Sample records for dipyridamole

  1. Aspirin and Extended-Release Dipyridamole

    ... dipyridamole is in a class of drugs called antiplatelet agents. It works by preventing excessive blood clotting. It ... Univasc), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); anticoagulants ('blood thinners') such as warfarin (Coumadin) and heparin; ...

  2. Protection of irradiated mice by dipyridamole

    Moritani, Toshio (Showa Univ., Tokyo (Japan). School of Medicine)


    Dipyridamole (Persantin), a vasodilatory drug with antiplatelet activity, has been recently reported to inhibit lipid peroxidation and scavenge oxygen radicals. The radioprotective effects of dipyridamole were studied in ddy mice. When the mice were irradiated to 8.0 Gy, 30 days-lethality was reduced from 89% (control group) to 56% (0.5 mg/mouse and 1.0 mg/mouse i.p. injection of dipyridamole), and to 33% (2.0 mg/mouse and 4.0 mg/mouse i.p. injection). The dose required to kill 50% of the dipyridamole-tested mice within 30 days (LD{sub 50/30}) was 7.56 Gy compared to 6.63 Gy for the control mice. The results suggested that dipyridamole has significant radioprotective effect, so we clinically studied on its radioprotective effects using white-cell counts and platelet counts of 12 patients with breast cancer. Dipyridamole (150 mg/day) was administered to 6 of patients during radiation therapy. There was no statistically significant difference between these two groups. These results suggest the other factor than radioprotective effects on bone marrow. (author).




    Full Text Available A sensitive, specific, precise and cost effective High Performance Liquid Chromatographic method of analysis for dipyridamole in presence of its degradation products is developed and validated. The method employed Targa C8 column i.e., (250 X 4.6 mm 5 μm particle size column as stationary phase. The mobile phase consists of acetonitrile and pH3.0 buffer in the ratio of 35:65 %. It is pumped through the chromatographic system at a flow rate of 1.2 ml/min. The UV detector is operated at 282 nm. This system was found to give good resolution between dipyridamole and its degradation products. Method was validated as per ICH guidelines

  4. Dipyridamole prevents triple-negative breast-cancer progression.

    Spano, Daniela; Marshall, Jean-Claude; Marino, Natascia; De Martino, Daniela; Romano, Alessia; Scoppettuolo, Maria Nunzia; Bello, Anna Maria; Di Dato, Valeria; Navas, Luigi; De Vita, Gennaro; Medaglia, Chiara; Steeg, Patricia S; Zollo, Massimo


    Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated β-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the expression of IkBα (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways.

  5. Dipyridamole may induce migraine in patients with migraine without aura

    Kruuse, C; Lassen, L H; Iversen, Helle Klingenberg


    Dipyridamole inhibits phosphodiesterase 5 (PDE5) and adenosine re-uptake. The most prominent side-effect is headache. We examined the migraine-generating effects of dipyridamole as well as the cerebral blood velocity response in a single-blind study, including 10 patients with migraine without aura...... and 10 healthy subjects. Dipyridamole 0.142 mg/kg per min was administered intravenously. Headache intensity was scored on a verbal rating scale along with pain characteristics and accompanying symptoms. Blood velocity in the middle cerebral artery (V(mca)), blood pressure and heart rate were recorded...... of dipyridamole on the cGMP signalling pathway as well as a possible bidirectional effect of adenosine on migraine induction....

  6. Determination of dipyridamole by modified extraction-gravimetry with a surface acoustic wave resonator sensor.

    Liu, D Z; Wang, R H; Nie, L H; Yao, S Z


    A simple and sensitive extraction-gravimetric method for the determination of dipyridamole is presented. The method is based on the extraction of free dipyridamole with chloroform, after neutralization with a basic agent, followed by measurement of the frequency shift response of the specially designed surface acoustic wave resonator sensor after evaporation of the extractant from the surface of the resonator. The frequency shift response was proportional to the amount of dipyridamole in the range 0.065-1.12 micrograms. Experimental parameters and the effect of interfering substances on the assay of dipyridamole were also examined in this study. The method was applied to the determination of dipyridamole in tablets.

  7. Classical and pleiotropic actions of dipyridamole: Not enough light to illuminate the dark tunnel?

    Balakumar, Pitchai; Nyo, Ying Hui; Renushia, Raja; Raaginey, Devarajan; Oh, Ann Nah; Varatharajan, Rajavel; Dhanaraj, Sokkalingam A


    Dipyridamole is a platelet inhibitor indicated for the secondary prevention of transient ischemic attack. It inhibits the enzyme phosphodiesterase, elevates cAMP and cGMP levels and prevents platelet aggregation. Dipyridamole inhibits the cellular uptake of adenosine into red blood cells, platelets and endothelial cells that results in increased extracellular availability of adenosine, leading to modulation of cardiovascular function. The antiplatelet action of dipyridamole might offer therapeutic benefits in secondary stroke prevention in combination with aspirin. Inflammation and oxidative stress play an important role in atherosclerosis and thrombosis development, leading to stroke progression. Studies demonstrated anti-inflammatory, anti-oxidant and anti-proliferative actions of dipyridamole. These pleiotropic potentials of dipyridamole might contribute to improved therapeutic outcomes when used with aspirin in preventing secondary stroke. Dipyridamole was documented as a coronary vasodilator 5 decades ago. The therapeutic failure of dipyridamole as a coronary vasodilator is linked with induction of 'coronary steal' phenomenon in which by dilating resistance vessels in non-ischemic zone, dipyridamole diverts the already reduced blood flow away from the area of ischemic myocardium. Dipyridamole at high-dose could cause a marked 'coronary steal' effect. Dipyridamole, however, at low-dose could have a minimal hemodynamic effect. Low-dose dipyridamole treatment has a therapeutic potential in partially preventing diabetes mellitus-induced experimental vascular endothelial and renal abnormalities by enhancing endothelial nitric oxide signals and inducing renovascular reduction of oxidative stress. In spite of plenteous research on dipyridamole's use in clinics, its precise clinical application is still obscure. This review sheds lights on pleiotropic pharmacological actions and therapeutic potentials of dipyridamole.

  8. Use of intravenous dipyridamole in thallium 201 myocardial perfusion imaging

    Zeller, F.P.; Blend, M.J.


    Thallium 201 myocardial perfusion imaging is a standard method of evaluating regional myocardial blood flow. Myocardial perfusion is best evaluated at rest and during exercise, however, alternative methods have been sought to increase coronary blood flow in patients incapable of performing adequate exercise. A promising new method is the use of intravenous dipyridamole for pharmacologic stress imaging. It has distinct advantages over traditional treadmill exercise testing. The primary advantage of combining intravenous dipyridamole and thallium 201 is for testing patients in whom exercise is impractical or contraindicated. Examples include patients taking beta blockers and those who have had myocardial infarction or have severe peripheral vascular disease. To date, this agent has been available only to clinical investigators in approved protocols. With continued success, it should be approved for general use in the near future. 33 references.

  9. Platelet adhesion studies on dipyridamole coated polyurethane surfaces

    Aldenhoff Y. B.J.


    Full Text Available Surface modification of polyurethanes (PUs by covalent attachment of dipyridamole (Persantinregistered is known to reduce adherence of blood platelets upon exposure to human platelet rich plasma (PRP. This effect was investigated in further detail. First platelet adhesion under static conditions was studied with four different biomaterial surfaces: untreated PU, PU immobilised with conjugate molecule 1, PU immobilised with conjugate molecule 2, and PU immobilised with conjugate molecule 3. In PU immobilised with 1 dipyridamole is directly linked to the surface, in PU immobilised with 2 there is a short hydrophilic spacer chain in between the surface and the dipyridamole, while conjugate molecule 3 is merely the spacer chain. Scanning electron microscopy (SEM was used to characterise platelet adhesion from human PRP under static conditions, and fluorescence imaging microscopy was used to study platelet adhesion from whole blood under flow. SEM experiments encompassed both density measurements and analysis of the morphology of adherent platelets. In the static experiments the surface immobilised with 2 showed the lowest platelet adherence. No difference between the three modified surfaces emerged from the flow experiments. The surfaces were also incubated with washed blood platelets and labeled with Oregon-Green Annexin V. No capture of Oregon-Green Annexin V was seen, implying that the adhered platelets did not expose any phosphatidyl serine at their exteriour surface.

  10. Dipyridamole treatment is associated with improved renal outcome and patient survival in advanced chronic kidney disease.

    Hung, Chi-Chih; Yang, Mei-Li; Lin, Ming-Yen; Lin, Hugo You-Hsien; Lim, Lee-Moay; Kuo, Hung-Tien; Hwang, Shang-Jyh; Tsai, Jer-Chia; Chen, Hung-Chun


    Dipyridamole has been shown to decrease proteinuria and improve renal function progression especially in early chronic kidney disease (CKD) patients with glomerulonephropathy. A combination therapy of dipyridamole with aspirin could prevent second strokes in the general population. Whether these effects of dipyridamole are also true in advanced CKD patients and whether dipyridamole could improve renal outcomes or patient survival is unknown. We retrospectively analyzed an observational cohort of 3074 participants with CKD stage 3-5 from southern Taiwan, of whom 871 (28.3%) had received dipyridamole treatment ≥50 mg/d for ≥3 months and more than half of the observation period. The mean age was 63.6 ± 13.4 years and the mean estimated glomerular filtration rate (eGFR) was 25.5 mL/min/1.73 m(2). After inverse probability of treatment weighted adjustment by propensity score, there were no differences between the dipyridamole-treated and untreated groups. Dipyridamole treatment was associated with decreased odds for rapid eGFR decline [odds ratio, 0.755; 95% confidence interval (CI), 0.595-0.958; p = 0.007] and progression of urine protein-to-creatinine ratio (odds ratio, 0.655; 95% CI, 0.517-0.832; p = 0.002). In survival analysis, the dipyridamole-treated group was also associated with a decreased risk for end-stage renal disease (hazard ratio, 0.847; 95% CI, 0.733-0.980; p = 0.011) and all-cause mortality (hazard ratio, 0.765; 95% CI, 0.606-0.971; p = 0.001) but not for cardiovascular events. Our findings demonstrate that dipyridamole treatment is significantly associated with better renal outcomes and patient survival in patients with CKD stage 3-5. Further investigations are warranted to confirm these independent positive effects.

  11. Severe bronchospasm followed by respiratory arrest during thallium-dipyridamole imaging

    Lette, J.; Cerino, M.; Laverdiere, M.; Tremblay, J.; Prenovault, J.


    We describe the occurrence of sudden severe bronchospasm and respiratory arrest following dipyridamole infusion in a patient with chronic obstructive pulmonary disease predominantly of the emphysematous type. The severe reaction was unexpected because the patient had tolerated well withdrawal of aminophylline derivatives for 48 hours and was receiving chronic prednisone 20 mg qd. Although the diagnostic and prognostic gains from dipyridamole imaging far outweigh the small risk associated with the test, patients with chronic pulmonary obstructive disease must be closely monitored during thallium-dipyridamole imaging.

  12. Dipyridamole dilates large cerebral arteries concomitant to headache induction in healthy subjects

    Kruuse, Christina; Jacobsen, T B; Lassen, L H


    Dipyridamole is used for secondary prophylaxis in ischemic stroke and as a vasodilator agent in myocardial scintigraphy. An important side effect to administering dipyridamole is headache. The aim of the current study was to investigate the effects of dipyridamole on cerebral blood flow, large...... artery diameter, and headache induction. Twelve healthy subjects were included in this single-blind placebo-controlled study in which placebo (0.9% NaCl) and dipyridamole 0.142 mg/kg x min were administered intravenously over 4 minutes 1 hour apart. Blood flow velocity in the middle cerebral artery (Vmax......) was recorded by transcranial Doppler and regional cerebral blood flow in the middle cerebral artery (rCBFmca) was measured using single photon emission computed tomography and 133Xenon-inhalation. Blood pressure, heart rate, and pCO2 were measured repeatedly. Headache response was scored every 10 minutes...

  13. Clinical value of dipyridamole brain perfusion imaging in the diagnosis of ischemic cerebrovascular disease


    Using dipyridamole stress test to evaluate cerebral blood flow reserve in cerebrovascular disease (CVD). Dipyridamole stress tests were performed first, the baseline SPECT images were obtained under similar conditions 2-5 days later. By visual and semiquantitative analysis, the responses of cerebral blood flow to dipyridamole were divided into the following four patterns: A: The dipyridamole SPECT showed an expanded area of hypoperfusion, Asymmetry Index(AI) and Uptake Rate(UR) were all decreased; B: Rest images was normal but new hypoperfused areas appeared on stress test with decreased Al and UR; C: Hypoperfused areas were decreased in size or disappeared after stress test with increased Al and UR; D: No changes showed in cerebral perfusion imaging patterns, and in Al and UR between stress and rest studies. Dipyridarnole brain perfusion imaging may be helpful to the diagnosis of CVD, to the decision the therapeutic plan, and to predicting the therapeutic effect.

  14. Ocular Applications of Dipyridamole: A Review of Indications and Routes of Administration.

    Rogosnitzky, Moshe; Isakov, Itzhak; Wlassoff, Wjatschesslaw; Ingram, April; Barishak, Y Robert


    Dipyridamole was introduced decades ago as a treatment for angina, subsequently found to inhibit platelet aggregation. It is most commonly used, and approved for use in thromboembolism prevention, following surgery. Some of its recognized effects such as adenosine uptake inhibition, elevation of cAMP and cGMP levels, vasodilation, and tissue perfusion are important in various ocular disorders. For this reason, dipyridamole represents an interesting candidate as a therapeutic target for the treatment of eye disorders affecting different ocular structures. The aim of this article is to review the evidence and current understanding of the mechanisms by which dipyridamole exerts its effects on different ocular tissues, discuss the role of dipyridamole in clinical practice, and highlight areas of use and routes of administration.

  15. Voltammetric oxidation of dipyridamole in aqueous acid solutions

    Castilho Marilza


    Full Text Available The electrochemical oxidation of dipyridamole (DIP has been studied in acidified aqueous solutions at platinum electrodes employing cyclic voltammetry and controlled-potential electrolysis. The progress of the anodic oxidation as a function of time was monitored by cyclic voltammetry with platinum ultramicroelectrodes, absorption and fluorescence optical spectroscopies, the resulting integrated charge being indicative of a two electron process. The cyclic voltammograms registered for low scan speeds are characterized by a single irreversible diffusion controlled anodic wave, the related cathodic wave being also observable for scan speeds higher than 1 V s-1. Oxidation reaction stoichiommetric parameters were obtained through Tafel slopes resulting in unitary reaction orders for DIP and H+.

  16. Acute electrophysiological effects of dipyridamole on sinus node function in patients with sick sinus syndrome.

    Yeşil, M; Bayata, S; Postaci, N; Aydin, C


    One of the most widely used tests for evaluation of sinus node function is sinus node recovery time (SNRT), which requires right heart catheterization. On the other hand SNRT has high specificity but only moderate sensitivity in the diagnosis of sick sinus syndrome (SSS). The authors studied acute electrophysiologic effects of dipyridamole (0.40 mg/kg IV) in 16 patients with clinical SSS. All of them had normal SNRT and had undergone permanent DDD pacemaker implantation. By the aid of temporary pacing inhibition, the authors noninvasively measured the corrected sinus node recovery time (SNRTc) and sinus cycle length (SCL) before and after dipyridamole administration. SCL was slightly decreased from a mean basal value of 1025 +/-323 to 913+/-213 msec after dipyridamole administration (mean -10%), but this was not statistically significant. SNRTc was increased from a mean basal value of 344+/-91 to 606+/-156 msec after dipyridamole administration (+76% Pnode function. SNRT measurement after intravenous dipyridamole may increase sensitivity of this test in patients with suspected SSS and normal SNRT.

  17. Distribution of dipyridamole in blood components among post-stroke patients treated with extended release formulation.

    Serebruany, Victor; Sabaeva, Elena; Booze, Christopher; Atar, Oliver D; Eisert, Christian; Hanley, Dan


    Extended release dipyridamole (ERD) is widely used in patients after ischaemic stroke; however, the ability of this antithrombotic agent to be stored in different blood cells has never been explored in post-stroke patients. We hypothesised that since ERD is known to be highly lipophilic, the drug may be present not only in plasma, but also accumulated in platelets, leukocytes, and erythrocytes. Fifteen patients after documented ischaemic stroke were treated with Aggrenox (ERD and low-dose aspirin combination) BID for 30 days, and 12 of them completed the study. ERD concentrations in blood cells and platelet-poor plasma were measured by spectrofluorimetry at Baseline, Day 14, and Day 30 after the initiation of therapy. The background level of spectrofluorometry readings differs slightly among the blood components (132-211 ng/ml) due to the differences in the preparation of samples and cell isolation techniques. As expected, two weeks of ERD therapy produced steady-state plasma concentration of dipyridamole already at Day 14 (1,680 +/- 542 ng/ ml), followed by a slight not significant decrease at one month (1,619 +/- 408 ng/ml). Two weeks of therapy was sufficient to achieve a consistent dipyridamole accumulation in erythrocytes (361 +/- 43 ng/ml), but not in platelets (244 +/- 78 ng/ml), or leukocytes (275 +/- 49 ng/ml). In fact, white blood cells continued dipyridamole intake beyond 14 days period, and this increase (398 +/- 66 ng/ml) was significant (p = 0.02) at 30 days. Treatment with ERD in post-stroke patients resulted not only in achievement of therapeutic plasma dipyridamole concentrations, but also deposition of the drug in erythrocytes and leukocytes, but not in platelets. If confirmed, these data will affect our better understanding of dipyridamole pleiotropy, and may explain long-term benefit of ERD formulation.

  18. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim


    BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly...... assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes...

  19. High Performance Liquid Chromatographic Method for Determination of Dipyridamole in Human Plasma



    Full Text Available A simple, rapid and specific high-performance liquid chromatographic procedure is reported for"nquantitative determination of dipyridamole in human -plasma. The assay uses a reversed-phase"nhigh-performance liquid chromatographic (HPLC and UV detection at 280nm and has a limit"nof detection of approximately 5ng/mL. The mobile phase consists of MeOH-H20 (60:40"nadjusted to pH 3.3. Dipyridamole was extracted from plasma by back-extraction procedure, with"npropranolol as the internal standard. The reproducibility of the method is satisfactory

  20. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    Sacco, Ralph L.; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Renee H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P. L.; Chen, Sien-Tsong; Cunha, Luis; Dahlof, Bjorn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo


    Background: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens - aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. Methods: In this double-blind, 2-by-2 factorial trial, we randomly a

  1. Usefulness of dipyridamole stress myocardial imaging in patients who have exercise limitations due to various orthopedic disorders

    Tagawa, Hirofumi; Ashihara, Toshiaki; Fukuyama, Takaya; Matsui, Kanji; Yamamoto, Sumiki; Yamamoto, Susumu [Matsuyama Red Cross Hospital, Ehime (Japan)


    To evaluate the presence of coronary artery disease in patients unable to exercise adequately because of chronic rheumatoid arthritis, osteoarthritis, hip bone fractures or disk herniation, we performed dipyridamole-stress thallium-201 myocardial imaging in thirty-three patients. Twelve of the 33 patients showed perfusion defect and redistribution by thallium imaging. Coronary angiography was performed in 9 patients out of these 12 dipyridamole-positive patients and significant coronary artery stenosis was detected in 7 of them (78%). Due to these results of dipyridamole-imaging and coronary angiograms, surgical intervention for the underlying bone or joint disorder was performed under cardioprotective strategy in 15 patients, in which no cardiovascular events occurred. Thus, dipyridamole-stress myocardial imaging is a satisfactory alternative to the exercise test for detecting coronary artery disease in patients with bone or joint disorders. (author).

  2. Dilazep and dipyridamole inhibit tissue factor expression on monocytes induced by IgG from patients with antiphospholipid syndrome

    Hong ZHON


    AIM: To investigate whether antiplatelet agents, dilazep and dipyridamole, inhibit tissue factor (TF) expression on monocytes induced by IgG from patients with antiphospholipid syndrome (APS). METHODS: Freshly isolated peripheral blood monocytes were allowed to adhere on plastic and then cultured in media containing patient or control antibodies and/or other agonists with or without dilazep or dipyridamole. The TF activity on monocytes was investigated by measuring factor VIIa-dependent generation of factor Xa, using a chromogenic substrate and the TF mRNA expression was examined by real-time PCR (TaqMan PCR). RESULTS: The TF activity on monocytes induced by APS IgG (250 mg/L) was inhibited by dilazep (0.15-150 μmol/L) and dipyridamole (0.2-200 μrmol/L) in a dose-dependent fashion. But, the TF mRNA expression induced by APS IgG was not inhibited. Theophylline (500 μmol/L), an adenosine receptor antagonist, could counteract the inhibitory effect of dilazep and dipyridamole on TF activity. CONCLUSION: Antiplatelet agents, dilazep and dipyridamole, block APS IgG-induced monocytes TF expression at a post-transcriptional level, partly by adenosine receptor pathway. Pharmacological agents that block monocytes TF activity, such as dilazep and dipyridamole, are a novel therapeutic approach in APS.

  3. Significance of silent ischemia in dipyridamole perfusion scintigraphy. Evaluation in patients with angina

    Kitaoka, Hiroaki; Takata, Jun; Yamada, Mitsutoshi; Seo, Hiromi; Doi, Yoshinori [Kochi Medical School, Nankoku (Japan)


    The significance of silent myocardial ischemia detected by dipyridamole perfusion scintigraphy was evaluated in 80 patients with stable angina and reversible defects (RD) but no infarction. The patients consisted of 26 patients with silent RD and 54 patients with painful RD. There was no significant difference in the incidence of coronary risk factors between the two groups, except for hyperlipidemia which was less frequently observed in patients with silent RD than in those with painful RD (8% vs 41%), Coronary angiography revealed a higher prevalence of insignificant lesions or single vessel disease in patients with silent RD than in those with painful RD (73% vs 39%). Dipyridamole perfusion scintigraphy revealed a lower degree of RD in patients with silent RD than in those with painful RD (4.4{+-}3.3 vs 9.0{+-}4.1 segments), though there was no significant difference in the localization of RD between these two groups. Treadmill stress testing revealed a lower incidence of chest pain in patients with silent RD than in those with painful RD (26% vs 65%), despite the mean exercise-duration being significantly longer in the former than in the latter (5.5{+-}1.7 vs 3.9{+-}11.7 min). Although initial percutaneous transluminal coronary angioplasty (PTCA) and/or coronary artery bypass grafting (CABG) were less frequently performed in patients with silent RD than in those with painful RD (12% vs 31%), there was no significant difference in the cardiac event rate during the mean follow-up period of 24{+-}14 months between the two groups. Patients with stable angina and silent RD on dipyridamole perfusion scintigraphy may have less extensive coronary lesions and smaller amounts of ischemic myocardium than patients with painful RD. Dipyridamole perfusion scintigraphy is useful for detecting and evaluating silent myocardial ischemia, even in those patients who cannot exercise adequately. (J.P.N.).

  4. Assay of dipyridamole in human serum using cathodic adsorptive square-wave stripping voltammetry.

    Ghoneim, M M; Tawfik, A; Radi, A


    A rapid and sensitive square-wave voltammetric procedure was optimized for the determination of dipyridamole after its adsorption preconcentration onto a hanging mercury drop electrode. The peak current of the first of the two peaks developed for this drug in Britton-Robinson buffer at pH 8.0 has been considered for the present analytical study. An accumulation potential of -1.0 V versus Ag/AgCl/KCl(s), pulse amplitude a =100 mV, scan increment Delta E =10 mV, and frequency f =120 Hz were the optimal experimental parameters. Dipyridamole can be determined in the concentration range of 9.0 x 10(-9) to 5.0 x 10(-6) M using accumulation times of 30-300 s. A detection limit of 4.0 x 10(-11) M was achieved after a 300 s accumulation time. Applicability to serum samples was illustrated. The average recoveries for dipyridamole spiked to serum at 0.25-4.50 micro g ml(-1) were 96.0-102.0%, and the higher standard deviation was 2.9%. A detection limit of 0.06 micro g mL(-1) of serum was obtained.

  5. BCG vaccine combined with dipyridamole in the treatment of HBV infection

    Xu Wen Gao; Shi Ying Jia; Xue Mei Liu


    AIM To investigate the effect of BCG vaccine and dipyridamole in treating hepatitis B due to their anti-virus effects.METHODS Among 602 patients with positive HBeAg, 512 were allocated to the treatment group and 90patients to the control group. There was no significant difference in disease and age between the two groups.All the patients in the treatment group with no abnormal findings by chest X-ray fluoroscopy, whose localskin scleromata diameters were less than 7 mm after the 1:2000 OT test, were given BCG vaccine 0.1 mlintracutaneously at the deltoid once a month, and simultaneously took dipyridamole 50 mg twice a day forfour to eight months. The hepatic function, B-mode ultrasound and the five markers of hepatitis B wereroutinely examined before each injection. The results at one month after the last injection in the treatmentgroup were compared with those of the control group.RESULTS The recovery rates of hepatic functions and the rates of improvement of the symptoms and signsin the treatment group were better than those in the control group. The negative transformation rates ofHBeAg and the positive transformation rates of HBeAb were 60.3% and 31.6% in the treatment group vs.13.3% and 13.0% in the control group (P0.05. Test x2, x2=1.11, 0.22).CONCLUSION The application of BCG vaccine in combination with dipyridamole increased the negativetransformation rate of HBeAg and the positive transformation rate of HBeAb, improved the clinicalsymptoms, signs and hepatic function of the patients. These two drugs had significant anti-HBV effect andshowed good efficacy in the treatment of HBV infection.

  6. Usefulness of Dipyridamole Myocardial Perfusion SPECT in Patients with Left Bundle Branch Block

    Naser Aslanabadi


    Full Text Available Background: Diagnosis of coronary artery disease (CAD in patients with left bundle branch block (LBBB is considered as a challenge in cardiology due to the low accuracy of noninvasive methods such as basal and stress electrocardiography (ECG. This diagnostic challenge can be reduced but not eliminated using dipyridamole as a stress method instead of exercise. The aim of this study was to assess the diagnostic value of dipyridamole stress Tc-99m Sestamibi single photon emission computed tomography (SPECT myocardial perfusion imaging in patients with complete LBBB. Methods: We studied 40 patients with permanent and complete LBBB using Tc-99m Sestamibi SPECT and dipyridamole stress to evaluate CAD. Perfusion defect was considered fixed when there was no difference between rest and stress score, while reversible defect was defined as a segment with higher score on stress images. All patients underwent coronary angiography. Results: Eleven patients (27.5% had normal myocardial perfusion SPECT and 29 patients (72.5% had reversible perfusion defects. Angiography was positive in 30 patients, while 10 cases showed normal angiography. The sensitivity, specificity, positive predict value and negative predict value of our study for detecting >50% coronary stenosis was 86.6%, 70%, 89% and 64% respectively. Conclusion: We found 33 (82.5% patients with concordant angiography and myocardial perfusion SPECT results (p=0.002. Angiography was positive in 90% of patients with reversible perfusion defects on myocardial perfusion SPECT. In summary, Tc-99m Sestamibi SPECT in patients with LBBB showed high accuracy (82.5% in detecting >50% coronary stenosis.

  7. Reverse screening approach to identify potential anti-cancer targets of dipyridamole

    Ge, Shu-Min; Zhan, Dong-Ling; Zhang, Shu-Hua; Song, Li-Qiang; Han, Wei-Wei


    Dipyridamole (DIP) inhibits thrombus formation when given chronically, and causes vasodilation over a short time. To date, DIP can increase the anticancer drugs (5-fluorouracil, methotrexate, piperidine, vincristine) concentration in cancer cells and hence enhance the efficacy of treatment cancer. The inhibition of DIP may result in increased 5-fluorouracil efficacy and diminish the drug side effects. But the actual molecular targets remain unknown. In this study, reverse protein-ligands docking, and quantum mechanics were used to search for the potential molecular targets of DIP. The quantum mechanics calculation was performed by using Gaussian 03 program package. Reverse pharmacophore mapping was used to search for potential molecular target candidates for a given small molecule. The docking study was used for exploring the potential anti-cancer targets of dipyridamole. The two predicted binders with the statistically significant prediction are dihydropyrimidine dehydrogenase (DPD) (PDB Id: 1GTE) and human spindle checkpoint kinase Bub1 (PDB Id: 3E7E). Structure analysis suggests that electrostatic interaction and hydrogen bonding play an important role in their binding process. The strong functional linkage of DIP and 5FU supports our prediction. In conclusion, these results generate a tractable set of anticancer proteins. The exploration of polypharmacology will provide us new opportunities in treating systematic diseases, such as the cancers. The results would generate a tractable set of anticancer target proteins for future experimental validations. PMID:28077994

  8. Assessment by dipyridamole-thallium-201 myocardial scintigraphy of coronary risk before peripheral vascular surgery

    Sachs, R.N.; Tellier, P.; Larmignat, P.; Azorin, J.; Fischbein, L.; Beaudet, B.; Cadilhac, P.; Cupa, M.; De Saint Florent, G.; Vulpillat, M.


    From October 1983 to January 1985, 46 patients (38 men and 8 women; average age, 60 years; range, 37 to 83 years) underwent peripheral vascular surgery of either the internal carotid artery or the arteries of the lower limbs. Each patient had a thorough clinical examination, an ECG, and a dipyridamole-thallium-201 myocardial scan before operation. On the basis of results, they were divided into two groups: 20 patients with and 26 patients without chronic ischemic heart disease. Three major cardiac events were noted during or after a period of 1 month after surgery: There were two deaths due to cardiac ischemic events and one patient had postoperative unstable angina pectoris. These three patients were classified in the coronary group (NS). When the patients were classified on the basis of whether or not there was thallium redistribution on serial images after infusion of dipyridamole, 14 with redistribution and 32 without redistribution were noted. The three patients who had major cardiac events were in the former group (p less than 0.04). Our data suggest that patients in whom redistribution occurs have a high incidence of postoperative ischemic events. These patients should be considered for particular preoperative coronary care to avoid major postoperative cardiac events and to increase chances of survival.

  9. Preparation of dipyridamole suppository%双嘧达莫栓的研制

    李仲昆; 王崇静; 等


    目的:研究治疗小儿轮状病毒性腹泻的有效药物。[ HT 5”H〗方法:将双嘧达莫制成栓剂并建立其质量标准。结果:双嘧达莫栓能有效治疗该疾病,总治愈率为56.3%,有效率为96.9%,病毒清除率为96.9 %。含量测定的回收率为99.2%,RSD为1.8%。结论:本质量标准可有效控制双嘧达莫栓的质量。%Objective:To prepare the effective agent for treatme nt of virus diarrhea in children.Methods:To prepare dipyridamole s uppository from its bulk and to establish the standard for quality control.Results and conclusion:Dipyridamole suppository was effective in t reatment of virus diarrhea in children with an effective rate of 96.9% and a vir us eradication rate of 96.9%.The quality control standard was reliable with a re covery rate of 99.2% and a RSD of 1.8%.

  10. Fourteen-Year Follow-Up From CABADAS : Vitamin K Antagonists or Dipyridamole Not Superior to Aspirin

    Veeger, Nic J. G. M.; Zijlstra, Felix; Hillege, Hans L.; van der Meer, Jan


    Background. Secondary prophylaxis using aspirin is standard of care after coronary artery bypass graft surgery. Limited data are available for long-term results. We evaluated the effect of aspirin, aspirin with dipyridamole, and vitamin K antagonists (VKA) on 14-year clinical outcome of patients inc

  11. Fourteen-Year Follow-Up From CABADAS : Vitamin K Antagonists or Dipyridamole Not Superior to Aspirin

    Veeger, Nic J. G. M.; Zijlstra, Felix; Hillege, Hans L.; van der Meer, Jan


    Background. Secondary prophylaxis using aspirin is standard of care after coronary artery bypass graft surgery. Limited data are available for long-term results. We evaluated the effect of aspirin, aspirin with dipyridamole, and vitamin K antagonists (VKA) on 14-year clinical outcome of patients

  12. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Cortinas, Inés Vidal, E-mail:; Beretta, Mario; Alonso, Omar; Mut, Fernando [Departamento de Medicina Nuclear do Hospital ‘Asociación Española’, Br. Artigas 1515, Montevideo (Uruguay)


    Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity. In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols. In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection. Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001). The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

  13. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Cortinas, Inés Vidal; Beretta, Mario; Alonso, Omar; Mut, Fernando


    Background Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity. Objectives In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols. Methods In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection. Results Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001). Conclusions The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP. PMID:26039661

  14. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Inés Vidal Cortinas


    Full Text Available AbstractBackground:Myocardial perfusion scintigraphy (MPS in patients not reaching 85% of the maximum predicted heart rate (MPHR has reduced sensitivity.Objectives:In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols.Methods:In patients not reaching a sufficient exercise (SE test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection.Results:Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR and 67 underwent the dipyridamole alone test (DIP. They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43. For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35. Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001.Conclusions:The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

  15. Comparison of exercise, dobutamine-atropine and dipyridamole-atropine stress echocardiography in detecting coronary artery disease

    Nedeljkovic, Ivana; Ostojic, Miodrag; Beleslin, Branko; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Nedeljkovic, Milan; Stojkovic, Sinisa; Stankovic, Goran; Saponjski, Jovica; Petrasinovic, Zorica; Giga, Vojislav; Mitrovic, Predrag


    Background Dipyridamole and dobutamine stress echocardiography testing are most widely utilized, but their sensitivity remained suboptimal in comparison to routine exercise stress echocardiography. The aim of our study is to compare, head-to-head, exercise, dobutamine and dipyridamole stress echocardiography tests, performed with state-of-the-art protocols in a large scale prospective group of patients. Methods Dipyridamole-atropine (Dipatro: 0.84 mg/kg over 10 min i.v. dipyridamole with addition of up to 1 mg of atropine), dobutamine-atropine (Dobatro: up to 40 mcg/kg/min i.v. dobutamine with addition of up to 1 mg of atropine) and exercise (Ex, Bruce) were performed in 166 pts. Of them, 117 pts without resting wall motion abnormalities were enrolled in study (91 male; mean age 54 ± 10 years; previous non-transmural myocardial infarction in 32 pts, angina pectoris in 69 pts and atypical chest pain in 16 pts). Tests were performed in random sequence, in 3 different days, within 5 day period under identical therapy. All patients underwent coronary angiography. Results Significant coronary artery disease (CAD; ≥50% diameter stenosis) was present in 69 pts (57 pts 1-vessel CAD, 12 multivessel CAD) and absent in 48 pts. Sensitivity (Sn) was 96%, 93% and 90%, whereas specificity (Sp) was 92%, 92% and 87% for Dobatro, Dipatro and Ex, respectively (p = ns). Concomitant beta blocker therapy did not influence peak rate-pressure product and Sn of Dobatro and Dipatro (p = ns). Conclusion When state-of-the-art protocols are used, dipyridamole and dobutamine stress echocardiography have comparable and high diagnostic accuracy, similar to maximal post-exercise treadmill stress echocardiography. PMID:16672046

  16. Comparison of exercise, dobutamine-atropine and dipyridamole-atropine stress echocardiography in detecting coronary artery disease

    Petrasinovic Zorica


    Full Text Available Abstract Background Dipyridamole and dobutamine stress echocardiography testing are most widely utilized, but their sensitivity remained suboptimal in comparison to routine exercise stress echocardiography. The aim of our study is to compare, head-to-head, exercise, dobutamine and dipyridamole stress echocardiography tests, performed with state-of-the-art protocols in a large scale prospective group of patients. Methods Dipyridamole-atropine (Dipatro: 0.84 mg/kg over 10 min i.v. dipyridamole with addition of up to 1 mg of atropine, dobutamine-atropine (Dobatro: up to 40 mcg/kg/min i.v. dobutamine with addition of up to 1 mg of atropine and exercise (Ex, Bruce were performed in 166 pts. Of them, 117 pts without resting wall motion abnormalities were enrolled in study (91 male; mean age 54 ± 10 years; previous non-transmural myocardial infarction in 32 pts, angina pectoris in 69 pts and atypical chest pain in 16 pts. Tests were performed in random sequence, in 3 different days, within 5 day period under identical therapy. All patients underwent coronary angiography. Results Significant coronary artery disease (CAD; ≥50% diameter stenosis was present in 69 pts (57 pts 1-vessel CAD, 12 multivessel CAD and absent in 48 pts. Sensitivity (Sn was 96%, 93% and 90%, whereas specificity (Sp was 92%, 92% and 87% for Dobatro, Dipatro and Ex, respectively (p = ns. Concomitant beta blocker therapy did not influence peak rate-pressure product and Sn of Dobatro and Dipatro (p = ns. Conclusion When state-of-the-art protocols are used, dipyridamole and dobutamine stress echocardiography have comparable and high diagnostic accuracy, similar to maximal post-exercise treadmill stress echocardiography.

  17. In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused by Acid-Reducing Agents.

    Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L


    Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.

  18. Effect of surfactants, gastric emptying, and dosage form on supersaturation of dipyridamole in an in vitro model simulating the stomach and duodenum.

    Mitra, A; Fadda, H M


    The purpose of this study was to investigate the influence of gastric emptying patterns, surfactants, and dosage form on the supersaturation of a poorly soluble weakly basic drug, dipyridamole, using an in vitro model mimicking the dynamic environment of the upper gastrointestinal tract, and, furthermore, to evaluate the usefulness of this model in establishing correlations to in vivo bioavailability for drugs with solubility/dissolution limited absorption. A simulated stomach duodenum model comprising four compartments was used to assess supersaturation and precipitation kinetics as a function of time. It integrates physiologically relevant fluid volumes, fluid transfer rates, and pH changes of the upper GI tract. Monoexponential gastric emptying patterns simulating the fasted state were compared to linear gastric emptying patterns simulating the fed state. The effect of different surfactants commonly used in oral preparations, specifically, sodium lauryl sulfate (SLS), poloxamer-188, and polysorbate-80, on dipyridamole supersaturation was investigated while maintaining surface tension of the simulated gastric fluids at physiological levels and without obtaining artificial micellar solubilization of the drug. The supersaturation behavior of different dose strengths of dipyridamole was explored. Significant levels of dipyridamole supersaturation were observed in the duodenal compartment under all the different in vivo relevant conditions explored. Dipyridamole supersaturation ratios of up to 11-fold have been observed, and supersaturation has been maintained for up to 120 min. Lower duodenal concentrations of dipyridamole were observed under linear gastric emptying patterns compared to mononexponential gastric emptying. The mean duodenal area under concentration-time curves (AUC60min) for the dipyridamole concentration profile in the duodenal compartment is significantly different for all the surfactants explored (P supersaturation/precipitation kinetics of weakly

  19. Effects of dipyridamole and aminophylline on hemodynamics, regional myocardial blood flow and thallium-201 washout in the setting of a critical coronary stenosis

    Granato, J.E.; Watson, D.D.; Belardinelli, L.; Cannon, J.M.; Beller, G.A. (Univ. of Virginia Health Sciences Center, Charlottesville (USA))


    Experiments were performed to characterize the interaction of intravenous dipyridamole and aminophylline on thallium-201 transport kinetics, regional myocardial blood flow and systemic hemodynamics in the presence of a critical coronary artery stenosis. In 12 dogs with a critical left anterior descending coronary artery stenosis, arterial pressure decreased from a mean value (+/- SEM) of 107 +/- 6 to 94 +/- 3 mm Hg and distal left anterior descending artery pressure decreased from 70 +/- 7 to 55 +/- 4 mm Hg after intravenous administration of dipyridamole. In the left anterior descending perfusion zone, the endocardial/epicardial flow ratio decreased from 0.70 to 0.36 and the intrinsic thallium washout rate was significantly prolonged. Intravenous aminophylline reversed the dipyridamole-induced systemic hypotension and transmural coronary steal and restored the thallium washout rate to baseline values. In six other dogs, aminophylline alone resulted in no alterations in systemic and coronary hemodynamics or regional myocardial blood flow. As expected, dipyridamole-induced vasodilation and coronary steal were prevented by aminophylline pretreatment. These data show that in a canine model of partial coronary stenosis, systemic hypotension, adverse regional flow effects and prolonged thallium-201 washout consequent to intravenously administered dipyridamole are promptly reversed by intravenous aminophylline administration. Aminophylline alone had no significant hemodynamic and coronary flow effects. This study provides further insight into the altered thallium kinetics occurring as a consequence of dipyridamole-induced vasodilation and suggests that the prompt reversal of symptoms and signs of ischemia with aminophylline in patients receiving intravenous dipyridamole for clinical imaging studies probably reflects the reversal of transmural coronary steal.

  20. Dipyridamole increases gap junction coupling in bovine GM-7373 aortic endothelial cells by a cAMP-protein kinase A dependent pathway.

    Begandt, D; Bintig, W; Oberheide, K; Schlie, S; Ngezahayo, A


    The scrape-loading/dye transfer technique was applied on the bovine aortic endothelial cell line GM-7373 to analyze the effects of the antithrombolytic drug dipyridamole on gap junction coupling in endothelial cells. We found that a cell treatment for 24 h with dipyridamole in therapeutically relevant concentrations (1-100 microM) increased gap junction coupling in a dose dependent manner. Similar to dipyridamole, forskolin as well as 8-Br-cAMP increased the gap junction coupling, while dibutyryl-cGMP (db-cGMP) did not affect the gap junction coupling of the GM-7373 endothelial cells. In parallel, a pharmacological inhibition of protein kinase A (PKA) with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89), antagonised the action of dipyridamole on gap junction coupling. We propose that the observed dipyridamole induced increase in gap junction coupling in endothelial cells is related to a cAMP-PKA dependent phosphorylation pathway. The report shows that gap junction coupling in endothelial cells is a suitable therapeutic target for treatment of cardiovascular diseases.

  1. Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery : a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants

    van der Meer, J; Hillege, H. L.; Kootstra, G. J.; Ascoop, C. A. P. L.; Pfisterer, M.; van Gilst, W. H.; Lie, K. I.


    Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been




    Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been establishe

  3. Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts.

    Punnakitikashem, Primana; Truong, Danh; Menon, Jyothi U; Nguyen, Kytai T; Hong, Yi


    Acellular biodegradable small diameter vascular grafts (SDVGs) require antithrombosis, intimal hyperplasia inhibition and rapid endothelialization to improve the graft patency. However, current antithrombosis and antiproliferation approaches often conflict with endothelial cell layer formation on SDVGs. To address this limitation, biodegradable elastic polyurethane urea (BPU) and the drug dipyridamole (DPA) were mixed and then electrospun into a biodegradable fibrous scaffold. The BPU would provide the appropriate mechanical support, while the DPA in the scaffold would offer biofunctions as required above. We found that the resulting scaffolds had tensile strengths and strains comparable with human coronary artery. The DPA in the scaffolds was continuously released up to 91 days in phosphate buffer solution at 37 °C, with a low burst release within the first 3 days. Compared to BPU alone, improved non-thrombogenicity of the DPA-loaded BPU scaffolds was evidenced with extended human blood clotting time, lower TAT complex concentration, lower hemolysis and reduced human platelet deposition. The scaffolds with a higher DPA content (5 and 10%) inhibited proliferation of human aortic smooth muscle cell significantly. Furthermore, the DPA-loaded scaffolds had no adverse effect on human aortic endothelial cell growth, yet it improved their proliferation. The attractive mechanical properties and biofunctions of the DPA-loaded BPU scaffold indicate its potential as an acellular biodegradable SDVG for vascular replacement.

  4. Improved dissolution and pharmacokinetic behavior of dipyridamole formulation with microenvironmental pH-modifier under hypochlorhydria.

    Onoue, Satomi; Inoue, Ryo; Taniguchi, Chika; Kawabata, Yohei; Yamashita, Kazuhiro; Wada, Koichi; Yamauchi, Yukinori; Yamada, Shizuo


    The present study aimed to develop and characterize new formulations of dipyridamole (DP), a pH-dependent poorly soluble drug, employing an acidic pH-modifier for improving dissolution and absorption under hypochlorhydric condition. Granule formulations of DP (DPG) with and without fumaric acid (FA) were prepared with wet granulation, physicochemical properties of which were characterized focusing on morphology, dissolution and stability. Pharmacokinetic profiling of orally dosed DPG or DPG with 60% loading of FA (DPG/FA60) was carried out in omeprazole-treated rats as a hypochlorhydric model. Although pH-dependent dissolution behavior was observed in DPG, DPG/FA exhibited high rate and extent of dissolution in both acidic and neutral media. Complete supersaturation was achieved with a 2 h testing period in pH6.8 medium, and co-existing fumaric acid had no impact on the chemical/photochemical stability of DP in solid-state. After oral administration of DPG or DPG/FA60 (10 mg-DP/kg), there was ca. 40% reduction of AUC(0-3) for DPG in omeprazole-treated rats as compared to that in normal rats; however, AUC(0-3) for DPG/FA60 under hypochlorhydria was almost identical to that of DPG in normal rats. Given the improved systemic exposure early after oral administration in hypochlorhydric rats, the DPG/FA might provide better clinical outcomes in hypochlorhydric patients.

  5. Controlled release profiles of dipyridamole from biodegradable microspheres on the base of poly(3-hydroxybutyrate.


    Full Text Available Novel biodegradable microspheres on the base of poly(3-hydroxybutyrate (PHB designed for controlled release of antithrombotic drug, namely dipyridamole (DPD, have been kinetically studied. The profiles of release from the microspheres with different diameters 4, 9, 63, and 92 µm present the progression of nonlinear and linear stages. Diffusionkinetic equation describing both linear (PHB hydrolysis and nonlinear (diffusion stages of the DPD release profiles from the spherical subjects has been written down as the sum of two terms: desorption from the homogeneous sphere in accordance with diffusion mechanism and the zero-order release. In contrast to the diffusivity dependence on microsphere size, the constant characteristics (k of linearity are scarcely affected by the diameter of PHB microparticles. The view of the kinetic profiles as well as the low rate of DPD release are in satisfactory agreement with kinetics of weight loss measured in vitro for the PHB films. Taking into account kinetic results, we suppose that the degradation of both films and PHB microspheres is responsible for the linear stage of DPD release profiles. In the nearest future, combination of biodegradable PHB and DPD as a representative of proliferation cell inhibitors will give possibility to elaborate the novel injectable therapeutic system for a local, long-term, antiproliferative action.

