned (P<0.0001). The comparison between MPFF, ruscus extract and hydroxyethylrutoside on the reduction of ankle edema was in favour of MPFF. This was significant (P<0.0001), while the efficacy of the latter two venoactive agents was comparable.. This meta-analysis confirms the validity of the grade A assigned to MPFF in the management of symptoms and edema in recent international guidelines.

Topics: Ankle; Cardiovascular Agents; Edema; Evidence-Based Medicine; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Veins; Venous Insufficiency

An International Task Force made up of a panel of 16 experts has reviewed and objectively evaluated all aspects of chronic venous disease of the leg (CVDL). All available publications on CVDL from 1983 to 1997 were identified through computerized search in Medline and by a manual search. Next, three different screenings were performed in order to select only relevant papers providing a level of scientific evidence that was considered moderate to strong. Final conclusions and further therapeutic recommendations were made based on these publications. Medication, compression, local therapy, sclerotherapy, and surgery are the accepted available therapeutic options for CVDL. For edema, the following recommendations can be made: edema is an early sign of CVDL, but before starting any treatment, nonvenous causes of edema should be excluded. Medication and compression are the therapeutic options for edema that are accepted by the Task Force. Evaluation of their efficacy is based on objective measures of edema. Several well-conducted, placebo-controlled trials have shown efficacy of drugs such as micronized purified flavonoid fraction, rutosides, calcium dobesilate, and coumarin rutin. Graduated compression stockings have been shown to be effective; compression needs to be exerted at least at 35 mm Hg. Bandages, if properly applied, both fixed and stretched, can produce favorable results. Sclerotherapy or surgery is not indicated unless there is saphenofemoral or saphenopopliteal reflux. In the absence of such reflux or following deep venous thrombosis, there is no evidence to support sclerotherapy or surgery.

Topics: Anticoagulants; Bandages; Calcium Dobesilate; Cardiovascular Agents; Chronic Disease; Controlled Clinical Trials as Topic; Coumarins; Diosmin; Edema; Femoral Vein; Hemostatics; Humans; Leg; Placebos; Rutin; Saphenous Vein; Sclerotherapy; Vasodilator Agents; Venous Insufficiency; Venous Thrombosis

Knowledge of the dosage, rate and route of administration, and potential side effects of drugs used to treat cardiac disease in horses has been refined. The judicious use of these drugs can increase exercise capacity, improve health, and potentially prolong life. Currently, antiarrhythmics (quinidine, lidocaine), positive inotropies (digoxin), and diuretics (furosemide) are the primary agents used to treat cardiovascular disease in horses. The development of newer drugs (verapamil, milrinone, bumetanide) and their usefulness in therapy for horses with cardiovascular disease require further investigation.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Edema; Female; Heart Rate; Horse Diseases; Horses; Male; Myocardial Contraction

Our current understanding of the pathophysiology of chronic venous disease (CVD) suggests that veno-active drugs (VAD) can provide effective symptom relief. Few studies have conducted head-to-head comparisons of VAD and placebo while also assessing objective measures (such as water plethysmography findings and tibiotarsal joint range of motion) and patient-reported quality of life outcomes.. To compare the effects of different VAD on limb volume reduction, tibiotarsal range of motion, and quality of life.. 136 patients with CVD (CEAP grades 2-5) were randomly allocated into four groups to receive micronized diosmin + hesperidin, aminaphthone, coumarin + troxerutin, or placebo (starch). Patients were administered a questionnaire consisting of a quality of life (QoL) measure designed specifically for persons with CVD, and underwent tibiotarsal joint angle measurement and water plethysmography of the lower extremity before and 30 days after pharmacological intervention. Assessors were blind to the treatment groups.. Nine patients dropped out of the trial. Data collected from the 127 remaining patients was considered for statistical analysis. There were no differences in tibiotarsal joint range of motion. Volume reductions ≥100 mL were more frequent in the diosmin + hesperidin group than in any other group. QoL scores were best in the aminaphthone group, and between-group differences were found on individual analysis of questionnaire items.. Use of VAD was associated with significant improvements in QoL as compared with placebo. VAD may be effective for providing symptom relief in patients with CVD.