  6. Dipyridamole, cold pressor test, and demonstration of endothelial dysfunction: a PET study of myocardial perfusion in diabetes

    Kjaer, Andreas; Meyer, Christian; Nielsen, Flemming S;


    Much evidence suggests endothelial dysfunction to be present in non-insulin-dependent diabetes mellitus (NIDDM) and to be important for the development of myocardial ischemia. Endothelial function in the coronary vessels may be studied in various ways. We compared the effect of cold pressor testing...... coronary disease, endothelial dysfunction is strongly suggested by an impaired increase in CBF both to dipyridamole and to CPT. This dysfunction was reversed by infusion of an ACE inhibitor. Although ACE inhibition during CPT did induce significant increases in CBF in the patients, the changes during ACE...

  7. Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block

    Estêvan Vieira Cabeda


    Full Text Available AbstractBackground:Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB.Objective:To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA (stenosis ≥ 70% as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA and compare the results with those of single photon emission computed tomography (SPECT myocardial perfusion scintigraphy.Methods:Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution’s ethics committee.Results:The patients’ mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001. The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001. In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001.Conclusion:The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB.


    赵世华; DidierRevel; PierreCroisille; JeanP.Roux; MarcJanier; IsabelleMagnin


    Breath-hold cine MRI was employed for the identification of severe coronary artery stenoscs after 0.56mg/kg of dipyridamole was infused. Fourteen patients without myocardial infarction but with ≥70% diameter narrowing of 1. or 2 major coronary artaries were studied. Each patient tmderwent coronary angiography, MRI at rest and during stress. Segmental wall motion abnormalities were visually assessed in a cine loop, followed by quantitative analysis by calculation of percent systolic wall thickening(%SWth). The results showed that the sensitivities of 70% and 90% were present for the qualitative and quantitative analyses, respectively, in respect to the approximate specificities(82% & 86%). Further quantitative analysis showed that sensitivities and specifieities were 88% and 88% for 1-vessel disease versus 92% and 83% for 2-vessd disease; 86% and 100% for LAD, 100% and 70% for LCX, 89% and 100% for RCA. We concloded that quantitative analysis is significantly superior to qualitative analysis for the identification of severe coronary stenosis while dipyridamole-induced wall motion abnormalities were assessed by breath-hold cine MRI.

  9. Prevalence and correlates of increased lung/heart ratio of thallium-201 during dipyridamole stress imaging for suspected coronary artery disease

    Villanueva, F.S.; Kaul, S.; Smith, W.H.; Watson, D.D.; Varma, S.K.; Beller, G.A. (Univ. of Virginia School of Medicine, Charlottesville (USA))


    There is little information concerning the prevalence and clinical correlates of increased pulmonary thallium-201 uptake during dipyridamole thallium-201 stress imaging. Accordingly, the clinical characteristics and quantitative thallium-201 findings were correlated with quantitative lung/heart thallium-201 ratio in 87 patients undergoing dipyridamole thallium-201 stress testing. Nineteen patients (22%) had an elevated ratio (greater than 0.51). These patients were more likely to have had an infarction, to be taking beta blockers, and have a lower rate-pressure product after dipyridamole administration than those with a normal ratio (p less than 0.03). An elevated ratio was associated with a greater likelihood of initial, redistribution and persistent defects, as well as left ventricular cavity dilatation on thallium-201 imaging (p less than 0.05). In addition, the number of myocardial segments demonstrating initial, redistribution and persistent defects was also greater in patients with increased ratios (p less than 0.03). Multivariate analysis demonstrated that the presence of redistribution and left ventricular cavity dilatation were the most significant correlates of lung/heart thallium-201 ratio. It is concluded that the prevalence of increased lung/heart thallium-201 ratio with dipyridamole thallium-201 stress imaging is similar to that seen with exercise stress imaging. As with exercise thallium-201 imaging, increased pulmonary thallium-201 uptake may be a marker of functionally more significant coronary artery disease.

  10. The combination of acetylsalicylic acid and dipyridamole is more effective in secondary prevention following transient ischaemic attack or cerebral infarction: The debate is closed

    Luijckx, G.J.; De Keyser, J.H.A.


    The European/Australasian stroke prevention in reversible ischaemia trial (ESPRIT) confirms that long-term administration of the combination acetylsalicylic acid and dipyridamole is more effective than acetylsalicylic acid in reducing the risk of vascular events after cerebral ischaemia of arterial

  11. Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: first results from the TRinity AntiPlatelet responsiveness (TrAP) study.

    Tobin, William Oliver


    Ex vivo dipyridamole \\'non-responsiveness\\' has not been extensively studied in ischaemic cerebrovascular disease. Platelet surface marker expression, leucocyte-platelet complex formation and inhibition of platelet function at high shear stress as detected by the PFA-100(R) Collagen-Adenosine-diphosphate (C-ADP) and Collagen-Epinephrine cartridges was assessed in 52 patients within 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke on aspirin, and then 14 d (14 d) and >90 d (90 d) after adding dipyridamole. A novel definition of \\'Dipyridamole non-responsiveness\\' was used. The median C-ADP closure time increased following addition of dipyridamole, remained elevated at 90 d (P <\\/= 0.03), and was unaffected by aspirin dose. 59% at 14 d and 56% at 90 d were \\'dipyridamole non-responders\\' on the PFA-100. The proportion of non-responders at 14 and 90 d was similar (P= 0.9). Compared with baseline (4.6%), median monocyte-platelet complexes increased at 14 d (5.0%, P= 0.03) and 90 d (4.9%, P= 0.04). Low C-ADP closure times were associated with increased monocyte-platelet complexes at 14 d (r= -0.32, P= 0.02) and 90 d (r= -0.33, P = 0.02). Monocyte-platelet complexes increased in the subgroup of dipyridamole non-responders on the PFA-100 (P<\\/= 0.045), but not in responders (P >\\/= 0.5), at 14 and 90 d versus baseline. Additional inhibition of platelet function has been detected with the PFA-100 when dipyridamole is added to aspirin. Elevated monocyte-platelet complexes may contribute to ex vivo dipyridamole non-responsiveness.

  12. 双嘧达莫的合成工艺改进%Process Improvement on the Synthesis of Dipyridamole

    张秋荣; 蒋腾飞; 王惠; 邵坤鹏; 刘宏民


    Dipyridamole in total yield of 25.2% was synthesized by the condensation reaction of ethyl acetoacetate with thiourea, then nitration and oxidation, reduction, cyclization, chlorination, nucleo-philic substitution. The structure was confirmed by !H NMR and HR-MS.%以乙酰乙酸乙酯为原料,与硫脲缩合成嘧啶环后,经硝化和氧化、硝基还原、与尿素缩合生成2,4,6,8-四羟基嘧啶[5,4-d]并嘧啶,再经氯代、亲核取代等反应合成了抗血栓药双嘧达莫,总收率25.2%,其结构经1H NMR和HR-MS确证.

  13. Comparison of Adenosine Stress Myocardial Perfusion Scintigraphy and Oral Dipyridamole Stress Myocardial Perfusion Scintigraphy for Hemodynamic Changes and Adverse Effects

    Ahmet Yanarateş


    Full Text Available Objective: Similar effects can be achieved during stress myocardial perfusion scintigraphy (MPS using pharmacological agents to create cardiac stress for patients who are unable to exercise. In our study, we aimed to show the hemodynamic changes and adverse effects caused by adenosine and to compare the results with dipyridamole stress MPS. Materials and Methods: Sixty-five patients with suspected coronary artery disease were included in our study. Fifty patients in whom stress MPS with intravenous adenosine was performed (group A and 15 patients who underwent oral dipyridamole stress MPS (group B were retrospectively evaluated. During the test, blood pressure measurements and electrocardiographic follow-up were performed in all patients and side effects were noted. Results: At least one side effect occurred in 68% of the group A and in 46% of the group B patients. There was no statistically significant difference between the two groups in terms of side effects that occurred during the pharmacological stress. During the maximum stress, there was an increase of 15.80±11.60 beats/min in heart beats in group A and 5.53±4.54 beats/min in group B. There was a statistically significant difference between the groups in terms of heart rate increase per minute. When we compared reduction in systolic blood pressure and diastolic blood pressure, there was no statistically significant difference between the two groups. Conclusion: Although side effects are more often seen with adenosine, rapid decline in complaints was observed when adenosine infusion was terminated and there was no need for patient follow-up due to short half life of adenosine. We believe that these favourable advantages will increase the use of adenosine in clinical practice.

  14. Head-to-head comparison of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia in an animal model of coronary artery stenosis

    A. Schmidt


    Full Text Available To compare the sensitivity of dipyridamole, dobutamine and pacing stress echocardiography for the detection of myocardial ischemia we produced a physiologically significant stenosis in the left circumflex artery of 14 open-chest dogs (range: 50 to 89% reduction in luminal diameter. In each study, dobutamine (5 to 40 µg kg-1 min-1 in 3-min stages and pacing (20 bpm increments, each 2 min, up to 260 bpm were performed randomly, and then followed by dipyridamole (up to 0.84 mg/kg over 10 min. The positivity of stress echocardiography tests was quantitatively determined by a significant (P<0.05 reduction of or failure to increase absolute and percent systolic wall thickening in the stenotic artery supplied wall, as compared to the opposite wall (areas related to the left anterior descending artery. Systolic and diastolic frozen images were analyzed off-line by two blinded observers in the control and stress conditions. The results showed that 1 the sensitivity of dobutamine, dipyridamole and pacing stress tests was 57, 57 and 36%, respectively; 2 in animals with positive tests, the mean percent change of wall thickening in left ventricular ischemic segments was larger in the pacing (-19 ± 11% and dipyridamole (-18 ± 16% tests as compared to dobutamine (-9 ± 6% (P = 0.05, but a similar mean reduction of wall thickening was observed when this variable was normalized to a control left ventricular segment (area related to the left anterior descending artery (pacing: -16 ± 7%; dipyridamole: -25 ± 16%; dobutamine: -26 ± 10%; not significant, and 3 a significant correlation was observed between magnitude of coronary stenosis and left ventricular segmental dysfunction induced by ischemia in dogs submitted to positive stress tests. We conclude that the dobutamine and dipyridamole stress tests showed identical sensitivities for the detection of myocardial ischemia in this one-vessel disease animal model with a wide range of left circumflex artery

  15. Fenofibrate and dipyridamole treatments in low-doses either alone or in combination blunted the development of nephropathy in diabetic rats.

    Balakumar, Pitchai; Varatharajan, Rajavel; Nyo, Ying Hui; Renushia, Raja; Raaginey, Devarajan; Oh, Ann Nah; Akhtar, Shaikh Sohrab; Rupeshkumar, Mani; Sundram, Karupiah; Dhanaraj, Sokkalingam A


    Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins. Hematoxylin-eosin, periodic acid Schiff and Masson trichrome staining confirmed renal pathological changes in diabetic rats that included glomerular capsular wall distortion, mesangial cell expansion, glomerular microvascular condensation, tubular damage and degeneration and fibrosis. Low-dose fenofibrate (30mg/kg, p.o., 4 weeks) and low-dose dipyridamole (20mg/kg, p.o., 4 weeks) treatment either alone or in combination considerably reduced renal structural and functional abnormalities in diabetic rats, but without affecting the elevated glucose level. Fenofibrate, but not dipyridamole, significantly prevented the lipid alteration and importantly the uric acid elevation in diabetic rats. Lisinopril (5mg/kg, p.o., 4 weeks, reference compound), prevented the hyperglycemia, lipid alteration and development of diabetic nephropathy. Lipid alteration and uric acid elevation, besides hyperglycemia, could play key roles in the development of nephropathy. Low-doses of fenofibrate and dipyridamole treatment either alone or in combination markedly prevented the diabetes-induced nephropathy. Their combination was as effective as to their individual treatment, but not superior in preventing the development of diabetic nephropathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Usefulness of coronary flow reserve over regional wall motion when added to dual-imaging dipyridamole echocardiography.

    Rigo, Fausto; Richieri, Margherita; Pasanisi, Emilio; Cutaia, Valeria; Zanella, Carlo; Della Valentina, Patrizia; Di Pede, Francesco; Raviele, Antonio; Picano, Eugenio


    Vasodilator stress echocardiography allows semi-simultaneous imaging of left anterior descending (LAD) coronary flow and regional wall function. To assess the relative (and additive?) value of regional flow and function for noninvasive identification of angiographically assessed LAD disease in patients with chest pain syndrome, we studied 230 consecutive in-hospital patients (134 men, aged 63.5 +/- 11 years) with chest pain syndrome and normal regional and global left ventricular function. All patients underwent stress echocardiography with dipyridamole (up to 0.84 mg/kg over 10 minutes), including wall motion analysis by 2-dimensional echocardiography and coronary flow reserve (CFR) evaluation of the LAD artery by Doppler, with or without contrast injection. A new regional wall motion abnormality in >or=2 contiguous segments was required for 2-dimensional echocardiographic positivity. CFR was evaluated as the ratio of dipyridamole to peak diastolic coronary blood flow velocity at rest. All patients underwent coronary angiography within 60 days; a quantitatively assessed diameter reduction >50% of the LAD artery was considered significant. Of the 230 patients, 70 had LAD disease. A regional wall motion abnormality in LAD territory was present in 52 patients, and reduced CFR (<1.9) in 62 patients. Sensitivity for detecting LAD disease was 74% for 2-dimensional echocardiography (95% confidence interval [CI] 64% to 84%) and 81% for CFR <1.9 (95% CI 72% to 90%); specificity was 91% (95% CI 87% to 96%) for 2-dimensional echocardiography and 84% for CFR (95% CI 79% to 90%). Accuracy was 86% for 2-dimensional echocardiography (95% CI 82% to 91%) and 83.5% for CFR (95% CI 79% to 88%). When 2-dimensional echocardiography and CFR criteria were considered, sensitivity increased to 93% (95% CI 87% to 99%), with 80.6% specificity (95% CI 74.5% to 86.7%). CFR was assessed during vasodilator stress echocardiography. Its diagnostic accuracy for detecting LAD disease was comparable

  17. "ECG variability contour" method reveals amplitude changes in both ischemic patients and normal subjects during Dipyridamole stress: a preliminary report.

    Dori, Guy; Gershinsky, Michal; Ben-Haim, Simona; Lewis, Basil S; Bitterman, Haim


    To detect and quantify consistent ECG amplitude changes, the "ECG variability contour" (EVC) method was proposed. Using this method we investigated amplitude changes in subjects undergoing myocardial perfusion imaging (MPI) with Dipyridamole (Dp). Fifty-three patients having reversible perfusion defects and 19 normal subjects (NS) who were free of: perfusion defects on their MPI, standard ST-T changes during Dp stress, and a negative clinical follow up. Mean ∏¹() was similar for the NS and patient group (6.2 ± 6.1 vs. 6.3 ± 6.2, P = 0.95). was 4.6 ± 3.0 in patients not having ST-T changes during Dp stress (n = 42), whereas in patients having ST-T changes (n = 11) it was 13.1 ± 10.2 (P was smaller than , which in turn was smaller than . The values of , , and for the NS, patients without and with ST-T changes were: 26.8 ± 28.6, 42.6 ± 41.8, 44.9 ± 36.5; 19.6 ± 20.8, 26.4 ± 31.4, 38.7 ± 27.3; 51.0 ± 30.0, 71.0 ± 36.8, 75.1 ± 20.9, respectively (P EVC method. The EVC method did not distinguish between NS and patients in this clinical setting.

  18. Dipyridamole potentiated the trypanocidal effect of nifurtimox and improved the cardiac function in NMRI mice with acute chagasic myocarditis

    Sonia Santeliz

    Full Text Available BACKGROUND As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy. OBJECTIVE To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx in epimastigote axenic cultures and in mice with acute Chagas disease. METHODS NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods. FINDINGS In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved. MAIN CONCLUSION DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.

  19. Preparation and characterization of dipyridamole solid dispersions for stabilization of supersaturation: effect of precipitation inhibitors type and molecular weight.

    Vora, Chintan; Patadia, Riddhish; Mittal, Karan; Mashru, Rajashree


    Dipyridamole (DPL) is a weakly basic BCS class II drug which precipitates upon entering into intestine leading to pH dependant and variable absorption. Thus, research envisaged focuses on developing formulations that maintain supersaturation following upon acid to neutral pH transition. In an endeavor to accomplish the objective, solid dispersion (SD) with hydroxypropylmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) was prepared by a quench cooling method. The three molecular weight grades of HPMC (HPMC E5, HPMC E15 and HPMC E50) and two molecular weight grades of PVP (PVP K30 and PVP K90) were investigated to observe effect of increasing molecular weight on stabilizing DPL supersaturated solutions. Equilibrium solubility studies revealed increase in solubility with both HPMC and PVP with greater benefit from HPMC. In vitro supersaturated dissolution results demonstrated that HPMC formulations provided greater degree and extent of supersaturation as compared to PVP formulations. The formulation with HPMC E50 provided maximum stabilization to supersaturation upon acid to neutral pH transition. Moreover, the effect of increase in molecular weight was more pronounced in HPMC rather than PVP. Stronger interactions were observed for DPL with HPMC, while no interaction was observed with PVP which was evident from Fourier transform infra-red studies. Differential scanning calorimetry and powder X-ray diffraction studies revealed the amorphous state of DPL in SD.

  20. Correlation between dobutamine stress transesophageal echocardiography, thallium 201-dipyridamole scintigraphy and coronary angiography in the early detection of myocardial ischemia.

    Rosas-Munive, E; Abundes-Velasco, A; Villa-Godínez, G; López-Winter, J F


    In order to establish the sensitivity and specificity of transesophageal stress echocardiography with dobutamine (TEE-dobutamine) in the early detection of myocardial ischemia we studied 30 consecutive patients from the Coronary Care Unit (CCU) of the Hospital de Cardiología, Centro Médico Nacional Siglo XXI. The results were correlated with thallium-201-dipyridamole scintigraphy (TDS), and coronary angiography. Two groups were formed: Group I-20 patients, 18 females/2 males, aged 37-73 years (mean 55 years) within the first week of myocardial infarction and/or unstable angina; Group II-10 patients, five males/five females, aged 35-65 years (mean 48 years) with atypical chest pain but with high suspicion of CHD. All group I patients, and none of group II, had significant stenoses on coronary angiography. Twenty patients had a positive TDS (18 patients from group I and two from group II). Twenty one patients had a positive test with TEE-dobutamine, 20 from group I and one from group II, which yields a sensitivity of 100%, a specificity of 90%, positive predictive value of 95% and negative predictive value of 100%.

  1. Prognostic importance of scintigraphic left ventricular cavity dilation during intravenous dipyridamole technetium-99m sestamibi myocardial tomographic imaging in predicting coronary events.

    McClellan, J R; Travin, M I; Herman, S D; Baron, J I; Golub, R J; Gallagher, J J; Waters, D; Heller, G V


    Left ventricular (LV) cavity dilation during stress myocardial perfusion imaging has been associated with multivessel disease, and may be an independent prognostic marker in addition to perfusion defects. The present study examines the predictive value for future cardiac events of transient or fixed LV dilation during dipyridamole technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging. The study included 512 consecutive patients who underwent SPECT imaging with Tc-99m sestamibi after dipyridamole infusion. Transient LV dilation was seen in 70 patients (14%) and 74 had fixed cavity dilation (14%); cavity size was normal in 368 patients (72%). Each perfusion scan was classified as normal or abnormal, and if abnormal, defects were categorized as transient or fixed, and as small, medium, or large (depending upon the number of abnormal vascular territories). Events during a mean follow-up of 12.8 +/- 6.8 months were tabulated by direct review of hospital charts and death certificates. The cardiac event rate (cardiac death or nonfatal infarction) was 1.9% in patients with normal cavity size, 11.4% with transient LV dilation, and 13.5% with fixed LV dilation (p < 0.01). Compared with patients with normal cavity size, those with transient LV dilation were more likely to sustain a myocardial infarction (p < 0.01) and those with fixed dilation more frequently suffered cardiac death (p < 0.01) and hospitalization for heart failure (p < 0.01). The group with the highest risk had both a large perfusion defect and cavity dilation. By Cox proportional hazard regression analysis, both transient and fixed LV dilation were strong independent predictors of cardiac events. Transient or fixed LV dilation are commonly seen during dipyridamole Tc-99m sestamibi SPECT imaging (14% incidence for each) and are useful predictors of cardiac events.

  2. Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

    Ishii, M; Himeno, W; Sawa, M; Iemura, M; Furui, J; Muta, H; Sugahara, Y; Egami, K; Akagi, T; Ishibashi, M; Kato, H


    The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

  3. 联合应用双嘧达莫和阿司匹林在卒中二级预防中的疗效评价%Evaluation of Dipyridamole and Acetylsalicylic Acid in the Secondary Prevention of Stroke

    张雄; 王丽娟


    @@ 1文献类型 预防. 2证据水平 1b. 3文献来源 ①Diener HC, Cunha L, Forbes C, et al.European Stroke Prevention Study 2. Dipyridamole and Acetylsalicylic acid in the secondary prevention of stroke [J]. J Neurol Sci, 1996, 143(1-2):1-13.②Sacco RL, Sivenius J, Diener HC. Efficacy of Aspirin plus extended-release Dipyridamole in preventing recurrent stroke in high-risk populations [J]. Arch Neurol, 2005,62(3):403-408.

  4. Insulin sensitivity and inhibition by forskolin, dipyridamole and pentobarbital of glucose transport in three L6 muscle cell lines


    L6 skeletal muscle myoblasts stably overexpressing glucose transporter GLUT1 or GLUT4 with exofacial myc-epitope tags were characterized for their response to insulin. In clonally selected cultures, 2-deoxyglucose uptake into L6-GLUT1myc myoblasts and myotubes was linear within the time of study. In L6-GLUT1myc and L6-GLUT4myc myoblasts, 100 nmol/L insulin treatment increased the GLUT1 content of the plasma membrane by 1.58±0.01 fold and the GLUT4 content 1.96±0.11 fold, as well as the 2-deoxyglucose uptake 1.53±0.09 and 1.86±0.17 fold respectively, all by a wortmannin-inhibitable manner. The phosphorylation of Akt in these two cell lines was increased by insulin. L6-GLUT1myc myoblasts showed a dose-dependent stimulation of glucose uptake by insulin, with unaltered sensitivity and maximal responsiveness compared with wild type cells. By contrast, the improved insulin responsiveness and sensitivity of glucose uptake were observed in L6-GLUT4myc myoblasts. Earlier studies indicated that forskolin might affect insulin-stimulated GLUT4 translocation. A 65% decrease of insulin-stimulated 2-deoxyglucose uptake in GLUT4myc cells was not due to an effect on GLUT4 mobilization to the plasma membrane, but instead on direct inhibition of GLUT4. Forskolin and dipyridamole are more potent inhibitors of GLUT4 than GLUT1. Alternatively, pentobarbital inhibits GLUT1 more than GLUT4. The use of these inhibitors confirmed that the overexpressed GLUT1 or GLUT4 are the major functional glucose transporters in unstimulated and insulin-stimulated L6 myoblasts. Therefore, L6-GLUT1myc and L6-GLUT4myc cells provide a platform to screen compounds that may have differential effects on GLUT isoform activity or may influence GLUT isoform mobilization to the cell surface of muscle cells.

  5. Simultaneous Determination of Aspirin, Dipyridamole and Two of Their Related Impurities in Capsules by Validated TLC-Densitometric and HPLC Methods.

    El-Ragehy, Nariman A; Hassan, Nagiba Y; Tantawy, Mahmoud A; Abdelkawy, Mohamed


    Aspirin (ASP) and dipyridamole (DIP) are widely used as a combination in pharmaceutical formulations for treatment of strokes. Many of these formulations are containing tartaric acid as an excipient (in DIP pellets formulation for sustained release), which increases the probability of formation of dipyridamole tartaric acid ester impurity (DIP-I). On the other hand, salicylic acid (SAL) is considered to be one of the synthesis impurities and a degradation product of ASP. In this work, two chromatographic methods, namely, TLC-densitometry and HPLC, have been established and validated for simultaneous determination of ASP, DIP, SAL and DIP-I. Good separation was achieved by using silica gel as stationary phase and toluene-methanol-ethyl acetate (2:3:5, by volume) as mobile phase in the case of TLC-densitometry and Zorbax ODS column with mobile phase consisting of phosphate buffer (pH 3.3)-acetonitrile-triethylamine (40:60:0.03, by volume) for HPLC. Influence of different organic solvents in mobile phase composition has been studied to optimize the separation efficiency in TLC densitometry. Moreover, factors affecting the efficiency of HPLC, like pH of the buffer used, organic solvent ratio in the mobile phase and flow rate, have been carefully studied using one variable at a time approach. Finally, the proposed methods were validated as per ICH guidelines. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  6. Effects of low-dose aspirin (50-mg/day), low-dose aspirin plus dipyridamole, and oral anticoagulant agents after internal mammary artery bypass-grafting : Patency and clinical outcome at 1 year

    van der Meer, J; de la Rivière, Aart Brutel; van Gilst, Wiek H.; Hillege, Hans L.; Pfisterer, M; Kootstra, G. J.; Dunselmann, P. H. J. M.; MULDER, BJM; Lie, Kong I.


    Objectives. This study was performed to compare the efficacy and safety of aspirin, aspirin plus dipyridamole, and oral anti coagulant agents in the prevention of internal mammary artery graft occlusion. Background. Antithrombotic drugs increase vein graft patency after coronary artery bypass

  7. Comparison of the myocardial blood flow response to regadenoson and dipyridamole: a quantitative analysis in patients referred for clinical {sup 82}Rb myocardial perfusion PET

    Goudarzi, Behnaz; Fukushima, Kenji; Bravo, Paco; Merrill, Jennifer [Johns Hopkins University, Division of Nuclear Medicine, Russell H Morgan Department of Radiology, Baltimore, MD (United States); Bengel, Frank M. [Johns Hopkins University, Division of Nuclear Medicine, Russell H Morgan Department of Radiology, Baltimore, MD (United States); Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany)


    Regadenoson is a novel selective A{sub 2A} adenosine receptor agonist, which is administered as an intravenous bolus at a fixed dose. It is currently not clear if the absolute flow increase in response to this fixed dose is a function of distribution volume in individual patients or if it is generally comparable to the previous standard agents dipyridamole or adenosine, which are dosed based on weight. We used quantitative analysis of clinical {sup 82}Rb PET/CT studies to obtain further insights. A total of 104 subjects with normal clinical rest/stress {sup 82}Rb perfusion PET/CT were included in a retrospective analysis. To rule out confounding factors, none had evidence of prior cardiac disease, ischaemia or infarction, cardiomyopathy, diabetes with insulin use, calcium score >400, renal disease or other significant systemic disease. A group of 52 patients stressed with regadenoson were compared with a group of 52 patients stressed with dipyridamole before regadenoson became available. The groups were matched for clinical characteristics, risk factors and baseline haemodynamics. Myocardial blood flow (MBF) and myocardial flow reserve (MFR) were quantified using a previously validated retention model, after resampling of dynamic studies from list-mode {sup 82}Rb datasets. At rest, heart rate, blood pressure and MBF were comparable between the groups. Regadenoson resulted in a significantly higher heart rate (34 {+-} 14 vs. 23 {+-} 10 beats per minute increase from baseline; p < 0.01) and rate-pressure product. Patients in the regadenoson group reported less severe symptoms and required less aminophylline. Stress MBF and MFR were not different between the groups (2.2 {+-} 0.6 vs. 2.1 {+-} 0.6 ml/min/g, p = 0.39, and 2.9 {+-} 0.8 vs. 2.8 {+-} 0.7, p = 0.31, respectively). In the regadenoson group, there was no correlation between stress flow or MFR and body weight or BMI. Despite its administration at a fixed dose, regadenoson results in an absolute increase in MBF

  8. The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

    Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L


    The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and

  9. Preparation and bioavailability of dipyridamole tablets%双嘧达莫片剂的制备及家犬体内的生物利用

    马骋; 王岩; 孙清; 郑力; 王思玲; 姜同英


    Objective To prepare dipyridamole tablets in nanotechnology and study its bioavailability. Methods The nanosuspensions were prepared using precipitation-ultrasonication method and high pressure homog-enization. The liquid nanosuspensions were solidified by spray drier. SEM (scanning electron microscope) was used to observe its morphology character, DSC (differential scanning calorimetry) and XRD( X-ray diffraction analysis) were applied to study its crystalline form,and IR was carried out to analyze the interaction between drugs and its stabilizer. Moreover, the tablets were prepared by direct compression technology, and its bioavailability was study by pharmacokinetic experiments on 3 dogs. Results The preparation remained to be the same crystal form as the raw material but with low crystallinity, and the dissolution rate of dipyridamole tablets was obviously improved. The relative bioavailability of test tablets was 185%. Conclusions The bioavailabilities of dipyridamole tablets in dogs are improved by using nanotechnology.%目的 制备双嘧达莫片剂并研究该片剂生物利用度.方法 采用超声沉淀法结合高压均质技术制备粒径为300 nm双嘧达莫纳米混悬剂,以喷雾干燥法对其进行固化,用扫描电镜(scanning electron microscope,SEM)观察粒子形态,差示扫描热分析法(differential scanning calorimetry,DSC),X射线衍射(X-ray diffraction analysis,XRD)和红外光谱法分析喷干粉末中药物的存在状态和与稳定剂之间相互作用.通过粉末直接压片法制备双嘧达莫片剂,并与市售普通片相比较,测定双嘧达莫片剂相对生物利用度.结果 药物以晶体形式存在于片剂中,且溶出度显著提高,相对生物利用度为185%.结论 采用纳米技术分散双嘧达莫后,所制备的片剂能够提高药物在家犬体内的生物利用度.

  10. Poly(DL-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate): synthesis, characterization, micellization behavior in aqueous solutions, and encapsulation of the hydrophobic drug dipyridamole.

    Karanikolopoulos, Nikos; Zamurovic, Miljana; Pitsikalis, Marinos; Hadjichristidis, Nikos


    We synthesized a series of well-defined poly(dl-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PDLLA-b-PDMAEMA) amphiphilic diblock copolymers by employing a three-step procedure: (a) ring-opening polymerization (ROP) of dl-lactide using n-decanol and stannous octoate, Sn(Oct)(2), as the initiating system, (b) reaction of the PDLLA hydroxyl end groups with bromoisobutyryl bromide, and (c) atom transfer radical polymerization, ATRP, of DMAEMA with the newly created bromoisobutyryl initiating site. The aggregation behavior of the prepared block copolymers was investigated by dynamic light scattering and zeta potential measurements at 25 degrees C in aqueous solutions of different pH values. The hydrophobic drug dipyridamole was efficiently incorporated into the copolymer aggregates in aqueous solutions of pH 7.40. High partition coefficient values were determined by fluorescence spectroscopy.

  11. Withholding or Continuing Beta-Blocker Treatment Before Dipyridamole Myocardial Perfusion Imaging for the Diagnosis of Coronary Artery Disease? a Randomized Clinical Trial

    Babak Fallahi


    Full Text Available Although it has been shown that acute beta-blocker administration may reduce the presence or severity of myocardial perfusion defects with dipyridamole stress, little information is available about the potential effect of chronic beta-blocker treatment on the sensitivity of dipyridamole myocardial perfusion imaging (DMPI.Methods As a randomized clinical trial, one hundred twenty patients (103 male and 17 female with angiographically confirmed CAD who were on long-term beta blocker therapy ([greater than or equal to]3 months enrolled in a randomized clinical trial study. The patients were allocated into two groups: Group A (n=60 in whom the beta-blocker agent was discontinued for 72h before DMPI and Group B (n=60 without discontinuation of beta-blockers prior to DMPI.ResultsNo significant difference was noted between the groups concerning age, sex, type of the injected radiotracer and number of involved coronary vessels. The mean rank of total perfusion scores for whole myocardium (irrespective of reversibility or irreversibility in group B was not significantly different from that of group A, (65.75 vs. 55.25, P=0.096. Regarding the only irreversible perfusion defects, the mean rank of perfusion score in group B was higher than that of group A for whole myocardium (72 vs. 49, P=0.0001; however, no difference was noted between two groups for only reversible perfusion defects (61.0 vs. 60.0, P=0.898. The overall sensitivity of DMPI for the diagnosis of CAD in group A (91.7% was not statistically different from group B (90%.ConclusionBeta-blocker withholding before DMPI did not generally affect the sensitivity of the test for the diagnostic purposes in our study. Thus, beta-blocker withdrawal for just the purpose of diagnostic imaging is not mandatory particularly when medication discontinuation may cause the patients to face increased risk of heart events.

  12. Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography

    Brown, K.A.; Rimmer, J.; Haisch, C. (Univ. of Vermont College of Medicine, Burlington (USA))


    The ability of noninvasive risk stratification using dipyridamole-thallium-201 (Tl-201) imaging and radionuclide ventriculography to predict perioperative and long-term cardiac events (myocardial infarction or cardiac death) was evaluated in 36 uremic diabetic and 29 nondiabetic candidates for renal allograft surgery. Of the 35 patients who underwent renal allograft surgery 8 +/- 7 months after the study, none had transient Tl-201 defects (although 13 had depressed left ventricular ejection fraction) and none developed perioperative cardiac events. During a mean follow-up of 23 +/- 11 months, 6 (9%) patients developed cardiac events. Logistic regression analysis was used to compare the predictive value of clinical data (including age, sex, diabetes, chest pain history, allograft recipient) and radionuclide data. Presence of transient Tl-201 defect and left ventricular ejection fraction were the only significant predictors of future cardiac events (p less than 0.01). No other patient variables, including diabetes or receiving a renal allograft, had either univariate or multivariate predictive value. All 3 patients with transient Tl-201 defects had cardiac events compared with only 3 of 62 (5%) patients without transient Tl-201 defect (p less than 0.0001). Mean left ventricular ejection fraction was lower in patients with cardiac events (44 +/- 13%) compared with patients without cardiac events (57 +/- 9%, p less than 0.005). Overall, 5 of 6 patients with cardiac events had either transient Tl-201 defects or depressed left ventricular ejection fraction. Dipyridamole-Tl-201 imaging and radionuclide ventriculography may be helpful in identifying uremic candidates for renal allograft surgery who are at low risk for perioperative and long-term cardiac events.

  13. Dipyridamole-dobutamine-stress-magnetic resonance imaging for the assessment of myocardial viability in patients with chronic coronary artery disease and comparison to positron emission tomography

    Kaiser, B


    The purpose of this study was to evaluate the diagnostic value of (infra-low-dose)dipyridamole-(low-dose)-dobutamine-stress-MRI (DDS-MRI) for the assessment of myocardial viability by comparing the results to those of positron emission tomography (PET). Multisectional baseline- and stress-CINE-MRI as well as (18F)-fluorodeoxyglucose (18F-FDG)and (13N)-ammonia-PET were performed in 8 patients with chronic coronary artery disease and left ventricular dysfunction. MRI data analysis included the quantitative assessment of enddiastolic wall thickness (EDWT) and systolic wall thickening (SWT) for both baseline and stress examination in a total of 864 myocardial segments (6 slices, 18 seg./slice). MRI- and PET-results were compared in 128 corresponding myocardial regions following a 16-regions-model covering the entire left ventricle from apex to base. MRI viability criterions were a mean regional EDWT > 5.5 mm or a mean regional stress-induced SWT > 1.5 mm. PET defined regional myocardial viability either by a norm...

  14. Clinical investigation of inhomogeneity of washout rate in dipyridamole stress thallium scintigraphy. Implication of new parameter for the indication of coronary intervention

    Arao, Masato; Setsuta, Koichi [Tokyo Metropolitan Komagome Hospital (Japan); Seino, Yoshihiko; Takano, Teruo


    The standard deviation of the washout rate in dipyridamole stress thallium-201 myocardial single photon emission computed tomography (SPECT) was correlated with the severity of coronary artery lesions and the viability of ischemic myocardium to provide a new quantitative parameter for judging indications for coronary intervention therapy. Dipyridamole stress thallium-201 SPECT was performed in 233 patients for differential diagnosis of angina pectoris during the 40 months beginning in October 1995, and 57 patients were investigated who underwent coronary angiography within 6 months of the SPECT. The washout rate standard deviation (WRSD) in 720 fractions in the bull's-eye view of the SPECT was determined. The conventional washout rate extent score (WRES) and washout rate severity score (WRSS) on the washout rate map were also determined. Based on the coronary angiography findings, patients were divided into 3 groups: zero-vessel group (zero-vessel disease, n=20), one-vessel group (one-vessel disease, n=18), and multivessel group (two- or three-vessel disease, n=19). The patients were also divided into 2 other groups: Int group (n=21), who underwent coronary intervention therapy, and Med group (n=36), in whom intervention therapy was not indicated. All 3 parameters, WRSD, WRES and WRSS, showed significant differences between the 3 groups, and more coronary arteries affected by coronary artery stenosis were associated with higher WRSD (zero-vessel group: 5.4{+-}1.5, one-vessel group: 7.0{+-}3.7, multivessel group 11.4{+-}6.7; p<0.001), WRES (3.3{+-}5.0, 15.5{+-}18.1, 23.0{+-}25.4; p<0.01), and WRSS (1.4{+-}2.8, 25.4{+-}40.2, 84.8{+-}114.5; p<0.01). WRSD (Med group: 5.9{+-}2.7, Int group: 11.3{+-}6.4; p<0.001), WRES (7.3{+-}12.0, 24.7{+-}24.9; p<0.01), and WRSS (9.9{+-}29.3, 82.9{+-}108.2; p<0.01) were all significantly higher in the Int group compared with the Med group. There were significant correlations between Gensini's score and WRSD (r=0.51, p=0

  15. Spray drying as a fast and simple technique for the preparation of extended release dipyridamole (DYP) microparticles in a fixed dose combination (FDC) product with aspirin.

    Hamishehkar, H; Valizadeh, H; Alasty, P; Monajjemzadeh, F


    Recent advances have proven that the combinational therapy of extended release dipyridamole (DYP) and fast release aspirin (ASP) can improve clinical indices of heart failure in several vascular disorders. Although pharmaceutical industries always supported fast, simple and cost saving techniques in their productions, there is no simple reported method available for this purpose. The aim of this study was to check the possibility of preparing a FDC product, containing individual dosage units of extended release DYP microparticles and fast release ASP, using the spray-drying technique as a practice compatible with pharmaceutical industries. Solid dispersions of DYP in different polymeric substances (ethyl cellulose, carnauba wax, and Eudragit PO 100), were prepared using the spray-drying method. The physicochemical properties and structure of the prepared microparticles were analyzed using different techniques, such as the particle size analyzer (PSA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X ray diffraction (XRD), and USP dissolution tester. ASP tablets were prepared individually and tested according to pharmacopeia. Results showed that prepared microparticles measured about 2.3 µm in size. Statistical analysis of the release data revealed that there is no significant difference in the mean release amount of the selected formulation compared to the innovative brand (Aggrenox®). Findings proposed a new formulation (F7) as an alternative to innovative brand and proved spray drying as a practice compatible with pharmaceutical industries and as a successful method for sustaining the DYP release rate from prepared microparticles in a FDC dosage form. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Phentolamine plus Ginkgo Dipyridamole Injection for Chronic Pulmonary Heart Disease%酚妥拉明联合银杏达莫治疗慢性肺源性心脏病疗效观察

    马继扬; 高健; 梁民勇; 陈继兴; 文启孝


    Objective: To observe the clinical effect of phentolamine combined with ginkgo dipyridamole injection in the treatment of chronic pulmonary heart disease with heart failure.Methods: A total of 90 patients were randomly divided into control group (n=45) and therapy group (n=45).Two groups were treated with medical treatment such as control infection, oxygentherapy, cardiotonic and diuresis.On the basis of the above therapy, the treatment group were added phentolamine 20 mg combined with ginkgo dipyridamole injection 25 mL with 10% Glucose 500 ml in intravenous drip, quotidie, 10 days for a course of treatment. Results: The therapeutic effect, results of blood gas analysis and blood rheology, and heart function in therapy group were better than the control group, with statistically significant difference (P<0.05). Conclusion: Phentolamine combined with ginkgo dipyridamole injection in treatment of chronic pulmonary heart disease with heart failure is effective and safe. It deserves to be popularized.%观察酚妥拉明联合银杏达莫对慢性肺源性心脏病心衰患者的疗效,为临床治疗提供依据.方法:将90例患者随机分为治疗组和对照组各45例.两组采用常规内科治疗如控制感染、氧疗、强心、利尿等,治疗组在上述治疗基础上加用酚妥拉明20mg+银杏达莫25 mL于10%葡萄糖注射液500mL中静脉滴注,1次/d,疗程均为10d.结果:治疗组的疗效、血气分析、血液流变学、功能的改善优于对照组,差异具有统计学意义(P<0.05).结论:酚妥拉明联合银杏达莫对慢性肺源性心脏病心衰患者具有良好的疗效及安全性,值得临床推广应用.

  17. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial

    Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim


    telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER......-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed...... of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically...

  18. Synthesis, characterization and molecular modelling of a novel dipyridamole supramolecule - X-ray structure, quantum mechanics and molecular dynamics study to comprehend the hydrogen bond structure-activity relationship

    Vepuri, Suresh B.; Devarajegowda, H. C.; Soliman, Mahmoud E.


    Hydrochloride salt formation for Active Pharmaceutical Ingredients (APIs) is the primary choice to impart aqueous solubility and to promote dissolution. Dipyridamole (DIP) is a cardiovascular drug which is practically insoluble in water. We discovered a new form of DIP called as dipyridamole hydrochloride trihydrate (DIPHT), which was prepared by an unusual method of reacting the DIP with hydrated hydrochloric acid (HCl) that was liberated in situ by the reaction of ferric chloride with water. The liberated HCl was consumed as reagent in situ by the scavenger (API) and was converted to a hydrochloride trihydrate. The product was characterized by FTIR, mass spectroscopy, PXRD and DSC. Supramolecular structure of this novel DIPHT was revealed by single crystal XRD. A sustained intramolecular hydrogen bond alliance was found in DIP and the DIPHT. Stability of this hydrogen bond was further evaluated by means of molecular modelling studies. We performed electron calculations using quantum mechanics (QM) on both the base and salt structures to compare their geometry and molecular orbital energy levels. Molecular Dynamics (MD) simulations were also conducted in explicit solvent models to provide more insights into the hydrogen bond strength and conformational preferences of the base and salt structure. Together with QM and MD, we were able to explain the influence of hydrogen bonds on proton uptake activity of DIP and stability of DIP and DIPHT. DIPHT which can dissolve faster than DIP in water may enhance the dissolution and bioavailability of the drug. As the current drug development research is shifting to repurpose the existing drugs in order to subside the untoward risks in new drug development, we believe that DIPHT with its intrinsic aqueous solubility could bring more application for DIP and generate interest within the pharmaceutical industry.

  19. Left ventricular function in response to dipyridamole stress: head-to-head comparison between {sup 82}Rubidium PET and {sup 99m}Tc-sestamibi SPECT ECG-gated myocardial perfusion imaging

    Giorgi, Maria Clementina; Meneghetti, Jose Claudio; Soares, Jose; Izaki, Marisa; Falcao, Andrea; Imada, Rodrigo; Chalela, William; Oliveira, Marco Antonio de; Nomura, Cesar [Department of Radiology and Nuclear Medicine and Molecular Imaging Service - Heart Institute of the University of Sao Paulo Medical School, Sao Paulo (Brazil); Verberne, Hein J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, P.O. Box 22700, Amsterdam (Netherlands)


    Myocardial perfusion imaging (MPI) with {sup 99m}Tc-sestamibi (sestamibi) SPECT and rubidium-82 ({sup 82}Rb) PET both allow for combined assessment of perfusion and left ventricular (LV) function. We sought to compare parameters of LV function obtained with both methods using a single dipyridamole stress dose. A group of 221 consecutive patients (65.2 ± 10.4 years, 52.9% male) underwent consecutive sestamibi and {sup 82}Rb MPI after a single dipyridamole stress dose. Sestamibi and {sup 82}Rb summed rest (SRS), stress (SSS) and difference (SDS) scores, and LV end-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were compared. Bland-Altman analysis showed that with increasing ESV and EDV the difference between the two perfusion tracers increased both at rest and post-stress. The mean difference in EDV and ESV between the two perfusion tracers at rest could both be independently explained by the {sup 82}Rb SDS and the sestamibi SRS. The combined models explained approximately 30% of the variation in these volumes between the two perfusion tracers (R{sup 2} = 0.261, p = 0.005; R{sup 2} = 0.296, p < 0.001, for EDV and ESV respectively). However, the mean difference in LVEF between sestamibi and {sup 82}Rb showed no significant trend post-stress (R{sup 2} = 0.001, p = 0.70) and only a modest linear increase with increasing LVEF values at rest (R{sup 2} = 0.032, p = 0.009). Differences in left ventricular volumes between sestamibi and {sup 82}Rb MPI increase with increasing volumes. However, these differences did only marginally affect LVEF between sestamibi and {sup 82}Rb. In clinical practice these results should be taken into account when comparing functional derived parameters between sestamibi and {sup 82}Rb MPI. (orig.)