Topics: Biomechanical Phenomena; Brazil; Cardiovascular Agents; Chronic Disease; Coumarins; Diosmin; Double-Blind Method; Drug Therapy, Combination; Edema; Female; Foot Joints; Hesperidin; Humans; Hydroxyethylrutoside; Male; para-Aminobenzoates; Plethysmography; Quality of Life; Range of Motion, Articular; Recovery of Function; Surveys and Questionnaires; Time Factors; Treatment Outcome; Venous Insufficiency

The aim of this study was to investigate the effect of a red-vine-leaf extract (AS195, Antistax(®), Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany) on the volume of the leg and clinical symptoms in patients with chronic venous insufficiency (CVI).. A multicentre, randomised, double-blind and placebo-controlled study was carried out with 720 mg AS195 per day over 12 weeks in CVI patients (CEAP Grades 3-4a) and moderate-to-severe clinical symptoms. Efficacy endpoints were changes in limb volume determined by water displacement volumetry, clinical CVI symptoms assessed on a 10-cm visual analogue scale and global efficacy evaluations.. The full-analysis set included 248 patients (placebo: n = 122; AS195: n = 126). After 12 weeks, AS195 significantly reduced lower limb volume by a mean of 19.9 standard error (SE) 8.9 ml over placebo (95% confidence interval (CI): -37.5, -2.3; p = 0.0268; analysis of covariance, ANCOVA). The standardised effect size of 0.28 for volume reduction indicates a clinically relevant effect. On Day 84, the symptom of 'pain in the legs' assessed by visual analogue scale decreased in the AS195 group compared with the placebo group: mean difference -6.6 SD 3.3 mm (95% CI: -13.1,-0.1; p = 0.047). Other symptoms showed no significant change. The tolerability of AS195 was similar to that of placebo.. AS195 treatment for 84 days resulted in an approximately 20 ml reduction of limb volume in the active treatment group compared with the placebo group. Patients reported subjective improvement following treatment with AS195 compared with placebo. However, patients' overall rating of efficacy did not correlate well with measured reductions in limb volume.. ClinicalTrials.gov NCT00855179.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Double-Blind Method; Edema; Female; Germany; Humans; Male; Middle Aged; Pain; Pain Measurement; Placebo Effect; Plant Extracts; Plant Leaves; Quercetin; Tablets; Time Factors; Treatment Outcome; Venous Insufficiency; Vitis; Young Adult

The RELIEF study (Reflux assEssment and quality of life improvement with micronized Flavonoids in chronic venous insufficiency [CVI]) is a prospective, controlled, multicenter, international study performed in patients with or without venous reflux. This study was conducted between March 1997 and December 1998 in 23 countries worldwide with the participation of more than 10,000 patients suffering from CVI. The European countries, the subject of this report, were represented by the Czech and Slovak Republics, Hungary, Poland, Russia, and Spain. The principal aims of the study were: 1. To validate the first quality-of-life scale specific to chronic venous insufficiency (CMVIQ) in different languages and to assess the evolution of quality of life in patients suffering from CVI, with or without venous reflux, treated with micronized purified flavonoid fraction (MPFF*) (1,000 mg/day). 2. To collect international epidemiologic data on venous reflux assessed with pocket Doppler and photoplethysmography. 3. To assess the evolution of symptoms and signs with a specific emphasis on edema through validated Leg-O-Meter measurement (heaviness, pain, cramps, sensation of swelling, edema) in patients suffering from CVI and treated with MPFF, 1,000 mg/day, during 6 months. The first country-by-country statistical analysis and the European consolidated analysis are now available. The CIVIQ questionnaires adapted to each participating country have been validated with highly significant validity and reproducibility (p<0.0001). All dimensions have demonstrated a highly significant and evolving improvement during the study. The results show several interesting findings concerning the epidemiologic data and, of these, two were particularly interesting: - More than 50% of patients suffering from CVI (class 0 to 4 of the CEAP classification) were reflux-free, which means that they were suffering from functional CVI. Patient distribution between the different classes of the CEAP classification changed in a statistically significant manner after 6 months' treatment with MPFF; the number of patients in the more severe classes decreased to the benefit of the less severe classes. Symptoms such as pain, leg heaviness, sensation of swelling, and cramps were significantly improved (p=0.0001). This was associated with a significant decrease in edema, when present, measured by leg circumferences with the Leg-O-Meter (p=0.0001). In conclusion, the European results of the RELIEF study showe