  20. The efficacy of dipyridamole combined with narceine in the protection of internal arteriovenous fistula%潘生丁联用罂粟碱保护动静脉内瘘效果观察

    彭卫平; 钟观宝; 叶晓莲; 张青; 黄登鹏


    Objective To investigate an effective method for protection of arteriovenous fistula ( AVF ) in patients on maintenance hemodialysis.Methods 85 patients on maintenance hemodialysis who required surgery for arteriovenous fistula were randomly divided into dipyridamole and narceine group ( n =43 ) and aspirin group ( n =42 ).The incidence rates of vascular stenosis, occlusion of blood vessels, vascular ectasia, and vascular sclerosis were observed.Volume of blood flow to fistula,bleeding time after needle removal,dynamic venous pressure,and KT/V values?? were compared.Results In dipyridamole and narceine group,occlusion of blood vessels occurred in one patient ( 2.33% ) and vascular stenosis developed in 6 ( 13.95% ); whereas in the control group,occlusion of blood vessels occurred in 8 patients ( 19.05% ) and vascular stenosis developed in 15 ( 35.71% ),with a significant statistical difference ( P< 0.05 ).There were significant differences in volume of blood flow to fistula,bleeding time after needle removal,dynamic venous pressure,and KT/V ( P< 0.05 ).Conclusions Dipyridamole combined with narceine can effectively protect internal arteriovenous fistula and prolong its lifespan.%目的 探讨维持性血液透析患者动静脉内瘘(AVF)有效的保护方法.方法 85例维持性血液透析需行动静脉内瘘手术的患者随机分为2组,即潘生丁与罂粟碱联合治疗组(n=43),阿司匹林对照组(n=42),观察两组患者血管狭窄、血管闭塞、血管瘤样扩张、血管硬结的发生率及内瘘血流量、拔针后出血时间、动态静脉压、KT/V数值比较.结果 治疗组43例中出现闭塞1例,占2.33%,血管狭窄6例,占13.95%,对照组42例中出现闭塞8例,占19.05%,血管狭窄15例,占35.71%,两组比较有统计学意义(P<0.05);治疗组与对照组内瘘血流量、拔针后出血时间、动态静脉压、KT/V比较均有统计学意义(P< 0.05).结论 潘生丁联用罂粟碱可有效保护动

  1. Comparison of platelet clumping and complete blood count results with Sysmex XT-2000iV in feline blood sampled on EDTA or EDTA plus CTAD (citrate, theophylline, adenosine and dipyridamole).

    Granat, Fanny; Geffré, Anne; Braun, Jean-Pierre; Trumel, Catherine


    False thrombocytopenia may result from platelet aggregation, especially in feline ethylenediamine tetra-acetic acid (EDTA) blood specimens. Citrate, theophylline, adenosine and dipyridamole (CTAD) was added to 46 feline EDTA specimens to test its anti-aggregation action. Platelet aggregation was estimated from blood films and a complete blood count was performed with a Sysmex XT-2000iV analyser. Platelet aggregation score was >2 in 11/46 EDTA tubes and only in one EDTA+CTAD specimen. The platelet count was higher in all CTAD-supplemented tubes except one, medians measured by cytometry being 225.5 × 10(9)/l and 249.0 × 10(9)/l in EDTA and EDTA+CTAD, respectively (P = 0.007). Adding CTAD had statistically and analytically significant but moderate effects on other blood variables, the most intense variations being observed for reticulocytes (about 3% higher in EDTA specimens) and reticulocyte indexes. Addition of CTAD to EDTA when sampling feline blood is a useful option to reduce platelet clumping.

  2. Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block; Perfusao miocardica de estresse com dipiridamol por tomografia computadorizada em pacientes com bloqueio de ramo esquerdo

    Cabeda, Estevan Vieira; Rochitte, Carlos Eduardo; Nomura, Cesar Higa; Parga, Jose Rodrigues; Avila, Luiz Francisco Rodrigues; Falcao, Andrea Maria Gomes; Soares Junior, Jose [Instituto do Coracao (InCor), Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil)


    Background: Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB). Objective: To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. Methods: Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution's ethics committee. Results: The patients' mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001). Conclusion: The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB. (author)

  3. 东菱克栓酶联合银杏达莫注射液治疗突发性耳聋疗效观察%Batroxobin injection combined Ginkgo biloba extract and dipyridamole injection efficacy of treatment of sudden deafness



    Objective Summary Batroxobin injection combined Cinkgo biloba extract and dipyridamole injection efficacy of treatment of sudden deafness,Treatment of sudden deafness of effective drug. Method Selected 108 cases (120 ears) in patients with sudden deafness diagnosis, Randomly divided into treatment and control groups, The treatment for 2 weeks. Result Treatment group was 85% .Control group was 66% ,Two groups was highly significant difference ( P <0.05) ,No serious adverse reactions and complications. Conclusion Batroxobin injection combined Ginkgo biloba extract and dipyridamole injection assisted treatment of sudden deafness results were satisfactory.%目的 总结东菱克栓酶联合银杏达莫注射液治疗突发性耳聋的疗效,探讨治疗突发性耳聋的有效药物.方法 选择108例(120耳)突发性耳聋明确诊断患者,随机分成治疗组和对照组,两组疗程均为2周.结果 治疗组有效率85%,对照组有效率66%,两组比较有极显著性差异(P<0.05),未见严重的不良反应和并发症.结论 银杏达莫辅助治疗突发性耳聋疗效满意.

  4. Imaging the impact of cyclosporin A and dipyridamole on P-glycoprotein (ABCB1) function at the blood-brain barrier: A [(11)C]-N-desmethyl-loperamide PET study in nonhuman primates.

    Damont, Annelaure; Goutal, Sébastien; Auvity, Sylvain; Valette, Héric; Kuhnast, Bertrand; Saba, Wadad; Tournier, Nicolas


    Cyclosporin A (CsA) and dipyridamole (DPy) are potent inhibitors of the P-glycoprotein (P-gp; ABCB1) in vitro. Their efficacy at inhibiting P-gp at the blood-brain barrier (BBB) is difficult to predict. Efficient and readily available (i.e. marketed) P-gp inhibitors are needed as probes to investigate the role of P-gp at the human BBB. In this study, the P-gp inhibition potency at the BBB of therapeutic doses of CsA or DPy was evaluated in baboons using Positron Emission Tomography (PET) imaging with [(11)C]-N-desmethyl-loperamide ([(11)C]dLop), a radiolabeled P-gp substrate. The preparation of dLop as authentic standard and [(11)C]dLop as radiotracer were revisited so as to improve their production yields. [(11)C]dLop PET imaging was performed in the absence (n=3, baseline condition) and the presence of CsA (15mg/kg/h i.v., n=3). Three animals were injected with i.v. DPy at either 0.56 or 0.96 or 2mg/kg (n=1), corresponding to the usual, maximal and twice the maximal dose in patients, respectively, administered immediately before PET. [(11)C]dLop brain kinetics as well as [(11)C]dLop kinetics and radiometabolites in arterial plasma were measured to calculate [(11)C]dLop area-under the time-activity curve from 10 to 30min in the brain (AUCbrain) and in plasma (AUCplasma). [(11)C]dLop brain uptake was described by AUCR=AUCbrain/AUCplasma. CsA as well as DPy did not measurably influence [(11)C]dLop plasma kinetics and metabolism. Baseline AUCR (0.85±0.29) was significantly enhanced in the presence of CsA (AUCR=10.8±3.6). Injection of pharmacologic dose of DPy did not enhance [(11)C]dLop brain distribution with AUCR being 1.2, 0.9 and 1.1 after administration of 0.56, 0.96 and 2mg/kg DPy doses, respectively. We used [(11)C]dLop PET imaging in baboons, a relevant in vivo model of P-gp function at the BBB, to show the P-gp inhibition potency of therapeutic dose CsA. Despite in vitro P-gp inhibition potency, usual doses DPy are not likely to inhibit P-gp function at

  5. Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes

    Shaw, J.H.; Wolfe, R.R.


    We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC.

  6. Assessment of the injury and repair of cardiac myocyctes after reperfusion with stress 99mTc-MIBI dipyridamole myocardial imaging%99mTc-MIBI双嘧达莫负荷显像评估心肌细胞损伤和再灌注后的可修复性

    陈宪英; 张国旭; 王治国; 贾迎; 王影; 张彤


    目的研究犬陈旧性心肌梗死 (陈旧心梗 )损伤区心肌细胞损伤与修复的形态学变化与 99mTc-MIBI摄取量的关系.方法选择犬 12只,建立陈旧心梗模型, 5个月后取心脏 ,通过透射电镜( TEM)观察 99mTc-MIBI硝酸甘油介入和双嘧达莫负荷心肌显像缺损区和可逆性缺损区内心肌细胞的超微结构.结果硝酸甘油介入 99mTc-MIBI放射性分布缺损区无完整的心肌细胞; 99mTc-MIBI双嘧达莫负荷心肌显像可逆性缺损区,主要为低血流灌注的心肌细胞,心肌细胞部分线粒体肿胀、变形严重,基质密度下降、有灶状空化,线粒体空泡散在分布、少数连续分布,膜和嵴不完整;部分线粒体轻度变形,基质密度降低程度较轻,有点状空化,嵴排列不整齐或部分凋落.在近正常心肌一侧,多数心肌细胞的线粒体近似卵圆形,线粒体膜基本完整,基质密度轻度降低,嵴排列较整齐,偶见损伤较严重的线粒体.结论 99mTc-MIBI的心肌摄取量与细胞损伤的程度有关;在 99mTc-MIBI心肌显像可逆性缺损区,血流灌注改善后,大部分损伤的心肌细胞有修复的可能性.%Aim To study the relationship of 99mTc-MIBI uptake to the morphology of injury and repair of cardiac myocytes in the injured area of old myocardial infarction (OMI) in dogs. Methods Twelve dogs were divided into 2 groups of 6 dogs to undergo ligation of left anterior descending coronary artery (LAD) by 85% or 95% respectively so as to create OMI models. Five months after, dipyridamole and 99mTc-MIBI were injected intravenously so as to obtain myocardial tomography. One day after, nitroglycerin was given sublingually and then 99mTc-MIBI of the same dose was injected intravenously to obtain nitroglycerin intervention myocardial tomography. The reversible defect area, necrosis area, and normal area were identified by comparison of the stress dipyridamole myocardial imaging and the nitroglycerin intervention myocardial

  7. Clinical Evaluation of Aspirin and Sustained-release Dipyridamole in the Prevention and Treatment of Ischaemic Cerebrovascular Events After Acute Ischemic Stroke%阿司匹林联合缓释型双嘧达莫防治急性缺血性卒中后脑血管缺血事件的临床评价

    冯慧玲; 杨冠涛


    目的 评价阿司匹林联合缓释型双嘧达莫防治急性缺血性卒中后脑血管缺血事件的临床作用.方法 选择2009年2月-2012年1月清苑县人民医院收治的63例急性缺血性卒中患者作为研究对象,根据抗血小板治疗药物使用情况分为A组33例和B组30例,A组采用阿司匹林联合缓释型双嘧达莫治疗,B组仅采用阿司匹林治疗,比较两组对脑血管缺血事件的防治作用.结果 A、B两组治疗后的神经功能缺损评分均明显改善,以A组改善更为明显(P<0.05);随访6个月,A组脑血管缺血事件发生率为3.0%,B组为23.3%,组间差异有统计学意义(P<0.05);两组均无严重不良反应发生.结论 阿司匹林联合缓释型双嘧达莫防治急性缺血性卒中后脑血管缺血事件的临床作用显著,能明显改善患者的神经功能,减少脑血管缺血事件的发生,并且安全性好,是临床首选的药物治疗方案之一.%Objective To evaluate the clinical effect of aspirin and sustained - release dipyridamole in the prevention and treatment of ischaemic cerebrovascular events after acute ischemic stroke. Methods From February 2009 to January 2012, 63 patients with acute ischemic stroke in the People's Hospital of Qingyuan County were selected as the research objects. According to the usage of antiplatelet therapy, they were divided into group A (n= 33) and group B (n= 30). The patients in group A were treated with aspirin plus sustained — release dipyridamole, while the patients in group B were only treated with aspirin. The prevention and treatment effects in the two groups were compared. Results After the treatment, the neurological deficit scores of groups A and B were both significantly improved, but the score in group A was improved more significantly (P< 0.05). Six- month follow — up outcome showed that the incidence rates of ischaemic cerebrovascular event in groups A and B were 3.0% and 23.3% respectively, and the difference

  8. Effect of leflunomide combined with ginkgo leaf extract and dipyridamole injection on hypercoagulable state in patients with nephrotic syndrome%来氟米特联合银杏达莫对肾病综合征患者高凝状态的影响



    目的:分析来氟米特联合银杏达莫治疗肾病综合征( NS)的疗效,改善NS患者高凝状态。方法将90例NS患者随机分为2组,每组45例。对照组给予来氟米特治疗,观察组给予来氟米特联合银杏达莫治疗,治疗1个月;治疗前、后检测血液高凝状态指标,观察治疗效果。结果治疗后两组肾功能指标较治疗前均有所改善,但组间比较差异无统计学意义(P>0.05);治疗后观察组载脂蛋白B/载脂蛋白A-Ⅰ(ApoB/ApoA-Ⅰ)、血浆纤维蛋白原( FIB)、纤维蛋白原降解产物( FDP)低于治疗前及对照组,抗凝血酶Ⅲ( AT-Ⅲ)活性高于治疗前及对照组,差异有统计学意义(P0. 05);apolipoprotein B/apolipoprotein A-Ⅰ(ApoB/ApoA-Ⅰ),plasma fibrinogen (FIB),fibrinogen degradation products(FDP)of observation group after treatment were lower than before treatment and control group,antithrombinⅢ( AT-Ⅲ) activity were higher than before treatment and control group,the differences were significant(P<0. 05). Conclusion For NS patients,based on the treatment of leflunomide,treated with ginkgo leaf extract and dipyridamole injection can effective improve hypercoagulable state.

  9. Valor prognóstico da ecocardiografia sob estresse com dipiridamol em mulheres Valor pronóstico de la ecocardiografía bajo estrés con dipiridamol en mujeres Prognostic value of dipyridamole stress echocardiography in women

    Maria Celita de Almeida


    ,5%, negativa en 128 (87,1% e inconclusiva en 5 (3,4%. Eventos ocurrieron en 8 pacientes, 7 tenían EEDI positiva. Los otros 138 no tuvieron eventos. De esos, 128 tenían EEDI negativa. La sensibilidad, la especificidad, la precisión, los valores predictivos positivo y negativo del test frente a los eventos fueron respectivamente: 83%, 95%, 94%, 42% y 99%. La sobrevida libre de eventos para pacientes con EEDI negativa fue de 99,2%, comparada con 58% para EEDI positiva (p BACKGROUND: Stress echocardiography is an important diagnostic and prognostic tool in ischemic heart disease. OBJECTIVE: To evaluate the role of dipyridamole stress echocardiography (DSE in the investigation of myocardial ischemia in women and its ability to predict combined events (cardiovascular death, acute myocardial infarction [AMI], unstable angina, coronary artery bypass grafting [surgery or percutaneous intervention] at an average follow-up of 16 months. METHODS: A prospective study using the protocol of dipyridamole at 0.84 mg in 10 minutes, associated with atropine (0.25 mg/min up to 1.0 mg. RESULTS: This study evaluated 147 women. DSE was positive in 14 patients (9.5%, negative in 128 (87.1% and inconclusive in 5 (3.4%. Events occurred in 8 patients, 7 had positive DSE. The other 138 did not present any events. Our of these, 128 had negative DSE. The sensitivity, specificity, accuracy, the positive and negative predictive values of the test before the events were respectively: 83%, 95%, 94%, 42% and 99%. The event-free survival for patients with negative DSE was 99.2% compared with 58% for positive DSE (p < 0.001. Univariate analysis identified the DSE result, basal electrocardiogram (ECG, LV ejection fraction, dyslipidemia, wall motion score index at rest and peak, history of AMI, coronary artery bypass grafting, as prognostic predictors related to outcomes. The results of DSE and ECG remained significantly associated with outcomes in the multivariate analysis (p < 0.001. CONCLUSION: The baseline

  10. Structural and dynamic characterization of ultrafine fibers based on the poly-3-hydroxybutyrate-dipyridamole system

    Olkhov, A. A.; Karpova, S. G.; Staroverova, O. V.; Krutikova, A. A.; Orlov, N. A.; Kucherenko, E. L.; Iordanskii, A. L.


    The fibrous materials (the mats) based on poly-3-hydroxybutyrate (PHB) containing the drug, dipiridomole (DPD) were produced by electrospinning (ES). Thermophysical and dynamical properties of the single filaments and the mats were studied by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and probe electron paramagnetic resonance spectroscopy (EPR). The effect of annealing temperature on the structure and crystallinity of the fibers was examined. It was shown that the loading of DPD influences on both the melting enthalpy and the morphology of the fibers. Besides the analysis of EPR spectra revealed that there are two populations of spin-probes distributed in the rigid and nonrigid amorphous regions of the PHB fibers respectively. For all fibrous materials with different content of DPD (0-5%) the correlation between thermophysical (DSC) and dynamic data (EPR) was observed.

  11. Use of the oral platelet inhibitors dipyridamole and acetylsalicylic acid is associated with increased risk of fracture

    Vestergaard, Peter; Steinberg, Thomas H; Schwarz, P


    ). Clopidogrel is the most widely used, and in combination with acetylsalicylic acid it is the standard of care for acute coronary syndromes and percutaneous coronary interventions. However, the modes of action involve pathways that are involved in the metabolic activity in bone cells and pharmacologic...... modulation of these pathways may therefore have effects on bone. METHODS: In the current study, we assessed the association between platelet inhibitor use and fracture incidence in a population-based epidemiological study performed within the Danish population consisting of approximately 5.3million...... is not associated with increased fracture risk. CONCLUSIONS: Use of some oral platelet inhibitors is associated with increased risk of fractures, and more studies are warranted to determine the potential effect of platelet inhibitors on bone metabolism in vivo....

  12. A novel gastro-floating multiparticulate system for dipyridamole (DIP) based on a porous and low-density matrix core: in vitro and in vivo evaluation.

    Li, Zhao; Xu, Heming; Li, Shujuan; Li, Qijun; Zhang, Wenji; Ye, Tiantian; Yang, Xinggang; Pan, Weisan


    The study was aimed to develop a novel gastro-floating multiparticulate system based on a porous and low-density matrix core with excellent floatability. The gastro-floating pellets (GFP) were composed of a porous matrix core, a drug loaded layer (DIP and HPMC), a sub-coating layer (HPMC) and a retarding layer (Eudragit(®) NE 30D). The porous matrix cores were evaluated in specific. EC was chosen as the matrix membrane for its rigidity and minimal expansion to large extent. The porous matrix core was achieved by the complete release of the bulk water soluble excipient from the EC coated beads, and mannitol was selected as the optimal water soluble excipient. SEM photomicrographs confirmed the structure of porous matrix cores. The compositions of GFP were investigated and optimized by orthogonal array design. The optimized formulation could sustain the drug release for 12h and float on the dissolution medium for at least 12h without lag time to float. The pharmacokinetic study was conducted in beagle dogs, and the relative bioavailability of the test preparation was 193.11±3.43%. In conclusion, the novel gastro-floating pellets can be developed as a promising approach for the gastro-retentive drug delivery systems.

  13. Determination of terpene lactone in Ginkgo Folium Extract and Dipyridamole Injection from different manufacturers%不同厂家银杏达莫注射液中萜类内酯测定

    金英华; 何正有; 王艳峰; 安静; 姚洁; 李维; 邹昆


    目的 对3家企业生产的银杏达莫注射液中的萜类内酯进行定量测定,为进一步提高药品质量提供科学依据.方法 药品经前处理后采用HPLC-ELSD法进行分析,采用色谱柱Welch C18(250mm×4.6mm,5 μm);流动相甲醇-异丙醇-水(9:7.5:83.5);体积流量1 mL/min;柱温35℃;检测器条件气体体积流量3.0 L/min;漂移管温度105℃.结果 3家企业生产的银杏达莫注射液中均含有萜类内酯,所测样品中萜类内酯的质量浓度介于0.30 ~0.80 mg/mL之间.结论 本方法专属性强、分析准确、稳定、重复性好,可用于银杏达莫注射液中萜类内酯的定量测定.

  14. 银杏达莫注射液致过敏性休克1例%One patient with anaphylactic shock caused by Ginkgo leaf extract and dipyridamole injection

    胥丹; 丛英珍


    银杏达莫(Ginkgo leaf exteact and dipyidamole)注射液为复方制剂,含银杏总黄酮(Ginkgo flavonoids)和双嘧达莫(dipyidamole),适用于预防和治疗冠心病、血栓栓塞性疾病。本文报道1例静脉滴注银杏达莫注射液后发生过敏性休克的病例。

  15. Musical hallucinations induced by drugs.

    Tomar, Astha; Cheung, Gary


    Dipyridamole is an antiplatelet agent and a vasodilator which is increasingly being used for the secondary prevention of ischaemic stroke and transient ischemic attack, either alone or in combination with acetylsalicylic acid. We describe an 83-year-old woman who had developed musical hallucinations within days of initiating dipyridamole. Her psychiatric and neurological evaluation was otherwise unremarkable. After the discontinuation of dipyridamole the hallucinations ceased within a couple of days. To the best of our knowledge this is the first case of auditory hallucinations associated with dipyridamole reported in the literature.

  16. Clinical evaluation of iterative reconstruction (ordered-subset expectation maximization) in dynamic positron emission tomography: quantitative effects on kinetic modeling with N-13 ammonia in healthy subjects

    Hove, Jens D; Rasmussen, Rune; Freiberg, Jacob


    emission tomography (PET) studies from 20 normal volunteers at rest and during dipyridamole stimulation were analyzed. Image data were reconstructed with either FBP or OSEM. FBP- and OSEM-derived input functions and tissue curves were compared together with the myocardial blood flow and spillover values...... and OSEM flow values were observed with a flow underestimation of 45% (rest/dipyridamole) in the septum and of 5% (rest) and 15% (dipyridamole) in the lateral myocardial wall. CONCLUSIONS: OSEM reconstruction of myocardial perfusion images with N-13 ammonia and PET produces high-quality images for visual...

  17. Comparison of antiplatelet regimens in secondary stroke prevention

    Christiansen, Christine Benn; Pallisgaard, Jannik; Gerds, Thomas Alexander


    BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent...... were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus...... the combination of acetylsalicylic acid and dipyridamole were 1.02 (95% confidence interval [CI]: 0.89-1.17) for ischemic stroke and 1.06 (95% CI: 0.83-1.35) for bleeding. Adjusted HRs for acetylsalicylic acid versus the combination of acetylsalicylic acid and dipyridamole were 1.48 (95% CI: 1.31-1.67) for stroke...

  18. Rosuvastatin increases extracellular adenosine formation in humans in vivo: a new perspective on cardiovascular protection.

    Meijer, P; Oyen, W.J.G.; Dekker, D.; Broek, P.H.H. van den; Wouters, C.W.; Boerman, O.C.; Scheffer, G. J.; Smits, P; Rongen, G.A.P.J.M.


    OBJECTIVE: Statins may increase extracellular adenosine formation from adenosine monophosphate by enhancing ecto-5'-nucleotidase activity. This theory was tested in humans using dipyridamole-induced vasodilation as a read-out for local adenosine formation. Dipyridamole inhibits the transport of extracellular adenosine into the cytosol resulting in increased extracellular adenosine and subsequent vasodilation. In addition, we studied the effect of statin therapy in a forearm model of ischemia-...

  19. 双嘧达莫阿司匹林胃内漂浮胶囊的制备及犬体内外相关性研究%Studies on Preparation of Gastric Floating Capsules Loaded with Dipyridamole and Aspirin and in vitro-in vivo Correlation in Dogs

    张军; 平其能



  20. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial : a double-blind, active and placebo-controlled study

    Dienert, Hans-Christoph; Saccot, Ralph L.; Yusuft, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Renee H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P. L.; Chen, Sien-Tsong; Cunha, Luis; Dahlof, Bjorn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo


    Background The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist tel

  1. Effect of Ginkgo leaf extract/dipyridamole injection on venous thrombosis in rats and the possible mechanism%银杏达莫注射液抑制大鼠静脉血栓形成及作用机制探讨

    王巧云; 刘永云; 徐理华; 刘金苹; 李娜


    目的:研究银杏达莫注射液对大鼠静脉血栓形成的影响,并探讨其作用机制.方法:建立大鼠静脉血栓模型和血瘀模型,分别测定血栓重量、凝血时间参数、优球蛋白溶解时间(ELT)和血液流变学等指标.结果:在静脉血栓模型大鼠,银杏达莫注射液低、中、高剂量组(0.9,1.8,2.25 mL·kg-1)能明显降低静脉血栓重量(P<O.05或P<0.01),低、中剂量能明显缩短ELT,但低剂量显著延长活化部分凝血活酶时间、凝血酶原时间和凝血酶时间(P<0.05或P<O.01).在血瘀模型大鼠,银杏达莫注射液高剂量组(2.25 mL·kg-1)大鼠的全血黏度、血浆黏度、红细胞压积均显著低于模型大鼠(P<0.05或P<0.01).结论:在一定剂量下,银杏达莫注射液能够抑制静脉血栓的形成,其机制可能与改善血液流变学性质和增加纤溶作用等有关.

  2. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial : a double-blind, active and placebo-controlled study

    Dienert, Hans-Christoph; Saccot, Ralph L.; Yusuft, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Renee H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P. L.; Chen, Sien-Tsong; Cunha, Luis; Dahlof, Bjorn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo


    Background The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist

  3. Optimization of a floating osmotic pump system of dipyridamole using central composite design-response surface methodology%星点设计-效应面法优化双嘧达莫漂浮渗透泵给药系统

    张志宏; 唐歆; 彭博; 聂淑芳; 李想; 潘卫三


    本文设计了双嘧达莫气囊式漂浮渗透泵.采用中国药典(2005版)附录XD释放度测定法第三法装置同时评价制剂的体外释放和漂浮性能.以聚氧乙烯(PEO WSR303)用量(X1,mg)、NaCl用量(X2,mg)和致孔剂用量(PEG4000,X3,%)为自变量,自制处方溶出曲线与目标溶出曲线相比而得的相似因子(f2)为应变量,采用星点设计-效应面法优化系统.优化模型为 f2=-29.3+2.35X3-0.n3X1,2-0.046X2,+0.145X1X2(R=0.996),当包农增重8%~9%、X1:20~34、X2:30~57、X3:50时溶出曲线和目标溶出曲线相似,从优化模型可得致孔剂用量最小值为35.1%,所得优化模型在试验范围内预测效果良好.

  4. Decompression Mechanisms and Decompression Schedule Calculations.


    34 . , . . .. ".* , ... . .... . . . . .’ - .* . . .4 ’o . ffffffffffffffffffffffffffffffA - . . "- f . -. ft SECURITY CLASSIFICATION OF TIs PAUL i ben...5. Philp , R.B., P.B. Bennett, J.C. Andersen, G.N. Fields, B.A. McIntyre, I. Francey, and W. Briner. Effects of asprin and dipyridamole on platelet

  5. CLSM as quantitative method to determine the size of drug crystals in a solid dispersion

    de Waard, Hans; Hessels, Martin J T; Boon, Maarten; Sjollema, Klaas A; Hinrichs, Wouter L J; Eissens, Anko C; Frijlink, Henderik W


    PURPOSE: To test whether confocal laser scanning microscopy (CLSM) can be used as an analytical tool to determine the drug crystal size in a powder mixture or a crystalline solid dispersion. METHODS: Crystals of the autofluorescent drug dipyridamole were incorporated in a matrix of crystalline manni

  6. The role of cGMP hydrolysing phosphodiesterases 1 and 5 in cerebral artery dilatation

    Kruuse, Christina; Rybalkin, S D; Khurana, T S;


    -IBMX) and the phosphodiesterase 5 inhibitors zaprinast and dipyridamole induced dilatation of cerebral arteries. The dilatory response to 8-MM-IBMX was reduced by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 microM) and endothelial removal and restored by sodium nitroprusside (0.1 microM) pretreatment, indicating...

  7. Long-term use of antiplatelet drugs by stroke patients

    Ostergaard, Kamilla; Hallas, Jesper; Bak, Søren


    in a cohort of stroke patients discharged from a Danish neurology department. The antiplatelet drugs comprised acetylsalicylic acid (ASA), clopidogrel and dipyridamole (if combined with ASA use). Non-persistence was defined as failure to present a prescription for antiplatelet drugs within 180 days after...

  8. Chest pain with myocardial ischemia in a child: should we think about coronary slow flow phenomenon?

    Kocabaş, Abdullah; Kardelen, Fırat; Akçurin, Gayaz; Ertuğ, Halil


    The coronary slow flow phenomenon (CSFP) is an angiographic finding characterized by delayed opacification of epicardial coronary arteries in the absence of stenotic lesion. Herein, we present a 13-year-old boy with recurrent chest pain who was diagnosed with acute ST-segment elevation myocardial infarction associated with CSFP, which has not been reported previously in the pediatric age group. Coronary angiography revealed only the presence of slow flow in the left anterior descending (LAD) coronary artery. Myocardial perfusion scintigraphy revealed a reversible perfusion defect in the LAD territory, which regressed partially at rest and showed complete improvement after dipyridamole infusion. All the symptoms, electrocardiogram abnormalities and cardiac markers returned to normal after dipyridamole treatment during the follow-up. We conclude that CSFP should be kept in mind in the differential diagnosis of chest pain with myocardial ischemia in the pediatric age group.

  9. Decreased myocardial perfusion reserve in diabetic autonomic neuropathy

    Taskiran, Mustafa; Fritz-Hansen, Thomas; Rasmussen, Verner


    The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy are unknown. To investigate the effect of autonomic neuropathy on myocardial function, we performed dynamic contrast-enhanced magnetic resonance perfusion imaging during baseline...... conditions and after Dipyridamole-induced vasodilatation in nine type 1 diabetic patients with autonomic neuropathy (AN+), defined by cardiovascular tests, as well as in 10 type 1 diabetic patients without autonomic neuropathy (AN-) and 10 healthy control subjects. Baseline myocardial perfusion index (K...... blood pressure response to Dipyridamole and myocardial perfusion reserve index. We conclude that type 1 diabetic patients with autonomic neuropathy have a decreased myocardial perfusion reserve capacity when challenged with a vasodilatator, a finding that may in part be the pathophysiological substrate...

  10. Clinical trials in thrombosis: secondary prevention of myocardial infarction.

    Klimt, C R; Doub, P H; Doub, N H


    Numerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin, and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that anti-platelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

  11. Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

    Tobin, W O


    The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised \\'anti-coagulant\\' effects of dipyridamole in ischaemic CVD.

  12. Antitrombotisk behandling ved iskaemisk apopleksi og transitorisk cerebral iskaemi

    Overgaard, Karsten; Poulsen, Tina Svenstrup; Husted, Steen E


    includes anticoagulation in patients with cardioembolic stroke and antiplatelet agents aspirin possibly combined with dipyridamole or clopidogrel alone in patients with non-cardioembolic stroke. Other individual risks may modify this treatment regimen. Udgivelsesdato: 2007-Oct-1......In acute ischemic stroke and transient ischemic attack (TIA), aspirin is recommended to all patients (except immediately following thrombolysis). Heparin and anticoagulant therapy using vitamin K antagonists should be avoided in the acute phase. Secondary preventive antithrombotic treatment...

  13. Effect of {beta}{sub 1} adrenergic receptor blockade on myocardial blood flow and vasodilatory capacity

    Boettcher, M.; Czernin, J.; Sun, K. [Univ. of California, Los Angeles, CA (United States)] [and others


    The {beta}{sub 1} receptor blockade reduces cardiac work and may thereby lower myocardial blood flow (MBF) at rest. The effect of {beta}{sub 1} receptor blockade on hyperemic MBF is unknown. To evaluate the effect of selective {beta}{sub 1} receptor blockade on MBF at rest and during dipyridamole induced hyperemia, 10 healthy volunteers (8 men, 2 women, mean age 24 {+-} 5 yr) were studied using {sup 13}N-ammonia PET (two-compartment model) under control conditions and again during metoprolol (50 mg orally 12 hr and 1 hr before the study). The resting rate pressure product (6628 {+-} 504 versus 5225 {+-} 807) and heart rate (63 {+-} 6-54 {plus_minus} 5 bpm) declined during metoprolol (p < 0.05). Similarly, heart rate and rate pressure product declined from the baseline dipyridamole study to dipyridamole plus metoprolol (p < 0.05). Resting MBF declined in proportion to cardiac work by approximately 20% from 0.61 {+-} 0.09-0.51 {+-} 0.10 ml/g/min (p < 0.05). In contrast, hyperemic MBF increased when metoprolol was added to dipyridamole (1.86 {plus_minus} 0.27 {+-} 0.45 ml/g/min; p<0.05). The decrease in resting MBF together with the increase in hyperemic MBF resulted in a significant increase in the myocardial flow reserve during metoprolol (3.14 {+-} 0.80-4.61 {+-} 0.68; p<0.01). The {beta}{sub 1} receptor blockade increases coronary vasodilatory capacity and myocardial flow reserve. However, the mechanisms accounting for this finding remain uncertain. 32 refs., 2 figs., 2 tabs.

  14. Técnicas de caracterização para investigar interações no nível molecular em filmes de Langmuir e Langmuir-Blodgett (LB) Characterization techniques to investigate molecular-level interactions in Langmuir and Langmuir-Blodgett (LB) films


    This paper discusses fundamental concepts for the characterization of Langmuir monolayers and Langmuir-Blodgett (LB) films, with emphasis on investigations of material properties at the molecular level. By way of illustration, results for phospholipid monolayers interacting with the drug dipyridamole are highlighted. These results were obtained with several techniques, including in situ grazing incidence X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, fluorescence microscop...

  15. A comparison of the cardioprotective effects of calcium antagonists from different classes upon ischaemic damage in the guinea-pig working heart.

    Hugtenburg, J G; Mathy, M J; Veldsema-Currie, R D; Boddeke, H W; Beckeringh, J J; van Zwieten, P A


    The cardioprotective effects of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and the coronary vasodilator dipyridamole were evaluated in the guinea-pig working heart with respect to cardiac function and high energy phosphate content after 45 min of global ischaemia and 25 min of reperfusion. All drugs, with the exception of dipyridamole, induced a negative inotropic effect, which resulted in a decrease of the aortic pressure (AoP), of its first derivative dAoP/dt and the cardiac output. To compare the anti-ischaemic effect of the calcium antagonists, concentrations were selected that reduced the dAoP/dt by 10% (EC10) and 30% (EC30), respectively. With the exception of nifedipine at the EC10 and bepridil and CERM 11956 at the EC30, perfusion with the calcium antagonists and dipyridamole (3 mumol/l) improved the recovery of contractile function after global ischaemia and reperfusion to a value between 60 and 80% of the controls in normoxic hearts. Pretreatment with nifedipine, verapamil, diltiazem, lidoflazine and mioflazine, but not with bepridil, CERM 11956 and dipyridamole led to slightly increased ATP levels in ischaemic hearts as compared to the control value in ischaemic hearts. After subsequent reperfusion for 25 min, for all drugs, ATP levels were further enhanced to 50% of the level in normoxic hearts; phosphocreatine levels reached normoxic values. In particular at the EC30, the effects of calcium antagonists on cardiac function varied in accordance with their known pharmacological and physiological profile. However, there appeared to exist no direct relationship between their beneficial effects on contractile activity and those on the levels of high energy phosphates after ischaemia and reperfusion.

  16. The influence of calcium antagonists on the adenine nucleotide metabolism in the guinea-pig working heart during ischaemia and reperfusion.

    Hugtenburg, J G; Mathy, M J; de Haan, N; Beckeringh, J J; van Zwieten, P A


    With the aim of gaining more insight into the metabolism of adenine nucleotides in working normoxic guinea-pigs and in hearts subjected to 45 min of global ischaemia and subsequent reperfusion for 25 min, we evaluated the effect of nifedipine, verapamil, diltiazem, bepridil, CERM 11956, lidoflazine, mioflazine and dipyridamole on the adenine nucleotide catabolite levels in these hearts. The drugs were applied at the concentrations that reduced the aortic dP/dt of normoxic working hearts by 10% (EC10) and 30% (EC30). In globally ischaemic hearts there was a large accumulation of adenine nucleotide catabolites. Inosine proved to be the major catabolite. The drugs, with the exception of bepridil, CERM 11956 and dipyridamole (3 mumol/l), decreased the accumulation of catabolites. In hearts treated with mioflazine and dipyridamole the amount of adenosine increased. A deficit in the balance between adenine nucleotides and catabolites indicated that in globally ischaemic hearts there was a large accumulation of inosine monophosphate. Indeed, a substantial amount of inosine monophosphate was determined in untreated hearts, and hearts treated with nifedipine (EC30) and mioflazine (EC10). During the first 5 min of reperfusion a large quantity of catabolites, mainly inosine, was washed out. During 20 min of subsequent reperfusion in untreated hearts and in nifedipine and mioflazine-treated hearts the efflux of catabolites returned to normoxic values. Similar to the effect in ischaemic hearts, in early perfusate from lidoflazine, mioflazine and dipyridamole-treated hearts the adenosine/inosine ratio was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Effect of streptozotocin-induced diabetes on myocardial blood flow reserve assessed by myocardial contrast echocardiography in rats

    Weytjens Caroline; Garbar Christian; Degaillier Céline; Hernot Sophie; Droogmans Steven; Cosyns Bernard; Roosens Bram; Schoors Danny; Lahoutte Tony; Franken Philippe R; Van Camp Guy


    Abstract The role of structural and functional abnormalities of small vessels in diabetes cardiomyopathy remains unclear. Myocardial contrast echocardiography allows the quantification of myocardial blood flow at rest and during dipyridamole infusion. The aim of the study was to determine the myocardial blood flow reserve in normal rats compared with Streptozotocin-induced diabetic rats using contrast echocardiography. Methods We prospectively studied 40 Wistar rats. Diabetes was induced by ...

  18. Novel pyrimidopyrimidine derivatives for inhibition of cellular proliferation and motility induced by h-prune in breast cancer.

    Virgilio, Antonella; Spano, Daniela; Esposito, Veronica; Di Dato, Valeria; Citarella, Giuseppe; Marino, Natascia; Maffia, Veronica; De Martino, Daniela; De Antonellis, Pasqualino; Galeone, Aldo; Zollo, Massimo


    The human (h)-prune protein is a member of the DHH protein superfamily and it has a cAMP phosphodiesterase activity. Its overexpression in breast, colorectal and gastric cancers correlates with depth of invasion and a high degree of lymph-node metastasis. One mechanism by which h-prune stimulates cell motility and metastasis processes is through its phosphodiesterase activity, which can be suppressed by dipyridamole, a pyrimido[5,4-d]pyrimidine analogue. To obtain new and more potent agents that have high specificity towards inhibition of this h-prune activity, we followed structure-activity-relationship methodologies starting from dipyridamole and synthesised eight new pyrimido-pyrimidine derivatives. We analysed these newly generated compounds for specificity towards h-prune activities in vitro in cellular models using scintillation proximity assay for cAMP-PDE activity, cell index in cell proliferation assays and transwell methodology for two-dimensional cell migration in a top-down strategy of selection. Our findings show that two pyrimido[5,4-d]pyrimidine compounds are more effective than dipyridamole in two highly metastatic cellular models of breast cancer in vitro. Future studies will assess their therapeutic effectiveness against breast and other cancers where there is over-expression of h-prune, and in ad-hoc, proof of concept, animal models.

  19. Quantification of left ventricular dilatation in myocardial perfusion scintigraphy

    Gonzalez, Mauren B. Azambuja, E-mail:, E-mail: [Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil). Clinica Medica. Programa de Pos-Graduacao em Medicina e Ciencias da Saude; Azambuja, Roberto Alves [Hospital Sao Vicente de Paulo, Passo Fundo, RS (Brazil); Bodanese, Luiz Carlos [Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil). Hospital Sao Lucas. Serv. de Cardiologia


    Background: the rate of transient dilatation can be determined by exercise testing or pharmacological stress test. It is unknown whether the type of stress has an impact on average transient dilatation index values. Objective: to compare average transient dilation index values in 99mTc-sestamibi scintigraphy in patients undergoing treadmill stress test, versus dipyridamole stress test. The secondary purpose was to evaluate the impact on the average index value by demographic characteristics, risk factors for coronary artery disease and severity of ischemia. Methods: the cross-sectional study included 200 patients between 40 and 70 years old, with or without risk factors for ischemic heart disease, with or without a previous diagnosis of ischemic heart disease. The separation between groups was sequential. The software 4D-MSPECT calculated the transient dilatation index and provided a scoring system for perfusion analysis. Results: the average transient dilation index value of the group undergoing exercise stress test was 1.06 ({+-}0.23). For the group undergoing the dipyridamole stress test, it was 1.10 ({+-}0.22); (p = 0.200). There was no association between the type of stress and the average transient dilatation index values. An association was found between the average index values and age only for those patients from the exercise test group (p = 0.009). Conclusion: the results of our study demonstrate that the transient dilation index does not differ when patients undergo exercise stress test on a treadmill or pharmacological stress by dipyridamole. (author)

  20. Technetium-99m sestamibi single-photon emission tomography detects subclinical myocardial perfusion abnormalities in patients with systemic lupus erythematosus

    Schillaci, O. [Nuclear Medicine, University of l`Aquila (Italy); Lagana, B.; Gentile, R.; Tubani, L.; Baratta, L. [Department of Clinical Medicine, University ``La Sapienza``, Rome (Italy); Danieli, R.; Scopinaro, F. [Section of Nuclear Medicine, Department of Experimental Medicine and Pathology, University ``La Sapienza``, Rome (Italy)


    In patients with systemic lupus erythematosus, involvement of the cardiovascular system is the third leading cause of death. However, although autopsy studies have demonstrated a high incidence of abnormalities in both the myocardium and coronary vessels, clinical manifestations have been reported in only a small percentage of cases. The aim of this study was to evaluate myocardial perfusion in asymptomatic lupus patients using technetium-99m sestamibi single-photon emission tomography (SPET). Twenty-eight patients without overt cardiac involvement and risk factors were studied with {sup 99m}Tc-sestamibi SPET at rest and after dipyridamole infusion. Perfusion abnormalities were detected in 18 cases: six had persistent defects, three had reversible defects, seven had both persistent and reversible defects, and two showed rest defects which normalized on dipyridamole images (``reverse redistribution pattern``). Coronary angiography was performed in eight patients with positive {sup 99m}Tc-sestamibi SPET, and showed normal epicardial vessels in all the cases. These results indicate that {sup 99m}Tc-sestamibi SPET reveals a high prevalence (18 out of 28 patients in this study, i.e. 64%) of myocardial perfusion abnormalities in asymptomatic lupus patients, probably due to the primary immunological damage of this autoimmune disease. In conclusion, rest/dipyridamole {sup 99m}Tc-sestamibi SPET can be a useful non-invasive method to identify subclinical myocardial involvement in systemic lupus erythematosus, and patients potentially at risk of later cardiac events. (orig.) With 2 figs., 2 tabs., 21 refs.

  1. High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva.

    Cappato, Serena; Tonachini, Laura; Giacopelli, Francesca; Tirone, Mario; Galietta, Luis J V; Sormani, Martina; Giovenzana, Anna; Spinelli, Antonello E; Canciani, Barbara; Brunelli, Silvia; Ravazzolo, Roberto; Bocciardi, Renata


    The ACVR1 gene encodes a type I receptor of bone morphogenetic proteins (BMPs). Activating mutations in ACVR1 are responsible for fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by congenital toe malformation and progressive heterotopic endochondral ossification leading to severe and cumulative disability. Until now, no therapy has been available to prevent soft-tissue swelling (flare-ups) that trigger the ossification process. With the aim of finding a new therapeutic strategy for FOP, we developed a high-throughput screening (HTS) assay to identify inhibitors of ACVR1 gene expression among drugs already approved for the therapy of other diseases. The screening, based on an ACVR1 promoter assay, was followed by an in vitro and in vivo test to validate and characterize candidate molecules. Among compounds that modulate the ACVR1 promoter activity, we selected the one showing the highest inhibitory effect, dipyridamole, a drug that is currently used as a platelet anti-aggregant. The inhibitory effect was detectable on ACVR1 gene expression, on the whole Smad-dependent BMP signaling pathway, and on chondrogenic and osteogenic differentiation processes by in vitro cellular assays. Moreover, dipyridamole reduced the process of heterotopic bone formation in vivo Our drug repositioning strategy has led to the identification of dipyridamole as a possible therapeutic tool for the treatment of FOP. Furthermore, our study has also defined a pipeline of assays that will be useful for the evaluation of other pharmacological inhibitors of heterotopic ossification.

  2. Determinants of the response of left ventricular ejection fraction to vasodilator stress in electrocardiographically gated {sup 82}rubidium myocardial perfusion PET

    Brown, Tracy L.Y.; Merrill, Jennifer; Bengel, Frank M. [Johns Hopkins University, Department of Radiology and Radiological Sciences, Division of Nuclear Medicine, Baltimore, MD (United States); Volokh, Lana [GE Healthcare, Haifa (Israel)


    Myocardial perfusion imaging with {sup 82}Rb PET allows for ECG-gated studies to be obtained early after radiotracer injection, capturing ventricular function close to peak pharmacologic action of dipyridamole. This is different from gated SPECT and may potentially provide additional diagnostic information. We sought to identify potential correlates of the PET-derived ejection fraction response to vasodilator stress. One hundred ten consecutive patients undergoing {sup 82}Rb PET myocardial perfusion imaging during evaluation for coronary artery disease were included. Using a GE Discovery STRx PET-CT scanner, ECG-gated images (eight bins) were obtained at rest and 4 min after dipyridamole infusion, 90 s after infusion of 1,480-2,220 MBq of {sup 82}Rb. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were determined using a five-point scoring system and 20-segment model. Ejection fraction was calculated using automated QGS software. Significant reversibility (SDS {>=} 4) was found in 23 patients (21%). Mean LVEF in all patients was 47 {+-} 13% at rest and 53 {+-} 13% during dipyridamole. LVEF increased in 89 patients, and decreased in 17 patients during vasodilation. The change in LVEF was inversely correlated with SDS (r = -0.26; p = 0.007). Additionally, it was inversely correlated with resting LVEF (r = -0.20; p = 0.03) and SSS (r = -0.25; p = 0.009). No significant correlations were observed with SRS, heart rate, blood pressure, age, hypertension, hypercholesterolemia, or pretest likelihood of disease. At multivariate regression analysis, SDS was an independent predictor of the change in LVEF. Gated {sup 82}Rb PET during pharmacologic stress allows for assessment of the functional response to vasodilation. The magnitude of LVEF increase is determined by stress perfusion/reversible perfusion defects. Functional response to hyperemia may thus be incorporated in future evaluations of diagnostic and prognostic algorithms based on {sup 82}Rb PET. (orig.)