Topics: Cardiovascular Agents; Chronic Disease; Diosmin; Edema; Female; Humans; Leg; Male; Middle Aged; Muscle Cramp; Pain; Photoplethysmography; Prospective Studies; Quality of Life; Regional Blood Flow; Reproducibility of Results; Sensation; Ultrasonography, Doppler; Venous Insufficiency

Due to the prevalence of cardiovascular diseases, therapeutic drugs such as atenolol (ATE), metoprolol (MET), atorvastatin (ATO), and bezafibrate (BZB) have been widely used and thus frequently detected in surface water at ng·L

Topics: Animals; Cardiovascular Agents; Ecosystem; Edema; Embryo, Nonmammalian; Epigenesis, Genetic; Larva; Water Pollutants, Chemical; Zebrafish

Ranolazine is approved for patients with chronic stable angina but has not been formally studied in patients with refractory angina pectoris (RAP). Patients with RAP have limited therapeutic options and significant limitations in their quality of life. The Ranolazine Refractory Angina Registry was designed to evaluate the safety, tolerability, and effectiveness of ranolazine in RAP patients in order to expand treatment options for this challenging patient population. Using an extensive prospective database, we enrolled 158 consecutive patients evaluated in a dedicated RAP clinic. Angina class, medications, major adverse cardiac events including death, myocardial infarction, and revascularization were obtained at 12, 24, and 36 months. At 3 years, 95 (60%) patients remained on ranolazine. A ≥2 class improvement in angina was seen in 48% (38 of 80 patients with known Canadian Cardiovascular Society class) of those who remained on ranolazine. Discontinuation due to side effects, ineffectiveness, cost, and progression of disease were the principle reasons for discontinuation, but primarily occurred within the first year. In conclusion, ranolazine is an effective antianginal therapy at 3-year follow-up in patients with RAP and may reduce cardiac readmission.

Topics: Aged; Angina Pectoris; Cardiovascular Agents; Constipation; Deprescriptions; Diabetes Mellitus; Disease Progression; Dizziness; Drug Costs; Dyslipidemias; Edema; Female; Humans; Hypertension; Male; Medication Adherence; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Nausea; Ranolazine; Registries; Smoking; Treatment Failure; Treatment Outcome

Patient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.. Concept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.. During concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.. Development of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program.

Topics: Aged; Aged, 80 and over; Cardiac Myosins; Cardiovascular Agents; Clinical Trials as Topic; Dizziness; Dyspnea; Edema; Fatigue; Female; Focus Groups; Heart Failure; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Qualitative Research; Quality of Life; Sleep Initiation and Maintenance Disorders; United States; United States Food and Drug Administration; Urea

Lower extremity ischemia-reperfusion injury (IRI)-prolonged ischemia and the subsequent restoration of circulation-may result from thrombotic occlusion, embolism, trauma, or tourniquet application in surgery. The aim of this study was to assess the effect of low-molecular-weight dextran sulfate (DXS) on skeletal muscle IRI.. Rats were subjected to 3 h of ischemia and 2 or 24 h of reperfusion. To induce ischemia the femoral artery was clamped and a tourniquet placed under the maintenance of the venous return. DXS was injected systemically 10 min before reperfusion. Muscle and lung tissue samples were analyzed for deposition of immunoglobulin M (IgM), IgG, C1q, C3b/c, fibrin, and expression of vascular endothelial-cadherin and bradykinin receptors b1 and b2.. Antibody deposition in reperfused legs was reduced by DXS after 2 h (P < 0.001, IgM and IgG) and 24 h (P < 0.001, IgM), C3b/c deposition was reduced in muscle and lung tissue (P < 0.001), whereas C1q deposition was reduced only in muscle (P < 0.05). DXS reduced fibrin deposits in contralateral legs after 24 h of reperfusion but did not reduce edema in muscle and lung tissue or improve muscle viability. Bradykinin receptor b1 and vascular endothelial-cadherin expression were increased in lung tissue after 24 h of reperfusion in DXS-treated and non-treated rats but bradykinin receptor b2 was not affected by IRI.. In contrast to studies in myocardial infarction, DXS did not reduce IRI in this model. Neither edema formation nor viability was improved, whereas deposition of complement and coagulation components was significantly reduced. Our data suggest that skeletal muscle IRI may not be caused by the complement or coagulation alone, but the kinin system may play an important role.