  3. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)


    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

  4. Design, synthesis, and evaluation of 2-diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein conjugate (8MDP-fluor), as a novel equilibrative nucleoside transporter probe.

    Lin, Wenwei; Buolamwini, John K


    Nucleoside transporters are integral membrane glycoproteins that play critical roles in physiological nucleoside and nucleobase fluxes, and influence the efficacy of many nucleoside chemotherapy drugs. Fluorescent reporter ligands/substrates have been shown to be useful in the analysis of nucleoside transporter (NT) protein expression and discovery of new NT inhibitors. In this study, we have developed a novel dipyridamole (DP)-based equilibrative nucleoside transporter 1 (ENT1) fluorescent probe. The potent ENT1 and ENT2 inhibitor analogue of dipyridamole, 2,6-bis(diethanolamino)-4,8-diheptamethyleneiminopyrimido[5,4-d]pyrimidine (4, 8MDP), was modified to replace one β-hydroxyethyl group of the amino substituent at the 2-position with a β-aminoethyl group and then conjugated through the amino group to 6-(fluorescein-5-carboxamido)hexanoyl moiety to obtain a new fluorescent molecule, 2-diethanolamino-4,8-diheptamethyleneimino-2-(N-aminoethyl-N-ethanolamino)-6-(N,N-diethanolamino)pyrimido[5,4-d]pyrimidine-fluorescein conjugate, designated 8MDP-fluorescein (8MDP-fluor, 6). The binding affinities of 8MDP-fluor at ENT1 and ENT2 are reflected by the uridine uptake inhibitory K(i) values of 52.1 nM and 285 nM, respectively. 8MDP-fluor was successfully demonstrated to be a flow cytometric probe for ENT1 comparable to the nitrobenzylmercaptopurine riboside (NBMPR) analogue ENT1 fluorescent probe SAENTA-X8-fluorescein (SAENTA-fluor, 1). This is the first reported dipyridamole-based ENT1 fluorescent probe, which adds a novel tool for probing ENT1, and possibly ENT2.

  5. Validation of (1- sup 11 C)acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium

    Armbrecht, J.J.; Buxton, D.B.; Schelbert, H.R. (Univ. of California, Los Angeles (USA))


    Extraction and clearance kinetics of (1-11C)acetate were examined in 65 experiments in 30 open-chest dogs. Twenty-nine studies were performed at control, 13 during ischemia, eight after reperfusion, 13 during dipyridamole-induced hyperemia, and two during alteration of cardiac workload. (1-11C)acetate was injected directly into the left anterior descending coronary artery, and myocardial tissue-time activity curves were recorded with a gamma probe. The single-pass extraction fraction averaged 64.2 +/- 9.7% in control, 65.3 +/- 9.1% in ischemia, 70.0 +/- 4.4% in reperfusion, and 46.5 +/- 7.4% in dipyridamole-induced hyperemia groups. 11C clearance was biexponential in all cases. The rate constant k1 for the first rapid clearance phase correlated closely with myocardial oxygen consumption (r = 0.94) in control, ischemia, reperfusion, and dipyridamole-induced hyperemia groups. Monoexponential fitting of only the first linear part of the clearance curve yielded the rate constant kmono, which also correlated with myocardial oxygen consumption (r = 0.96). Arterial lactate concentrations and the amount of free fatty acid oxygen equivalents consumed by the myocardium were shown to have a small but statistically significant impact on the relation between (1-11C)acetate clearance rate constants and myocardial oxygen consumption. The fraction of 14CO2 activity contributing to overall 14C activity leaving the myocardium after simultaneous injection of (1-14C)acetate (n = 24) was relatively high in all cases , indicating that externally measured 11C clearance corresponds to CO2 production and thus to tricarboxylic acid cycle activity. In conclusion, the results validate the use of (1-11C)acetate as a tracer of oxidative myocardial metabolism for use with positron emission tomography.

  6. Prevalence of Ex Vivo High On-treatment Platelet Reactivity on Antiplatelet Therapy after Transient Ischemic Attack or Ischemic Stroke on the PFA-100(®) and VerifyNow(®).

    Kinsella, Justin A


    BACKGROUND: The prevalence of ex vivo high on-treatment platelet reactivity (HTPR) to commonly prescribed antiplatelet regimens after transient ischemic attack (TIA) or ischemic stroke is uncertain. METHODS: Platelet function inhibition was simultaneously assessed with modified light transmission aggregometry (VerifyNow; Accumetrics Inc, San Diego, CA) and with a moderately high shear stress platelet function analyzer (PFA-100; Siemens Medical Solutions USA, Inc, Malvern, PA) in a pilot, cross-sectional study of TIA or ischemic stroke patients. Patients were assessed on aspirin-dipyridamole combination therapy (n = 51) or clopidogrel monotherapy (n = 25). RESULTS: On the VerifyNow, HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole combination therapy (≥550 aspirin reaction units on the aspirin cartridge). Eleven of 25 (44%) patients had HTPR on clopidogrel (≥194 P2Y12 reaction units on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin-dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI) cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both regimens (P < .001). CONCLUSIONS: The prevalence of ex vivo antiplatelet HTPR after TIA or ischemic stroke is markedly influenced by the method used to assess platelet reactivity. The PFA-100 C-ADP cartridge is not sensitive at detecting the antiplatelet effects of clopidogrel ex vivo. Larger prospective studies with the VerifyNow and with the PFA-100 C-EPI and recently released Innovance PFA P2Y cartridges (Siemens Medical Solutions USA, Inc) in addition to newer tests of platelet function are warranted to assess whether platelet function monitoring predicts clinical outcome in ischemic cerebrovascular disease.

  7. Blood oxygen level-dependent (BOLD) MRI: A novel technique for the assessment of myocardial ischemia as identified by nuclear imaging SPECT.

    Egred, M; Waiter, G D; Redpath, T W; Semple, S K I; Al-Mohammad, A; Walton, S


    The different levels of deoxyhemoglobin in the ischemic myocardium, induced by stressors such as dipyridamole, can be detected by blood oxygen level-dependent (BOLD) MRI and may be used to diagnose myocardial ischemia. The aim of this study was to assess the signal change in the myocardium on BOLD MRI as well as wall thickening between rest and dipyridamole stress images in ischemic and non-ischemic myocardium as identified on SPECT imaging. Twelve patients with stress-induced myocardial ischemia on SPECT underwent rest and dipyridamole stress MRI using a double breath-hold, T2()-weighted, ECG-gated sequence to produce BOLD contrast images as well as cine-MRI for wall thickening assessment in 10 of the 12 patients. Signal change on BOLD MRI and wall thickening were compared between rest and stress images in ischemic and non-ischemic myocardial segments as identified on SPECT. In each patient, two MRI slices containing 16 segments per slice were analysed. In total, there were 384 segments for BOLD analysis and 320 for wall thickening. For BOLD signal 137 segments correlated to segments with reversible ischemia on SPECT and 247 to normal segments, while for wall thickening 112 segments correlated to segments with reversible ischemia and 208 to normal segments. The average BOLD MRI signal intensity change was -13.8 (+/-16.3)% in the ischemic segments compared to -10.3 (+/-14.7)% in the non-ischemic segments (p=0.05). The average wall thickening was 6.4 (+/-3.4) mm in the ischemic segments compared to 8.7 (+/-3.8) mm in the non-ischemic segments (p<0.0001). Stress-induced ischemic myocardium has a different signal change and wall thickening than non-ischemic myocardium and may be differentiated on BOLD MRI. Larger studies are needed to define a threshold for detection and to determine the sensitivity and specificity of this technique.

  8. Evidence of a cold immunoglobulin M autoantibody against 78-kD platelet glycoprotein in a case of EDTA-dependent pseudothrombocytopenia.

    De Caterina, M; Fratellanza, G; Grimaldi, E; Varriale, V; Scopacasa, F; Di Maro, G; Formisano, S


    Pseudothrombocytopenia is a phenomenon in which the electronic count shows spuriously low platelet counts in subjects with normal platelet levels. The mechanism of anticoagulant-dependent pseudothrombocytopenia appears to involve cold reactive agglutinins against platelet antigens. The authors report a case of EDTA-dependent pseudothrombocytopenia with evidence of a cold immunoglobulin M antibody against 78-kD platelet membrane glycoprotein (GP). Cell counts were performed by Coulter Counter S-Plus VI (Coulter, Hialeah, FL) in the following anticoagulants: EDTA, Na-citrate, and citrate-theophylline-adenosine-dipyridamole. Anti-platelet antibodies and platelet membrane GP antigens were assayed by an immunofluorescence technique as described by Van dem Borne in 1978. An immunoglobulin M/lambda anti-platelet antibody was found to react in serum as well as in plasma EDTA at room temperature, but not at 37 degrees C. This antibody appeared to be directed against GP78 membrane antigen because this antigen was not detectable by immunofluorescence in platelets collected in EDTA and Na-citrate anticoagulant, whereas a fluorescence signal was revealed in platelets collected in citrate-theophylline-adenosine-dipyridamole. This evidence was confirmed by platelet clumping inhibition tests in which target platelets were pretreated with anti-GP monoclonal antibodies. Clumping in the presence of pseudothrombocytopenia serum was inhibited by anti-GP78kD and anti-GPIIb/IIIa but not by anti-Ib. In this case, GP78 appears to be involved in platelet clumping, together with IIb/IIIa complex. The partial inhibition of the phenomenon observed in citrate-theophylline-adenosine-dipyridamole is probably related to a lower expression of the membrane antigens in platelets collected in this anticoagulant.

  9. Extra cardiac activity detected on myocardial perfusion scintigraphy after intra-arterial injection of 99mTc-MIBI

    Afzelius, Pia; Henriksen, Jens H


    , prolongation of the study and interference of the extra cardiac activity with the cardiac image reconstructions. Whole-body scintigraphy disclosed an arterial flow distribution of activity to skeletal muscles in left shoulder and upper limb. CONCLUSION: Accidentally injected radiotracer retrogradely...... (dipyridamol) imaging and followed by rest imaging day 2 was performed. RESULTS: On day 2, when rest perfusion scintigraphy was carried out, extra cardiac activity was present in the left part of thorax and in the left upper extremity resulting in reduced accumulation of 99mTc-MIBI in cardiac tissue...... into the arterial system resulted in an unusual extra cardiac activity interfering with later image processing....

  10. Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors

    Thastrup, Ole; Knudsen, J B; Lemmich, J;


    Certain esters of dihydropyranocoumarin and dihydrofuranocoumarin alcohols have previously been shown to inhibit the cAMP-phosphodiesterase from bovine heart. We now report that these naturally occurring coumarins inhibit the high affinity (Km = 1.1 microM) cAMP-phosphodiesterase from human...... platelets with activities that closely correlate with those obtained using phosphodiesterase from bovine heart tissue. Additionally the coumarins inhibit the aggregation of human platelets induced with ADP, adrenaline and collagen with activities comparable to those of dipyridamole. A lack of significant...

  11. Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

    Fritz-Hansen, T; Rostrup, Egill; Søndergaard, Lise


    The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole......-induced vasodilation in 10 healthy volunteers and in 10 patients with ischemic heart disease. Ki increased by a factor of 2.5+/-1.2 (mean +/- SD) from 55+/-16 ml 100 g(-1)min(-1) at rest to 136+/-46 ml 100 g(-1)min(-1) (P

  12. Quantification of MRI measured myocardial perfusion reserve in healthy humans: a comparison with positron emission tomography

    Fritz-Hansen, Thomas; Hove, Jens D; Kofoed, Klaus F


    PURPOSE: To validate a noninvasive quantitative MRI technique, the K(i) perfusion method, for myocardial perfusion in humans using (13)N-ammonia PET as a reference method. MATERIALS AND METHODS: Ten healthy males (64 +/- 8 years) were examined with combined PET and MRI perfusion imaging at rest...... and during stress induced by dipyridamole in order to determine the myocardial perfusion reserve. Myocardial and blood time concentration curves obtained by Gd-DTPA-enhanced MRI and (13)N-ammonia PET were fitted by a two-compartment perfusion model. RESULTS: Mean perfusion values (+/-SD) derived from the MRI...... as a quantitative marker for myocardial perfusion in healthy humans....

  13. SPECT Myocardial Blood Flow Quantitation Concludes Equivocal Myocardial Perfusion SPECT Studies to Increase Diagnostic Benefits.

    Chen, Lung-Ching; Lin, Chih-Yuan; Chen, Ing-Jou; Ku, Chi-Tai; Chen, Yen-Kung; Hsu, Bailing


    Recently, myocardial blood flow quantitation with dynamic SPECT/CT has been reported to enhance the detection of coronary artery disease in human. This advance has created important clinical applications to coronary artery disease diagnosis and management for areas where myocardial perfusion PET tracers are not available. We present 2 clinical cases that undergone a combined test of 1-day rest/dipyridamole-stress dynamic SPECT and ECG-gated myocardial perfusion SPECT scans using an integrated imaging protocol and demonstrate that flow parameters are capable to conclude equivocal myocardial perfusion SPECT studies, therefore increasing diagnostic benefits to add value in making clinical decisions.

  14. Effect of pre-analytical handling on haematological variables in minipigs

    Olsen, A K; Bladbjerg, E-M; Jensen, A L


    Pre-analytical handling may be an important determinant of haematological variables, if analysis is delayed. We investigated the effect of anticoagulants, i.e. tripotassium ethylenediamine-tetraacetic acid (EDTA) and citric acid, theophylline, adenosine, dipyridamole (CTAD), storage time (0.5, 1......, the samples must be stored in a refrigerator until analysis. Our studies underline that time delay before analysis of haematological variables can cause increased variation, and should therefore be limited as far as possible in order to reduce the number of animals needed to make reliable conclusions...

  15. Myocardial perfusion imaging in Denmark: activity from 1997 to 2001 and current practice

    Petersen, Claus Leth; Kjaer, Andreas


    A questionnaire was sent to all departments of nuclear medicine in Denmark (n=20) asking for details of myocardial perfusion imaging (MPI), including the number of patients examined each year from 1997 to 2001 and the current clinical and technical practice. All (100%) departments replied...... studies was dipyridamole/adenosine in 76%, exercise in 18% and dobutamine in 6%. Despite these encouraging figures, MPI activity for 2001 remained well below what is recommended by other national and international societies. The anticipated further increase in nuclear cardiology is encouraging...

  16. Roles of myocardial blood volume and flow in coronary artery disease: an experimental MRI study at rest and during hyperemia

    McCommis, Kyle S.; Goldstein, Thomas A.; Pilgram, Thomas [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Abendschein, Dana R. [Washington University School of Medicine, Center for Cardiovascular Research, St. Louis, MO (United States); Misselwitz, Bernd [Bayer Schering Pharma AG, Berlin (Germany); Gropler, Robert J. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Washington University School of Medicine, Center for Cardiovascular Research, St. Louis, MO (United States); Zheng, Jie [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Cardiovascular Imaging Lab, St. Louis, MO (United States)


    To validate fast perfusion mapping techniques in a setting of coronary artery stenosis, and to further assess the relationship of absolute myocardial blood volume (MBV) and blood flow (MBF) to global myocardial oxygen demand. A group of 27 mongrel dogs were divided into 10 controls and 17 with acute coronary stenosis. On 1.5-T MRI, first-pass perfusion imaging with a bolus injection of a blood-pool contrast agent was performed to determine myocardial perfusion both at rest and during either dipyridamole-induced vasodilation or dobutamine-induced stress. Regional values of MBF and MBV were quantified by using a fast mapping technique. Color microspheres and {sup 99m}Tc-labeled red blood cells were injected to obtain respective gold standards. Microsphere-measured MBF and {sup 99m}Tc-measured MBV reference values correlated well with the MR results. Given the same changes in MBF, changes in MBV are twofold greater with dobutamine than with dipyridamole. Under dobutamine stress, MBV shows better association with total myocardial oxygen demand than MBF. Coronary stenosis progressively reduced this association in the presence of increased stenosis severity. MR first-pass perfusion can rapidly estimate regional MBF and MBV. Absolute quantification of MBV may add additional information on stenosis severity and myocardial viability compared with standard qualitative clinical evaluations of myocardial perfusion. (orig.)

  17. Arterial pressure changes monitoring with a new precordial noninvasive sensor

    Faita Francesco


    Full Text Available Abstract Background Recently, a cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been validated. A further application is the assessment of Second Heart Sound (S2 amplitude variations at increasing heart rates. The aim of this study was to assess the relationship between second heart sound amplitude variations at increasing heart rates and hemodynamic changes. Methods The transcutaneous force sensor was positioned in the precordial region in 146 consecutive patients referred for exercise (n = 99, dipyridamole (n = 41, or pacing stress (n = 6. The curve of S2 peak amplitude variation as a function of heart rate was computed as the increment with respect to the resting value. Results A consistent S2 signal was obtained in all patients. Baseline S2 was 7.2 ± 3.3 mg, increasing to 12.7 ± 7.7 mg at peak stress. S2 percentage increase was + 133 ± 104% in the 99 exercise, + 2 ± 22% in the 41 dipyridamole, and + 31 ± 27% in the 6 pacing patients (p Conclusion S2 recording quantitatively documents systemic pressure changes.

  18. Assessment of Renal Perfusion in a Canine Model Using FS069, A New Transpulmonary Echocontrast Agent.

    Mobarek, Sameh K.; Kates, Marc A.; Murgo, Joseph P.; Moreno, Carlos A.; Revall, Susan; Cheirif, Jorge


    We have previously demonstrated the safety and efficacy of FS069, a new transpulmonary echocontrast agent, for myocardial opacification. To our knowledge, no information exists regarding the use of this agent for transcutaneous assessment of renal perfusion. We studied 14 mongrel dogs using intravenously administered FS069. Renal ultrasound imaging was performed with a Hewlett-Packard Sonos 1500 using a 3.5-MHz transducer. Renal blood flow (ReBF) was altered using renal artery occlusion in four dogs and dipyridamole (0.56 mg/kg IV) in ten dogs. Renal perfusion was quantitatively assessed before and after each intervention using background subtracted peak intensity. ReBF was assessed with radiolabeled microspheres in ten dogs. Renal opacification was observed in all 14 dogs at baseline. The intravenous contrast dose required to produce optimal renal opacification ranged from 0.3-0.7 cc. After renal artery occlusion, peak intensity was reduced from 5.4 +/- 5.8 to 0.93 +/- 1.1 units (r = 0.99, P change from baseline). The inverse relation between ReBF and peak intensity observed suggests vasoconstriction of the afferent arterioles in response to dipyridamole and a reduced clearance of the contrast. These findings are in agreement with previous data demonstrating decreased renal thallium clearance postdipyridamole administration. Our data document the feasibility to assess renal perfusion under various flow states after intravenous injection of FS069.

  19. Assessing the impact of polymers on the pH-induced precipitation behavior of poorly water soluble compounds using synchrotron wide angle X-ray scattering.

    Hsieh, Yi-Ling; Box, Karl; Taylor, Lynne S


    The aim of this study was to investigate the pH-induced precipitation behavior of four ionizable compounds (papaverine, dipyridamole, glyburide, and warfarin) in the absence and presence of polymers. Polymers selected included nonionic, anionic, and cationic polymers. Precipitates were analyzed immediately after formation using high-energy radiation wide-angle X-ray scattering analysis and polarized light microscopy. Papaverine immediately crystallized to the original solid-state form upon creation of a highly supersaturated solution and polymers were unable to prevent crystallization. Dipyridamole also crystallized rapidly, forming a metastable polymorph that was stabilized by several of the cellulosic polymers. For glyburide and warfarin, although the compounds readily crystallized in the absence of the polymers, several of the polymers were able to prevent crystallization for more than 6 h. In general, measurements of solution concentration immediately following precipitation corroborated the solid-state analysis results, with the solution phase for the noncrystalline precipitates having a concentration considerably higher than that of the equilibrium solubility value, whereas for the crystalline precipitates, values were closer to the equilibrium solubility. Thus, precipitation to a noncrystalline solid was found to be promoted by the presence of some polymers, resulting in the formation of a supersaturated solution.

  20. Complications during pharmacological stress echocardiography: a video-case series

    Bigi Riccardo


    Full Text Available Abstract Background Stress echocardiography is a cost-effective tool for the modern noninvasive diagnosis of coronary artery disease. Several physical and pharmacological stresses are used in combination with echocardiographic imaging, usually exercise, dobutamine and dipyridamole. The safety of a stress is (or should be a major determinant in the choice of testing. Although large scale single center experiences and multicenter trial information are available for both dobutamine and dipyridamole stress echo testing, complications or side effects still can occur even in the most experienced laboratories with the most skilled operators. Case presentation We decided to present a case collection of severe complications during pharmacological stress echo testing, including a ventricular tachycardia, cardiogenic shock, transient ischemic attack, torsade de pointe, fatal ventricular fibrillation, and free wall rupture. Conclusion We believe that, in this field, every past complication described is a future complication avoided; what happens in your lab is more true of what you read in journals; and Good Clinical Practice is not "not having complications", but to describe the complications you had.

  1. Impairment of left ventricular regional wall motion in diabetes mellitus without coronary artery disease

    Sakamoto, Ken`ya; Shimonagata, Tuyoshi; Nanto, Shinsuke; Kuroda, Akio; Morozumi, Takakazu; Kamado, Kenji; Nagata, Seiki [Kansai Rosai Hospital, Amagasaki, Hyogo (Japan); Yamasaki, Yoshimitsu


    To elucidate the mechanisms of diabetic cardiomyopathy, dual SPECT imaging with thallium-201 (Tl-201) and I-123 beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analogue of free fatty acid (FFA), and dipyridamole-infusion Tl-201 scintigraphy were performed in 28 NIDDM patients without coronary artery disease. Twenty eight patients were divided into two groups based on the presence of wall motion abnormalities on cineangiographic left ventriculography (LVG). Nineteen patients with normal wall motion documented on LVG (group A) out of 28 evaluated patients demonstrated normal Tl-201 and I-123 BMIPP uptake in dual SPECT imaging, whereas 9 patients with reduced wall motion (group B) demonstrated reduced I-123 BMIPP uptake when compared with Tl-201 uptake. On dipyridamole-infusion Tl-201 scintigraphy, transient perfusion defects were demonstrated in 4 patients of group B and two patients of group A (p<0.05). These results suggest that small vessel disease and the impairment of myocardial free fatty acid metabolism are etiologic or contributory factors for regional wall motion abnormality in diabetic cardiomyopathy. (author)

  2. Renal transepithelial transport of nucleosides.

    Nelson, J A; Vidale, E; Enigbokan, M


    Previous work from this and other laboratories has suggested that the mammalian kidney has unique mechanisms for handling purine nucleosides. For example, in humans and in mice, adenosine undergoes net renal reabsorption whereas deoxyadenosine is secreted [Kuttesch and Nelson: Cancer Chemother. Pharmacol. 8, 221 (1982)]. The relationships between these renal transport systems and classical renal organic cation and anion, carbohydrate, and cell membrane nucleoside transport carriers are not established. To investigate possible relationships between such carriers, we have tested effects of selected classical transport inhibitors on the renal clearances of adenosine, deoxyadenosine, 5'-deoxy-5-fluorouridine (5'-dFUR), and 5-fluorouracil in mice. The secretion of deoxyadenosine and 5'-dFUR, but not the reabsorption of adenosine or 5-fluorouracil, was prevented by the classical nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine. Cimetidine, an inhibitor of the organic cation secretory system, also inhibited the secretion of 5'-dFUR, although it did not inhibit deoxyadenosine secretion in earlier studies [Nelson et al.: Biochem. Pharmacol. 32, 2323 (1983)]. The specific inhibitor of glucose renal reabsorption, phloridzin, failed to inhibit the reabsorption of adenosine or the secretion of deoxyadenosine. Failure of the nucleoside transport inhibitors and phloridzin to prevent adenosine reabsorption suggests that adenosine reabsorption may occur via a unique process. On the other hand, inhibition of the net secretion of deoxyadenosine and 5'-dFUR by dipyridamole and nitrobenzylthioinosine implies a role for the carrier that is sensitive to these compounds in the renal secretion (active transport) of these nucleosides.

  3. Antimalarial action of nitrobenzylthioinosine in combination with purine nucleoside antimetabolites.

    Gero, A M; Scott, H V; O'Sullivan, W J; Christopherson, R I


    The infection of human erythrocytes by two strains of the human malarial parasite, Plasmodium falciparum (FCQ-27 or the multi-drug-resistant strain K-1), markedly changed the transport characteristics of the nucleosides, adenosine and tubercidin, compared to uninfected erythrocytes. A component of the transport of these nucleosides was insensitive to the classical mammalian nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR). In vitro studies with tubercidin demonstrated ID50 values of 0.43 and 0.51 microM for FCQ-27 and K-1, respectively. In addition, the nucleoside transport inhibitors NBMPR, nitrobenzylthioguanosine (NBTGR), dilazep and dipyridamole also independently exhibited antimalarial activity in vitro. The combination of tubercidin and NBMPR or NBTGR in vitro demonstrated synergistic activity, whilst tubercidin together with dilazep or dipyridamole showed subadditive activity. Analysis by HPLC indicated that NBMPR could permeate the infected cell membrane and provided evidence for the catabolism of NBMPR in vitro, with subsequent alteration of the purine pool in the infected erythrocyte. These observations further indicated the possibility of the utilization of cytotoxic nucleosides against P. falciparum infection in conjunction with a nucleoside transport inhibitor to protect the host tissue.

  4. 血小板黏附的检测方法及临床应用%The Testing Method and Its Clinical Application of Platelet Adhesion



    对血小板检测中血小板黏附试验的方法及检测方法及临床资料进行分析。黏附率增高见于高凝状态和血栓性疾病,黏附率降低见于 vWD、巨大血小板(BBS)综合征、血小板无力症、尿毒症、肝硬化及服用阿司匹林、双嘧达莫(潘生丁)、保泰松等药物以后,做好血小板黏附质量控制,对异常结果应结合临床资料进行分析。%The testing method and its clinical application of platelet adhesion to be investigated. Adhesion rate increasing is to be seen in hypercroagulable state and thrombotic diseases,while,reduced adhesion rate is to be seen in vWD,and Soulier(BBS) syndrome,Glanzmann’s disease, uremia,liver cirrhosis and after-taking aspirin,dipyridamole (dipyridamole),phenylbutazone. It is suggested to keep platelet quality in good and analyze the abnormal results combined with analyzing clinical treatment data.

  5. Analysis of structure and dynamics of superfine polyhydroxybutyrate fibers for targeted drug delivery

    Olkhov, A.; Kucherenko, E.; Pantyukhov, P.; Zykova, A.; Karpova, S.; Iordanskii, A.


    Creation of polymer matrix systems for targeted drug delivery into a living organism is a challenging problem of modern treatment of various diseases and injuries. Poly-3-hydroxybutyrate (PHB) is commonly used for development of therapeutic systems. The aim of this article is to examine the changes in structure and morphology of fibers in presence of dipyridamole (DPD) as model drug for controlled release. It was found that addition of dipyridamole led to disappearance of spindle-shaped nodules on fibers of PHB in comparison with pure PHB. The research of thermophysical parameters showed that specific melting enthalpy (and the degree of crystallinity) of PHB fibers increased with the addition of DPD. With the increasing of DPD content in PHB fibers, more perfect and equilibrium crystal structure was formed. According to analysis of intercrystalline regions of PHB fibers, it was found that as the crystallinity of PHB in intergranular regions rose, the corresponding decrease of radical rotation speed was observed. It was concluded that fibers of PHB can be used for creating therapeutic systems for targeted and prolonged drug delivery.

  6. Correlation between myocardial dysfunction and perfusion impairment in diabetic rats with velocity vector imaging and myocardial contrast echocardiography.

    Wei, Zhangrui; Zhang, Haibin; Su, Haili; Zhu, Ting; Zhu, Yongsheng; Zhang, Jun


    The purpose of this study was to investigate whether myocardial systolic dysfunction and perfusion impairment occur in diabetic rats, and to assess their relationship using velocity vector imaging (VVI) and myocardial contrast echocardiography (MCE). Forty-six rats were randomly divided into either control or the diabetes mellitus (DM) groups. DM was induced by intraperitoneal administration of streptozotocin. Twelve weeks later, 39 survival rats underwent VVI and MCE in short-axis view at the middle level of the left ventricle, both at rest and after dipyridamole stress. VVI-derived contractile parameters included peak systolic velocity (Vs ), circumferential strain (εc ), strain rate (SRc ), and their reserves. MCE-derived perfusion parameters consisted of myocardial blood flow (MBF) and myocardial flow reserve (MFR). At rest, SRc in the DM group was significantly lower than in the control group, Vs , εc , and MBF did not differ significantly between groups. After dipyridamole stress, all VVI parameters and their reserves in the DM group were significantly lower than those in the control group, MBF and MFR were substantially lower than those in the control group, too. Meanwhile, significant correlations between VVI parameter reserves and MFR were observed in the DM group. Both myocardial systolic function and perfusion were impaired in DM rats. Decreased MFR could be an important contributor to the reduction in myocardial contractile reserve.

  7. A combination turbidity and supernatant microplate assay to rank-order the supersaturation limits of early drug candidates.

    Morrison, John S; Nophsker, Michelle J; Haskell, Roy J


    A unique opportunity exists at the drug discovery stage to overcome inherently poor solubility by selecting drug candidates with superior supersaturation propensity. Existing supersaturation assays compare either precipitation-resistant or precipitation-inhibiting excipients, or higher-energy polymorphic forms, but not multiple compounds or multiple concentrations. Furthermore, these assays lack sufficient throughput and compound conservation necessary for implementation in the discovery environment. A microplate-based combination turbidity and supernatant concentration assay was therefore developed to determine the extent to which different compounds remain in solution as a function of applied concentration in biorelevant media over a specific period of time. Dimethyl sulfoxide stock solutions at multiple concentrations of four poorly soluble, weak base compounds (Dipyridamole, Ketoconazole, Albendazole, and Cinnarizine) were diluted with pH 6.5 buffer as well as FaSSIF. All samples were monitored for precipitation by turbidity at 600 nm over 1 h and the final supernatant concentrations were measured. The maximum supersaturation ratio was calculated from the supersaturation limit and the equilibrium solubility in each media. Compounds were rank-ordered by supersaturation ratio: Ketoconazole > Dipyridamole > Cinnarizine ∼ Albendazole. These in vitro results correlated well with oral AUC ratios from published in vivo pH effect studies, thereby confirming the validity of this approach. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Usefulness of {sup 99m}Tc-tetrofosmin myocardial scintigraphy before and after coronary intervention

    Adachi, Itaru; Hou, Nobuyoshi; Komori, Tsuyoshi; Tabuchi, Koujiro; Matsui, Ritsuo; Sueyoshi, Kouzou; Narabayashi, Isamu; Matsuda, Shigeki; Tamoto, Shigemi [Osaka Medical Coll., Takatsuki (Japan)


    Dipyridamole-loading {sup 99m}Tc-tetrofosmin myocardial scintigraphy was performed for patients with coronary artery disease who underwent percutaneous transluminal coronary angiography (PTCA) in order to examine whether SPECT imaging prior to treatment is useful for the determination of prognosis after coronary intervention. Thirty-six patients including 9 with angina pectoris (AP), 22 with old myocardial infarction (OMI) and 5 OMI with AP were underwent dipyridamole-loading {sup 99m}Tc-tetrofosmin myocardial SPECT before and after coronary intervention. The length of follow-up was 185{+-}107 days after PTCA. Improvement of myocardial uptake was observed on myocardial SPECT in all cases with AP. Improvement of the myocardial uptake was observed 50% (4/8) of patients with OMI who had no myocardial viability. It was suggested that the improvement of myocardial uptake after PTCA was due to incomplete fill-in in cases with AP and that presence of fill-in was important for level of fill-in in patients with AP. The improvement of myocardial uptake in the scar tissue in patients with OMI contributed to the hibernating myocardium. We concluded that correct detection of hibernating myocardium was difficult despite the superior imaging capacity of {sup 99m}Tc-tetrofosmin myocardial SPECT. (author)

  9. Prevention of cardiac complications in peripheral vascular surgery

    Cutler, B.S.


    The prevalence of severe coronary artery disease in peripheral vascular patients exceeds 50 per cent. Complications of coronary artery disease are the most common causes of mortality following peripheral vascular operations. To reduce the incidence of cardiac complications, it is first necessary to identify patients at risk through screening tests. Screening methods in current use include risk factor analysis, exercise testing, routine coronary angiography, and dipyridamole thallium-201 scintigraphy. The risk factor approach has the advantage of being widely applicable since it makes use of historical, physical, and electrocardiographic findings that are already familiar to surgeons and anesthesiologists. It is also inexpensive. However, it may overlook the patient who has no symptoms of coronary artery disease, possibly as a result of the sedentary lifestyle imposed by complications of peripheral vascular disease. The electrocardiographically monitored stress test will identify the asymptomatic patient with occult coronary disease and is helpful in predicting operative risk. However, a meaningful test is dependent on the patient's ability to exercise--an activity that is frequently limited by claudication, amputation, or arthritis. Exercise testing also suffers from a lack of sensitivity and specificity when compared with coronary arteriography. Routine preoperative coronary angiography overcomes the exercise limitation of treadmill testing but is not widely applicable as a screening test for reasons of cost and inherent risk. Dipyridamole thallium-201 scanning, on the other hand, is safe and of relatively low cost and does not require exercise.

  10. Development of a nanoporous and multilayer drug-delivery platform for medical implants

    Karagkiozaki V


    Full Text Available Varvara Karagkiozaki,1 Eleftherios Vavoulidis,1 Panagiotis G Karagiannidis,1 Maria Gioti,1 Dimitrios G Fatouros,2 Ioannis S Vizirianakis,3 Stergios Logothetidis11Lab for Thin Films–Nanosystems and Nanometrology, Physics Department, 2Department of Pharmaceutical Technology, 3Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, GreeceAbstract: Biodegradable polymers can be applied to a variety of implants for controlled and local drug delivery. The aim of this study is to develop a biodegradable and nanoporous polymeric platform for a wide spectrum of drug-eluting implants with special focus on stent-coating applications. It was synthesized by poly(DL-lactide-co-glycolide (PLGA 65:35, PLGA 75:25 and polycaprolactone (PCL in a multilayer configuration by means of a spin-coating technique. The antiplatelet drug dipyridamole was loaded into the surface nanopores of the platform. Surface characterization was made by atomic force microscopy (AFM and spectroscopic ellipsometry (SE. Platelet adhesion and drug-release kinetic studies were then carried out. The study revealed that the multilayer films are highly nanoporous, whereas the single layers of PLGA are atomically smooth and spherulites are formed in PCL. Their nanoporosity (pore diameter, depth, density, surface roughness can be tailored by tuning the growth parameters (eg, spinning speed, polymer concentration, essential for drug-delivery performance. The origin of pore formation may be attributed to the phase separation of polymer blends via the spinodal decomposition mechanism. SE studies revealed the structural characteristics, film thickness, and optical properties even of the single layers in the triple-layer construct, providing substantial information for drug loading and complement AFM findings. Platelet adhesion studies showed that the dipyridamole-loaded coatings inhibit platelet aggregation that is a prerequisite for clotting. Finally, the films

  11. Impaired myocardial perfusion reserve in microvascular angina (syndrome X): Assessment by vasodilation {sup 99m}Tc-MIBI-SPECT; Einschraenkung der myokardialen Perfusionsreserve bei Mikrovaskular-Angina (Syndrom X): Nachweis durch {sup 99m}Tc-MIBI-SPECT

    Langes, K. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Kardiologie; Beuthien-Baumann, B. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Nuklearmedizin; Luebeck, M. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Nuklearmedizin; Fuchs, C. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Nuklearmedizin; Schneider, M.A. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Kardiologie; Volk, C. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Kardiologie; Nienaber, C.A. [Universitaetskrankenhaus Eppendorf, Hamburg (Germany). Abt. fuer Kardiologie


    Aim: In 22 patients with typical chest pain and normal coronary arteries (microvascular angina, syndrome X) {sup 99m}Tc-MIBI-SPECT was examined in regard to assess impairment of myocardial perfusion reserve. Method: The study was performed with {sup 99m}Tc-MIBI-SPECT at rest and under vasodilation with dipyridamole. The findings were compared with a normal database. A normal perfusion reserve was said to be an increase >20% of the {sup 99m}Tc-MIBI-activity. Results: In 2/22 (9%) of the patients the perfusion reserve lay >20% i.e. 37%. In 91% of the patients a diminution or even decrease of the perfusion was to be seen. From these 9/22 (41%) of the patients showed a diminution of the {sup 99m}Tc-MIBI by 6%. 11/22 patients had a decrease of the perfusion under vasodilation with dipyridamole i.e. a lower activity of 99mTc-MIBI 13%. Conclusion: Vasodilation {sup 99m}Tc-MIBI-SPECT offers good imaging quality and enables semiquantitative assessment of myocardial perfusion reserve in patients with microvascular angina. (orig.) [Deutsch] Ziel: An 22 Patienten mit typischer Angina pectoris und normalen Koronararterien (Mikrovaskular-Angina, Syndrom X) wurde geprueft, ob mit {sup 99m}Tc-MIBI-SPECT eine Einschraenkung der myokardialen Perfusionsreserve nachweisbar ist. Methode: Die Untersuchung mit {sup 99m}Tc-MIBI-SPECT erfolgte in Ruhe und unter Vasodilatation nach einer Infusion mit Dipyridamol im Vergleich zu einer normalen Datenbank. Eine normale myokardiale Perfusionsreserve wurde bei einer differenziellen {sup 99m}Tc-MIBI-Aufnahme von {>=}20% angesehen. Ergebnisse: 2/22 (9%) der Patienten wiesen eine Perfusionsreserve >20% mit im Mittel 37% auf, 91% der Patienten wiesen eine relativ oder absolut verminderte {sup 99m}Tc-MIBI-Aufnahme unter Vasodilatation auf. Bei 9/22 (41%) Patienten war die Perfusionsreserve relativ gemindert mit einer Zunahme der {sup 99m}Tc-MIBI-Aktivitaet von 6%, bei 11/22 wurde eine Abnahme der {sup 99m}Tc-MIBI-Aktivitaet um 13% unter

  12. Clinical utility of digital dobutamine stress echocardiography in the noninvasive evaluation of coronary artery disease.

    Madu, E C; Ahmar, W; Arthur, J; Fraker, T D


    Exercise electrocardiography is an established mode of evaluation for patients with suspected coronary artery disease. It also provides prognostic information and guides therapeutic management in patients with established disease. However, some patients are unable to exercise because of orthopedic problems, neurologic diseases, peripheral vascular disease, or deconditioning. In the past, these patients have been referred for angiography to help assess their disease. Recently, however, new techniques to assess myocardial perfusion and/or function, including stress echocardiography, have been used in the noninvasive assessment of coronary artery disease in this group of patients. Echocardiography has been used in combination with different drugs, including dobutamine, dipyridamole, and adenosine. Dobutamine is probably the single most studied drug for stress echocardiography. Dobutamine stress echocardiography is a safe, feasible, and valuable technique for evaluating coronary artery disease.

  13. Quantification of MRI measured myocardial perfusion reserve in healthy humans: A comparison with positron emission tomography

    Fritz-Hansen, T.; Hove, J.D.; Kofoed, K.F.;


    and during stress induced by dipyridamole in order to determine the myocardial perfusion reserve. Myocardial and blood time concentration curves obtained by Gd-DTPA-enhanced MRI and N-13-ammonia PET were fitted by a two-compartment perfusion model. Results: Mean perfusion values (+/- SD) derived from the MRI......Purpose: To validate a noninvasive quantitative MRI technique, the K-i perfusion method, for myocardial perfusion in humans using N-13-ammonia PET as a reference method. Materials and Methods: Ten healthy males (64 +/- 8 years) were examined with combined PET and MRI perfusion imaging at rest...... method at rest and at hyperemia were 80 +/- 20 and 183 +/- 56 mL/min/100 g, respectively. The same data for PET were 71 +/- 16 and 203 +/- 67 mL/min/100 g. A linear relationship was observed between MRI and PET-derived myocardial perfusion reserve for regional and global data. Linear regression...

  14. [Rupture of a superior mesenteric artery aneurysm in pediatric age: case report and literature review].

    Gander, R; Pérez, M; Bueno, J; Lara, A; Segarra, A; Martínez, M A; Lloret, J


    Splanchnic artery aneurysms are rare in children. High mortality from rupture justifies its treatment, with various therapeutic options among which stand out surgery and recently, endovascular treatment. A 11 year old girl presented with abdominal pain and sudden drop in hematocrit. The urgent abdominal CT angiography showed a saccular aneurysm of the superior mesenteric artery (SMA) at 4 cm from the ostium with dissection and active bleeding. A selective angiography was performed which confirmed the dissection. A self-expanding stent was placed in the main trunk of the SMA and a transcatheter coil and onyx embolization of the aneurysm was performed. The control angiogram showed no evidence of residual perfusion of the false lumen and demonstrated proper vascularization of the distal jejunum-ileal branches. Dual antiplatelet therapy with aspirin and dipyridamole was begun. After 24 months of follow-up the patient is asymptomatic. Endovascular treatment of a SMA aneurysm is effective in the pediatric patient, even in emergency situations.

  15. Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction

    Michelsen, Marie Mide; Mygind, Naja Dam; Pena, Adam


    stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. RESULTS: MBFR was systematically higher......BACKGROUND: Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard...... for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR. METHODS: From a cohort of women with angina and no obstructive coronary artery...

  16. Platelet aggregation inhibitors in primary and secondary prevention of ischemic stroke

    Gorenoi, Vitali; Kulp, Werner; Greiner, Wolfgang; von der Schulenburg, Johann-Matthias


    Background The ischaemic stroke (IS) is one of the most frequent cause of death in Germany. Besides of non-drug many drug-based interventions are used in primary or secondary prevention of IS, among them the thrombocyte aggregation inhibitors (TAI). Objectives The evaluation addresses the questions on medical efficacy and cost-effectiveness of the TAI administration in the prevention of IS as compared to the management of risk factors alone as well as to the use of anticoagulant drugs. Methods The literature search for articles published after 1997 was conducted in December 2003 in the most important medical and economic databases. The medical analysis was performed on the basis of the most up-to date meta-analyses of randomised controlled trials (RCT) as well as of new published RCT. The data from the studies for stroke, bleeding complications as well as for the combined endpoint "severe vascular events" (SVE: death or stroke or myocardial infarction) were summarised in meta-analyses. In order to include grey literature contact has been taken up with the pharmaceutical manufacturers of TAI. Results are presented in a descriptive way. Results The medical analysis included data from 184 RCT (vs. placebo) and from 22 RCT (vs. anticoagulant drugs). The absolute reduction of IS (4.8% vs. 6.6%; p<0,00001) and SVE (10.0% vs. 12.4%; p<0,00001) were definitely higher than the absolute increase of bleeding complications (1.6% vs. 0.9%; p<0,00001), but relatively similar to this absolute increase in a subpopulation with a low risk for SVE. With regard to the stroke prevention, evidence of efficacy could be yielded for acetylsalicil acid (ASA), dipyridamole, cilostazol, ridogrel and the combination ASA with dipyridamole. ASA is less effective than anticoagulants in the prevention of ischaemic stroke in atrial fibrillation, however, it causes fewer bleeding complications. Low dosed ASA can be considered cost-effective in secondary prevention of ischemic stroke, which is not

  17. Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

    Fritz-Hansen, T; Rostrup, Egill; Søndergaard, Lise;


    The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole......-induced vasodilation in 10 healthy volunteers and in 10 patients with ischemic heart disease. Ki increased by a factor of 2.5+/-1.2 (mean +/- SD) from 55+/-16 ml 100 g(-1)min(-1) at rest to 136+/-46 ml 100 g(-1)min(-1) (P ... during vasodilation in ischemic regions (50+/-18 versus 49+/-30 ml 100 g(-1)min(-1) (P > 0.4)). Ki increased in nonischemic regions by a factor of 2.0+/-0.8 from 44+/-17 to 81+/-32 ml 100 g(-1)min(-1) during vasodilation (P transfer constant is sensitive...

  18. In vivo labelling in several rat tissues of 'peripheral type' benzodiazepine binding sites

    Benavides, J.; Guilloux, F.; Rufat, P.; Uzan, A.; Renault, C.; Dubroeucq, M.C.; Gueremy, C.; Le Fur, G. (Pharmuka Laboratoires, 92 - Gennevilliers (France))


    'Peripheral type' benzodiazepine binding sites in several rat tissues were labelled by intravenous injection of (/sup 3/H)PK 11195 and (/sup 3/H)RO5-4864. Binding was saturable in all tissues studied and regional distribution paralleled the in vitro binding. A similar potency order of displacing compounds was found in vivo and in vitro PK 11195 > PK 11211 > RO5-4864 > diazepam > dipyridamole > clonazepam. These results demonstrate the feasibility of using this technique to examine the effects of pharmacological manipulation on the binding sites in their native state. However, some properties (broader maximum during time course, higher percentage of particulate binding in the brain and independence of temperature) make (/sup 3/H)PK 11195 the most suitable ligand for this kind of studies.

  19. Short-term oral treatment with the angiotensin II receptor antagonist losartan does not improve coronary vasomotor function in asymptomatic type 2 diabetes patients

    Kjaer, Andreas; Kristoffersen, Ulrik Sloth; Tarnow, Lise;


    with 100mg/d of losartan. Baseline myocardial perfusion was similar at all three sessions (0.89+/-0.05, 0.90+/-0.08 and 0.84+/-0.05mL/(ming) tissue, respectively). Likewise, maximal hyperaemic perfusion after i.v. dipyridamole (0.56mg/kg bwt) was low but similar at the three sessions (2.01+/-0.14, 2.......05+/-0.17 and 1.90+/-0.20mL/(ming) tissue, respectively). Myocardial perfusion reserve, i.e. maximal hyperaemic flow relative to baseline flow, was also low, but similar before and after treatment with losartan (2.36+/-0.24, 2.44+/-0.24 and 2.62+/-0.42mL/(ming) tissue, respectively). CONCLUSIONS: Oral treatment...

  20. Effects of drugs on platelet function.

    Morse, E E


    Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

  1. Micro-scale prediction method for API-solubility in polymeric matrices and process model for forming amorphous solid dispersion by hot-melt extrusion.

    Bochmann, Esther S; Neumann, Dirk; Gryczke, Andreas; Wagner, Karl G


    A new predictive micro-scale solubility and process model for amorphous solid dispersions (ASDs) by hot-melt extrusion (HME) is presented. It is based on DSC measurements consisting of an annealing step and a subsequent analysis of the glass transition temperature (Tg). The application of a complex mathematical model (BCKV-equation) to describe the dependency of Tg on the active pharmaceutical ingredient (API)/polymer ratio, enables the prediction of API solubility at ambient conditions (25°C). Furthermore, estimation of the minimal processing temperature for forming ASDs during HME trials could be defined and was additionally confirmed by X-ray powder diffraction data. The suitability of the DSC method was confirmed with melt rheological trials (small amplitude oscillatory system). As an example, ball milled physical mixtures of dipyridamole, indomethacin, itraconazole and nifedipine in poly(vinylpyrrolidone-co-vinylacetate) (copovidone) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used.

  2. Role of Calcium in Phosphatidylserine Externalisation in Red Blood Cells from Sickle Cell Patients

    Erwin Weiss


    Full Text Available Phosphatidylserine exposure occurs in red blood cells (RBCs from sickle cell disease (SCD patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates Ca2+ entry, providing an obvious link with phosphatidylserine exposure. The role of Ca2+ was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [Ca2+] was increased. This effect was inhibited by dipyridamole, intracellular Ca2+ chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high K+ saline. Ca2+ levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with Ca2+ entry through the deoxygenation-induced pathway (Psickle, activating the Gardos channel. [Ca2+] required for phosphatidylserine scrambling are in the range achievable in vivo.

  3. Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

    Fritz-Hansen, T; Rostrup, Egill; Søndergaard, Lise


    during vasodilation in ischemic regions (50+/-18 versus 49+/-30 ml 100 g(-1)min(-1) (P > 0.4)). Ki increased in nonischemic regions by a factor of 2.0+/-0.8 from 44+/-17 to 81+/-32 ml 100 g(-1)min(-1) during vasodilation (P transfer constant is sensitive......The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole......-induced vasodilation in 10 healthy volunteers and in 10 patients with ischemic heart disease. Ki increased by a factor of 2.5+/-1.2 (mean +/- SD) from 55+/-16 ml 100 g(-1)min(-1) at rest to 136+/-46 ml 100 g(-1)min(-1) (P



    Objective. The aim of this study was to detect coronary artery disease using99m Tc-MIBI myocardial perfusion imaging in patients with valvular disease.Methods. Thirty patients with valvular disease confirmed by echocardiography underwent 99mTc-MIBI myocardial perfusion imaging using multiSPECT 1h after stress test (exercise, dipyridamole or dobutamine test) and were performed coronary angiography within 1 month before valvular operation.Results.For 29 out of the 30 patients, the results of 99mTc-MIBI myocardial perfusion imaging were similar with those of coronary angiography, the concordance rate was 96.7% and the negative predictability was 100%.Conclusion.99m Tc-MIBI myocardial perfusion imaging is a reliable non-invasive method for detecting coronary artery disease in patients with valvular disease and so as to draw up suitable operation programs for them.

  5. Single photon emission computed tomography of technetium-99m tetrofosmin myocardial perfusion imaging in patients with systemic lupus erythematosus-A preliminary report

    Lin, Jen-Jhy; Hsu, Hsiu-Bao; Sun, Shung-Shung; Kao, Chia-Hung [China Medical Coll., Taichung, Taiwan (China). Hospital; Wang, Jhi-Joung [Chi-Mei Medical Center, Tainan, Taiwan (China); Ho, Shung-Tai [National Defense Medical Center, Taipei, Taiwan (China). School of Medicine


    The purpose of this study was to evaluate the utility of single-photon emission computed tomography (SPECT) of technetium-99m tetrofosmin (Tc-99m TF) myocardial perfusion imaging to detect myocardial involvement in patients with systemic lupus erythematosus (SLE). Three groups of subjects-group 1: 25 SLE female patients with non-specific cardiac symptoms and signs, group 2: 25 female SLE patients without any cardiac symptoms and signs, and group 3: 25 female healthy controls-were evaluated by comparing rest and dipyridamole-stress Tc-99m TF myocardial perfusion SPECT. Tc-99m TF myocardial perfusion SPECT revealed perfusion defects in 88% and 40% of the cases in groups 1 and 2, respectively. However, no cases in group 3 demonstrated myocardial perfusion defects. Tc-99m TF myocardial perfusion SPECT is a useful noninvasive imaging modality to detect cardiac involvement in SLE patients with or without cardiac symptoms and signs. (author)

  6. Crucial role for LKB1 to AMPKalpha2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes

    Habets, Daphna D. J.; Coumans, Will A.; El Hasnaoui, Mohammed;


    Enhanced contractile activity increases cardiac long-chain fatty acid (LCFA) uptake via translocation of CD36 to the sarcolemma, similarly to increase in glucose uptake via GLUT4 translocation. AMP-activated protein kinase (AMPK) is assumed to mediate contraction-induced LCFA utilization. However......, the stimulating effects of oligomycin and AICAR on palmitate and deoxyglucose uptake and palmitate oxidation were almost completely lost. Moreover, in AMPKalpha2- and LKB1-knockout cardiomyocytes, oligomycin-induced LCFA and deoxyglucose uptake were completely abolished. However, the stimulatory effect...... of dipyridamole on palmitate uptake and oxidation was preserved in AMPKalpha2-kinase-dead cardiomyocytes. In conclusion, in the heart there is a signaling axis consisting of LKB1 and AMPKalpha2 which activation results in enhanced LCFA utilization, similarly to enhanced glucose uptake. In addition, an unknown...

  7. Effects of isradipine and other calcium antagonists on arteriovenous-shunt flow in anesthetized rabbits and cats

    Hof, R.P.


    The effects of vasodilators on arteriovenous (AV)-shunt flow was investigated in anesthetized cats and rabbits, using the tracer microsphere method. In cats, the calcium antagonist isradipine reduced AV-shunt flow; verapamil showed a similar tendency and nicardipine was without effect. Dihydralazine strongly increased, but nitroglycerin and dipyridamole decreased AV-shunt flow. In rabbits, the effects of isradipine and verapamil were similar to those seen in cats. Sodium nitroprusside had no effect, whereas prazosin, minoxidil, and the potassium-channel activator cromakalim increased AV-shunt flow. The contrasting effects of drugs sharing the same mechanism of action suggest that target-tissue selectivity is more important than the mechanism of action. An increase of AV-shunt flow is unlikely to be beneficial but could be associated with a number of undesirable side effects. It might negatively affect migraine sufferers and, if AV-shunt dilatation shows no tolerance development, it represents an unnecessary hemodynamic burden for the heart.

  8. Accurate platelet counting in an insidious case of pseudothrombocytopenia.

    Lombarts, A J; Zijlstra, J J; Peters, R H; Thomasson, C G; Franck, P F


    Anticoagulant-induced aggregation of platelets leads to pseudothrombocytopenia. Blood cell counters generally trigger alarms to alert the user. We describe an insidious case of pseudothrombocytopenia, where the complete absence of Coulter counter alarms both in ethylenediaminetetraacetic acid blood and in citrate or acid citrate dextrose blood samples was compounded by the fact that the massive aggregates were exclusively found at the edges of the blood smear. Non-recognition of pseudothrombocytopenia can have serious diagnostic and therapeutic consequences. While the anti-aggregant mixture citrate-theophylline-adenosine-dipyridamole completely failed in preventing pseudothrombocytopenia, addition of iloprost to anticoagulants only partially prevented the aggregation. Only the prior addition of gentamicin to any anticoagulant used resulted in a complete prevention of pseudothrombocytopenia and enabled to count accurately the platelets.

  9. Secondary prevention of myocardial infarction with drugs.

    Klimt, C R; Forman, S A


    Clinical trials in the field of secondary prevention of myocardial infarctions are reviewed, with emphasis on those studies that were randomized and included at least 100 patients. Standardized total mortality data, when available, are provided. Five groups of drugs are reviewed: 1) antiarrhythmic drugs, including studies of phenytoin, tocainide, mexiletine and aprindine. Important, commonly used drugs in this group, which apparently have not been submitted to clinical trials, include procainamide and lidocaine; 2) lipid-lowering drugs, including estradiol, conjugated equine estrogen, dextrothyroxine, clofibrate and nicotinic acid; 3) anticoagulant drugs, the oldest and most controversial preventive drug measure. In this group, only the oral drug derivatives of indandione or coumarin have been tested, and no appropriate studies of parenteral heparin were found; 4) platelet-active drugs--six studies dealing with aspirin alone, one combining aspirin and dipyridamole, and one study of sulfinpyrazone are reviewed; and 5) beta-adrenergic blocking drugs, including practolol and timolol.

  10. Clinical aspects of 100 patients with Kawasaki disease.

    Tizard, E J; Suzuki, A; Levin, M; Dillon, M J


    We report 101 episodes of Kawasaki disease in 100 patients seen over a 12 year period. A total of 35 patients had cardiac involvement ranging from pericardial effusion to coronary artery aneurysms with ischaemic complications, which resulted in death in one patient. Laboratory investigations showed leucocytosis, thrombocytosis, and a raised erythrocyte sedimentation rate to be common features and the first two variables were significantly associated with cardiac involvement. Treatment regimens changed over the study period. Aspirin was used in most patients often in conjunction with dipyridamole and from 1986 intravenous immunoglobulin was given routinely to those patients seen early in the illness. Additional therapeutic measures in individual patients included prostacyclin, heparin, streptokinase, and plasma exchange/exchange transfusion. Attention is drawn to the uncertainity of the long term cardiovascular consequences in the light of adults reported with premature atherosclerotic lesions of similar appearance to those seen in Kawasaki disease.

  11. Myocardial perfusion of infarcted and normal myocardium in propofol-anesthetized minipigs using 82Rubidium PET

    Rasmussen, Thomas; Larsen, Bjarke Follin; Kastrup, Jens


    propofol, used for anesthesia, can influence myocardial perfusion and coronary flow reserve due to its vasorelaxant effect, and interactions might exist between propofol and used stress agents, potentially affecting the result of the examination. We present cardiac 82Rb-PET studies performed in propofol...... challenges. Animals, which have been anesthetized during PET acquisition, might react differently to used stress medications, and therefore difficulties might exist while evaluating the resulting PET images using standard software packages from commercial vendors optimized for human hearts. Furthermore......-anesthetized minipigs with normal and infarcted myocardium stressed with both adenosine and dipyridamole. Despite the mentioned challenges, we were able to trace the small minipig heart with software designed for human cardiac PET and to achieve blood flow measurements comparable with results in humans with both...


    V.S. Giri Prasad


    Full Text Available Ischemia and hemorrhage are the conditions which may lead to stroke. As stroke is a medical emergency, treated with medications such as aspirin, clopidogrel and dipyridamole. In the present study the combination and individual adverse effects of aspirin and clopidogrel medication were studied. The study during was around nine months in one of the private hospital at Hyderabad, Andhra Pradesh, India. Adverse effects evaluation was based on WHO guide lines and Naranjo’s Algorithm. Total 69 stroke patients were taken in to studies. 46 (66.66% were males and 23 (33.33% were females. The number of ischemic stroke patients was 39(56.5% and hemorrhage stroke was 30(43.4%. Among 41 patients, 19 patients was on Aspirin (46.34%, 10 patients was on clopidogral (24.34% and 12 patients was on combinations medication (29.26%. Adverse effects reported among the antiplatelate users were 6 patients. Among these 6 patients 4 patients were observed with upper gastrointestinal bleeding (UGI the overall percentage was 66.66% and 2 patients were observed with Vomiting, the overall percentage was 33.33%. In this study, the relative risk reduction for secondary stroke prevention was 37% with use of a combination of extended- release dipyridamole and aspirin. Importantly, the risk of major bleeding attributable to the combination therapy was no greater than that seen with aspirin alone. The benefit of clopidogrel over aspirin for the prevention of vascular events was a relative risk reduction of 8.7%.In addition, there was less major bleeding in the clopidogrel group, yielding a relative net benefit of about 10%. This study revels clopidogrel is the safe drug when compared with Aspirin and as well as combination therapy.

  13. Chronotropic response to vasodilator-stress in patients submitted to myocardial perfusion imaging: impact on the accuracy in detecting coronary stenosis

    Gimelli, Alessia; Coceani, Michele; Quaranta, Angela; Emdin, Michele [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); Liga, Riccardo [University Hospital of Pisa, Cardio-Thoracic and Vascular Department, Pisa (Italy); Marzullo, Paolo [Fondazione Toscana Gabriele Monasterio, Pisa (Italy); CNR, Institute of Clinical Physiology, Pisa (Italy)


    A lower heart rate response (HRR) during vasodilator MPI has been shown to have a relevant adverse prognostic impact. We sought to evaluate the interaction among individual HRR to vasodilator stress and myocardial perfusion imaging (MPI) accuracy in patients with suspected ischemic heart disease (IHD). One hundred and sixty-five consecutive patients were submitted to vasodilator-stress MPI on a cardiac camera equipped with cadmium-zinc-thelluride detectors and coronary angiography. A coronary stenosis >70 % was considered significant. In every patient, the summed difference score (SDS) was computed from MPI images. Patients were categorized according to the tertiles of the distribution of individual HRR during dipyridamole: ''Group 1'' (HRR < 8 bpm; lowest tertile); ''Group 2'' (8 ≤ HRR ≤ 12 bpm; middle tertile); ''Group 3'' (HRR >12 bpm; highest tertile). Significant coronary artery disease (CAD) was present in 102 (62 %) patients. In the overall population, MPI showed a significant accuracy (AUC: 0.81, 95 % CI 0.74-0.86; p < 0.001) in unmasking the presence of significant coronary stenosis. Interestingly, in patients with a blunted HRR during dipyridamole (''Group 1'') MPI showed a significantly lower sensitivity (68 %) in detecting CAD than in those with a higher HRR (''Group 3'') (91 %, p = 0.007), despite a preserved specificity (76 % vs 77 %, P=NS). Similarly, the correlation among CAD extent and post-stress LV functional stunning was limited to ''Group 3'' patients, while it disappeared in those with blunted HRR. In patients with suspected IHD, MPI sensitivity is strongly influenced by the magnitude of patient heart rate increase to the pharmacologic stressor, suggesting an interaction among blunted HRR and lower accuracy in unmasking CAD. (orig.)

  14. Study on the Mechanism of Intestinal Absorption of Epimedins A, B and C in the Caco-2 Cell Model

    Yan Chen


    Full Text Available Epimedium spp. is commonly used in Traditional Chinese Medicine. Epimedins A, B, and C are three major bioactive flavonoids found in Epimedium spp. that share similar chemical structures. In this study, the intestinal absorption mechanism of these three compounds was investigated using the Caco-2 cell monolayer model in both the apical-to-basolateral (A-B and the basolateral-to-apical (B-A direction. The absorption permeability (PAB of epimedins A, B, and C were extremely low and increased as the concentration of the epimedins increased from 5 to 20 μM, but, at 40 μM, the PAB values were reduced. Meanwhile, the amount of transported compounds increased in a time-dependent manner. The PAB of epimedins A and C were significantly increased and efflux ratios decreased in the presence of verapamil (an inhibitor of P-glycoprotein and dipyridamole (an inhibitor of breast cancer resistance protein while, in the presence of MK571 (an inhibitor of multidrug resistance proteins, the absorption of epimedins A and C did not change significantly, indicating that P-gp and BCRP might be involved in the transport of epimedins A and C. The PAB of epimedin B significantly increased while its secretory permeability (PBA significantly decreased in the presence of dipyridamole, indicating that BCRP might be involved in the transport of epimedin B. No obvious changes in the transport of epimedin B were observed in the presence of verapamil and MK571. In summary, our results clearly demonstrate, for the first time, that poor bioavailability of these three prenylated flavonoids is the result of poor intrinsic permeability and efflux by apical efflux transporters.

  15. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke

    Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.


    Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

  16. Evidence for an A2/Ra adenosine receptor in the guinea-pig trachea

    Brown, C.M.; Collis, M.G.


    1 An attempt was made to determine whether the extracellular adenosine receptor that mediates relaxation in the guinea-pig trachea is of the A1/Ri or A2/Ra subtype. 2 Dose-response curves to adenosine and a number of 5′- and N6-substituted analogues were constructed for the isolated guinea-pig trachea, contracted with carbachol. 3 The 5′-substituted analogues of adenosine were the most potent compounds tested, the order of potency being 5′-N-cyclopropylcarboxamide adenosine (NCPCA) > 5′-N-ethylcarboxamide adenosine (NECA) > 2-chloroadenosine > L-N6-phenylisopropyladenosine (L-PIA) > adenosine > D-N6-phenylisopropyladenosine (D-PIA). 4 The difference in potency between the stereoisomers D- and L-PIA on the isolated trachea was at the most five fold. 5 Responses to low doses of adenosine and its analogues were attenuated after treatment with either theophylline or 8-phenyltheophylline. The responses to 2-chloroadenosine were affected to a lesser extent than were those to the other purines. 6 Adenosine transport inhibitors, dipyridamole and dilazep, potentiated responses to adenosine, did not affect those to NCPCA, NECA, L-PIA and D-PIA but significantly reduced the responses to high doses of 2-chloroadenosine. 7 Relaxations evoked by 9-β-D-xylofuranosyladenosine which can activate intracellular but not extracellular adenosine receptors, were attenuated by dipyridamole but unaffected by 8-phenyltheophylline. 8 The results support the existence of an extracellular A2/Ra subtype of adenosine receptor and an intracellular purine-sensitive site, both of which mediate relaxation. PMID:6286021

  17. Reduced coronary flow reserve in patients with primary hyperparathyroidism: a study by G-SPECT myocardial perfusion imaging

    Marini, Cecilia [CNR Institute of Bioimages and Molecular Physiology Milan, Genoa (Italy); Giusti, Massimo; Vera, Lara; Minuto, Francesco [University of Genoa, Department of Endocrinological and Metabolic Sciences, Genoa (Italy); Armonino, Riccardo; Ghigliotti, Giorgio; Bezante, Gian Paolo; Morbelli, Silvia; Pomposelli, Elena; Massollo, Michela; Gandolfo, Patrizia; Sambuceti, Gianmario [University of Genoa, Department of Internal Medicine, Genoa (Italy)


    The mechanisms underlying increased cardiovascular risk in primary hyperparathyroidism (pHPT) have not been fully defined. Recently, this issue has become the subject of renewed interest due to the increasing evidence that the endothelium and vascular wall are targets for parathyroid hormone (PTH). The aim of this study was to measure regional coronary flow reserve (CFR) to determine whether the vascular damage induced by pHPT extends to affect the coronary microvascular function. A total of 22 pHPT patients without a history of coronary artery disease and 7 age-matched control subjects were recruited. Dipyridamole myocardial blood flow (MBF) was assessed using {sup 99m}Tc-sestamibi by measuring first-transit counts in the pulmonary artery and myocardial count rate from G-SPECT images. Baseline MBF was estimated 2 h later according to the same procedure. Regional CFR was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular model. Three pHPT patients showed reversible perfusion defects and were excluded from the analysis. In the remaining 19, CFR was significantly lower with respect to the control subjects (1.88 {+-} 0.64 vs. 3.36 {+-} 0.66, respectively; p < 0.01). Moreover, patients studied for more than 28 months from pHPT diagnosis showed lower CFR values than the others (1.42 {+-} 0.18 vs. 2.25 {+-} 0.64, respectively; p < 0.01). Consequently, the time from diagnosis to the nuclear study showed a reasonable correlation with the degree of CFR impairment (Spearman's rho -0.667, p < 0.02). pHPT is associated with a significant dysfunction of the coronary microcirculation. This disorder might contribute to the high cardiovascular risk of conditions characterized by chronic elevations in serum PTH levels. (orig.)

  18. MR assessment of absolute myocardial blood flow and vasodilator flow reserve in patients with hypertrophic cardiomyopathy

    Kawada, Nanaka; Sakuma, Hajime; Takeda, Kan; Nakagawa, Tsuyoshi; Yamakado, Tetsu; Nakano, Takeshi [Mie Univ., Tsu (Japan). School of Medicine


    Absolute coronary blood flow per myocardial mass and coronary flow reserve for the entire left ventricle were evaluated in normals and in patients with hypertrophic cardiomyopathy (HCM) by using fast cine MR imaging and fast velocity encoded cine (VENC) MR imaging. Nine healthy volunteers and 8 patients with HCM were studied with a 1.5 T imager. Breath-hold cine MR images encompassing the whole left ventricle were acquired on short axis imaging planes in order to evaluate myocardial mass. A fast VENC MR images were obtained to measure blood flow volume in the coronary sinus before and after dipyridamole administration (TR/TE=15/5 ms, FOV=28 x 22 cm, slice thickness=5 mm). Coronary flow reserve was calculated as a ratio of hyperemic to baseline coronary flow volumes. In the baseline state, coronary blood flow per myocardial mass was significantly lower in patients with HCM than in normal myocardium (0.56{+-}0.23 vs. 0.78{+-}0.27 ml/min/g, p<0.05). After dipyridamole administration, coronary blood flow per myocardial mass in patients with HCM increased substantially less than that in healthy subjects (0.99{+-}0.38 vs. 2.22{+-}0.55 ml/min/g, p<0.01), resulting in the significantly decreased coronary flow reserve ratio in HCM in comparison with that in normal myocardium (1.86{+-}0.56 vs. 3.11{+-}1.37, p<0.05). In conclusion, breath-hold velocity encoded cine MR imaging is a noninvasive technique which can provide assessments of altered coronary blood flow volume per myocardial mass and vasodilator flow reserve in patients with HCM. (author)

  19. Effect of multidrug resistance gene-1(mdr1) overexpression on in-vitro uptake of {sup 99m}Tc-sestaMIBI in murine L1210 leukemia cells

    Chun, Kyung Ah; Lee, Jae Tae; Lee, Sang Woo; Kang, Do Young; Sohn, Snag Kyun; Lee, Jong Kee; Jun, Soo Han; Lee, Kyu Bo [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of); Chung, June Key [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)


    To determine whether {sup 99m}Tc-MIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively {sup 99m}Tc-MIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular {sup 99m}Tc-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr 1 gene) overexpression. We measured percentage uptake of {sup 99m}Tc-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of {sup 99m}Tc-MIBI were also evaluated with or without overexpression of mdr1 gene in cultured murine leukemia L1210 cells. The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of {sup 99m}Tc-MIBI was higher in mdr1 negative L1210 cells than those of mdr1 positive cells, and higher when incubated in 37 .deg. C than 4 .deg. C. In the presence of verapamil, cyclosporin or dipyridamole, {sup 99m}Tc-MIBI uptake was increased upto 604% in mdr1 positive cells. Cellular uptake of {sup 99m}Tc-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MDR-reversing agents increase cellular uptake. These results suggest the {sup 99m}Tc-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents in vitro.

  20. Kinetic analysis of ligand binding to the Ehrlich cell nucleoside transporter: Pharmacological characterization of allosteric interactions with the sup 3 Hnitrobenzylthioinosine binding site

    Hammond, J.R. (Department of Pharmacology and Toxicology, University of Western Ontario, London (Canada))


    Kinetic analysis of the binding of {sup 3}Hnitrobenzylthioinosine ({sup 3}H NBMPR) to Ehrlich ascites tumor cell plasma membranes was conducted in the presence and absence of a variety of nucleoside transport inhibitors and substrates. The association of {sup 3}H NBMPR with Ehrlich cell membranes occurred in two distinct phases, possibly reflecting functional conformation changes in the {sup 3}HNBMPR binding site/nucleoside transporter complex. Inhibitors of the equilibrium binding of {sup 3}HNBMPR, tested at submaximal inhibitory concentrations, generally decreased the rate of association of {sup 3}HNBMPR, but the magnitude of this effect varied significantly with the agent tested. Adenosine and diazepam had relatively minor effects on the association rate, whereas dipyridamole and mioflazine slowed the rate dramatically. Inhibitors of nucleoside transport also decreased the rate of dissociation of {sup 3}HNBMPR, with an order of potency significantly different from their relative potencies as inhibitors of the equilibrium binding of {sup 3}HNBMPR. Dilazep, dipyridamole, and mioflazine were effective inhibitors of both {sup 3}HNBMPR dissociation and equilibrium binding. The lidoflazine analogue R75231, on the other hand, had no effect on the rate of dissociation of {sup 3}HNBMPR at concentrations below 300 microM, even though it was one of the most potent inhibitors of {sup 3}HNBMPR binding tested (Ki less than 100 nM). In contrast, a series of natural substrates for the nucleoside transport system enhanced the rate of dissociation of {sup 3}HNBMPR with an order of effectiveness that paralleled their relative affinities for the permeant site of the transporter. The most effective enhancers of {sup 3}HNBMPR dissociation, however, were the benzodiazepines diazepam, chlordiazepoxide, and triazolam.

  1. Development of early myocardial perfusion in diabetic rats:the stress myocardial contrast echocardiography s tudy%负荷心肌超声造影评价糖尿病大鼠早期心肌灌注演变规律

    段云燕; 张军; 卫张蕊; 苏海砾; 刘丽文; 郑敏娟; 朱霆; 李红玲


    Objective To investigate the development of early myocardial perfusion with myocardial contrast echocardiography (MCE) combined with dipyridamole stress echocardiography in diabetic rats . Methods The diabetes mellitus (DM) group comprised 40 male diabetic rats ,induced with streptozotocin . The control group comprised 40 normal male rats ,comparable body weights with the DM group .The DM group was divided into four subgroups (0 week ,2 weeks ,4 weeks and 8 weeks after diabetic model established) and the control group was also divided into four subgroups matched with the DM group .Each rat was performed with conventional echocardiography ,MCE at baseline and after dipyridamole stress .The reserve parameters were compared between the control group and the DM group .In addition ,the differences among four subgroups in the control group and the DM group were compared ,respectively .Results MCE demonstrated that the 4 weeks and 8 weeks DM subgroup had lower myocardial blood velocity reserve and myocardial blood flow reserve than the control subgroup .The myocardial blood volume reserve was reduced in the 8 weeks DM subgroup ,too .Conclusions The impairment of myocardial perfusion in the DM rats are detected earlier with the MCE combined with dipyridamole stress .%目的:应用实时心肌超声造影(MCE)结合潘生丁负荷研究早期糖尿病(DM )大鼠心肌灌注障碍的发生、发展过程和演变规律。方法对照组和DM组各40只大鼠,分为0周、2周、4周和8周四个亚组,于DM成模后不同时间点进行常规超声、MCE并结合潘生丁负荷检查,对各个时间点对照组和DM组两组间各项参数进行比较,同时对组内各个时间点参数进行比较。结果静息MCE指标显示最早从8周亚组可以检出DM组的心肌血容量和心肌血流量的指标较对照组明显减低。潘生丁负荷后DM 组从4周亚组开始血流速度储备和心肌血流量储备较对照组减低,8周亚组的三

  2. Qualitative and semi-quantitative evaluation of myocardium perfusion with 3 T stress cardiac MRI.

    Yun, Chun-Ho; Tsai, Jui-Peng; Tsai, Cheng-Ting; Mok, Greta S P; Sun, Jing-Yi; Hung, Chung-Lieh; Wu, Tung-Hsin; Huang, Wu-Ta; Yang, Fei-Shih; Lee, Jason Jeun-Shenn; Cury, Ricardo C; Fares, Anas; Nshisso, Lemba Dina; Bezerra, Hiram G


    3 T MRI has been adopted by some centers as the primary choice for assessment of myocardial perfusion over conventional 1.5 T MRI. However, there is no data published on the potential additional value of incorporating semi-quantitative data from 3 T MRI. This study sought to determine the performance of qualitative 3 T stress magnetic resonance myocardial perfusion imaging (3 T-MRMPI) and the potential incremental benefit of using a semi-quantitative perfusion technique in patients with suspected coronary artery disease (CAD). Fifty eight patients (41 men; mean age: 59 years) referred for elective diagnostic angiography underwent stress 3 T MRMPI with a 32-channel cardiac receiver coil. The MR protocol included gadolinium-enhanced stress first-pass perfusion (0.56 mg/kg, dipyridamole), rest perfusion, and delayed enhancement (DE). Visual analysis was performed in two steps. Ischemia was defined as a territory with perfusion defect at stress study but no DE or a territory with DE but additional peri-infarcted perfusion defect at stress study. Semi-quantitative analysis was calculated by using the upslope of the signal intensity-time curve during the first pass of contrast medium during dipyridamole stress and at rest. ROC analysis was used to determine the MPRI threshold that maximized sensitivity. Quantitative coronary angiography served as the reference standard with significant stenosis defined as >70 % diameter stenosis. Diagnostic performance was determined on a per-patient and per-vessel basis. Qualitative assessment had an overall sensitivity and specificity for detecting significant stenoses of 77 % and 80 %, respectively. By adding MPRI analysis, in cases with negative qualitative assessment, the overall sensitivity increased to 83 %. The impact of MPRI differed depending on the territory; with the sensitivity for detection of left circumflex (LCx) stenosis improving the most after semi-quantification analysis, (66 % versus 83 %). Pure

  3. Molecular imaging of alkylguanine-DNA alkyltransferase: further evaluation of radioiodinated derivatives of O {sup 6}-benzylguanine

    Shankar, Sriram [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Friedman, Henry [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Department of Pediatrics, Duke University Medical Center, Durham, NC 27710 (United States); Vaidyanathan, Ganesan [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)]. E-mail:


    Purpose: An inverse correlation has been established between tumor levels of the DNA repair protein alkylguanine-DNA alkyltransferase (AGT) and a positive outcome after alkylator chemotherapy. Quantitative imaging of AGT could provide important information for patient-specific cancer treatment. Several radiolabeled analogues of O {sup 6}-benzylguanine (BG), a potent AGT inactivator, have been developed and shown to be capable of labeling pure AGT protein. Herein, two of these analogues - O {sup 6}-3-[*I]iodobenzylguanine ([*I]IBG) and O {sup 6}-3-[*I]iodobenzyl-2'-deoxyguanosine ([*I]IBdG) - were further evaluated in two murine xenograft models. (AcO){sub 2}-[{sup 131}I]IBdG, a peracetylated derivative of IBdG, also was investigated as an alternative agent. Methods: Several biodistribution studies of radioiodinated IBG and IBdG were performed in TE-671 human rhabdomyosarcoma and DAOY human medulloblastoma murine xenograft models. Mice were treated with BG or its nucleoside analogue dBG to deplete the tumor AGT content. The effect of unlabeled IBG and that of 7,8-benzoflavone (BF), an inhibitor of the cytochrome P-450 isozyme CYP1A2, on the tumor uptake of the tracers was determined. The uptake of (AcO){sub 2}-[{sup 131}I]IBdG along with that of [{sup 125}I]IBdG in DAOY cells in vitro was determined in the presence and absence of a nucleoside transporter inhibitor, dipyridamole. Results: Pretreatment of mice either with BG or dBG failed to reduce tumor levels of [*I]IBG or [*I]IBdG even though such treatments completely depleted tumor AGT content. Treatment of mice with BF increased tumor uptake of [{sup 125}I]IBG by 56%; however, differentiation of tumors with and without AGT still was not possible. (AcO){sub 2}-[{sup 131}I]IBdG, a peracetylated derivative of IBdG, had a higher uptake in vitro in DAOY tumor cells. However, its uptake, like that of [{sup 125}I]IBdG, was blocked by dipyridamole. Conclusions: Taken together, these results suggest that labeled

  4. Drug effects on platelet adherence to collagen and damaged vessel walls.

    Packham, M A; Cazenave, J P; Kinlough-Rathbone, R L; Mustard, J F


    The interaction of platelets with damaged vessel walls leads to the formation of platelet-fibrin thrombi and may also contribute to the development of atherosclerotic lesions because platelets adherent to exposed collagen release a mitogen that stimulates smooth muscle cell proliferation. The first step in thrombus formation, platelet adherence to an injured vessel wall, can be studied quantitatively by the use of platelets labeled with 51chromium. In these investigations, rabbit aortas were damaged by passage of a balloon catheter and segments of the aortas were everted on probes that were rotated in platelet suspensions. Collagen-coated glass cylinders were also used. Adherence was measured in a medium containing approximately physiologic concentrations of calcium, magnesium, protein and red blood cells. Conditions of testing influence the effect of non-steroidal anti-inflammatory drugs, sulfinpyrazone, and dipyridamole on platelet adherence. Aspirin and sulfinpyrazone were not inhibitory when tested in a medium with a 40% hematocrit; this indicates that products formed by platelets from arachidonate probably do not play a major part in the adherence of the first layer of platelets to the surface, although they may be involved in thrombus formation. Indomethacin, dipyridamole, prostaglandin E1, methylprednisolone and penicillin G and related antibiotics did inhibit platelet adherence although the concentrations required were higher than would likely be achieved in vivo upon administration to human patients. None of the non-steroidal anti-inflammatory drugs inhibited the release of granule contents from adherent platelets. Pretreatment of the damaged vessel wall with aspirin increased platelet adherence, presumably because it prevented the formation of PGI2 by the vessel wall. Platelet adherence to undamaged or damaged vessel walls was enhanced by prior exposure of the wall to thrombin. Platelet reactions with aggregating agents and platelet survival can be

  5. Sympathetic reinnervation in cardiac transplants: {sup 123}I-MIBG and {sup 201}Tl/{sup 99m}Tc-MIBI scintigraphy

    Kim, J. H.; Oh, S. J.; Son, M. S.; Son, J. W.; Choi, I. S.; Shin, E. K.; Park, C. H. [Gachon Medical School, Gil Heart Cener, Inchon (Korea, Republic of)


    The purpose was to evaluate cardiac sympathetic reinnervation and hemodynamic changes after orthotopic heart transplantation (TPL). We performed 24 serial or followup cardiac 123I-MIBG imaging and rest 201Tl/99mTc-MIBI dipyridamole stress gated myocardial perfusion SPECT (g-MPS) in 15 patients (M:F=10:5;mean ages=34.5{+-}13.0 yr; idiopathic:rheumatic=14:1; one heart lung TPL)(10.80 {+-}11.88 (1-48) mo) after TPL 123I-MIBG imagings were performed in anterior position 15 minutes, 4 and 24 hours after i.v. injection of 148 MBq 123I MIBG. Image quantitation was based on the ratio of heart to mediastinal MIBG uptake (HMR) Compared to HMR on 15 min images (1.48 {+-} 0.28), neither four nor 24 hour delayed images (1.26 {+-} 0.23 vs. 1.06 {+-} 0.26: p<0.05, respectively, ANOVA) showed definite delayed localization of MIBG. 12 subjects with <13 (4.9 {+-}3.7) months after TPL had no visible 123I-MIBG uptake on early 15 min imaging however, 12 subjects with 13 to 48(28.6{+-}12.8) months had visible cardiac 123I-MIBG uptake (HMR: 1.65{+-}0.21 vs. 1.32{+-}0.26; p=0.002). One-year followup 123I-MIBG scintigraphy in nine pts showed significantly increased HMR(1.40{+-}0.31 to 1.61{+-}0.16, p<0.05) but a plateau was reached at HMR value of 2.0, which was still lower than 3.0 in normal controls. Plasma NE was increased according to I-123 MIBG myocardial uptake. Annual G-MPS detected an allograft atherosclerosis in one pt and showed progressive normalization of tachycardia and significant deterioration of LVEF and cardiac indices according to severity of rejection. To dipyridamole stress, transplant heats showed significant subnormal hemodynamic responses. Partial sympathetic late reinnervation can occur <1 year after TPL, and reached a plateau of two-third of normal value. G-MPS seems to be a useful screening test for the detection of allograft atherosclerosis and rejection.

  6. Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes

    Marini, Cecilia [CNR Institute of Bioimages and Molecular Physiology, Milan, Section of Genoa (Italy); Bezante, GianPaolo; Modonesi, Elisa; Rollando, Daniela; Balbi, Manrico; Brunelli, Claudio [University of Genoa, Department of Internal Medicine, Cardiology, Genoa (Italy); Gandolfo, Patrizia; Morbelli, Silvia D.; Armonino, Riccardo [University of Genoa, Department of Internal Medicine, Nuclear Medicine, Genoa (Italy); DePascale, Angelo; Maggi, Davide; Albertelli, Manuela; Cordera, Renzo [University of Genoa, Department of Endocrinological Metabolic Sciences, Diabetology, Genoa (Italy); Sambuceti, Gianmario [University of Genoa, Department of Internal Medicine, Nuclear Medicine, Genoa (Italy); Advanced Biotechnology Center, Genoa (Italy)


    The aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2). A total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using {sup 99m}Tc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session. Estimated MPR was higher in control subjects than in patients (3.36 {+-} 0.66 vs 1.91 {+-} 0.61, respectively, p < 0.01). In patients, LAD CFR and LAD MPR were 2.01 {+-} 0.78 vs 1.93 {+-} 0.63, respectively (p = ns). The agreement between the two techniques was documented by their close correlation (r = 0.92, p < 0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10 {+-} 0.71 vs 1.83 {+-} 0.71, respectively, p = ns). Finally, MPR was closely correlated with age (r = -0.50, p < 0.01) and time elapsed from the diagnosis of DM2 (r = -0.51, p < 0.01). LV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects. (orig.)

  7. Myocardial perfusion scintigraphy in Germany in 2009: utilization and state of the practice

    Lindner, Oliver; Burchert, Wolfgang [University Hospital of the Ruhr University Bochum, Institute of Radiology, Nuclear Medicine and Molecular Imaging, Heart and Diabetes Centre North Rhine-Westphalia, Bad Oeynhausen (Germany); Bengel, Frank M. [Hanover University School of Medicine, Department of Nuclear Medicine, Hannover (Germany); Zimmermann, Rainer [Klinikum Pforzheim GmbH, Cardiology Department, Pforzheim (Germany); Dahl, Juergen vom [Kliniken Maria Hilf GmbH, Cardiology Department, Moenchengladbach (Germany); Schaefers, Michael [Westfaelische Wilhelms Universitaet Muenster, European Institute of Molecular Imaging, Muenster (Germany)


    Since 2006, the working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine, in cooperation with the working group Nuclear Cardiology of the German Cardiac Society, has been surveying the utilization and technical realization of myocardial perfusion scintigraphy (MPS) in Germany. This paper presents the results of the reporting year 2009. A total of 291 centres participated in the inquiry, including 179 private practices (PP), 86 hospitals (HO) and 26 university hospitals (UH). MPS of 98,103 patients were reported. The MPS numbers per million population (pmp) were estimated at 2,360; 76% of the MPS were performed in PP, 17% in HO and 7% in UH. The ratio of MPS to coronary angiography to revascularization was 0.5 to 2.3 to 1. Data from 134 centres which participated in the surveys from 2005 to 2009 showed a decrease in MPS utilization of 2.2%. Nearly half of the MPS were requested by ambulatory care cardiologists. Of all MPS studies, 89% were conducted with {sup 99m}Tc perfusion tracers. Ergometry was the preferred stress test (69%). Adenosine was used in 16%, adenosine + exercise in 7%, dipyridamole in 3%, dipyridamole + exercise in 5% and dobutamine in <1%. Gated single proton emission computed tomography (SPECT) acquisition was performed in 56% of all rest MPS and in 56% of all stress MPS. Both rest and stress MPS were ECG gated in 41%. Only 33% of the centres always performed a quantification of the perfusion studies, whereas 51% did not apply any quantification; 4% of the MPS studies were corrected for attenuation, and 17 centres used transmission sources of 12 CT-based systems. A scan activity of 2,380 MPS pmp is in the upper third of the European range. The ratios to coronary angiography and to revascularization suggest that angiography dominates diagnosis and management of coronary artery disease (CAD). The clinical and technical realizations reveal that the predominant goals of further trainings to optimize MPS are in the field

  8. Sympathetic reinnervation in cardiac transplants : preliminary results {sup 123}I-MIBG and {sup 201}Tl/{sup 99m}Tc-MIBI scintigraphy

    Kim, Joug Ho; Oh, Se Jin; Son, Min Soo; Son, Ji Won; Choi, In Seok; Shin, Euk Kyun; Park, Kuk Yang; Kim, Ju E. [International Medicine and Thoraic Surgery, Inchon (Korea, Republic of)


    Iodine-123 metaiodobenzylguanidine ({sup 123}I-MIBG) is a norepinephrine (NE) analogue. To determine whether cardiac sympathetic reinnervation occurs after orthotopic heart transplantation (TPL). Nine patients (M : F=7 :2; mean ages=34{+-}24.1 yr; idiopathic:rheumatic = 8: 1) within 197.{+-}14.3 (4-36) months after TPL performed both {sup 123}I-MIBG scintigraphy and {sup 201}Tl/{sup 99m}Tc-MIBI dipyridamole stress gated myocardial perfusion SPECT (g-MPS). {sup 23}I-MIBG imagings were performed in anterior position 15 minutes, 4 and 24 hours after i.v. injection of 148 MBq {sup 123}I MIBG. Image quantitation was based on the ratio of hear to mediastinal MIBG uptake (HMR). Six subjects with <14 (4.3{+-}1.4) months after TPL had no visible {sup 123}I-MIBG uptake on early 15. min imaging however, three subjects with 26 to 36(32.0{+-}5.3) months had visible cardiac {sup 123}I-MIBG uptake (HMR:1.24{+-}0.09 vs. 1.8{+-}0.2). Correlation was found between plasma NE concentration and HMR(r=0.80: p<0.05). Compared to HMR on 15 min images (1.5{+-}0.3), neither four nor 24 hour delayed images (1.3{+-}0.3 vs. 1.1{+-}0.1 : p<0.05, respectively, ANOVA) showed definite delayed localization of MIBG. The uptakes in the liver, lung, salivary glands and spleen were present. To dipyridamole stress, transplant hearts showed significant subnormal hemodynamic responses of HR, s-BP, d-BP, and rate pressure product (95.4{+-}13.8 to 107.4{+-}14.6, 131.0{+-}16.7 to 123.6{+-}13.4, 79.1{+-}12.7 to 72.2{+-}12.7, 124.5{+-}19.6 to 133.0{+-}23.6 p<0.05, respectively). G-MPS of one patient shod an apicoanterior wall reversible perfusion defect which was confirmed as 90% distal left anterior descending artery stenosis by coronary angiography. MIBG uptake seems to involve mainly the specific sodium and energy dependent uptake-1 pathway, and the non-neuronal uptake-2 involving simple diffusion is not significant. Conclusively, partial sympathetic late reinnervation of the transplant human hearts can

  9. Mechanisms of relaxation induced by flavonoid ayanin in isolated aorta rings from Wistar rats

    Rosalía Carrón


    Full Text Available Introduction: This study shows the relaxant effect induced by ayanin in aorta rings from Wistar rats linked to nitric oxide/cyclic-GMP pathway.  This flavonoid is the prevalent compound obtained from Croton schiedeanus Schlecht (Euphorbiaceae, specie used in Colombian folk medicine for the treatment of arterial hypertension. Objectives: To identify possible action mechanisms of vascular relaxation induced by ayanin (quercetin 3,4',7-trimethyl ether. Methodology: Isolated aorta rings from Wistar rats obtained at the Animal House of the University of Salamanca were contracted with KCl (80 mM or phenylephrine (PE, 10-6 M and exposed to ayanin (10-6-10-4 M.  Then, the effect of ayanin was assessed in deendothelized rings contracted with PE and in intact rings contracted with PE previously incubated with: ODQ (10-6 M, L-NAME (10-4 M, L-NAME plus D- and L-arginine (10-4 M, indomethacin (5x10-6 M, dipyridamole (3x10-7 M, glibenclamide (10-6 M, propranolol (10-6 M, verapamil (10-7 M or atropine (3x10-5 M.  In addition, the relaxant effect of acetylcholine (Ach, 10-8-3x10-4 M, and sodium nitroprusside (SNP, 10-9-3x10-5 M was assessed in the presence and absence of ayanin (10-6 M. Results: Ayanin induced a greater concentration-dependent relaxation in vessels contracted with phenylephrine (pEC50: 5.84±0.05, an effect significantly reduced by deendothelization and by both ODQ and L-NAME.  L-arginine was able to reverse the effect of L-NAME.  Indomethacin weakly inhibited ayanin response.  Dipyridamole, glibenclamide, propranolol, verapamil, and atropine did not affect ayanin relaxation.  Ayanin did not have any effect on the relaxation elicited by acetylcholine (ACh, while weakly decreasing the relaxation induced by sodium nitroprusside (SNP. Conclusion: Ayanin induces endothelium-dependent relaxation in the rat aorta mainly related to nitric oxide/cGMP pathway, according to the response observed in the presence of L-NAME, L-arginine and ODQ.