Topics: Animals; Antigens, CD; Cadherins; Cardiovascular Agents; Complement C1q; Complement C3b; Dextran Sulfate; Disease Models, Animal; Edema; Femoral Artery; Fibrin; Hindlimb; Immunoglobulin G; Immunoglobulin M; Male; Muscle, Skeletal; Peptide Fragments; Rats; Rats, Wistar; Receptors, Bradykinin; Reperfusion Injury; Tourniquets

To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract.. Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema. Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections. Vasorelaxant effect was estimated in endothelium-intact and -rubbed rings of porcine coronary arteries precontracted with high concentration of U46619.. The results showed a moderate antioxidant activity (40%), but potent anti-inflammatory activity (49.9%) on carrageenan-induced mice paw edema, and also as revealed by histopathologic examination, complete protection against AlCl₃-induced hepatic toxicity. Relaxant effects of the same extract on vascular preparation from porcine aorta precontracted with high concentration of U46619 were considerable at 10⁻¹ g/L, and comparable (P>0.05) between endothelium-intact (67.74%, IC₅₀=0.04 mg/mL) and -rubbed (72.72%, IC₅₀=0.075 mg/mL) aortic rings.. The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca²⁺ influx.

Topics: Aluminum Chloride; Aluminum Compounds; Analysis of Variance; Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Carrageenan; Chemical and Drug Induced Liver Injury; Chlorides; Edema; Female; Flavonoids; Flowers; Liver; Male; Mice; Nitric Oxide; Nitric Oxide Synthase Type III; Phenols; Plant Extracts; Populus; Protective Agents; Tannins

Topics: Aged; Cardiac Catheterization; Cardiovascular Agents; Diagnosis, Differential; Dyspnea; Echocardiography; Edema; Female; Humans; Leg; Myocardial Infarction; Takotsubo Cardiomyopathy

Although Bell's palsy is the most common acute facial paralysis, the cause of it is still unknown. This made the treatment for it remain very limited. Many methods are simply symptomatic treatment. Up to now we have known that Bell's palsy is related to viral infection and the pathomechanism of Bell's palsy involves inflammatory oedema and entrapment neuropathy in the narrow bony facial canal. So treatment plans for Bell's palsy mainly focus on antiviral therapy, relieving inflammatory oedema and accelerating facial nerve recovery. Sodium beta-aescin is derived from horse chestnut and its major constituent is aescigenin which has been approved by China national drug standard. The pharmacologic action of sodium beta-aescin is to relieve tissue oedema, recover vasopermeability and eliminate pressure caused by oedema. Nowadays sodium beta-aescin has been widely used clinically for encephaledema or tumefaction caused by trauma or operation. It also can be used for treating disease of digestive system and increasing intravenous tension and improving microcirculation. Although many papers had been published on the anti-edema effects of sodium beta-aescin, little was known about the effects in treating oedema complicated by Bell's palsy.