  10. The role of purinergic and dopaminergic systems on MK-801-induced antidepressant effects in zebrafish.

    da Silva, Raquel Bohrer; Siebel, Anna Maria; Bonan, Carla Denise


    Depression is a serious disease characterized by low mood, anhedonia, loss of interest in daily activities, appetite and sleep disturbances, reduced concentration, and psychomotor agitation. There is a growing interest in NMDA antagonists as a promising target for the development of new antidepressants. Considering that purinergic and dopaminergic systems are involved in depression and anxiety states, we characterized the role of these signaling pathways on MK-801-induced antidepressant effects in zebrafish. Animals treated with MK-801 at the doses of 5, 10, 15, or 20μM during 15, 30, or 60min spent longer time in the top area of aquariums in comparison to control group, indicating an anxiolytic/antidepressant effect induced by this drug. Animals treated with MK-801 spent longer time period at top area until 2 (5μM MK-801) and 4 (20μM MK-801) hours after treatment, returning to basal levels from 24h to 7days after exposure. Repeated MK-801 treatment did not induce cumulative effects, since animals treated daily during 7days had the same behavioral response pattern observed since the first until the 7th day. In order to investigate the effects of adenosine A1 and A2A receptor antagonist and agonist and the influence of modulation of adenosine levels on MK-801 effects, we treated zebrafish with caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI during 30min before MK-801 exposure. The non-specific adenosine receptor antagonist caffeine (50mg/kg) and the selective A1 receptor antagonist DPCPX (15mg/kg) prevented the behavioral changes induced by MK-801. The non-specific nucleoside transporter (NT) inhibitor dipyridamole (10mg/kg) exacerbated the behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride and SCH 23390) did not change the behavioral alterations induced by MK-801. Our findings demonstrated that antidepressant-like effects of MK-801 in zebrafish are mediated through adenosine A1 receptor activation.

  11. Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes – a randomized, single-blinded, cross-over pilot study

    Faber, Rebekka; Zander, Mette; Pena, Adam


    33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45). There was a small increase in CFR following liraglutide treatment (change 0.18, CI95% [-0.01; 0.36], p = 0.06) but no difference in effect in comparison with no treatment (difference between treatment allocation 0.16, CI95% [-0.08; 0.40], p = 0......-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes and no history of coronary artery disease were treated...... dipyridamole induced stress. Peripheral microvascular endothelial function was assessed by Endo-PAT2000®. Interventions were compared by two-sample t-test after ensuring no carry over effect. RESULTS: A total of 24 patients were included. Twenty patients completed the study (15 male; mean age 57 ± 9; mean BMI...

  12. Non-invasive assessment of functionally relevant coronary artery stenoses with quantitative CT perfusion: preliminary clinical experiences

    So, Aaron [Lawson Health Research Institute, Imaging Program, London, Ontario (Canada); Robarts Research Institute, Imaging Research Laboratories, London, Ontario (Canada); University of Western Ontario, Medical Biophysics, London, Ontario (Canada); Wisenberg, Gerald [Lawson Health Research Institute, Imaging Program, London, Ontario (Canada); University of Western Ontario, Medical Biophysics, London, Ontario (Canada); University of Western Ontario, Medical Imaging, London, Ontario (Canada); London Health Sciences Centre, Cardiology, London, Ontario (Canada); Islam, Ali; Amann, Justin; Romano, Walter [University of Western Ontario, Medical Imaging, London, Ontario (Canada); St. Joseph' s Health Care, Radiology, London, Ontario (Canada); Brown, James; Humen, Dennis; Jablonsky, George [London Health Sciences Centre, Cardiology, London, Ontario (Canada); Li, Jian-Ying; Hsieh, Jiang [GE Healthcare, CT Engineering, Waukesha, Wisconsin (United States); Lee, Ting-Yim [Lawson Health Research Institute, Imaging Program, London, Ontario (Canada); Robarts Research Institute, Imaging Research Laboratories, London, Ontario (Canada); University of Western Ontario, Medical Biophysics, London, Ontario (Canada); University of Western Ontario, Medical Imaging, London, Ontario (Canada)


    We developed a quantitative Dynamic Contrast-Enhanced CT (DCE-CT) technique for measuring Myocardial Perfusion Reserve (MPR) and Volume Reserve (MVR) and studied their relationship with coronary stenosis. Twenty-six patients with Coronary Artery Disease (CAD) were recruited. Degree of stenosis in each coronary artery was classified from catheter-based angiograms as Non-Stenosed (NS, angiographically normal or mildly irregular), Moderately Stenosed (MS, 50-80% reduction in luminal diameter), Severely Stenosed (SS, >80%) and SS with Collaterals (SSC). DCE-CT at rest and after dipyridamole infusion was performed using 64-slice CT. Mid-diastolic heart images were corrected for beam hardening and analyzed using proprietary software to calculate Myocardial Blood Flow (MBF, in mLmin{sup -1}100 g{sup -1}) and Blood Volume (MBV, in mL100 g{sup -1}) parametric maps. MPR and MVR in each coronary territory were calculated by dividing MBF and MBV after pharmacological stress by their respective baseline values. MPR and MVR in MS and SS territories were significantly lower than those of NS territories (p < 0.05 for all). Logistic regression analysis identified MPR MVR as the best predictor of {>=}50% coronary lesion than MPR or MVR alone. DCE-CT imaging with quantitative CT perfusion analysis could be useful for detecting coronary stenoses that are functionally significant. (orig.)

  13. Challenge of paediatric compounding to solid dosage forms sachets and hard capsules - Finnish perspective.

    Sivén, Mia; Kovanen, Satu; Siirola, Outi; Hepojoki, Tuomas; Isokirmo, Sari; Laihanen, Niina; Eränen, Tiina; Pellinen, Jukka; Juppo, Anne M


    The study evaluated the quality of compounded sachets and hard gelatine capsules and their feasibility in paediatric drug administration. Commercial tablets were compounded to sachets and capsules in hospital environment, and the uniformity of content and simulated drug dose were determined. Compounded formulations were successfully obtained for a range of drug substances; dipyridamole, spironolactone, warfarin and sotalol formulations were within acceptable limits for uniformity of content, in most cases. However, some loss of drug was seen. The type and amount of excipients were found to affect uniformity of content; good conformity of capsules was obtained using lactose monohydrate as filler, whereas microcrystalline cellulose was a better choice in sachets. In capsules, content uniformity was obtained for a range of drug doses. If the drug is aimed to be administered through a nasogastric tube, solubility of the drug and excipients should be considered, as they were found to affect the simulated drug dose in administration. Compounded sachets and capsules fulfilled the quality requirements in most cases. In compounding, the choice of excipients should be considered as they can affect conformity of the dosage form or its usability in practice. Quality assurance of compounded formulations should be taken into consideration in hospital pharmacies. © 2016 Royal Pharmaceutical Society.

  14. Myocardial perfusion scintigraphy in Germany. Results of the 2005 query and current status

    Lindner, O. [Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung, Herz- und Diabeteszentrum NRW, Bad Oeynhausen (Germany); Burchert, W. [Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung, Herz- und Diabeteszentrum NRW, Bad Oeynhausen (Germany); Arbeitsgemeinschaft ' ' Kardiovaskulaere Nuklearmedizin' ' der Deutschen Gesellschaft fuer Nuklearmedizin (Germany); Bengel, F.M. [Cardiovascular Nuclear Medicine, Johns Hopkins Medical Insts., Baltimore (United States); Arbeitsgruppe ' ' Nuklearkardiologische Diagnostik' ' der Deutschen Gesellschaft fuer Kardiologie (Germany); Zimmermann, R. [Arbeitsgruppe ' ' Nuklearkardiologische Diagnostik' ' der Deutschen Gesellschaft fuer Kardiologie (Germany); Medizinische Klinik, Klinikum Pforzheim GmbH (Germany); Dahl, J. vom [Klinik fuer Kardiologie, Kliniken Maria Hilf GmbH, Moenchengladbach (Germany); Schaefer, W.; Buell, U. [Klinik fuer Nuklearmedizin, Universitaetsklinikum Aachen (Germany); Schober, O. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Muenster (Germany); Schwaiger, M. [Nuklearmedizinische Klinik, Klinikum Rechts der Isar, Muenchen (Germany); Kluge, R. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Leipzig (Germany); Schaefers, M. [Arbeitsgemeinschaft ' ' Kardiovaskulaere Nuklearmedizin' ' der Deutschen Gesellschaft fuer Nuklearmedizin (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Muenster (Germany)


    The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine (DGN), in cooperation with the working group Nuclear Cardiology of the German Cardiac Society (DGK), decided to conduct a national survey on myocardial perfusion scintigraphy (MPS). Method: a questionnaire to evaluate MPS for the year 2005 was sent. Results: 346 completed questionnaires had been returned (213 private practices, 99 hospitals and 33 university hospitals). MPS of 112 707 patients were reported with 110 747 stress and 95 878 rest studies. The majority (> 75%) was performed with {sup 99m}Tc-MIBI or tetrofosmin. {sup 201}Tl stress-redistribution was used in 22 637 patients (20%). The types of stress were exercise in 78%, vasodilation with adenosine or dipyridamol in 21% and dobutamine in 1%. 99.97% of all MPS were SPECT studies. Gated SPECT was performed in 36% of the stress and in 32% of the rest studies. An attenuation correction was used in 21%. 29 institutions (8%) performed gated SPECT (stress and rest) and attenuation correction. 47% of all MPS were requested by ambulatory care cardiologists, 17% by internists, 12% by primary care physicians, 21% by hospital departments and 2% by others. Conclusion: in Germany, MPS is predominantly performed with {sup 99m}Tc-perfusion agents. The common type of stress is ergometry. Gated SPECT and attenuation correction do not yet represent standards of MPS practice in Germany, which indicates some potential of optimization. (orig.)

  15. Homology modeling, docking studies and molecular dynamic simulations using graphical processing unit architecture to probe the type-11 phosphodiesterase catalytic site: a computational approach for the rational design of selective inhibitors.

    Cichero, Elena; D'Ursi, Pasqualina; Moscatelli, Marco; Bruno, Olga; Orro, Alessandro; Rotolo, Chiara; Milanesi, Luciano; Fossa, Paola


    Phosphodiesterase 11 (PDE11) is the latest isoform of the PDEs family to be identified, acting on both cyclic adenosine monophosphate and cyclic guanosine monophosphate. The initial reports of PDE11 found evidence for PDE11 expression in skeletal muscle, prostate, testis, and salivary glands; however, the tissue distribution of PDE11 still remains a topic of active study and some controversy. Given the sequence similarity between PDE11 and PDE5, several PDE5 inhibitors have been shown to cross-react with PDE11. Accordingly, many non-selective inhibitors, such as IBMX, zaprinast, sildenafil, and dipyridamole, have been documented to inhibit PDE11. Only recently, a series of dihydrothieno[3,2-d]pyrimidin-4(3H)-one derivatives proved to be selective toward the PDE11 isoform. In the absence of experimental data about PDE11 X-ray structures, we found interesting to gain a better understanding of the enzyme-inhibitor interactions using in silico simulations. In this work, we describe a computational approach based on homology modeling, docking, and molecular dynamics simulation to derive a predictive 3D model of PDE11. Using a Graphical Processing Unit architecture, it is possible to perform long simulations, find stable interactions involved in the complex, and finally to suggest guideline for the identification and synthesis of potent and selective inhibitors.

  16. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J. [Institute of Biophysics, Academy of Sciences of the Czech Republic (Czech Republic)


    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 {mu}g/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  17. Responses to adenosine of isolated transverse or spiral strips of sensitized guinea pig trachea: role of epithelium%致敏离体豚鼠气管横向或螺旋条对腺苷的收缩

    Julian R THORNE; Kenneth J BROADLEY


    AIM: To determine the role of the epithelium in the re sponses to adenosine of isolated trachea from ovalbumin sensitized guinea pigs. METHODS: Spirally cut tra cheal preparations were superfused or immersed in organ baths and transversely cut strips were immersed. Epithe lium was removed mechanically from some strips and confirmed by histological examination of a random sample. Tissues were from unsensitized or ovalbumin sensitized guinea pigs. Isometric tension was measured and responses to adenosine recorded. RESULTS: In sensitized tissues, contractile responses to adenosine were evident as contractions of superfused spirals or as right wards shift of the concentration-response curve compared with non-sensitized immersed spirals. Epithelium re moval potentiated relaxation responses in both non sensitized and sensitized strips indicating release of con tractile mediators in both tissues. Dipyridamole potenti ated relaxation responses in sensitized tissues with and without epithelium. CONCLUSION: Sensitization re veals a contractile response to adenosine. The epithelium is not involved in this contractile response nor is it the major site of uptake of adenosine in both sensitized and non-sensitized tissues.

  18. Antithrombotic therapy for the CardioWest temporary total artificial heart.

    Ensor, Christopher R; Cahoon, William D; Crouch, Michael A; Katlaps, Gundars J; Hess, Michael L; Cooke, Richard H; Gunnerson, Kyle J; Kasirajan, Vigneshwar


    The CardioWest temporary total artificial heart serves as a viable bridge to orthotopic heart transplantation in patients who are experiencing end-stage refractory biventricular heart failure. This device is associated with a low, albeit still substantial, risk of thrombosis. Platelet interactions with artificial surfaces are complex and result in continuous activation of contact proteins despite therapeutic anticoagulation. We searched the medical literature (publication dates, January 1962-October 2009) in order to evaluate means of mitigating adverse events that have occurred after implantation of the CardioWest temporary total artificial heart.We conclude that the use of a multitargeted antithrombotic approach, involving anticoagulation (bivalirudin and warfarin) and antiplatelet therapy (dipyridamole and aspirin), can mitigate the procoagulative effects of mechanical circulatory assist devices, particularly those that are associated with the CardioWest temporary total artificial heart. Careful monitoring with use of a variant multisystem approach, involving efficacy tests (thrombelastography and light transmittance aggregometry), safety tests (laboratory analyses), and warfarin genomics, may maximize the therapeutic actions and minimize the bleeding risks that are associated with the multitargeted antithrombotic approach. The development and monitoring of individualized antithrombotic regimens require that informed health professionals appreciate the complexities and grasp the hazards that are associated with these therapies.

  19. Effect of storage conditions on the recrystallization of drugs in solid dispersions with crospovidone.

    Shibata, Yusuke; Fujii, Makiko; Suzuki, Ayako; Koizumi, Naoya; Kanada, Ken; Yamada, Masaki; Watanabe, Yoshiteru


    The physical stability of amorphous solid dispersions (SDs) is influenced by their storage conditions. The goal of this work was to investigate the factors affecting the recrystallization of drugs in SDs after storage under conditions of high temperature and high humidity. SDs of three drugs (dipyridamole, nifedipine and indomethacin) with different functional groups (amino, carbonyl and hydroxyl) and onset times for crystallization of the amorphous state were prepared using crospovidone (CrosPVP). All of the drugs in the SDs remained in an amorphous state at 25 °C/50% relative humidity (RH) in closed glass bottles for at least six months. Under conditions of high temperature (40 °C/75%RH/closed and 60 °C/open), differences in interactions between the hydrogen bond donors of the drugs and the amide carbonyl group of CrosPVP are essential factors for recrystallization of the drugs in the SDs. On the other hand, under condition of high humidity (40 °C/75%RH/open), in addition to the difference in the interaction between the drug and CrosPVP, the rate of increase in moisture content affects their recrystallization in SDs.

  20. Dobutamine stress radionuclide ventriculography reveals silent myocardial dysfunction in Kawasaki disease

    Hamamichi, Yuji; Ichida, Fukiko; Tsubata, Shinichi [Toyama Medical and Pharmaceutical Univ., Sugitani (Japan). Faculty of Medicine] (and others)


    Dobutamine (DOB) stress radionuclide ventriculography (RVG) is proposed for evaluating left ventricular performance in patients with Kawasaki disease (KD). Dobutamine stress RVG, up to 15{mu}g{center_dot}kg{sup -1}{center_dot}min{sup -1}, was performed in 40 patients with a history of KD, some of whom had a perfusion defect (PD group) on dipyridamole stress thallium-201 myocardial imaging, some of whom had no perfusion defects (NPD group), and some of whom had no coronary artery lesions (C group). No significant differences in either systolic or diastolic indices of the left ventricle at rest were observed between the 3 groups. Although hemodynamic responses were similar in all patients after DOB stress, early diastolic index of the first third filling fraction decreased only in the PD group and was significantly lower in this group compared with the C group (p<0.01). The asynchrony index increased significantly in those patients with coronary stenosis after DOB stress (p<0.05). No serious side-effects were observed during the study. Even late after onset, patients with myocardial ischemia as a result of KD still had impaired early diastolic filling and asynchronous relaxation of the left ventricle. As an alternative to exercise testing, DOB stress RVG is a safe and promising means for serially evaluating left ventricular performance in patients with KD. (author)

  1. [Effects of vasodilators on cyclic contraction induced by 3,4-diaminopyridine in isolated porcine coronary arteries].

    Ogawa, Y; Imai, S


    3,4-Diaminopyridine (3,4-DAP), which is known to decrease K conductance, produced spontaneous repetitive phasic contractions of a regular (28/60) and an irregular (15/60) cycle or tonic contraction (16/60) following a latent period of 5-100 min in isolated porcine coronary arteries. Effects of pinacidil, a newly-synthesized vasodilator, were investigated using the preparation in which 3,4-DAP produced phasic contractions of the regular cycle in comparison with those of various vasodilators. Pinacidil produced dose-dependent prolongation of the cycle and reduced the peak tension and the tension at the relaxation phase, a mode of action that closely resembles that of nicorandil, suggesting the increase in K conductance and hyperpolarization. Nifedipine (10(-8) M) and dilazep (10(-4) M) markedly reduced the peak tension, while adenosine, dipyridamole and nitroglycerin did not produce such effects. The latter three drugs produced a prolongation of the cycle and reduced the tension of the relaxation phase. These data suggest that reduction of K conductance and activation of the voltage-dependent Ca channel may play an important role in initiation of the spontaneous repetitive phasic contraction in porcine coronary artery.

  2. [Exacerbations of asthma--precipitating factors: drugs].

    Sanfiorenzo, C; Pipet, A


    Asthmatic exacerbations are sometimes triggered by medications, primarily the non-steroidal anti-inflammatory agents (NSAIDS) and beta-blockers. Asthma attacks induced by NSAIDS occur rapidly and can be severe. Widal syndrome is a specific disease entity whose physiopathology remains incompletely explained. Asthma is characteristically severe and steroid dependent; desensitisation with aspirin has been proposed, but this remains controversial. Beta-blockers are contra-indicated in asthma; the β1 "cardioselectivity" of some agents is not absolute, disappearing at high doses and the "partial agonists" are not better tolerated. However, certain authors have called into question the harmful effect of beta-blockade in moderate and stable asthma. More studies are needed, but the current data suggest that in some cases beta-blockers may be safe but their use requires close supervision. Other molecules can pose problems in asthmatics (dipyridamole, synthetic sex hormones and certain excipients). On the whole, there has been little innovation concerning the hazard that drugs can pose for some asthmatics. The task for the future will be to specify the physiopathology of Widal syndrome, and to clarify the categories of patients in whom beta-blockers can be safely employed as the public health consequences of cardiovascular pathologies make this an important issue for lung specialists.

  3. The successful treatment of rapidly progressive idiopathic membranoproliferative glomerulo-nephritis Type 1 in a 4-year-old male pediatric patient.

    Fujinaga, S; Ohtomo, Y; Hirano, D; Nishizaki, N; Someya, T; Ohtsuka, Y; Kaneko, K; Shimizu, T


    A multivariate analysis [4] revealed that the presence of crescent formation on initial biopsy irrespective of type of membranoproliferative glomerulonephritis (MPGN) was independently associated not only with end-stage renal disease but also with post-transplantation recurrence. In this study, we reported on a 4-year-old male pediatric patient requiring hemodialysis due to rapidly progressive idiopathic MPGN Type 1 with severe nephrotic syndrome and extensive cellular crescent formation on initial biopsy. The patient had been treated intravenously (i.v.) with 9 pulses of methylprednisolone, followed by daily prednisolone, resulting in the withdrawal of dialysis within 1 month. However, since active lesions in the second renal biopsy such as cellular crescents still remained and nephrotic range proteinuria had persisted for more than 2 months, the patient received additional 3 i.v. pulses of methylprednisolone, followed by combinations of alternate-day prednisolone, mizoribine, dipyridamole and warfarin, which lead to complete remission in a short-period of time. The patient has been off the combination therapy for 10 months because the third biopsy prior to the termination of this regimen showed decreased inflammatory activity. There is currently no established protocol for children with crescentic MPGN due to a rarity of its clinicopathological presentation. This case report indicates that early treatment with multiple pulses of methylprednisolone followed by the short-term combination therapy may be of benefit for children with rapidly progressive idiopathic MPGN Type 1, even when both diffuse crescentic changes and nephrotic syndrome are present at onset.

  4. Sleeping Beauty-Mediated Drug Resistance Gene Transfer in Human Hematopoietic Progenitor Cells

    Hyland, Kendra A.; Olson, Erik R.; McIvor, R. Scott


    The Sleeping Beauty (SB) transposon system can insert sequences into mammalian chromosomes, supporting long-term expression of both reporter and therapeutic genes. Hematopoietic progenitor cells (HPCs) are an ideal therapeutic gene transfer target as they are used in therapy for a variety of hematologic and metabolic conditions. As successful SB-mediated gene transfer into human CD34+ HPCs has been reported by several laboratories, we sought to extend these studies to the introduction of a therapeutic gene conferring resistance to methotrexate (MTX), potentially providing a chemoprotective effect after engraftment. SB-mediated transposition of hematopoietic progenitors, using a transposon encoding an L22Y variant dihydrofolate reductase fused to green fluorescent protein, conferred resistance to methotrexate and dipyridamole, a nucleoside transport inhibitor that tightens MTX selection conditions, as assessed by in vitro hematopoietic colony formation. Transposition of individual transgenes was confirmed by sequence analysis of transposon–chromosome junctions recovered by linear amplification-mediated PCR. These studies demonstrate the potential of SB-mediated transposition of HPCs for expression of drug resistance genes for selective and chemoprotective applications. PMID:26176276

  5. 速度向量成像结合潘生丁负荷在糖尿病大鼠心肌收缩功能评价中的应用价值%Value of velocity vector imaging and stress echocardiography in the assessment of systolic function of left ventricular in diabetic rats

    卫张蕊; 张军; 张海滨; 苏海砾; 施红


    目的 探讨速度向量成像(VVI)技术结合潘生丁负荷试验是否可以早期检测糖尿病(DM)大鼠左室壁潜在的心肌功能障碍.方法 雄性SD大鼠18只,腹腔注射链脲菌素复制DM模型,另12只体质量匹配的雄性SD大鼠腹腔注射等量柠檬酸缓冲液作为对照.分别在静息状态和潘生丁负荷后,对两组大鼠(12周)乳头肌水平左室短轴观行VVI及M型超声心动图检查,分别测量潘生丁负荷前后乳头肌水平左室短轴观各个节段心肌最大收缩速度(Vs)、切向应变(εc)、径向应变(εr)、收缩期最大切向应变率(SRc)、径向应变率(SRr)及室壁增厚率的平均值.处死动物,摘除心脏,行HE染色及透射电镜检查.结果 静息状态下,DM组SRc较对照组显著减低(P<0.05),其余指标与对照组的差异无统计学意义.潘生丁负荷后,DM组各指标均较对照组显著减低(P<0.05).而M型检测的两组间室壁增厚率的差异并无统计学意义(P>0.05).结论 VVI与负荷超声心动图相结合,可以更敏感地检测出DM大鼠潜在的室壁运动异常.SRc可能是更为敏感的指标,其在静息状态下便可以检测出这种室壁运动的异常.%Objective To investigate whether velocity vector imaging (VVI) combined with stress echocardiography could detect potential myocardial impairment of the left ventricle(LV) in diabetic rats.Methods DM rats ( n = 18,administered by STZ at 65 mg/kg) and control rats( n = 12) were performed with VVI and M-mode echocardiography both at rest and after dipyridamole stress 12 weeks later. Twodimensional echocardiographic cine loops and M-mode images of three consecutive beats were obtained from the short-axis views at the mid-LV level. The means of segmental peak systolic velocity(Vs), circumferential strain(εc) ,radial strain(εr), systolic circumferential and radial strain rate (SRc, SRr) and the percent wall thickening (WT% ,derived from M-mode) were obtained. After echocardiograms

  6. Protection against adriamycin (doxorubicin-induced toxicity in mice by several clinically used drugs.



    Full Text Available Protective effects of clinically used drugs against adriamycin (ADM-induced toxicity were studied in ICR mice. The control mice, which were administered 15 mg/kg of ADM twice, survived 7.48 +/- 1.99 days (mean +/- S.D.. The survival times of mice treated with the following drugs, expressed as a percent of that of the control group, were 293.6% for coenzyme Q10 (Co Q10, 2 mg/kg, 402.2% for dextran sulfate (MDS, 300 mg/kg, 121.6% for flavin adenine dinucleotide (20 mg/kg, 236.3% for adenosine triphosphate disodium (50 mg/kg, 213.7% for reduced glutathione (100 mg/kg, 121.6% for phytonadione (50 mg/kg, 155.2% for inositol nicotinate (Ino-N, 500 mg/kg, 335.5% for nicomol (1000 mg/kg, 157.5% for nicardipine (10 mg/kg and 123.3% for dipyridamol (50 mg/kg. Anti-hyperlipemic agents such as MDS, nicomol, Ino-N and Co Q10 strongly protected against the ADM-induced toxicity, and the mice administered these drugs lived significantly longer than the control mice. The mechanism of the protective effect was discussed.

  7. PDE8 regulates rapid Teff cell adhesion and proliferation independent of ICER.

    Amanda G Vang

    Full Text Available BACKGROUND: Abolishing the inhibitory signal of intracellular cAMP by phosphodiesterases (PDEs is a prerequisite for effector T (Teff cell function. While PDE4 plays a prominent role, its control of cAMP levels in Teff cells is not exclusive. T cell activation has been shown to induce PDE8, a PDE isoform with 40- to 100-fold greater affinity for cAMP than PDE4. Thus, we postulated that PDE8 is an important regulator of Teff cell functions. METHODOLOGY/PRINCIPAL FINDINGS: We found that Teff cells express PDE8 in vivo. Inhibition of PDE8 by the PDE inhibitor dipyridamole (DP activates cAMP signaling and suppresses two major integrins involved in Teff cell adhesion. Accordingly, DP as well as the novel PDE8-selective inhibitor PF-4957325-00 suppress firm attachment of Teff cells to endothelial cells. Analysis of downstream signaling shows that DP suppresses proliferation and cytokine expression of Teff cells from Crem-/- mice lacking the inducible cAMP early repressor (ICER. Importantly, endothelial cells also express PDE8. DP treatment decreases vascular adhesion molecule and chemokine expression, while upregulating the tight junction molecule claudin-5. In vivo, DP reduces CXCL12 gene expression as determined by in situ probing of the mouse microvasculature by cell-selective laser-capture microdissection. CONCLUSION/SIGNIFICANCE: Collectively, our data identify PDE8 as a novel target for suppression of Teff cell functions, including adhesion to endothelial cells.

  8. Adenosine improves cardiomyocyte respiratory efficiency.

    Babsky, A M; Doliba, M M; Doliba, N M; Osbakken, M D


    The role of adenosine on the regulation of mitochondrial function has been studied. In order to evaluate this the following experiments were done in isolated rat cardiomyocites and mitochondria using polarographic techniques. Cardiomyocyte oxygen consumption (MVO2) and mitochondrial respiratory function (State 3 and State 4, respiratory control index, and ADP/O ratio) were evaluated after exposure to adenosine. Cardiomyocyte MVO2 was significantly lower in cells previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) than in cells not exposed to adenosine (control). Addition of dipyridamole (10 microM) or 8-(p-Sulfophenyl) theophylline (50 microM) to cardiomyocytes before adenosine incubation prevented the adenosine-induced changes in MVO2. Mitochondria obtained from isolated perfused beating heart previously perfused with adenosine (10 microM, 30 min heart perfusion) also resulted in significant increases in ADP/O and respiratory control index compared to matching control. Mitochondria isolated from cardiomyocytes previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) resulted in a significant increase in mitochondrial ADP/O ratio compared to control. Adenosine-induced decrease in cardiomyocyte MVO2 may be related to an increase in efficiency of mitochondrial oxidative phosphorylation, and more economical use of oxygen, which is necessary for survival under ischemic stress.

  9. The review of myocardial positron emission computed tomography and positron imaging by gamma camera

    Ohtake, Tohru [Tokyo Univ. (Japan). Faculty of Medicine


    To measure myocardial blood flow, Nitrogen-13 ammonia, Oxygen-15 water, Rubidium-82 and et al. are used. Each has merit and demerit. By measuring myocardial coronary flow reserve, the decrease of flow reserve during dipyridamole in patients with hypercholesterolemia or diabetes mellitus without significant coronary stenosis was observed. The possibility of early detection of atherosclerosis was showed. As to myocardial metabolism, glucose metabolism is measured by Fluorine-18 fluorodeoxyglucose (FDG), and it is considered as useful for the evaluation of myocardial viability. We are using FDG to evaluate insulin resistance during insulin clamp in patients with diabetes mellitus by measuring glucose utilization rate of myocardium and skeletal muscle. FFA metabolism has been measured by {sup 11}C-palmitate, but absolute quantification has not been performed. Recently the method for absolute quantification was reported, and new radiopharmaceutical {sup 18}F-FTHA was reported. Oxygen metabolism has been estimated by {sup 11}C-acetate. Myocardial viability, cardiac efficiency was evaluated by oxygen metabolism. As to receptor or sympathetic nerve end, cardiac insufficiency or cardiac transplantation was evaluated. Imaging of positron emitting radiopharmaceutical by gamma camera has been performed. Collimator method is clinically useful for cardiac imaging of viability study. (author). 54 refs.

  10. Angiogenesis PET Tracer Uptake (68Ga-NODAGA-E[(cRGDyK]2 in Induced Myocardial Infarction in Minipigs

    Thomas Rasmussen


    Full Text Available Angiogenesis is part of the healing process following an ischemic injury and is vital for the post-ischemic repair of the myocardium. Therefore, it is of particular interest to be able to noninvasively monitor angiogenesis. This might, not only permit risk stratification of patients following myocardial infarction, but could also facilitate development and improvement of new therapies directed towards stimulation of the angiogenic response. During angiogenesis endothelial cells must adhere to one another to form new microvessels. αvβ3 integrin has been found to be highly expressed in activated endothelial cells and has been identified as a critical modulator of angiogenesis. 68Ga-NODAGA-E[c(RGDyK]2 (RGD has recently been developed by us as an angiogenesis positron-emission-tomography (PET ligand targeted towards αvβ3 integrin. In the present study, we induced myocardial infarction in Göttingen minipigs. Successful infarction was documented by 82Rubidium-dipyridamole stress PET and computed tomography. RGD uptake was demonstrated in the infarcted myocardium one week and one month after induction of infarction by RGD-PET. In conclusion, we demonstrated angiogenesis by noninvasive imaging using RGD-PET in minipigs hearts, which resemble human hearts. The perspectives are very intriguing and might permit the evaluation of new treatment strategies targeted towards increasing the angiogenetic response, e.g., stem-cell treatment.

  11. Removal efficiency of 66 pharmaceuticals during wastewater treatment process in Japan.

    Okuda, T; Kobayashi, Y; Nagao, R; Yamashita, N; Tanaka, H; Tanaka, S; Fujii, S; Konishi, C; Houwa, I


    Both biological treatment processes including conventional activated sludge (CAS) and biological nutrient removal (BNR) processes, and physico-chemical treatment processes including ozonation process and Title 22 process consisting of coagulation, sedimentation and filtration followed by UV or chlorination disinfection after the above biological processes, were compared from the viewpoint of removal efficiency. 66 pharmaceuticals including antibiotics, analgesics, psychoneurotic agents were measured with SPE-LC/MS/MS. 26 compounds out of 66 were detected in the influent ranging ng/L to microg/L order. Particularly, disopyramide, sulpiride, and dipyridamole that have been rarely detected before in the WWTP, occurred at concentration levels of more than 100 ng/L. The total concentration of the individual pharmaceuticals in the influent was efficiently removed by 80% during the biological treatment. But removal efficiencies of carbamazepine and crotamiton were less than 30%. The total concentration of the individual pharmaceuticals in the effluent from CAS process was 1.5 times higher than that from BNR process. Further, the total concentration of the individual pharmaceuticals in the discharge from WWTPs applying ozonation following activated sludge process was reduced to less than 20%. Physico-chemical treatment train called Title 22 treatment after CAS could not efficiently remove the pharmaceuticals. However, ozonation process followed by biological activated carbon process could efficiently reduce all the residual pharmaceuticals below their quantification limits.

  12. Iliac artery mural thrombus formation. Effect of antiplatelet therapy on 111In-platelet deposition in baboons

    Hanson, S.R.; Paxton, L.D.; Harker, L.A.


    To measure the rate, extent, and time course of arterial mural thrombus formation in vivo and to assess the effects of antiplatelet therapy in that setting, we have studied autologous /sup 111/In-platelet deposition induced by experimental iliac artery aneurysms in baboons. Scintillation camera imaging analyses were performed at 1, 24, 48, and 72 hours after implantation of the device. Correction for tissue attenuation was determined by using a small, comparably located /sup 111/In source implanted at the time of surgery. In five animals, /sup 111/In-platelet activity accumulated progressively after device implantation, reaching a maximum after the third day. Repeat image analysis carried out 2 weeks after the surgical procedure also showed progressive accumulation of /sup 111/In-platelets over 3 days but at markedly reduced amounts as compared with the initial study. In five additional animals, treatment with a combination of aspirin and dipyridamole begun 1 hour after surgical implantation reduced /sup 111/In-platelet deposition to negligible levels by the third day. Although platelet survival time was shortened and platelet turnover was reciprocally increased in all operated animals, platelet survival and turnover were not affected by antiplatelet therapy. We conclude that, in contrast to platelet survival and turnover measurements, /sup 111/In-platelet imaging is a reliable and sensitive method for localizing and quantifying focal arterial thrombi and for assessing the effects of antiplatelet therapy.

  13. Nuclear cardiology: Myocardial perfusion and function

    Seldin, D.W. (Lahey Clinic Medical Center, Burlington, MA (United States))


    Myocardial perfusion studies continue to be a major focus of research, with new investigations of the relationship of exercise-redistribution thallium imaging to diagnosis, prognosis, and case management. The redistribution phenomenon, which seemed to be fairly well understood a few years ago, is now recognized to be much more complex than originally thought, and various strategies have been proposed to clarify the meaning of persistent defects. Pharmacologic intervention with dipyridamole and adenosine has become available as an alternative to exercise, and comparisons with exercise imaging and catheterization results have been described. Thallium itself is no longer the sole single-photon perfusion radiopharmaceutical; two new technetium agents are now widely available. In addition to perfusion studies, advances in the study of ventricular function have been made, including reports of studies performed in conjunction with technetium perfusion studies, new insights into cardiac physiology, and the prognostic and case-management information that function studies provide. Finally, work has continued with monoclonal antibodies for the identification of areas of myocyte necrosis. 41 references.

  14. Effect of Shenkang injection combined with low molecular weight heparin sodium injection on a hypercoagulable state of the primary nephrotic syndrome%肾康注射液联合低分子量肝素钠注射液对原发性肾病综合征高凝状态的影响

    牛凯; 冯珍; 刘冰; 史亚男; 董春霞


    Objective To investigate the effect of Shenkang injection combined with low molecular weight heparin sodium injection on a hypercoagulable state of the primary nephrotic syndrome. Methods 88 patients with primary nephrotic syndrome (PNS) were randomly divided into four groups, Dipyridamole tablets group, Shenkang injection group, low molecular weight heparin sodium injection group and combination therapy group. Patients in four groups were treated by conventional blood pressure, lipid lowering therapy, and oral methylprednisolone. Dipyridamole tablets group ( n =21) received Dipyridamole tablets. Shenkang injection group ( n = 22) and low molecular weight heparin sodium injection group ( n = 22) separately received Shenkang injection and low molecular weight heparin sodium injection. Combination therapy group ( n =23) received Shenkang injection combined with low molecular weight heparin sodium injection. The course was four weeks in four groups. The changes of 24 h urinary protein excretion, serum albumin, prothrombin time (PT) , activated partial thromboplastin enzyme time (APTT) and fibrinogen ( FIB) were measured before and after treatment. Results 24 h urinary protein excretion and FIB in Shenkang injection group and low molecular weight heparin sodium injection group were decreased as compared with those in Dipyridamole tablets group ( P <0. 05). Plasma albumin, PT and APTT in Shenkang injection group and low molecular weight heparin sodium injection group were increased as compared with those in control group ( P < 0. 05 ). 24 h urine protein excretion in Shenkang injection group was decreased as compared with that in low molecular weight heparin sodium injection group ( P <0. 05) , plasma albumin was increased ( P <0. 05). 24 h urinary protein excretion and FIB in combination therapy group were significantly decreased as compared with those in other three treatment groups ( P < 0. 05 ). Plasma albumin, PT and APTT were obviously increased in comparison

  15. Preanalytical Procedures for DNA Studies: The Experience of the Interinstitutional Multidisciplinary BioBank (BioBIM).

    Palmirotta, Raffaele; Ludovici, Giorgia; De Marchis, Maria Laura; Savonarola, Annalisa; Leone, Barbara; Spila, Antonella; De Angelis, Francesco; Della Morte, David; Ferroni, Patrizia; Guadagni, Fiorella


    Preanalytical variables, including the anticoagulants and stabilizing agents, time, storage temperature, and methods of DNA extraction applied to blood samples, may affect quality and quantity of isolated nucleic acids for future genomic applications. Considering the large number of collected samples, standard operating procedure optimization for whole blood preservation before DNA extraction is a crucial step in a biological repository. Moreover, the future application of the biological material may not be known subsequent to its extraction. To define standard operating procedures for whole blood preservation before DNA extraction, we aimed to determine whether different combinations of anticoagulants, blood storage temperatures, and time intervals before storage at -80°C might have an impact on quality and quantity of subsequent extracted DNA. After spectrophotometer quantification, the quality and integrity of DNA were assessed by agarose gel electrophoresis, polymerase chain reaction, and real-time polymerase chain reaction methods. We observed that decrease in DNA recovery during blood storage time was more pronounced at room temperature than at 4°C. Based on our experience, we recommend as anticoagulants of choice sodium citrate and ethylenediaminetetraacetate, whereas sodium citrate theophylline adenosine dipyridamole could represent an alternative choice, excluding a priori lithium heparin and Fluoride-Oxalate. Based on the overall evaluation criteria, we conclude that the procedures necessary to preserve the whole blood before the DNA extraction may have a significant impact on downstream molecular biological applications.

  16. Incremental value of contrast myocardial perfusion to detect intermediate versus severe coronary artery stenosis during stress-echocardiography

    Ugo Fabrizio


    Full Text Available Abstract Background We aimed to compare the incremental value of contrast myocardial perfusion imaging (MPI for the detection of intermediate versus severe coronary artery stenosis during dipyridamole-atropine echocardiography (DASE. Wall motion (WM assessment during stress-echocardiography demonstrates suboptimal sensitivity to detect coronary artery disease (CAD, particularly in patients with isolated intermediate (50%-70% coronary stenosis. Methods We performed DASE with MPI in 150 patients with a suspected chest pain syndrome who were given clinical indication to coronary angiography. Results and discussion When CAD was defined as the presence of a ≥50% stenosis, the addition of MPI increased sensitivity (+30% and decreased specificity (-14%, with a final increase in total diagnostic accuracy (+16%, p Conclusions The addition of MPI on top of WM analysis during DASE increases the diagnostic sensitivity to detect obstructive CAD, whatever its definition (≥50% or > 70% stenosis, but it is mainly driven by the sensitivity increase in the intermediate group (50%-70% stenosis. The total diagnostic accuracy increased only when defining CAD as ≥50% stenosis, since in patients with severe stenosis (> 70% the decrease in specificity is not counterbalanced by the minor sensitivity increase.

  17. A Patient with Recurrent Arteriovenous Graft Thrombosis.

    Allon, Michael


    Arteriovenous grafts (AVGs) are prone to frequent thrombosis that is superimposed on underlying hemodynamically significant stenosis, most commonly at the graft-vein anastomosis. There has been great interest in detecting AVG stenosis in a timely fashion and performing preemptive angioplasty, in the belief that this will prevent AVG thrombosis. Three surveillance methods (static dialysis venous pressure, flow monitoring, and duplex ultrasound) can detect AVG stenosis. Whereas observational studies have reported that surveillance with preemptive angioplasty substantially reduces AVG thrombosis, randomized clinical trials have failed to confirm such a benefit. There is a high frequency of early AVG restenosis after angioplasty caused by aggressive neointimal hyperplasia resulting from vascular injury. Stent grafts prevent AVG restenosis better than balloon angioplasty, but they do not prevent AVG thrombosis. Several pharmacologic interventions to prevent AVG failure have been evaluated in randomized clinical trials. Anticoagulation or aspirin plus clopidogrel do not prevent AVG thrombosis, but increase hemorrhagic events. Treatment of hyperhomocysteinemia does not prevent AVG thrombosis. Dipyridamole plus aspirin modestly decreases AVG stenosis or thrombosis. Fish oil substantially decreases the frequency of AVG stenosis and thrombosis. In patients who have exhausted all options for vascular access in the upper extremities, thigh AVGs are a superior option to tunneled internal jugular vein central vein catheters (CVCs). An immediate-use AVG is a reasonable option in patients with recurrent CVC dysfunction or infection. Tunneled femoral CVCs have much worse survival than internal jugular CVCs.

  18. Preanalytical requirements for flow cytometric evaluation of platelet activation: choice of anticoagulant.

    Mody, M; Lazarus, A H; Semple, J W; Freedman, J


    Accurate assessment of in vivo or in vitro platelet activation requires optimal preanalytical conditions to prevent artefactual in vitro activation of the platelets. The choice of anticoagulant is one of the critical preanalytical conditions as anticoagulants exert different effects on the activation of platelets ex vivo. We tested the effectiveness of Diatube-H (also known as CTAD; sodium citrate, theophylline, adenosine and dipyridamole) and citrate vacutainer tubes in preventing artefactual activation of platelets and preserving functional reserve. Platelet surface expression of the CD62P (reflecting alpha granule release), CD63 (reflecting lysosomal release) and modulation of normal platelet membrane glycoproteins CD41a and CD42b, were measured in whole blood and in isolated platelets immediately after collection and at 6, 24 and 48 h after venipuncture. Samples taken into Diatube-H showed less spontaneous platelet activation than did those taken into citrate. To measure in vitro platelet functional reserve, thrombin was added as agonist to blood stored for varying periods up to 48 h. Although Diatube-H suppressed in vitro platelet activation for up to 4 h, in samples kept for 6-24 h before thrombin addition, the inhibitory effect was lost and platelets responded fully to agonist activation. Hence, Diatube-H preserved platelets and allowed for measurement of in vivo platelet activation as well as thrombin-induced in vitro platelet activation after 6-24 h, in both whole blood and isolated platelets.

  19. Overcome side identification in PPOP by making orifices on both layers.

    Zhang, Zhi-hong; Li, Wei; Nie, Shu-fang; Tang, Xin; Peng, Bo; Tian, Lei; Pan, Wei-san


    The original purpose of this research was to build a database for an expert system. Unexpectedly, it was found that the color-identifying device in push-pull osmotic pump (PPOP) manufacturing process could be unnecessary. Water-insoluble drug indapamide, gliclazide and dipyridamole were employed as model drugs. Bunches of conventional formulations were designed; and traditional preparation procedures were used. In vitro drug release was studied; and the similarity between the conditions of orifice only on the side of the drug layer and orifices of the same diameter on both sides was evaluated. It was found that the drug release from PPOP could be influenced by formulation and core hardness while it could hardly be influenced by orifice size. No significant difference was observed between the dissolution profiles of orifice only on the side of the drug layer and orifices of the same diameter on both sides. Mechanism of drug release was discussed. The conclusion was that the disadvantage of side identification in PPOP manufacturing process could be overcome by drilling orifices on both sides.

  20. Evaluation of the functionality of biodegradable polymeric platforms for drug delivery systems

    Gioti, M., E-mail:; Karagkiozaki, V.; Basgiouraki, A.; Karagiannidis, P.G.; Logothetidis, S.


    We present the development of a drug-loaded triple-layer platform consisting of thin film biodegradable polymers, in a properly designed form for the desired gradual degradation. Poly(DL-lactide-co-glycolide) (PLGA (65:35), PLGA (75:25)) and polycaprolactone (PCL) were grown by spin coating technique, to synthesize the platforms with the order PCL/PLGA (75:25)/PLGA (65:35) that determine their degradation rates. The outer PLGA (65:35) layer was loaded with dipyridamole, an antiplatelet drug. Spectroscopic ellipsometry (SE) in the Vis-far UV range was used to determine the nanostructure, as well as the content of the incorporated drug in the as-grown platforms. In situ and real-time SE measurements were carried out using a liquid cell for the dynamic evaluation of the fibrinogen and albumin protein adsorption processes. Atomic force microscopy studies justified the SE results concerning the nanopores formation in the polymeric platforms, and the dominant adsorption mechanisms of the proteins, which were defined by the drug incorporation in the platforms.

  1. Evidence for an A1-adenosine receptor in the guinea-pig atrium.

    Collis, M. G.