Topics: Bell Palsy; Cardiovascular Agents; Chemistry, Pharmaceutical; Drug Design; Edema; Escin; Facial Paralysis; Humans; Inflammation; Ischemia; Models, Biological; Models, Theoretical; Pharmaceutical Preparations; Sodium

This study investigated whether polydeoxyribonucleotide (PDRN) may be efficacious in the treatment of peripheral artery occlusive diseases, which are a major cause of morbidity in Western countries and still lack standardized treatment.. We investigated the effects of PDRN, a mixture of deoxyribonucleotides, in an experimental model of hind limb ischemia (HLI) in rats to stimulate vascular endothelial growth factor (VEGF)-A production and to avoid critical ischemia. The femoral artery was excised to induce HLI. Sham-operated on rats (sham HLI) were used as controls. Animals were treated daily with intraperitoneal PDRN (8 mg/kg) or its vehicle. Animals were euthanized at day 7, 14, and 21 after the evaluation of blood flow by laser Doppler. Dissected muscles were used to measure VEGF-A messenger RNA (mRNA) and protein expression, to evaluate edema, and to assess histologic damage.. Administration of PDRN dramatically increased VEGF mRNA throughout the study (day 14: HLI, 7 +/- 2.2 n-fold/beta-actin; HLI + PDRN, 13.3 +/- 3.8 n-fold/beta-actin; P < .0001) and protein expression (HLI, 11 +/- 3.4 integrated intensity; HLI + PDRN, 16 +/- 3.8 integrated intensity; P < .0001). The compound stimulated revascularization, as confirmed by blood flow restoration (P < .005 vs HLI + vehicle), and blunted the histologic damage and the degree of edema. PDRN did not modify VEGF-A expression and blood flow in sham HLI animals. Furthermore, the concomitant administration of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A(2A) receptor antagonist, abolished the positive effects of PDRN, confirming that PDRN acts through this receptor.. These results led us to hypothesize a role for PDRN in treating peripheral artery occlusive diseases.

Topics: Adenosine A2 Receptor Agonists; Angiogenesis Inducing Agents; Animals; Arterial Occlusive Diseases; Cardiovascular Agents; Disease Models, Animal; Edema; Hindlimb; Ischemia; Laser-Doppler Flowmetry; Male; Muscle, Skeletal; Neovascularization, Physiologic; Oxidative Stress; Peripheral Vascular Diseases; Polydeoxyribonucleotides; Rats; Rats, Sprague-Dawley; Receptors, Adenosine A2; Regional Blood Flow; RNA, Messenger; Time Factors; Up-Regulation; Vascular Endothelial Growth Factor A

To characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon 500), on this response.. A femoral arteriovenous fistula was created in Wistar rats (n=48). A cohort of 24 rats received oral treatment with MPFF (100 mg/kg/day body weight), 24 rats underwent the arteriovenous fistula procedure and received no treatment. At days 1, 7 and 21 the animals (n=8 at each time point) were killed. Experimental parameters measured included limb circumference, blood flow at the sapheno-femoral junction, leukocyte infiltration and gelatinase activity (matrix metalloproteinase, MMP).. The acute rise in venous hypertension was accompanied by limb edema and venous reflux together with an eventual loss of valve leaflets in the saphenous vein. There was an increase in granulocyte and macrophage infiltration into the venous wall and the surrounding tissue, and a lesser increase in T- and B-lymphocyte infiltration. These changes were accompanied by a local increase in the proteolytic enzymes, MMP-2 and MMP-9. Administration of MPFF reduced the edema and lessened the venous reflux produced by the acute arteriovenous fistula. Decreased levels of granulocyte and macrophage infiltration into the valves were also observed compared with untreated animals.. Venous hypertension caused by an arteriovenous fistula resulted in the development of venous reflux and an inflammatory reaction in venous valves culminating in their destruction. MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension.

Topics: Animals; Arteriovenous Shunt, Surgical; Blood Flow Velocity; Cardiovascular Agents; Chemotaxis, Leukocyte; Diosmin; Disease Models, Animal; Edema; Femoral Artery; Femoral Vein; Granulocytes; Lymphocytes; Macrophages; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Rats; Rats, Wistar; Regional Blood Flow; Saphenous Vein; Stress, Mechanical; Time Factors; Venous Insufficiency; Venous Pressure