    1 The purpose of this study was to determine whether the adenosine receptor that mediates a decrease in the force of contraction of the guinea-pig atrium is of the A1- or A2-sub-type. 2 Concentration-response curves to adenosine and a number of 5'- and N6-substituted analogues were constructed and the order of potency of the purines was: 5'-N-cyclopropylcarboxamide adenosine (NCPCA) = 5'-N-ethylcarboxamide adenosine (NECA) greater than N6cyclohexyladenosine (CHA) greater than L-N6-phenylisopropyl adenosine (L-PIA) = 2-chloroadenosine- greater than adenosine greater than D-N6-phenylisopropyl adenosine (D-PIA). 3 The difference in potency between the stereoisomers D- and L-PIA was over 100 fold. 4 The adenosine transport inhibitor, dipyridamole, potentiated submaximal responses to adenosine but had no significant effect on those evoked by the other purines. 5 Theophylline antagonized responses evoked by all purines, and with D-PIA revealed a positive inotropic effect that was abolished by atenolol. 6 The results indicate the existence of an adenosine A1-receptor in the guinea-pig atrium. PMID:6297647

  2. Morphine enhances the release of /sup 3/H-purines from rat brain cerebral cortical prisms

    Wu, P.H.; Phillis, J.W.; Yuen, H.


    In vitro experiments have shown that /sup 3/H-purines can be released from /sup 3/H-adenosine preloaded rat brain cortical prisms by a KCl-evoked depolarization. The KCl-evoked release of /sup 3/H-purines is dependent on the concentration of KCl present in the superfusate. At concentrations of 10(-7) approximately 10(-5)M morphine did not influence the basal release of /sup 3/H-purines from the prisms, although it enhanced the KCl-evoked release of /sup 3/H-purines. The enhancement of KCl-evoked /sup 3/H-purine release by morphine was concentration-dependent and was antagonized by naloxone, suggesting the involvement of opiate receptors. Uptake studies with rat brain cerebral cortical synaptosomes show that morphine is a very weak inhibitor of adenosine uptake. Comparisons with dipyridamole, a potent inhibitor of adenosine uptake, suggest that this low level of inhibition of the uptake did not contribute significantly to the release of /sup 3/H-purine by morphine seen in our experiments. It is therefore suggested that morphine enhances KCl-evoked /sup 3/H-purine release by an interaction with opiate receptors and that the resultant increase in extracellular purine (adenosine) levels may account for some of the actions of morphine.

  3. Myocardial blood flow quantification for evaluation of coronary artery disease by computed tomography

    Seitun, Sara; Clemente, Alberto; La Grutta, Ludovico; Toia, Patrizia; Runza, Giuseppe; Midiri, Massimo; Maffei, Erica


    During the last decade coronary computed tomography angiography (CTA) has become the preeminent non-invasive imaging modality to detect coronary artery disease (CAD) with high accuracy. However, CTA has a limited value in assessing the hemodynamic significance of a given stenosis due to a modest specificity and positive predictive value. In recent years, different CT techniques for detecting myocardial ischemia have emerged, such as CT-derived fractional flow reserve (FFR-CT), transluminal attenuation gradient (TAG), and myocardial CT perfusion (CTP) imaging. Myocardial CTP imaging can be performed with a single static scan during first pass of the contrast agent, with monoenergetic or dual-energy acquisition, or as a dynamic, time-resolved scan during stress by using coronary vasodilator agents (adenosine, dipyridamole, or regadenoson). A number of CTP techniques are available, which can assess myocardial perfusion in both a qualitative, semi-quantitative or quantitative manner. Once used primarily as research tools, these modalities are increasingly being used in routine clinical practice. All these techniques offer the substantial advantage of combining anatomical and functional evaluation of flow-limiting coronary stenosis in the same examination that would be beneficial for clinical decision-making. This review focuses on the state-of the-art and future trends of these evolving imaging modalities in the field of cardiology for the physiologic assessments of CAD. PMID:28540209

  4. Prognostic value of technetium-99m-labeled single-photon emission computerized tomography in the follow-up of patients after their first myocardial revascularization surgery

    Márcia Maria Sales dos Santos


    Full Text Available OBJECTIVE: To assess the prognostic value of Technetium-99m-labeled single-photon emission computerized tomography (SPECT in the follow-up of patients who had undergone their first myocardial revascularization. METHODS: We carried out a retrospective study of 280 revascularized patients undergoing myocardial scintigraphy under stress (exercise or pharmacological stress with dipyridamole and at rest according to a 2-day protocol. A set of clinical, stress electrocardiographic and scintigraphic variables was assessed. Cardiac events were classified as "major" (death, infarction, unstable angina and "any" (major event or coronary angioplasty or new myocardial revascularization surgery. RESULTS: Thirty-six major events occurred as follows: 3 deaths, 11 infarctions, and 22 unstable anginas. In regard to any event, 22 angioplasties and 7 new surgeries occurred in addition to major events, resulting a total of 65 events. The sensitivity of scintigraphy in prognosticating a major event or any event was, respectively, 55% and 58%, showing a negative predictive value of 90% and 83%, respectively. Diabetes mellitus, inconclusive stress electrocardiography, and a scintigraphic visualization of left ventricular enlargement were significant variables for the occurrence of a major event. On multivariate analysis, abnormal myocardial scintigraphy was a predictor of any event. CONCLUSION: Myocardial perfusion tomography with Technetium-99m may be used to identify high-risk patients after their first myocardial revascularization surgery.

  5. Radionuclide cardiac evaluation before and after trans-myocardial laser revascularization: two case reports; Evaluation cardioscintigraphique avant et apres laser transmyocardique: etude de deux cas cliniques

    Benamor, M.; Tainturier, C.; Ricci, A.; Dreyfus, G. [Centre Medico-Chirurgical Foch, 92 - Suresnes (France)


    Two patients aged 74 and 58 years old presenting with severe angina pectoris scored IV (CCS), who have become refractory to medical treatment and who were not candidates for coronary artery by pass graft, nor for percutaneous transluminal coronary angioplasty, were referred for tans-myocardial laser revascularization (TML). We present here the radionuclide cardiac evaluation results before and after TML. A clinical, ECG and radionuclide evaluation was performed after a conventional stress myocardial study using thallium-201 and injection of dipyridamole, followed by a gated SPECT radionuclide ventriculography. The data obtained included thallium-201 regional uptake, measurement of lung and liver uptake (lung/heart and liver/heart ratios) on the anterior tomographic projection view, left ventricular ejection fraction and regional wall motions. The results show a relative improvement for patient number 1 and an almost unchanged status for patient number 2; however, lung/heart and liver/heart ratios reflected more closely the complete alleviation of angina pectoris for both patients obtained four and five months after TML. This study, which is well correlated with published data in the literature, shows that objective improvements of cardiac perfusion and regional wall motions are not obvious despite the fact that a clear clinical improvements is obtained after TML. Additional controlled studies with a statistically significant number of patients are needed to determine the clinical opportunity and usefulness of this myocardial surgical revascularization procedure which is still currently in an investigational phase. (authors). 18 refs.

  6. Prognostic Value of Normal Perfusion but Impaired Left Ventricular Function in the Diabetic Heart on Quantitative Gated Myocardial Perfusion SPECT

    Jeong, Hwanjeong; Choi, Sehun; Han, Yeonhee [Research Institute of Chonbuk National Univ. Medical School and Hospitial, Jeonju (Korea, Republic of); Lee, Dong Soo; Lee, Hoyoung; Chung, Junekey [Seoul National Univ., Seoul (Korea, Republic of)


    This study aimed at identifying the predictive parameters on quantitative gated myocardial perfusion single-photon emission computed tomography (QG-SPECT) in diabetic patients with normal perfusion but impaired function. Methods Among the 533 consecutive diabetic patients, 379 patients with normal perfusion on rest Tl-201/dipyridamole-stress Tc-{sup 99m} sestamibi Gated SPECT were enrolled. Patients were grouped into those with normal post-stress left ventricular function (Group I) and those with impaired function (EF <50 or impaired regional wall motion, Group II). We investigated cardiac events and cause of death by chart review and telephone interview. Survival analysis and Cox proportional hazard model analysis were performed. Between the Group I and II, cardiac events as well as chest pain symptoms, smoking, diabetic complications were significantly different (P<0.05). On survival analysis, event free survival rate in Group II was significantly lower than in Group I (P=0.016). In univariate Cox proportional hazard analysis on overall cardiac event, Group (II over I), diabetic nephropathy, summed motion score (SMS), summed systolic thickening score (STS), numbers of abnormal segmental wall motion and systolic thickening predicted more cardiac events (P<0.05). Multivariate analysis showed that STS was the only independent predictor cardiac event. The functional parameter, especially summed systolic thickening score on QG-SPECT had prognostic values, despite normal perfusion, in predicting cardiac events in diabetic patients, and QG-SPECT provides clinically useful risk stratification in diabetic patients with normal perfusion.

  7. Uliginosin B, a Possible New Analgesic Drug, Acts by Modulating the Adenosinergic System

    Eveline Dischkaln Stolz


    Full Text Available Uliginosin B (ULI is a natural acylphloroglucinol that has been proposed as a new molecular scaffold for developing analgesic and antidepressant drugs. Its effects seem to be due to its ability to increase monoamines in the synaptic cleft by inhibiting their neuronal uptake without binding to their respective transporters, but its exact mode of action is still unknown. Considering the importance of the purinergic system to pain transmission and its modulation by monoamines availability, the aim of this study was to investigate the involvement of adenosinergic signaling in antinociceptive effect of uliginosin B. The selective adenosine A1 receptor antagonist DPCPX and the selective A2A antagonist ZM 241385 prevented the effect of ULI in the hot-plate test in mice. Pretreatment with inhibitors of adenosine reuptake (dipyridamole or adenosine deaminase (EHNA did not affect the ULI effect. On the other hand, its effect was completely prevented by an inhibitor of ecto-5′-nucleotidase (AMPCP. This finding was confirmed ex vivo, whereby ULI treatment increased AMP and ATP hydrolysis in spinal cord and cerebral cortex synaptosomes, respectively. Altogether, these data indicate that activation of A1 and A2A receptors and the modulation of ecto-5′-nucleotidase activity contribute to the antinociceptive effect of ULI.

  8. Thrombozyteninhibitortherapie zur Sekundärprophylaxe atherothrombotischer Ereignisse

    Theiss W


    Full Text Available Basierend auf einer Vielzahl randomisierter Studien sind Thrombozytenfunktionshemmer zum festen Bestandteil der medikamentösen Sekundärprophylaxe atherothrombotischer Erkrankungen geworden. Sie reduzieren die Gesamtmortalität sowie insbesondere die vaskulären Todesfälle, die Häufigkeit neuer Herzinfarkte und neuer Schlaganfälle und die Häufigkeit peripherer Gefäßverschlüsse nach peripheren Bypassoperationen und perkutaner transluminaler Angioplastie. Besonders gut dokumentiert ist ihre Wirksamkeit bei der koronaren Herzkrankheit und bei klinisch manifesten zerebralen Durchblutungsstörungen, aber auch ihr Wert bei symptomatischer peripherer arterieller Verschlußkrankheit ist gesichert. Am häufigsten wird Acetylsalicylsäure in einer Tagesdosis von 75 bis 375 mg verwendet. Inwieweit Dipyridamol in Kombination mit Acetylsalicylsäure eine weitere Verbesserung der Prophylaxe darstellt, ist umstritten; auch der Stellenwert der Kombination anderer Thrombozytenfunktionshemmer ist derzeit unklar. Unterschiedlich beurteilt wird auch, ob die Überlegenheit von Clopidogrel, einem Nachfolgepräparat von Ticlopidin, über Acetylsalicylsäure so gut belegt und so groß ist, daß sein Einsatz als Thrombozytenfunktionshemmer der ersten Wahl trotz des großen Preisunterschiedes generell gerechtfertigt ist.

  9. "Aspirin and Beyond" - Antiplättchensubstanzen in der Therapie der koronaren Herzkrankheit

    Niessner A


    Full Text Available Acetylsalicylsäure (ASS ist nach wie vor die Standardtherapie bei der koronaren Herzkrankheit (KHK, wenn auch die Wirksamkeit bei verschiedenen Indikationen unterschiedlich ist. Am eindrucksvollsten sind die Ergebnisse mit ASS bei der instabilen Angina pectoris (IAP gefolgt vom akuten Myokardinfarkt (AMI und der Sekundärprävention nach AMI. Eine signifikant positive Wirkung von ASS konnte auch in der Therapie der stabilen AP gezeigt werden, während die Wirkung in der primären Prophylaxe der KHK weniger gut abgesichert ist. Trotz jahrzehntelanger Erfahrung mit ASS muß die Frage einer optimalen Dosierung nach wie vor offen bleiben. Für eine möglichst niedrige Dosierung spricht vor allem die geringere Nebenwirkungsrate. Weitere ungelöste Probleme sind die "ASS-Resistance" sowie die Interferenz von ASS mit ACE-Hemmern. Dagegen zeigt ASS eine positive synergistische Wirkung mit anderen Pharmaka wie Thrombolytika (Streptokinase beim AMI, Dipyridamol (in der Sekundärprävention nach Schlaganfall, aber auch Heparinen (insbesondere bei der IAP. Positive synergistische Effekte bestehen auch zwischen ASS und GPIIb/IIIa-Blockern sowie zwischen ASS und Thienopyridinen. Die Entwicklung der Thienopyridine hat zweifelsohne bei einigen Indikationen eine signifikante Besserung der Ergebnisse gebracht. Infolge des besseren Nebenwirkungsprofils wird Tiklopidin zunehmend durch Clopidogrel ersetzt. Die Kombination von ASS + Clopidogrel darf bereits jetzt als Standardtherapie nach koronarem Stenting (vier Wochen Clopidogrel sowie bei der IAP (ASS + Clopidogrel durch drei bis zwölf Monate bezeichnet werden.

  10. Antiplatelet agents and proton pump inhibitors – personalizing treatment

    Eugene Lin


    Full Text Available Eugene Lin, Rajiv Padmanabhan, Majaz MoonisDepartment of Neurology, University of Massachusetts Medical School and UMass Memorial Medical Center, Worcester, Massachusetts, USAIntroduction: Antiplatelet therapy remains one of the cornerstones in the management of noncardioembolic ischemic stroke. However, a significant percentage of patients have concomitant gastroesophageal reflux or peptic ulcer disease that requires acid-reducing medications, the most powerful and effective being the proton pump inhibitors (PPIs. Antiplatelet efficacy, at least in vivo, and particularly for clopidogrel, has been shown to be reduced with concomitant proton pump inhibitor use. Whether this is clinically relevant is not clear from the limited studies available.Methods: We conducted an extensive review of studies available on Medline related to pharmacodynamic interactions between the antiplatelet medications and proton pump inhibitors as well as clinical studies that addressed this potential interaction.Results: Based on the present pharmacodynamic and clinical studies we did not find a significant interaction that would reduce the efficacy of antiplatelet agents with concomitant user of proton pump inhibitors.Conclusions: Patients on antiplatelet agents after a transient ischemic attack or ischemic stroke can safely use aspirin, and extended release dipyridamole/aspirin with proton pump inhibitors. Patients on clopidogrel may use other acid-reducing drugs besides proton pump inhibitors. In rare cases where proton pump inhibitors and clopidogrel have to be used concurrently, careful close monitoring for recurrent vascular events is required.Keywords: proton pump inhibitors, antiplatelet medications, clopidogrel, ischemic stroke, cardiovascular events

  11. Identification of the Ca²⁺ entry pathway involved in deoxygenation-induced phosphatidylserine exposure in red blood cells from patients with sickle cell disease.

    Cytlak, U M; Hannemann, A; Rees, D C; Gibson, J S


    Phosphatidylserine (PS) exposure in red blood cells (RBCs) from sickle cell disease (SCD) patients is increased compared to levels in normal individuals and may participate in the anaemic and ischaemic complications of SCD. Exposure is increased by deoxygenation and occurs with elevation of intracellular Ca²⁺ to low micromolar levels. The Ca²⁺ entry step has not been defined but a role for the deoxygenation-induced pathway, Psickle, is postulated. Partial Psickle inhibitors 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS), 4,4'-dithiocyano-2,2'-stilbene-disulphonic acid (DIDS) and dipyridamole inhibited deoxygenation-induced PS exposure (DIDS IC50, 118 nM). Inhibitors and activators of other pathways (including these stimulated by depolarisation, benzodiazepines, glutamate and stretch) were without effect. Zn²⁺ and Gd³⁺ stimulated PS exposure to high levels. In the case of Zn²⁺, this effect was independent of oxygen (and hence HbS polymerisation and RBC sickling) but required extracellular Ca²⁺. The effect was completely abolished when Zn²⁺ (100 μM) was added to RBCs suspended in autologous plasma, implying a requirement of high levels of free Zn²⁺.

  12. Low-dose adenosine stress echocardiography: Detection of myocardial viability

    Nedeljkovic Milan


    Full Text Available Abstract Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

  13. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease

    Ehtisham Javed


    Full Text Available Abstract Aim Evaluation of the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance for the diagnosis of significant obstructive coronary artery disease (CAD through meta-analysis of the available data. Methodology Original articles in any language published before July 2009 were selected from available databases (MEDLINE, Cochrane Library and BioMedCentral using the combined search terms of magnetic resonance, perfusion, and coronary angiography; with the exploded term coronary artery disease. Statistical analysis was only performed on studies that: (1 used a [greater than or equal to] 1.5 Tesla MR scanner; (2 employed invasive coronary angiography as the reference standard for diagnosing significant obstructive CAD, defined as a [greater than or equal to] 50% diameter stenosis; and (3 provided sufficient data to permit analysis. Results From the 263 citations identified, 55 relevant original articles were selected. Only 35 fulfilled all of the inclusion criteria, and of these 26 presented data on patient-based analysis. The overall patient-based analysis demonstrated a sensitivity of 89% (95% CI: 88-91%, and a specificity of 80% (95% CI: 78-83%. Adenosine stress perfusion CMR had better sensitivity than with dipyridamole (90% (88-92% versus 86% (80-90%, P = 0.022, and a tendency to a better specificity (81% (78-84% versus 77% (71-82%, P = 0.065. Conclusion Stress perfusion CMR is highly sensitive for detection of CAD but its specificity remains moderate.


    R. M. Magdeev


    Full Text Available Aim. To evaluate pharmacotherapy of ST-elevation myocardial infarction (STEMI in cardiology departments of Saratov hospitals of various types. Material and methods. The retrospective pharmacoepidemiological study was carried out with involved of 424 hospital charts of STEMI patients, discharged during the year from the cardiology department of Saratov municipal hospital (MH; n=216 and emergency cardiology department of Saratov clinical hospital (CH; n=208. Results. The real practice in the audited hospitals are not fully consistent with current guidelines for the STEMI patients management. The relationship between guidelines compliance and hospital type is clearly seen. Doctors in MH in comparison with them in CH more often prescribed respiratory analeptics (13.4% vs 5.3% , respectively, metabolic drugs (63.4% vs 37.5%, respectively and rarer used beta-blockers (50% vs 88.9%, respectively and thrombolytic therapy (3.7% vs 51%, respectively. In MH dipyridamole was used in 9.6% of patients as an alternative to the acetylsalicylic acid, and clopidogrel was not prescribed. At the same hospital clotting time was determined for monitoring of heparin therapy. Statins were rare used in both hospitals (26% in MH vs 40% in CH. Conclusion. The real clinical practice of STEMI patients management in Saratov hospitals are not completely consistent with current clinical guidelines. There are differences in STEMI patients therapy depending on hospital type.

  15. Transthoracic coronary flow reserve and dobutamine derived myocardial function: a 6-month evaluation after successful coronary angioplasty

    Pardo Moira


    Full Text Available Abstract After percutaneous transluminal coronary angioplasty (PTCA, stress-echocardiography and gated single photon emission computerized tomography (g-SPECT are usually performed but both tools have technical limitations. The present study evaluated results of PTCA of left anterior descending artery (LAD six months after PTCA, by combining transthoracic Doppler coronary flow reserve (CFR and color Tissue Doppler (C-TD dobutamine stress. Six months after PTCA of LAD, 24 men, free of angiographic evidence of restenosis, underwent standard Doppler-echocardiography, transthoracic CFR of distal LAD (hyperemic to basal diastolic coronary flow ratio and C-TD at rest and during dobutamine stress to quantify myocardial systolic (Sm and diastolic (Em and Am, Em/Am ratio peak velocities in middle posterior septum. Patients with myocardial infarction, coronary stenosis of non-LAD territory and heart failure were excluded. According to dipyridamole g-SPECT, 13 patients had normal perfusion and 11 with perfusion defects. The 2 groups were comparable for age, wall motion score index (WMSI and C-TD at rest. However, patients with perfusion defects had lower CFR (2.11 ± 0.4 versus 2.87 ± 0.6, p m at high-dose dobutamine (p m of middle septum (r = 0.55, p In conclusion, even in absence of epicardial coronary restenosis, stress perfusion imaging reflects a physiologic impairment in coronary microcirculation function whose magnitude is associated with the degree of regional functional impairment detectable by C-TD.

  16. Effect of a selective thromboxane synthase inhibitor on arterial graft patency and platelet deposition in dogs

    McDaniel, M.D.; Huntsman, W.T.; Miett, T.O.; Cronenwett, J.L.


    This study examined the effect of selective thromboxane synthase inhibition and nonselective cyclooxygenase inhibition on vascular graft patency and indium 111-labeled platelet deposition in 35 mongrel dogs undergoing carotid artery replacement with 4 mm X 4 cm polytetrafluoroethylene (PTFE) (one side) and Dacron (opposite side) end-to-end grafts. Aspirin-dipyridamole therapy improved one-week graft patency, from 46% in untreated dogs to 93% in treated dogs. Thromboxane synthase inhibition (U-63557A) improved graft patency in these dogs to 81%. Both drug treatments reduced platelet deposition on Dacron and PTFE grafts by 48% to 68% compared with control dogs. Dacron grafts accumulated significantly more platelets than PTFE grafts but had comparable patency rates. Low-dose aspirin therapy had no significant effect on either graft patency or platelet deposition. All treatment groups showed a 60% to 76% reduction in serum thromboxane B2, but only thromboxane synthase inhibitor treatment increased plasma 6-keto-prostaglandin F1 alpha by 100%. Selective thromboxane synthase inhibition improved small-caliber prosthetic graft patency to the same extent as did conventional cyclooxygenase inhibition in this preliminary study.

  17. Pharmacological characterization of rat paw edema induced by Cerastes gasperettii (cerastes venom

    A. K. Al-Asmari


    Full Text Available Inflammatory response induced by the venom of the Arabian sand viper Cerastes gasperettii was studied by measuring rat hind-paw edema. Cerastes gasperettii venom (CgV, 3.75-240 µg/paw, heated for 30s at 97°C, caused a marked dose and time-dependent edema in rat paw. Response was maximal 2h after venom administration and ceased within 24h. Heated CgV was routinely used in our experiments at the dose of 120 µg/paw. Among all the drugs and antivenoms tested, cyproheptadine and 5-nitroindazole were the most effective in inhibiting edema formation. Aprotinin, mepyramine, dexamethasone, diclofenac, dipyridamole, Nomega-nitro-L-arginine, quinacrine, and nordihydroguaiaretic acid showed statistically (p<0.001 significant inhibitory effect, but with variations in their inhibition degree. Equine polyspecific and rabbit monospecific antivenoms significantly (p<0.001 reduced edema when locally administered (subplantar but were ineffective when intravenously injected. We can conclude that the principal inflammatory mediators were serotonin, histamine, adenosine transport factors, phosphodiesterase (PDE, cyclooxygenase, lipoxygenase and phospholipase A2 (PLA2, in addition to other prostaglandins and cytokines.

  18. Lack of uptake, release and action of UTP at sympathetic perivascular nerve terminals in rabbit ear artery.

    Saïag, B; Shacoori, V; Bodin, P; Catheline, M; Burnstock, G


    A possible role of uridine 5'-triphosphate (UTP) and uridine at sympathetic nerve terminals was studied in the rabbit ear artery after incubation of isolated vessels with [3H]uridine or [3H]noradrenaline. It was found that [3H]uridine was taken up by rabbit ear artery. This uptake was largely suppressed after the removal of endothelium and was inhibited by ethidium bromide and dipyridamole. Chemical denervation of the vessels with 6-hydroxydopamine did not reduce the uptake. Following pre-incubation of the isolated vessels with [3H]uridine, there was a release of radioactivity from the superfused rabbit ear artery. UTP, UDP, UMP and uridine were detected by thin layer chromatography both in the superfusate and inside the vessels. Transmural electric stimulation (30 V, 5 Hz) induced a contraction of the vessels but did not increase the release of uridine nucleotides into the superfusate. [3H]Noradrenaline was released during electric stimulation and the addition of UTP (100 microM) had no effects on this release. To conclude, this study shows that in contrast to endothelial cells, the sympathetic nerve terminals of the rabbit ear artery do not take up uridine and do not release uridine-derived nucleotides. UTP at 100 microM is also unable to modulate the evoked release of noradrenaline. These results mainly confine the role of UTP in endothelium-derived vasodilatation via P2Y2 and/or P2Y4 receptors.

  19. Stress cine MRI for detection of coronary artery disease; Stress-Cine-MRT zur Primaeridagnostik der koronaren Herzkrankheit

    Sommer, T.; Hofer, U.; Schild, H. [Bonn Univ. (Germany). Radiologische Klinik; Omran, H. [Medizinische Universitaetsklinik II Bonn (Germany)


    Stress testing is the cornerstone in the diagnosis of patients with suspected coronary artery disease (CAD). Stress echocardiography has become a well-established modality for the detection of ischemia-induced wall motion abnormalities. However, display and reliable interpretation of stress echocardiography studies are user-dependent, the test reproducibility is low, and 10 to 15% of patients yield suboptimal or non-diagnostic images. Due to its high spatial and contrast resolution, MRI is known to permit an accurate determination of left ventricular function and wall thickness at rest. Early stress MRI studies provided promising results with respect to the detection of CAD. However, the clinical impact was limited due to long imaging time and problematic patient monitoring in the MRI environment. Recent technical improvements - namely ultrafast MR image acquisition - led to a significant reduction of imaging time and improved patient safety. Stress can be induced by physical exercise or pharmacologically by administration of a beta{sub 1}-agonist (dobutamine) or vasodilatator (dipyridamole and adenosine). The best developed and most promising stress MRI technique is a high-dose dobutamine/atropine stress protocol (10, 20, 30, 40 {mu}g/kg/min; optionally 0.25-mg fractions of atropine up to maximal dose 1 mg). Severe complications (myocardial infarction, ventricular fibrillation and sustained tachycardia, cardiogenic shock) may be expected in 0.25% of patients. Currently, data of three high-dose dobutamine stress MRI studies are available, revealing a good sensitivity (83 - 87%) and specificity (83 - 86%) in the assessment of CAD. The direct comparison between echocardiography and MRI for the detection of stress-induced wall motion abnormalities yielded better results for dobutamine-MRI in terms of sensitivity (86.2% vs. 74.3%; p < 0.05) and specificity (85.7% vs. 69.8% p < 0.05) as compared to dobutamine stress echocardiography. The superior results of MRI can

  20. Clinical Studies on Treatment of Acute Cerebral Infarction with Yinxing-damo Combined with Sodium Ozagrel%银杏达莫联合奥扎格雷钠治疗急性脑梗死临床研究

    臧玉豹; 汤伟; 王永


    目的 探讨银杏达莫注射液联合奥扎格雷钠注射液治疗急性脑梗死(Acutecerebralinfarction,ACI)临床疗效.方法 156例ACI患者按就诊顺序1:1比例随机分为治疗组和对照组,各78例. 两组患者均给予常规综合治疗,治疗组加用银杏达莫注射液20 mL稀释后静脉滴注,奥扎格雷钠氯化钠注射液80mg(100mL)静脉滴注,均1日1次;对照组加用复方丹参20mL稀释后静脉滴注,胞二磷胆碱1.0稀释后静脉滴注,均1日1次.两组疗程均为10d.结果 ①治疗组总有效率为92.3%(72/78),对照组总有效率为80.8%(63/78),治疗组治疗效果明显优于对照组(P<0.05);②治疗后治疗组DNDS改善明显优于对照组(P<0.01);③治疗组治疗后 DNDS明显低于治疗前(P<0.01). 结论 银杏达莫注射液联合奥扎格雷钠注射液治疗ACI具有疗效确切、安全可靠、副作用少等优点,值得临床推广使用.%OBJECTIVE To evaluate the clinical efficacy of Yinxingdamo injection combined with ozagrel sodi-uminjectioninthetreatmentofacutecerebralinfarction(ACI).METHODS 156casesofACIpatientsaccording to the order of the ratio of 1:1 were randomly divided into treatment group and control group,78 cases in each.Two groups of patients were given conventional therapy,the treatment group were further treated with ginkgo leaf extract and dipyridamole injection 20mL diluted intravenous drip, 80mg ozagrel sodium and sodium chloride injection (100mL) intravenous injection,1 times daily;the control group were further treated with Compound Danshen 20mL diluted intravenous drip, citicoline 1.0 diluted intravenous drip, 1 times daily.Two groups were treated for 10d.RESULTS ①Thetreatmentgrouptotaleffectiveratewas92.3%(72/78)thecontrolgrouptotaleffectiverate was 80.8%(63/78),treatment group was better than the control group (P<0.05);②After treatment,DNDS of treatment group improved significantly better than the control group ( P<0.01);③After treatment,DNDS was signif-icantly lower

  1. 应用心肌造影超声心动图结合速度向量成像对糖尿病大鼠心肌微循环与收缩功能障碍的相关性研究%Relationship between myocardial perfusion impairment and dysfunction in diabetic rats using myocardial contrast echocardiography and velocity vector imaging

    卫张蕊; 张军; 张海滨; 苏海砾; 施红; 朱霆; 朱永胜


    目的 应用心肌造影超声心动图(MCE)结合速度向量成像(VVI)技术研究糖尿病(DM)大鼠左室心肌微循环障碍与心肌收缩功能损伤之间的相关关系.方法 雄性SD大鼠23只,腹腔注射链脲菌素复制DM模型,另23只体质量匹配的雄性SD大鼠腹腔注射等量生理盐水作为对照.分别在静息状态和潘生丁负荷后,对两组大鼠(12周)乳头肌水平左室短轴行MCE和VVI检查,分别测定心肌血流量(MBF)、心肌血流储备(MFR)、收缩期最大圆周应变率(SRc)及其储备,分析MBF/MFR与SRc/SRc储备之间是否存在相关关系.结果 DM组大鼠的SRc、SRc储备、MBF及MFR均较对照组显著减低.DM组大鼠SRc与MBF之间没有明显相关性,而SR.储备与MFR之间呈现显著的负相关.结论 静息状态下,心肌血流量的降低并不是圆周应变率降低的主要决定因素,而潘生丁负荷后,心肌血流储备的降低可能是心肌圆周应变率储备降低的主要决定因素.%Objective To investigate whether myocardial dysfunction and perfusion impairment had happened in diabetes mellitus(DM)rats,and to assess the relationship between them by using myocardial contrast echocardiography(MCE)and velocity vector imaging(VVI).Methods MCE and VVI were performed from the short-axis views of the mid-left ventricular level both at rest and after dipyridamole stress in control rats and DM rafs(12 weeks after induction with streptozotocin).MCE-derived myocardial blood flow(MBF)and myocardial flow reserve(MFR)and VVI-derived circumferential strain rate(SRc)and SRc reserve were obtained.Results SRc(absolute value)and MBF in the DM group were significantly lower than those in the control group at rest(P =0.03 for SRc and P =0.005 for MBF).SRc reserve and MFR in the DM group were significantly lower than those in the control group after dipyridamole stress (P =0.000 for SRc reserve and P =0.014 for MFR).There was no significant correlation between SRc and MBF at rest in the

  2. Coupling of UDP-glucuronosyltransferases and multidrug resistance-associated proteins is responsible for the intestinal disposition and poor bioavailability of emodin

    Liu, Wei; Feng, Qian; Li, Ye; Ye, Ling [Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong (China); Hu, Ming, E-mail: [Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong (China); Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, TX 77030 (United States); Liu, Zhongqiu, E-mail: [Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong (China)


    Emodin is a poorly bioavailable but promising plant-derived anticancer drug candidate. The low oral bioavailability of emodin is due to its extensive glucuronidation in the intestine and liver. Caco-2 cell culture model was used to investigate the interplay between UDP-glucuronosyltransferases (UGTs) and efflux transporters in the intestinal disposition of emodin. Bidirectional transport assays of emodin at different concentrations were performed in the Caco-2 monolayers with or without multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP) efflux transporter chemical inhibitors. The bidirectional permeability of emodin and its glucuronide in the Caco-2 monolayers was determined. Emodin was rapidly metabolized to emodin glucuronide in Caco-2 cells. LTC4, a potent inhibitor of MRP2, decreased the efflux of emodin glucuronide and also substantially increased the intracellular glucuronide level in the basolateral-to-apical (B–A) direction. MK-571, chemical inhibitor of MRP2, MRP3, and MRP4, significantly reduced the efflux of glucuronide in the apical-to-basolateral (A–B) and B–A directions in a dose-dependent manner. However, dipyridamole, a BCRP chemical inhibitor demonstrated no effect on formation and efflux of emodin glucuronide in Caco-2 cells. In conclusion, UGT is a main metabolic pathway for emodin in the intestine, and the MRP family is composed of major efflux transporters responsible for the excretion of emodin glucuronide in the intestine. The coupling of UGTs and MRP efflux transporters causes the extensive metabolism, excretion, and low bioavailability of emodin. -- Highlights: ► Glucuronidation is the main reason for the poor oral bioavailability of emodin. ► Efflux transporters are involved in the excretion of emodin glucuronide. ► The intestine is the main organ for metabolism of emodin.

  3. A quantitative index of regional blood flow in canine myocardium derived noninvasively with N-13 ammonia and dynamic positron emission tomography

    Nienaber, C.A.; Ratib, O.; Gambhir, S.S.; Krivokapich, J.; Huang, S.C.; Phelps, M.E.; Schelbert, H.R. (Univ. of California, Los Angeles School of Medicine (USA))


    To derive a quantitative index of regional myocardial blood flow, the arterial input function of the flow tracer N-13 ammonia and the regional myocardial N-13 activity concentrations were noninvasively determined in 29 experiments in eight dogs. N-13 ammonia was administered intravenously and cross-sectional images were acquired dynamically using an ECAT III positron emission tomograph with an effective in-plane resolution of 13.46 mm full-width half-maximum. Time-activity curves were derived from the serial images by assigning regions of interest to the left ventricular myocardium and left ventricular blood pool. Tracer net extractions were estimated from the myocardial time-activity concentrations at various times after tracer injection and the integral of the arterial input function. Myocardial blood flow was altered by intravenous dipyridamole, morphine, propranolol and partial or complete occlusion of the left anterior descending coronary artery, and ranged from 9 to 860 ml/min per 100 g. Estimates of tracer net extractions were most accurate when determined from the myocardial N-13 activity concentrations at 60 s divided by the integral of the arterial input function to that time. These estimates correlated with regional myocardial blood flows determined independently by the microsphere technique by y = x (1 - 0.64(e-114/x); SEE = 22.9; r = 0.94). First pass extraction fractions of N-13 ammonia determined noninvasively with this approach declined with higher flows in a nonlinear fashion and were similar to those determined invasively by direct intracoronary N-13 ammonia injections. The findings indicate that an accurate index of regional myocardial blood flow can be obtained noninvasively by high temporal sampling of arterial and myocardial tracer activity concentrations with positron emission tomography.

  4. The central role of the nurse in process improvement relating to pharmacologic stress testing.

    Coats, Nancy P; Baranyay, Janie


    Pharmacologic stress myocardial perfusion imaging is a noninvasive method for evaluating coronary artery disease in patients unable to exercise sufficiently to achieve a heart rate high enough to facilitate satisfactory imaging. The nuclear cardiology nurse is an invaluable member of the laboratory team that performs these tests. In this specialist role, the nurse must have a thorough knowledge of the different pharmacologic stress agents (dipyridamole, adenosine, regadenoson, and dobutamine) that can be used. This should comprise an understanding of their mechanisms of action, contraindications, drug-drug interactions, adverse effects, and administration protocols. By drawing on this knowledge, the nurse is able to verify that the right agent has been selected for each patient based on his/her medical history. The nurse also can help patients follow pretest instructions (such as withholding caffeine and certain medications) by explaining that the measures are necessary for a safe and successful procedure and that violation may result in test cancellation or postponement. On the day of the stress test, the nurse has an important role in safeguarding the patient as well as providing support and reassurance throughout the different stages of the examination. Responsibilities include explaining the entire procedure to the patients, notably, what they will be asked to do, the effect of the stress agent, the timing of each step, the adverse effects that they may experience, how any adverse events will be managed, and the importance of remaining still during imaging. This central role of the nuclear cardiology nurse in overseeing the practical aspects of the pharmacologic stress test has important implications in terms of optimizing the productivity and efficiency of their noninvasive cardiology laboratory and nuclear medicine department.

  5. 川崎病患儿的护理%Nursing care of children with kawasaki disease



    目的:探讨川崎病患儿静脉滴注大剂量丙种球蛋白、口服阿司匹林、双嘧达莫等治疗的护理体会。方法:观察138例川崎病患儿临床表现,遵医嘱正确给药,观察给药后的疗效,并采取相应的护理措施。结果:由于药物使用及时,观察和护理得当,138例川崎病患儿全部治愈出院。结论:仔细评估、基础护理、药物护理、心理护理的措施对减轻川崎病患儿痛苦、治疗和预后有重要意义。%Objective:Investigate children with kawasaki disease high-dose intravenous drip gamma globulin, oral aspirin and dipyridamole nursing experience of treatment. Methods:Observe 138 cases of children with kawasaki disease clinical manifestations, prescribed dosing correctly, to observe the curative effect after the treatment, and take the corresponding nursing measures.Result:Due to drug use, timely observation and care properly, al 106 cases of children with kawasaki disease cure the hospital.Conclusion:Careful evaluation, basic nursing, medication nursing, psychological nursing measures to relief the children with kawasaki disease, treatment and prognosis.

  6. Diagnostic accuracy of stress perfusion CMR in comparison with quantitative coronary angiography: fully quantitative, semiquantitative, and qualitative assessment.

    Mordini, Federico E; Haddad, Tariq; Hsu, Li-Yueh; Kellman, Peter; Lowrey, Tracy B; Aletras, Anthony H; Bandettini, W Patricia; Arai, Andrew E


    This study's primary objective was to determine the sensitivity, specificity, and accuracy of fully quantitative stress perfusion cardiac magnetic resonance (CMR) versus a reference standard of quantitative coronary angiography. We hypothesized that fully quantitative analysis of stress perfusion CMR would have high diagnostic accuracy for identifying significant coronary artery stenosis and exceed the accuracy of semiquantitative measures of perfusion and qualitative interpretation. Relatively few studies apply fully quantitative CMR perfusion measures to patients with coronary disease and comparisons to semiquantitative and qualitative methods are limited. Dual bolus dipyridamole stress perfusion CMR exams were performed in 67 patients with clinical indications for assessment of myocardial ischemia. Stress perfusion images alone were analyzed with a fully quantitative perfusion (QP) method and 3 semiquantitative methods including contrast enhancement ratio, upslope index, and upslope integral. Comprehensive exams (cine imaging, stress/rest perfusion, late gadolinium enhancement) were analyzed qualitatively with 2 methods including the Duke algorithm and standard clinical interpretation. A 70% or greater stenosis by quantitative coronary angiography was considered abnormal. The optimum diagnostic threshold for QP determined by receiver-operating characteristic curve occurred when endocardial flow decreased to qualitative methods: Duke algorithm: 70%; and clinical interpretation: 78% (p quantitative stress perfusion CMR has high diagnostic accuracy for detecting obstructive coronary artery disease. QP outperforms semiquantitative measures of perfusion and qualitative methods that incorporate a combination of cine, perfusion, and late gadolinium enhancement imaging. These findings suggest a potential clinical role for quantitative stress perfusion CMR. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. [Myocardial perfusion scintigraphy 2012 in Germany. Results of the 6th Query].

    Lindner, O; Burchert, W; Schäfers, M; Schaefer, W


    The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 6th survey on myocardial perfusion scintigraphy (MPS) of the reporting year 2012. 278 questionnaires (177 private practices (PP), 78 hospitals (HO), 23 university hospitals (UH)) were evaluated. MPS of 105,941 patients were reported. 95% [2005 = 80%] of MPS studies were conducted with (99m)Tc perfusion radiopharmaceuticals and only 5% with 201Tl. 79% [2009 = 76%] of the MPS were performed in PP, 15% [2009 = 17%] in HO, and 6% [2009 = 7%] in UH. Data from 108 centres which participated in all surveys from 2005 to 2012 showed an increase in MPS numbers of 4.0% (PP +6.1%, HO +18.2%, UH -18.3%). 29% of all participants (27% of PP, 31% of HO, and 26% of UH) noticed no change and 26% of all participants (28% of PP, 17% of HO and 35% of UH) an increase in their MPS requests since the 2009 query. The type of stress was pharmacological in 39% [2009 = 31%]. Of these 61% with adenosine (39% with exercise), 22% with regadenoson (51% with exercise), 14% with dipyridamole (60% with exercise), and 3% with dobutamine. Gated SPECT was performed in 73% [2009 = 56%] of all rest, in 70% [2009 = 56%] of all stress and in 67% [47%] of all stress and rest MPS. Only 36% [2009 = 33%] of the centres performed a quantification of all their studies with scores, whereas 41% [2009 = 52%] did not apply any quantification. 60% [2009 = 49%] of the MPS were requested by ambulatory care cardiologists. The survey on MPS in Germany reveals a good conformity of imaging procedures with the current guideline. A positive development in MPS practice and referral can be stated. However, there is still some potential of MPS processing considering the quantitative perfusion analysis.

  8. Changes in haematology measurements with the Sysmex XT-2000iV during storage of feline blood sampled in EDTA or EDTA plus CTAD.

    Granat, Fanny; Geffré, Anne; Bourgès-Abella, Nathalie; Braun, Jean-Pierre; Trumel, Catherine


    In veterinary medicine a complete blood cell count (CBC) cannot always be performed within 24 h as usually recommended, particularly for specimens shipped to a reference laboratory. This raises the question of the stability of the variables, especially in ethylenediamine tetra-acetic acid (EDTA) feline blood specimens, known to be prone to in vitro platelet aggregation. Citrate, theophylline, adenosine and dipyridamole (CTAD) has been reported to limit platelet aggregation in feline blood specimens. The aim of this study was to measure the stability of the haematological variables and the platelet aggregation score in EDTA and EDTA plus CTAD (EDCT) feline blood specimens during 48 h of storage at room temperature. Forty-six feline EDTA and EDCT blood specimens were analysed with a Sysmex XT-2000iV analyser, and the platelet count and score of platelet aggregation were estimated immediately and after 24 and 48 h of storage. A significant increase in mean corpuscular volume, haematocrit, reticulocyte and eosinophil counts, and a significant decrease in mean corpuscular haemoglobin concentration and monocyte count were observed. Haemoglobin, mean corpuscular haemoglobin, and red blood cell, white blood cell, neutrophil and lymphocyte counts remained stable. Changes in reticulocyte indexes with time (low fluorescence ratio, medium fluorescence ratio, high fluorescence ratio and immature reticulocyte fraction) were not significant. Changes were generally more pronounced in EDTA than in EDCT. Platelet aggregation decreased markedly in initially highly aggregated EDTA specimens, and increased slightly in initially non- or mildly-aggregated EDTA or EDCT specimens. Platelet counts increased and decreased, or remained stable, respectively. CTAD can reduce storage-induced changes of the haematological variables in feline samples, thus improving the reliability of a CBC and limiting clinical misinterpretations.

  9. Stress-induced myocardial ischemia is associated with early post-stress left ventricular mechanical dyssynchrony as assessed by phase analysis of {sup 201}Tl gated SPECT myocardial perfusion imaging

    Chen, Chien-Cheng; Shen, Thau-Yun [Show Chwan Memorial Hospital, Department of Cardiology, Changhua (China); Chang, Ming-Che [Changhua Christian Hospital, Department of Nuclear Medicine, Changhua (China); Hung, Guang-Uei [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Changhua (China); China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China); Chen, Wan-Chen [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Changhua (China); Kao, Chia-Hung [China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China); Chen, Ji [Emory University School of Medicine, Department of Radiology and Imaging Sciences, Atlanta, GA (United States)


    In {sup 201}Tl SPECT myocardial perfusion imaging (MPI) data are acquired shortly after the stress injection to assess early post-stress left ventricle (LV) function. The purpose of this study was to use {sup 201}Tl SPECT MPI to investigate whether stress-induced myocardial ischemia is associated with LV mechanical dyssynchrony. Enrolled in the study were 75 patients who were referred for dipyridamole stress and rest {sup 201}Tl gated SPECT MPI. The early post-stress scan was started 5 min after injection, and followed by the rest scan 4 h later. The patients were divided into three groups: ischemia group (N = 25, summed stress score, SSS, {>=}5, summed rest score, SRS, <5), infarct group (N = 16, SSS {>=}5, SRS {>=}5) and normal group (N = 34, SSS <5, SRS <5). LV dyssynchrony parameters were calculated by phase analysis, and compared between the stress and rest images. In the ischemia group, LV dyssynchrony was significantly larger during stress than during rest. On the contrary, LV dyssynchrony during stress was significantly smaller than during rest in the normal and infarct groups. LV dyssynchrony during rest was significantly larger in the infarct group than in the normal and ischemia groups. There were no significant differences in LV dyssynchrony during rest between the normal and ischemia groups. Stress-induced myocardial ischemia caused dyssynchronous contraction in the ischemic region, leading to a deterioration in LV synchrony. Normal myocardium had more synchronous contraction during stress. The different dyssynchrony pattern between ischemic and normal myocardium early post-stress may aid the diagnosis of coronary artery disease using {sup 201}Tl gated SPECT MPI. (orig.)