Bothrops venoms cause local edema, pain, hemorrhage and necrosis. In this study, we investigated the ability of Bothrops lanceolatus venom to cause edema in rat hind paws and examined the mediators involved.. Hind paw edema was induced in male Wister rats by the subplantar injection of venom (12.5-100 microg/paw) in the absence and presence of antagonists. Edema was quantified by hydroplethysmometry at 0.25, 0.5, 2, 4, 6 and 24 h post-injection and was expressed as the percentage increase relative to the contralateral (control) paw. The ability of the venom to release histamine from rat peritoneal mast cells was also assessed.. Venom caused dose- and time-dependent edema that was maximal within 15 min but disappeared after 24 h and was accompanied by hemorrhage. Dexamethasone (1 mg/kg, s.c.), methysergide (6 mg/kg, i.p.), HOE 140 (0.6 mg/kg, i.v.) and mepyramine (6 mg/kg, i.p.) significantly ( p < 0.05) reduced edema formation, whereas indomethacin (10 mg/kg, i.p.) was ineffective. Dialysis did not affect venom-induced edema. Venom (1, 10 and 30 microg/ml) caused a concentration-dependent release of histamine (13 +/- 1%, 61.9 +/- 4.6% and 73.6 +/- 2.4%, respectively; n = 5) from rat peritoneal mast cells in vitro. Histological analysis confirmed the presence of edema, hemorrhage and neutrophil infiltration. Pretreating the venom with EDTA partially inhibited the edema and hemorrhage, but did not affect the migration of neutrophils.. B. lanceolatus venom produced dose- and time-dependent edema in rat paws. This edema was not dependent on low molecular weight substances in the venom, but was partially dependent on a hemorrhagin and also involved the release of arachidonic acid metabolites, bradykinin, histamine and serotonin.

Topics: Adrenergic beta-Antagonists; Animals; Antiemetics; Arachidonic Acid; Bothrops; Bradykinin; Cardiovascular Agents; Crotalid Venoms; Dexamethasone; Dose-Response Relationship, Drug; Edema; Edetic Acid; Extremities; Histamine; Histamine H1 Antagonists; Indomethacin; Mast Cells; Methysergide; Pyrilamine; Rats; Rats, Wistar; Serotonin; Time Factors; Vasoconstrictor Agents

Several phlebotropic drugs, or edema-protecting drugs, are available, the most important of which are found in the gamma-benzopyrone family (flavonoids). gamma-Benzopyrones can be plant extracts, semisynthetic preparations, or synthetic preparations. This family is divided into two different groups: flavones and flavonols, and flavanes (flavanones). The flavone group contains various types of molecule and includes diosmin. Here we discuss the pharmacologic aspects in edema associated with chronic venous insufficiency (CVI) of one of the reference phlebotropic drugs, micronized purified flavonoid fraction (MPFF), a semisynthetic preparation from the diosmin group, which represents the latest improvement in flavonoid formulation. Before we detail the pharmacologic aspects, a brief summary of the pathophysiology of edema in CVI is necessary. Several factors are implicated: the veins, which create the conditions favorable to edema; the microcirculation, which is the site of fluid transfer into the interstitial tissue; and the lymphatics, which have a limited possibility to reduce edema. Major discoveries are currently being made in CVI and the microcirculation. Results of studies show that MPFF decreases capillary permeability and increases capillary resistance, which could partly be explained by inhibition of leukocyte activation, migration, and adhesion. This inhibition is linked to a significant decrease in plasma levels of endothelial adhesion molecules (VCAM-1 and ICAM-1) after MPFF treatment. Thus, the CVI-induced damage to the microcirculation is counteracted by MPFF. The lymphatic system is also improved by MPFF treatment. The lymphagogue activity of MPFF has been demonstrated in experimental animal models and confirmed by microlymphographic measurement in patients suffering from severe CVI. The pharmacologic activity of MPFF in lymphedema was observed in a study using an animal model of acute lymphedema and in a study in patients with upper limb lymphedema secondary to breast cancer treatment. All these findings point to the importance of acting on each factor involved in the formation and maintenance of edema. This pharmacologic activity is indeed reflected by the clinical efficacy on edema observed during treatment with MPFF.

Topics: Animals; Capillary Permeability; Capillary Resistance; Cardiovascular Agents; Chronic Disease; Coumarins; Diosmin; Disease Models, Animal; Edema; Flavonoids; Humans; Intercellular Adhesion Molecule-1; Leukocytes; Lymphatic System; Lymphedema; Microcirculation; Vascular Cell Adhesion Molecule-1; Veins; Venous Insufficiency

Topics: Animals; Cardiovascular Agents; Croton Oil; Edema; Epoprostenol; Iloprost; Rabbits; Reference Values; Regional Blood Flow; Serotonin; Skin

The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively.

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Digoxin; Diuretics; Dobutamine; Dopamine; Drug Administration Schedule; Edema; Heart Diseases; Heart Failure; Heart Rate; Hemodynamics; Horse Diseases; Horses; Injections, Intravenous; Lidocaine; Procainamide; Propranolol; Quinidine

Topics: Adult; Cardiovascular Agents; Diosmin; Edema; Female; Flavonoids; Humans; Male; Middle Aged; Muscle Cramp; Pain; Vascular Diseases

Topics: Benzothiadiazines; Cardiovascular Agents; Diuretics; Drug Therapy; Edema; Flavonoids; Humans; Leg; Potassium; Potassium Chloride; Thrombosis

Topics: Cardiovascular Agents; Edema; Ergoloid Mesylates; Ergot Alkaloids; Leucine; para-Aminobenzoates; Thrombosis

Topics: Antirheumatic Agents; Cardiovascular Agents; Edema; Epinephrine; Ergot Alkaloids; Ergotamine; Hyaluronoglucosaminidase; Oxytocics

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Edema; Glucocorticoids; Humans

Four new derivatives of hydrocortisone, each containing in common a methyl grouping at the 16a-carbon position of the steroid molecule, have been synthesized and are being studied in human subjects. The compounds are 16a-methyl 9a-fluoroprednisolone (MK-125: hexadecadrol), 16a-methyl 9a-fluorohydrocortisone (MK-126), 16a-methylprednisolone (MK-110), and 16a-methylhydrocortisone (MK-117). Biologic tests in animals have indicated that these analogues exhibit, in varying degrees, striking alterations of several physiologic properties, including enhanced anti-inflammatory activity unassociated with corresponding disturbance of electrolyte metabolism. In the present study preliminary observations of the effects of the four new compounds were made in patients with rheumatoid arthritis. Clinical estimates of the antirheumatic potencies of the compounds, as compared with prednisolone, were accomplished by determining the milligram dosages required to maintain similar degrees of improvement of active rheumatoid manifestations. The approximate antirheumatic potencies of the compounds, on an average, were gauged as follows: for 16a-methyl 9a-fluoroprednisolone, about seven times greater than prednisolone; for 16a-methyl 9a-fluorohydrocortisone, about three times greater; for 16a-methylprednisolone, approximately one-third greater; and for 16a-methylhydrocortisone, about 70 per cent that of prednisolone. In the dosage used, none of the compounds promoted discernible salt and water retention. These observations would indicate that 16a-methyl 9a-fluoroprednisolone (hexadecadrol) possesses greater anti-inflammatory potency per milligram than any steroid yet produced. The therapeutic efficiency of the compound on longterm administration is being studied.

Topics: Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Dermatologic Agents; Dexamethasone; Edema; Glucocorticoids; Humans; Hydrocortisone; Methylprednisolone; Prednisolone

Topics: Alkaloids; Cardiovascular Agents; Edema; Epinephrine; Ergot Alkaloids; Pulmonary Edema; Secale

Topics: Alkaloids; Cardiovascular Agents; Edema; Ergot Alkaloids; Hydrocarbons, Chlorinated; Pulmonary Edema; Secale

Topics: Cardiovascular Agents; Curare; Edema; Epinephrine; Lung Diseases; Muscle Relaxants, Central; Poisons; Pulmonary Edema

Topics: Cardiovascular Agents; Edema; Lung Diseases; Muscle Relaxants, Central; Pulmonary Edema; Sympatholytics