  10. Oxidative stress/reactive metabolite gene expression signature in rat liver detects idiosyncratic hepatotoxicants

    Leone, Angelique; Nie, Alex; Brandon Parker, J.; Sawant, Sharmilee; Piechta, Leigh-Anne; Kelley, Michael F., E-mail:; Mark Kao, L.; Jim Proctor, S.; Verheyen, Geert; Johnson, Mark D.; Lord, Peter G.; McMillian, Michael K.


    Previously we reported a gene expression signature in rat liver for detecting a specific type of oxidative stress (OS) related to reactive metabolites (RM). High doses of the drugs disulfiram, ethinyl estradiol and nimesulide were used with another dozen paradigm OS/RM compounds, and three other drugs flutamide, phenacetin and sulindac were identified by this signature. In a second study, antiepileptic drugs were compared for covalent binding and their effects on OS/RM; felbamate, carbamazepine, and phenobarbital produced robust OS/RM gene expression. In the present study, liver RNA samples from drug-treated rats from more recent experiments were examined for statistical fit to the OS/RM signature. Of all 97 drugs examined, in addition to the nine drugs noted above, 19 more were identified as OS/RM-producing compounds—chlorpromazine, clozapine, cyproterone acetate, dantrolene, dipyridamole, glibenclamide, isoniazid, ketoconazole, methapyrilene, naltrexone, nifedipine, sulfamethoxazole, tamoxifen, coumarin, ritonavir, amitriptyline, valproic acid, enalapril, and chloramphenicol. Importantly, all of the OS/RM drugs listed above have been linked to idiosyncratic hepatotoxicity, excepting chloramphenicol, which does not have a package label for hepatotoxicity, but does have a black box warning for idiosyncratic bone marrow suppression. Most of these drugs are not acutely toxic in the rat. The OS/RM signature should be useful to avoid idiosyncratic hepatotoxicity of drug candidates. - Highlights: • 28 of 97 drugs gave a positive OS/RM gene expression signature in rat liver. • The specificity of the signature for human idiosyncratic hepatotoxicants was 98%. • The sensitivity of the signature for human idiosyncratic hepatotoxicants was 75%. • The signature can help eliminate hepatotoxicants from drug development.

  11. Quantification of myocardial blood flow with {sup 82}Rb dynamic PET imaging

    Lortie, Mireille; Beanlands, Rob S.B.; Yoshinaga, Keiichiro; Klein, Ran; DaSilva, Jean N.; DeKemp, Robert A. [University of Ottawa Heart Institute, Cardiac PET Centre, Ottawa, ON (Canada)


    The PET tracer {sup 82}Rb is commonly used to evaluate regional perfusion defects for the diagnosis of coronary artery disease. There is limited information on the quantification of myocardial blood flow and flow reserve with this tracer. The goal of this study was to investigate the use of a one-compartment model of {sup 82}Rb kinetics for the quantification of myocardial blood flow. Fourteen healthy volunteers underwent rest and dipyridamole stress imaging with both {sup 13}N-ammonia and {sup 82}Rb within a 2-week interval. Myocardial blood flow was estimated from the time-activity curves measured with {sup 13}N-ammonia using a standard two-compartment model. The uptake parameter of the one-compartment model was estimated from the time-activity curves measured with {sup 82}Rb. To describe the relationship between myocardial blood flow and the uptake parameter, a nonlinear extraction function was fitted to the data. This function was then used to convert estimates of the uptake parameter to flow estimates. The extraction function was validated with an independent data set obtained from 13 subjects with documented evidence of coronary artery disease (CAD). The one-compartment model described {sup 82}Rb kinetics very well (median R-square = 0.98). The flow estimates obtained with {sup 82}Rb were well correlated with those obtained with {sup 13}N-ammonia (r = 0.85), and the best-fit line did not differ significantly from the identity line. Data obtained from the subjects with CAD confirmed the validity of the estimated extraction function. It is possible to obtain accurate estimates of myocardial blood flow and flow reserve with a one-compartment model of {sup 82}Rb kinetics and a nonlinear extraction function. (orig.)

  12. Diagnostic significance of myocardial perfusion scintigraphy in identification and localization of culprit lesions in patients undergoing elective PTCA

    Baškot Branislav


    Full Text Available Background/Aim. The coronary angiography provides information on the anatomical state of the coronary tree, while myocardial perfusion scintigraphy (MPI facilitates the evaluation of the grade of ischaemia that a particular stenosis produces. The purpose of MPI is to detect the coronary stenosis that provokes the ischaemia and is termed the "culprit lesion". The aim of this study was to evaluate the accuracy of 1-day DypEX 99mTc-tetrofosmin tomography in the identification and localization of culprit lesion in the patients with known coronary artery disease (CAD. Methods. Ninety-one (91 patients with known CAD were studied. In all of them significant coronary narowing (≥ 75% luminal stenosis was angiographically detected. All the patients were submitted to 2 iv. injections of 99mTc-tetrofosmin, one in a peak of pharmacologic dipyridamole stress protocol with concomitant low level bicycle exercise 50W (DypEX and the other 3 h after exercise. Quantification of regional tetrofosmin uptake was performed using short-axis myocardial tomogram that was divided on 17-segments for each study. Reversibility scor (RS ≥ 3 determinated culprit lesion. Two of segments with scor 5 (index of reversibility scor - IRS in the territory of coronary artery stenoses determinated culprit lesion. Results. A total of 273 vascular territories (4641 segments were analyzed before percutaneous coronary intervention (PCI. Overall sensivity, specificity, and accuracy using RS ≥ 3 and IRS were 90.1%, 87.1%, 89.4%, with positive predictive value 95.8%, and 94.1%, 93.3%, 94%, with positive predictive value 98%, respectively. Conclusion. RS and IRS significantly improve sensitivity, specificity, and accuracy for determination of culprit lesion in patients undergoing PCI.

  13. Epigenetics and Vasculitis: a Comprehensive Review.

    Renauer, Paul; Coit, Patrick; Sawalha, Amr H


    Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies.

  14. V.A. Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: III. Definitions and review of design and baseline characteristics.

    Colwell, J A; Bingham, S F; Abraira, C; Anderson, J W; Kwaan, H C


    This report summarizes the major design features, methods, and baseline characteristics of patients enrolled in a Veterans Administration Cooperative Study. In eleven V.A. centers, 231 male diabetic patients who had either a recent amputation for gangrene (N = 207) or active gangrene (N = 24) were randomly assigned to a group which received aspirin (325 mg t.i.d.) plus dipyridamole (75 mg t.i.d.) (N = 110) or two placeboes t.i.d. (N = 121). Major end point were vascular death and amputation of the opposite extremity for gangrene. Forty-one percent of the 563 patients screened were enrolled during a 39 month period. Enrollment errors were found in 8.7%. Historically, the two groups were well matched regarding the following variables: age, duration of diabetes, insulin therapy, previous oral agent therapy, hypertension, myocardial infarction, congestive heart failure, renal disease, sensory neuropathy, and smoking. The drug therapy group had an increased frequency of a history of cerebrovascular disease (19% vs 7%, p = 0.01). The groups were well matched regarding amputation site, obesity, extent of lower extremity vascular disease, retinopathy, and neuropathy upon examination. Their baseline fasting values of glucose, cholesterol, triglycerides, and creatinine were also comparable. We conclude that this study should provide definitive data on the efficacy of these antiplatelet agents in preventing further vascular disease in this patient group. It should also provide new prospective data on the natural history of vascular disease, and the association of vascular risk factors with subsequent vascular events in this patient population.

  15. Quantification of regional myocardial oxygenation by magnetic resonance imaging: validation with positron emission tomography.

    McCommis, Kyle S; Goldstein, Thomas A; Abendschein, Dana R; Herrero, Pilar; Misselwitz, Bernd; Gropler, Robert J; Zheng, Jie


    A comprehensive evaluation of myocardial ischemia requires measures of both oxygen supply and demand. Positron emission tomography (PET) is currently the gold standard for such evaluations, but its use is limited because of its ionizing radiation, limited availability, and high cost. A cardiac MRI method was developed for assessing myocardial oxygenation. The purpose of this study was to evaluate and validate this technique compared with PET during pharmacological stress in a canine model of coronary artery stenosis. Twenty-one beagles and small mongrel dogs without coronary artery stenosis (controls) or with moderate to severe acute coronary artery stenosis underwent MRI and PET imaging at rest and during dipyridamole vasodilation or dobutamine stress to induce a wide range of changes in cardiac perfusion and oxygenation. MRI first-pass perfusion imaging was performed to quantify myocardial blood flow and volume. The MRI blood oxygen level-dependent technique was used to determine the myocardial oxygen extraction fraction during pharmacological hyperemia. Myocardial oxygen consumption was determined by the Fick law. In the same dogs, (15)O-water and (11)C-acetate were used to measure myocardial blood flow and myocardial oxygen consumption, respectively, by PET. Regional assessments were performed for both MR and PET. MRI data correlated nicely with PET values for myocardial blood flow (R(2)=0.79, P<0.001), myocardial oxygen consumption (R(2)=0.74, P<0.001), and oxygen extraction fraction (R(2)=0.66, P<0.01). Cardiac MRI methods may provide an alternative to radionuclide imaging in settings of myocardial ischemia. Our newly developed quantitative MRI oxygenation imaging technique may be a valuable noninvasive tool to directly evaluate myocardial energetics and efficiency.

  16. Inhibition by adenosine of histamine and leukotriene release from human basophils.

    Peachell, P T; Lichtenstein, L M; Schleimer, R P


    Adenosine inhibited the release of histamine and leukotriene C4 (LTC4) from immunologically-activated basophils in a dose-dependent manner. Structural congeners of adenosine also attenuated the elaboration of these two mediators from stimulated basophils and a rank order of potency for the inhibition was observed following the sequence 2-chloroadenosine greater than or equal to N-ethylcarboxamidoadenosine (NECA) greater than adenosine greater than or equal to R-phenylisopropyladenosine (R-PIA) greater than or equal to S-PIA. These same nucleosides modulated the generation of LTC4 more potently than the release of histamine. A number of methylxanthines, which are antagonists of cell surface adenosine receptors, reversed the inhibition by adenosine and its congeners of the release of both histamine and LTC4 to varying extents. Dipyridamole and nitrobenzylthioinosine (NBTI), agents that block the intracellular uptake of adenosine, antagonized the inhibition of histamine release by adenosine (and 2-chloroadenosine) but failed to reverse the attenuation of LTC4 generation by the nucleoside. These same uptake blockers were unable to antagonize the inhibitory effects of NECA on either histamine or LTC4 release. In purified basophils, NECA and R-PIA, and in that order of decreasing reactivity, increased total cell cyclic adenosine monophosphate (cAMP) levels and inhibited the stimulated release of mediators. In total, these results suggest that the basophil possesses a cell surface adenosine receptor which, on the basis of both pharmacological and biochemical criteria, most closely conforms to an A2/Ra-like receptor. However, in addition to an interaction at the cell surface, studies with agents that block the intracellular uptake of adenosine suggest that the nucleoside may also exert intracellular effects when countering the release of histamine (but not LTC4).

  17. Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials.

    Kwok, Chun Shing; Shoamanesh, Ashkan; Copley, Hannah Charlotte; Myint, Phyo Kyaw; Loke, Yoon K; Benavente, Oscar R


    Lacunar stroke accounts for ≈25% of ischemic stroke, but optimal antiplatelet regimen to prevent stroke recurrence remains unclear. We aimed to evaluate the efficacy of antiplatelet agents in secondary stroke prevention after a lacunar stroke. We searched MEDLINE, Embase, and the Cochrane library for randomized controlled trials that reported risk of recurrent stroke or death with antiplatelet therapy in patients with lacunar stroke. We used random effects meta-analysis and evaluated heterogeneity with I(2). We included 17 trials with 42,234 participants (mean age 64.4 years, 65% male) and follow up ranging from 4 weeks to 3.5 years. Compared with placebo, any single antiplatelet agent was associated with a significant reduction in recurrence of any stroke (risk ratio [RR] 0.77, 0.62-0.97, 2 studies) and ischemic stroke (RR 0.48, 0.30-0.78, 2 studies), but not for the composite outcome of any stroke, myocardial infarction, or death (RR 0.89, 0.75-1.05, 2 studies). When other antiplatelet agents (ticlodipine, cilostazol, and dipyridamole) were compared with aspirin, there was no consistent reduction in stroke recurrence (RR 0.91, 0.75-1.10, 3 studies). Dual antiplatelet therapy did not confer clear benefit over monotherapy (any stroke RR 0.83, 0.68-1.00, 3 studies; ischemic stroke RR 0.80, 0.62-1.02, 3 studies; composite outcome RR 0.90, 0.80-1.02, 3 studies). Our results suggest that any of the single antiplatelet agents compared with placebo in the included trials is adequate for secondary stroke prevention after lacunar stroke. Dual antiplatelet therapy should not be used for long-term stroke prevention in this stroke subtype. © 2015 American Heart Association, Inc.

  18. Thermodynamics and kinetics of inhibitor binding to human equilibrative nucleoside transporter subtype-1.

    Rehan, Shahid; Ashok, Yashwanth; Nanekar, Rahul; Jaakola, Veli-Pekka


    Many nucleoside transport inhibitors are in clinical use as anti-cancer, vasodilator and cardioprotective drugs. However, little is known about the binding energetics of these inhibitors to nucleoside transporters (NTs) due to their low endogenous expression levels and difficulties in the biophysical characterization of purified protein with ligands. Here, we present kinetics and thermodynamic analyses of inhibitor binding to the human equilibrative nucleoside transporter-1 (hENT1), also known as SLC29A1. Using a radioligand binding assay, we obtained equilibrium binding and kinetic rate constants of well-known NT inhibitors--[(3)H]nitrobenzylmercaptopurine ribonucleoside ([(3)H]NBMPR), dilazep, and dipyridamole--and the native permeant, adenosine, to hENT1. We observed that the equilibrium binding affinities for all inhibitors decreased whereas, the kinetic rate constants increased with increasing temperature. Furthermore, we found that binding is enthalpy driven and thus, an exothermic reaction, implying that the transporter does not discriminate between its inhibitors and substrates thermodynamically. This predominantly enthalpy-driven binding by four chemically distinct ligands suggests that the transporter may not tolerate diversity in the type of interactions that lead to high affinity binding. Consistent with this, the measured activation energy of [(3)H]NBMPR association was relatively large (20 kcal mol(-1)) suggesting a conformational change upon inhibitor binding. For all three inhibitors the enthalpy (ΔH°) and entropy (ΔS°) contributions to the reaction energetics were determined by van't Hoff analysis to be roughly similar (25-75% ΔG°). Gains in enthalpy with increasing polar surface area of inhibitors suggest that the binding is favored by electrostatic or polar interactions between the ligands and the transporter.

  19. [Stress echocardiography: development and significance].

    Attenhofer, C; Ritter, M; Jenni, R


    Exercise electrocardiography is still the primary method used in the non-invasive assessment of coronary artery disease. Stress echocardiography is now being increasingly used as a more sensitive adjunct technique to assess ischemia. Ischemia provoked by stress can induce reversible wall motion abnormalities which are disclosed by cross-sectional 2-dimensional echocardiography and standard projections. The types of stress used are physical exercise (bicycle, treadmill), atrial pacing or pharmacologic stimulation. In the latter, the catecholamine dobutamine has emerged as preferable to the vasodilators dipyridamole and adenosine. The diagnostic accuracy of dobutamine stress echocardiography is comparable to that of bicycle or treadmill exercise echocardiography, but dobutamine stress echocardiography is technically simpler and can be performed in patients unable to exercise. Its sensitivity in diagnosing ischemic or viable myocardium is comparable to that of nuclear methods, MRI or PET. In contrast to nuclear methods, stress echocardiography is however free of radiation. In the assessment of patients with coronary artery disease, stress echocardiography has been shown to be valuable for diagnosis, preoperative risk stratification and determination of prognosis. Furthermore, low dose dobutamine echocardiography can be used to detect viable myocardium. Despite these very promising aspects of the method, there are recognized disadvantages and limitations: stress echocardiography is very time-consuming and operator-dependent; its sensitivity correlates strongly with the number of studies performed; analysis of wall motion is performed qualitatively on a purely subjective level, and hence lacks the objectivity of a quantitative approach. These factors emphasize the need for intensive research to render stress echocardiographic analysis more objective. Automatic boundary detection of left ventricular endocardium, color-Doppler-based tissue imaging and three

  20. Diagnosis, management and prevention of ischemic stroke for non-neurologists

    Kavian Ghandehari


    Full Text Available Background: Stroke is the third common cause of disability and death. Diagnosis of stroke is based on its clinical manifestations and/or observation of infarct in the neuroimaging. Standard battery of diagnostic investigations and classification criteria is required for detection of stroke etiology. Materials and Method: This review article deals with the diagnosis and management of brain infarction particularly in our country and is provided for non-neurologists. Using online scientific search engines and in some parts referring to laboratory archives constituted base of this review article.Results: Acute stroke management is almost similar in its various etiologies. Neuroprotective drugs have little value in acute stroke management. At present time, a few Iranian medical centers have infrastructure of thrombolysis therapy. Prevention of stroke is based on the detection and control of its risk factors. Aspirin, 80 mg per day is the most common drug for stroke prevention. Co-administration of aspirin 80 mg/d and Dipyridamole 200-400 mg/d increases the preventive effects of aspirin. Clopidogrel 75 mg/d is the stroke preventive drug of choice in patients with peptic ulcer and coronary artery disease. Co-administration of aspirin and clopidogrel is more effective in stroke prevention but has more hemorrhagic complications. Using warfarin for stroke prevention is suggested only in patients who have facilities for repetitive coagulation tests. Carotid endarterectomy is indicated in symptomatic patients with more than 70% stenosis of extracranial internal carotid artery, if performed only by vascular surgeons experienced in carotid surgery.Conclusion: Many stroke patients are managed by general practitioners and non-neurologists, e.g. internists, cardiologists and neurosurgeons. This review article provides continuous medical education according to Iranian medical curriculum

  1. Myocardial perfusion scintigraphy 2007 in Germany. Results of the query and current status

    Lindner, O. [Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung, Herz- und Diabeteszentrum NRW, Bad Oeynhausen (Germany); Burchert, W. [Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung, Herz- und Diabeteszentrum NRW, Bad Oeynhausen (Germany); Arbeitsgemeinschaft Kardiovaskulaere Nuklearmedizin der Deutschen Gesellschaft fuer Nuklearmedizin (Germany); Bengel, F.M. [Cardiovascular Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore (United States); Arbeitsgruppe Nuklearkardiologische Diagnostik der Deutschen Gesellschaft fuer Kardiologie (Germany); Zimmermann, R. [Arbeitsgruppe Nuklearkardiologische Diagnostik der Deutschen Gesellschaft fuer Kardiologie (Germany); Medizinische Klinik, Klinikum Pforzheim GmbH, Pforzheim (Germany); Dahl, J. vom [Klinik fuer Kardiologie, Kliniken Maria Hilf GmbH, Moenchengladbach (Germany); Schaefer, W. [Klinik fuer Nuklearmedizin, Universitaetsklinikum Aachen (Germany); Schober, O. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Muenster UKM (Germany); Schaefers, M. [Arbeitsgemeinschaft Kardiovaskulaere Nuklearmedizin der Deutschen Gesellschaft fuer Nuklearmedizin (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Muenster UKM (Germany)


    Aim: This third survey of the working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine in cooperation with the working group Nuclear Cardiology of the German Cardiac Society was to deliver information on the procedures and in particular on the development of myocardial perfusion scintigraphy (MPS) from 2005 to 2007. Method: 370 questionnaires (222 private practices (PP), 117 hospitals (HO), 31 university hospitals (UH)) were evaluated. Results: MPS of 114,374 patients were reported, 83% were investigated with {sup 99m}Tc-perfusion tracers. 76% [2006=74%] were performed in PP, 15% [2006=17%] in HO and 9% [2006=9%] in UH. Diabetics represented 21% of all MPS patients in 2007. Data of 215 institutions which participated all from 2005 to 2007 showed an increase in MPS of 2.3% (PP +6.8%, HO -4.5%, UH -18.2%). The type of stress was pharmacological in 27% [2006 = 27%]; 67% adenosine (of these 25% with exercise), 31% dipyridamole (of these 55% with exercise), and 2% dobutamine. Gated SPECT was performed in 47% [2006 = 42%] of all rest and in 44% [2006 = 39%] of all stress MPS. 61% [2006 = 83%] of all institutions did not apply perfusion scores. 20% [2006 = 24%] of the institutions reported changes in the use of MPS by competing methods. Conclusion: There is a small increase of MPS between 2005 and 2007 despite competing methods. Gated SPECT has experienced more acceptance, but is still underrepresented. As compared to the European average and general standards of MPS a considerable backlog accounts to pharmacological stress tests, gated SPECT and perfusion scores. (orig.)

  2. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

    Zhang, Xiaoli; Schindler, Thomas H; Prior, John O; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng; Schelbert, Heinrich R


    The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p MFRs (r =-0.424, p MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

  3. 1 Cases of Extrapyramidal Symptoms Caused by Comound Paracetamol and Amantadine Hydrochloride Tablets%复方氨酚烷胺片致锥体外系症状1例

    张良芬; 赵韵超


    复方氨酚烷胺片不良反应为白细胞或血小板减少、食欲缺乏、恶心、呕吐、皮疹等。本文介绍因感冒自行服用"复方氨酚烷胺片(新秀)2片"后外出活动时突发全身不自主抖动,实属罕见,给予停服复方氨酚烷胺片,加用银杏达莫注射液(杏丁)输注5d后症状逐渐减轻,直至消失。出现的锥体外系症状副反应可能与特异体质或体敏感性有关。一旦有该症状,应立即停用药物,避免锥体外系等不良反应的发生。%The adverse reactions Comound Paracetamol and Amantadine Hydrochloride Tablets white cellor platelet reduction, lack of appetite, nausea, vomiting, skin rash. In this paper because of cold to take"Comound Paracetamol and Amantadine Hydrochloride Tablets (Rookie) 2"after traveling burst body involuntary jit er, rare, give of Comound Paracetamol and Amantadine Hydrochloride Tablets, plus Ginkgo Leaf Extract and Dipyridamole Injection (Xing Ding) infusion of 5 days after the symptoms gradual y reduced, until it disappeared. Extrapyramidal side ef ects may be related to the special physique or body sensitivity. Once the symptoms, should immediately stop using the drug, avoid adverse reaction of extrapyramidal system etc.

  4. Application of stressed cerebral blood flow perfusion imaging in cerebrovascular disease%负荷试验脑血流灌注显像在脑血管疾病中的应用

    尹立杰; 刘杰; 金超岭; 王荣福


    The incidence of ischemic cerebrovascular disease is currently high. The disease can be diagnosed and treated by numerous methods, including transcranial doppler, CT angiography, MRI, digital subtraction angiography and cerebral blood flow perfusion imaging of resting and stress states. In these methods, the clinical application of stressed cerebral blood flow perfusion imaging is very wide and includes vertical load tests, CO2 inhalation load tests, acetazolamide stress tests, dipyridamole stress tests, and adenosine stress tests. Stressed cerebral blood flow perfusion imaging can provide an objective basis for the early diagnosis, curative effect evaluation, prognostic estimation, and evaluation of brain reserve function.%目前,缺血性脑血管病发病率较高,对其诊治方法很多,包括经颅多普勒超声、 CT血管造影、 MRI、数字减影血管造影和静息及负荷试验脑血流灌注显像等。其中,负荷试验脑血流灌注显像包括直立负荷试验、 CO2吸入负荷试验、乙酰唑胺负荷试验、潘生丁负荷试验、腺苷负荷试验等,其临床应用非常广泛,为临床早期诊断、疗效评价、预后以及脑血流储备功能的评估提供了客观依据。

  5. Adenosine stress protocols for myocardial perfusion imaging

    Baškot Branislav


    Full Text Available Background/Aim. Treadmill test combined with myocardial perfusion scintigraphy (MPS is a commonly used technique in the assessment of coronary artery disease. There are many patients, however, who may not be able to undergo treadmill test. Such patients would benefit from pharmacological stress procedures combined with MPS. The most commonly used pharmacological agents for cardiac stress are coronary vasodilatators (adenosine, dipyridamol and catecholamines. Concomitant low-level treadmill exercise with adenosine pharmacologic stress (AdenoEX during MPS has become commonly used in recent years. A number of studies have demonstrated a beneficial impact of AdenoEX protocol. The aim of the study was, besides introducing into practice the two types of protocols of pharmatological stress test with adenosine, as a preparation for MPS, to compare and monitor the frequency of their side effects to quality, acquisition, as well as to standardize the onset time of acquisition (diagnostic imaging for both protocols. Methods. A total of 130 patients underwent pharmacological stress test with adenosine (vasodilatator. In 108 of the patients we performed concomitant exercise (AdenoEX of low level (50W by a bicycle ergometar. In 28 of the patients we performed Adenosine abbreviated protocol (AdenoSCAN. Side effects of adenosine were followed and compared between the two kinds of protocols AdenoEX and AdenoSCAN. Also compared were image quality and suggested time of acquisition after the stress test. Results. Numerous side effects were found, but being short-lived they did not require any active interventions. The benefit of AdenoEX versus AdenoSCAN included decreased side effects (62% vs 87%, improved safety and patients tolerance, improved target-to-background ratios because of less subdiaphragmatic activity, earlier acquisition, and improved sensitivity. Conclusion. The safety and efficacy of adenosine pharmacological stress is even better with concomitant

  6. Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates

    Faita Francesco


    Full Text Available Abstract A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration. Aims 1- To assess the feasibility and extra-value of operator-independent, force sensor-based, diastolic time recording during stress. Methods We enrolled 161 patients referred for stress echocardiography (exercise 115, dipyridamole 40, pacing 6 patients. The sensor was fastened in the precordial region by a standard ECG electrode. The acceleration signal was converted into digital and recorded together with ECG signal. Both systolic and diastolic times were acquired continuously during stress and were displayed by plotting times vs. heart rate. Diastolic filling rate was calculated as echo-measured mitral filling volume/sensor-monitored diastolic time. Results Diastolic time decreased during stress more markedly than systolic time. At peak stress 62 of the 161 pts showed reversal of the systolic/diastolic ratio with the duration of systole longer than diastole. In the exercise group, at 100 bpm HR, systolic/diastolic time ratio was lower in the 17 controls (0.74 ± 0.12 than in patients (0.86 ± 0.10, p Diastolic filling rate increased from 101 ± 36 (rest to 219 ± 92 ml/m2* s-1 at peak stress (p Conclusion Cardiological systolic and diastolic duration can be monitored during stress by using an acceleration force sensor. Simultaneous calculation of stroke volume allows monitoring diastolic filling rate. Stress-induced "systolic-diastolic mismatch" can be easily quantified and is associated to several cardiac diseases, possibly expanding the spectrum of information obtainable during stress.

  7. Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials.

    Geeganage, Chamila M; Diener, Hans-Christoph; Algra, Ale; Chen, Christopher; Topol, Eric J; Dengler, Reinhard; Markus, Hugh S; Bath, Matthew W; Bath, Philip M W


    Antiplatelets are recommended for patients with acute noncardioembolic stroke or transient ischemic attack. We compared the safety and efficacy of dual versus mono antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack. Completed randomized controlled trials of dual versus mono antiplatelet therapy in patients with acute (≤3 days) ischemic stroke/transient ischemic attack were identified using electronic bibliographic searches. The primary outcome was recurrent stroke (ischemic, hemorrhagic, unknown; fatal, nonfatal). Comparison of binary outcomes between treatment groups was analyzed with random effect models and described using risk ratios (95% CI). Twelve completed randomized trials involving 3766 patients were included. In comparison with mono antiplatelet therapy, dual therapy (aspirin+dipyridamole and aspirin+clopidogrel) significantly reduced stroke recurrence, dual 58 (3.3%) versus mono 91 (5.0%; risk ratio, 0.67; 95% CI, 0.49-0.93); composite vascular event (stroke, myocardial infarction, vascular death), dual 74 (4.4%) versus mono 106 (6%; risk ratio, 0.75; 95% CI, 0.56-0.99); and the combination of stroke, transient ischemic attack, acute coronary syndrome, and all death, dual 100 (1.7%) versus mono 136 (9.1%; risk ratio, 0.71; 95% CI, 0.56-0.91); dual therapy was also associated with a nonsignificant trend to increase major bleeding, dual 15 (0.9%) versus mono 6 (0.4%; risk ratio, 2.09; 95% CI, 0.86-5.06). Dual antiplatelet therapy appears to be safe and effective in reducing stroke recurrence and combined vascular events in patients with acute ischemic stroke or transient ischemic attack as compared with mono therapy. These results need to be tested in prospective studies.

  8. Myocardial perfusion scintigraphy 2008 in Germany. Results of the fourth query; Myokard-Perfusions-Szintigraphie 2008 in Deutschland. Ergebnisse der vierten Erhebung

    Lindner, O. [Herz- und Diabeteszentrum NRW, Bad Oeynhausen (Germany). Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung; Burchert, W. [Herz- und Diabeteszentrum NRW, Bad Oeynhausen (Germany). Inst. fuer Radiologie, Nuklearmedizin und Molekulare Bildgebung; Deutsche Gesellschaft fuer Nuklearmedizin (Germany). Arbeitsgemeinschaft ' Kardiovaskulaere Nuklearmedizin' ; Bengel, F.M. [Johns Hopkins Medical Institutions, Baltimore (United States). Cardiovascular Nuclear Medicine; Deutsche Gesellschaft fuer Nuklearmedizin (Germany). Arbeitsgruppe ' Nuklearkardiologische Diagnostik' ; Zimmermann, R. [Deutsche Gesellschaft fuer Nuklearmedizin (Germany). Arbeitsgruppe ' Nuklearkardiologische Diagnostik' ; Klinikum Pforzheim GmbH, Pforzheim (Germany). Medizinische Klinik; Dahl, J. vom [Kliniken Maria Hilf GmbH, Moenchengladbach (Germany). Klinik fuer Kardiologie; Schaefer, W. [Kliniken Maria Hilf GmbH, Moenchengladbach (Germany). Klinik fuer Nuklearmedizin; Schober, O. [Muenster Univ. (Germany). Inst. of Molecular Imaging; Schaefers, M. [Deutsche Gesellschaft fuer Nuklearmedizin (Germany). Arbeitsgemeinschaft ' Kardiovaskulaere Nuklearmedizin' ; Muenster Univ. (Germany). Inst. of Molecular Imaging


    Aim: The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine in cooperation with the working group Nuclear Cardiology of the German Cardiac Society herewith present the results of the 4{sup th} survey on myocardial perfusion scintigraphy (MPS) of the year 2008. Method: 310 questionnaires (191 private practices (PP), 93 hospitals (HO), 31 university hospitals (UH)) were evaluated. Results: MPS of 98 947 patients were reported. 15% of them were younger than 50 y, 57% between 50 and 70 y and 28% older than 70 y. 88% [2007: 83%] of all were studied with Tc-99m perfusion tracers. The patient radiation exposure of a stress and rest protocol considering German standard recommended doses was 8.5 mSv, of a stress-only protocol 1.9 mSv. 77% [2007: 76%] of the MPS were performed in PP, 15% [2007: 15%] in HO and 8% [2007: 9%] in UH. From 2005 to 2008 there was a mild increase in the MPS numbers by 1.2% (PP +7.1%, HO -5.5%, UH -31.4%). The type of stress was pharmacological in 30% [2007: 27%]; 68% adenosine (of these 22% with exercise), 29% dipyridamole (of these 64% with exercise), and <1% dobutamine. Gated SPECT was performed in 46% [2007: 47%] of all rest and in 42% [2007: 44%] of all stress MPS. 62% [2007: 61%] of all institutions did not use perfusion scores. Conclusion: The MPS numbers from 2005 to 2008 in Germany can be regarded as stable. However, there are considerable shifts from HO and UH to PP. The well known potential of MPS considering risk stratification and functional analysis has not been tapped so far. Both gated SPECT and a quantitative perfusion analysis should be performed routinely in every patient.

  9. A multifunctional drug combination shows highly potent therapeutic efficacy against human cancer xenografts in athymic mice.

    Xiu-Jun Liu

    Full Text Available The tumor microenvironment plays a crucial role during tumor development. Integrated combination of drugs that target tumor microenvironment is a promising approach to anticancer therapy. Here, we report a multifunctional combination of low-cytotoxic drugs composed of dipyridamole, bestatin and dexamethasone (DBDx which mainly acts on the tumor microenvironment shows highly potent antitumor efficacy in vivo. In mouse hepatoma H22 model, the triple drug combination showed synergistic and highly potent antitumor efficacy. The combination indices of various combinations of the triple drugs were between 0.2 and 0.5. DBDx inhibited the growth of a panel of human tumor xenografts and showed no obvious systemic toxicity. At tolerated doses, DBDx suppressed the growth of human hepatocellular carcinoma BEL-7402, HepG2, and lung adenocarcinoma A549 xenografts by 94.5%, 93.7% and 96.9%, respectively. Clonogenic assay demonstrated that DBDx showed weak cytotoxicity. Western blot showed that Flk1 and Nos3 were down-regulated in the DBDx-treated group. Proteomic analysis showed that DBDx mainly affected the metabolic process and immune system process; in addition, the angiogenesis and VEGF signaling pathway were also affected. Conclusively, DBDx, a multifunctional drug combination of three low-cytotoxic drugs, shows synergistic and highly potent antitumor efficacy evidently mediated by the modulation of tumor microenvironment. Based on its low-cytotoxic attributes and its broad-spectrum antitumor therapeutic efficacy, this multifunctional combination might be useful in the treatment of cancers, especially those refractory to conventional chemotherapeutics.

  10. A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

    Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A


    The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

  11. Robotic treadmill training improves cardiovascular function in spinal cord injury patients.

    Turiel, Maurizio; Sitia, Simona; Cicala, Silvana; Magagnin, Valentina; Bo, Ivano; Porta, Alberto; Caiani, Enrico; Ricci, Cristian; Licari, Vittorio; De Gennaro Colonna, Vito; Tomasoni, Livio


    Body weight supported treadmill training (BWSTT) assisted with a robotic driven gait orthosis (DGO) is an emerging tool in rehabilitating patients with lost sensorimotor function. Few information about the effects of BWSTT on cardiovascular system are available. The purpose of this study was to determine the effects of BWSTT on: 1) left ventricular (LV) systo-diastolic function; 2) coronary flow reserve (CFR); 3) endothelial function in patients with lost sensorimotor function due to neurologic lesions. Fourteen adults (males 10, age 50.6±17.1years) with motor incomplete spinal cord injuries (SCI) due to trauma or spondylotic diseases underwent standard echocardiographic examination, non invasive assessment of CFR by dipyridamole stress echo and determination of plasma asymmetric dimethylarginine (ADMA) levels at baseline and after 6weeks of BWSTT. At post training evaluation we observed lower LV end-diastolic (P=0.0164) and end-systolic volumes (P=0.0029) with increased ejection fraction (EF) (P=0.0266). We also observed a LV interventricular septum (IVS) (P=0.00469) increase. At the same time, we detected an improvement of LV diastolic function as witnessed by the reduction of isovolumic relaxation time (IVRT) (P=0.0404) and deceleration time (DT) (P=0.0405) with an increased E/A ratio (P=0.0040). Improved CFR (P=0.020) and reduced plasma ADMA levels (P=0.0005) have been observed too, in association with a reduction of the inflammatory status (C-reactive protein (CRP) (P=0.0022) and erythrocyte sedimentation rate (ESR) (P=0.0005)). For the first time, this study demonstrated that 6weeks of BWSTT improved not only the sensorimotor function but also systo-diastolic LV function, CFR and endothelial dysfunction associated with a reduction of the inflammatory status in patients with incomplete SCI. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Low-dose adenosine stress echocardiography: Detection of myocardial viability

    Djordjevic-Dikic, Ana; Ostojic, Miodrag; Beleslin, Branko; Nedeljkovic, Ivana; Stepanovic, Jelena; Stojkovic, Sinisa; Petrasinovic, Zorica; Nedeljkovic, Milan; Saponjski, Jovica; Giga, Vojislav


    Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months) were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 ± 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability. PMID:12812523

  13. Cardiac reflections and natural vibrations: Force-frequency relation recording system in the stress echo lab

    Pianelli Mascia


    Full Text Available Abstract Background The inherent ability of ventricular myocardium to increase its force of contraction in response to an increase in contraction frequency is known as the cardiac force-frequency relation (FFR. This relation can be easily obtained in the stress echo lab, where the force is computed as the systolic pressure/end-systolic volume index ratio, and measured for increasing heart rates during stress. Ideally, the noninvasive, imaging independent, objective assessment of FFR would greatly enhance its practical appeal. Objectives 1 – To evaluate the feasibility of the cardiac force measurement by a precordial cutaneous sensor. 2 – To build the curve of force variation as a function of the heart rate. 3 – To compare the standard stress echo results vs. this sensor operator-independent built FFR. Methods The transcutaneous force sensor was positioned in the precordial region in 88 consecutive patients referred for exercise, dipyridamole, or pacing stress. The force was measured as the myocardial vibrations amplitude in the isovolumic contraction period. FFR was computed as the curve of force variation as a function of heart rate. Standard echocardiographic FFR measurements were performed. Results A consistent FFR was obtained in all patients. Both the sensor built and the echo built FFR identifiy pts with normal or abnormal contractile reserve. The best cut-off value of the sensor built FFR was 15.5 g * 10-3 (Sensitivity = 0.85, Specificity = 0.77. Sensor built FFR slope and shape mirror pressure/volume relation during stress. This approach is extendable to daily physiological exercise and could be potentially attractive in home monitoring systems.

  14. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

    Saver, Jeffrey L; Carroll, John D; Thaler, David E; Smalling, Richard W; MacDonald, Lee A; Marks, David S; Tirschwell, David L


    Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory. We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group

  15. Quantitative relationship between coronary vasodilator reserve assessed by {sup 82}Rb PET imaging and coronary artery stenosis severity

    Anagnostopoulos, Constantinos [Brigham and Women' s Hospital, Division of Nuclear Medicine/PET, Boston, MA (United States); Royal Brompton Hospital, Department of Nuclear Medicine, London (United Kingdom); Brigham and Women' s Hospital, Harvard Medical School, London (United Kingdom); Almonacid, Alexandra; Popma, Jeffrey J. [Brigham and Women' s Hospital, Division of Cardiovascular Medicine, Department of Medicine, Boston, MA (United States); Brigham and Women' s Hospital, Harvard Medical School, London (United Kingdom); El Fakhri, Georges [Brigham and Women' s Hospital, Division of Nuclear Medicine/PET, Boston, MA (United States); Royal Brompton Hospital, Department of Cardiology, London (United Kingdom); Curillova, Zelmira; Dorbala, Sharmila; Di Carli, Marcelo F. [Brigham and Women' s Hospital, Division of Nuclear Medicine/PET, Boston, MA (United States); Brigham and Women' s Hospital, Cardiovascular Imaging, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Division of Cardiovascular Medicine, Department of Medicine, Boston, MA (United States); Brigham and Women' s Hospital, Harvard Medical School, London (United Kingdom); Sitek, Arkadiusz [Brigham and Women' s Hospital, Division of Nuclear Medicine/PET, Boston, MA (United States); Brigham and Women' s Hospital, Harvard Medical School, London (United Kingdom); Roughton, Michael [Royal Brompton Hospital, Department of Cardiology, London (United Kingdom)


    The relationship between myocardial blood flow (MBF) and stenosis severity has been determined previously using cyclotron-produced radiotracers such as {sup 15}O-H{sub 2}O and {sup 13}N-ammonia. An attractive alternative to overcome the limitations related to the use of cyclotron might be to use the generator-produced {sup 82}Rb as a flow tracer. The current study was undertaken to investigate the relationship between MBF and coronary vasodilator reserve (CVR) as measured by {sup 82}Rb positron emission tomography (PET) and the percent diameter stenosis as defined by quantitative coronary arteriography. We prospectively evaluated 22 individuals: 15 patients (60 {+-} 11 years of age) with angiographically documented coronary artery disease (CAD) and seven age-matched (56 {+-} 9 years) asymptomatic individuals without risk factors for CAD. Dynamic {sup 82}Rb PET was performed at rest and after dipyridamole vasodilation. MBF, CVR and an index of 'minimal coronary resistance' (MCR) were assessed in each of the three main coronary territories. Rest and stress MBF in regions subtended by vessels with less than 50% diameter stenosis was similar to that of the individuals with no risk factors for CAD. As a result, CVR was also similar in the two groups (1.9, interquartile [IQ] range from 1.7 to 2.7 vs. 2.2, IQ range from 2 to 3.4 respectively, p=0.09). CVR successfully differentiated coronary lesions with stenosis severity 70% to 89% from those with 50% to 69% stenosis (1, IQ range from 1 to 1.3 vs. 1.7, IQ range from 1.4 to 2), respectively, p=0.001. In addition, hyperaemic MBF (r{sup 2}=0.74, p<0.001), CVR (r {sup 2}=0.69, p<0.001) and MCR (r{sup 2}=0.78, p<0.001) measurements were inversely and non-linearly correlated to the percent diameter stenosis on angiography. MBF and CVR are inversely and non-linearly correlated to stenosis severity. Quantitative {sup 82}Rb PET can be a clinically useful tool for an accurate functional assessment of CAD. (orig.)

  16. Targeting the Plasmodium vivax equilibrative nucleoside transporter 1 (PvENT1 for antimalarial drug development

    Roman Deniskin


    Full Text Available Infection with Plasmodium falciparum and vivax cause most cases of malaria. Emerging resistance to current antimalarial medications makes new drug development imperative. Ideally a new antimalarial drug should treat both falciparum and vivax malaria. Because malaria parasites are purine auxotrophic, they rely on purines imported from the host erythrocyte via Equilibrative Nucleoside Transporters (ENTs. Thus, the purine import transporters represent a potential target for antimalarial drug development. For falciparum parasites the primary purine transporter is the P. falciparum Equilibrative Nucleoside Transporter Type 1 (PfENT1. Recently we identified potent PfENT1 inhibitors with nanomolar IC50 values using a robust, yeast-based high throughput screening assay. In the current work we characterized the Plasmodium vivax ENT1 (PvENT1 homologue and its sensitivity to the PfENT1 inhibitors. We expressed a yeast codon-optimized PvENT1 gene in Saccharomyces cerevisiae. PvENT1-expressing yeast imported both purines ([3H]adenosine and pyrimidines ([3H]uridine, whereas wild type (fui1Δ yeast did not. Based on radiolabel substrate uptake inhibition experiments, inosine had the lowest IC50 (3.8 μM, compared to guanosine (14.9 μM and adenosine (142 μM. For pyrimidines, thymidine had an IC50 of 183 μM (vs. cytidine and uridine; mM range. IC50 values were higher for nucleobases compared to the corresponding nucleosides; hypoxanthine had a 25-fold higher IC50 than inosine. The archetypal human ENT1 inhibitor 4-nitrobenzylthioinosine (NBMPR had no effect on PvENT1, whereas dipyridamole inhibited PvENT1, albeit with a 40 μM IC50, a 1000-fold less sensitive than human ENT1 (hENT1. The PfENT1 inhibitors blocked transport activity of PvENT1 and the five known naturally occurring non-synonymous single nucleotide polymorphisms (SNPs with similar IC50 values. Thus, the PfENT1 inhibitors also target PvENT1. This implies that development of novel

  17. Role of quantitative myocardial positron emission tomography for risk stratification in patients with hypertrophic cardiomyopathy: a 2016 reappraisal

    Castagnoli, Helga; Passeri, Alessandro; Berti, Valentina; Sciagra, Roberto [University of Florence, Department of Experimental and Clinical Biomedical Sciences - Nuclear Medicine Unit, Firenze (Italy); Ferrantini, Cecilia; Coppini, Raffaele; Baldini, Katia; Cecchi, Franco; Olivotto, Iacopo [Careggi University Hospital, Referral Center for Myocardial Diseases and Genetic Diagnostics Unit, Florence (Italy)


    Myocardial blood flow <1.1 mL/min/g following dipyridamole (Dip-MBF) assessed by positron emission tomography (PET) was identified in 2003 as an important outcome predictor in hypertrophic cardiomyopathy (HCM), based on scans performed in the 90s. However, such extreme Dip-MBF impairment is rarely observed in contemporary cohorts. We, therefore, reassessed the Dip-MBF threshold defining high-risk HCM patients. Dip-MBF was measured using {sup 13}N-ammonia in 100 HCM consecutive patients, prospectively enrolled and followed for 4.0 ± 2.2 years. Outcome was assessed based on tertiles of Dip-MBF. The study end-point was a combination of cardiovascular death, progression to severe functional limitation, cardioembolic stroke, life-threatening ventricular arrhythmias. Global Dip-MBF was 1.95 ± 0.85, ranging from 0.7 to 5.9 mL/min/g. Dip-MBF tertile cut-off values were: 0.73 to 1.53 mL/min/g (lowest), 1.54 to 2.13 mL/min/g (middle), and 2.14 to 5.89 mL/min/g (highest). During follow-up, lowest tertile Dip-MBF was associated with sevenfold independent risk of unfavorable outcome compared to the other two tertiles. Dip-MBF 1.35 mL/min/g was identified as the best threshold for outcome prediction. Regional perfusion analysis showed that all cardiac deaths (n = 4) occurred in patients in the lowest tertile of lateral wall Dip-MBF (≤1.72 mL/min/g); septal Dip-MBF was not predictive. Dip-MBF confirms its role as potent predictor of outcome in HCM. However, the threshold for prediction in a contemporary cohort is higher than that reported in earlier studies. Dip-MBF impairment in the lateral wall, possibly reflecting diffuse disease extending to non-hypertrophic regions, is a sensitive predictor of mortality in HCM. (orig.)

  18. Myocardial blood flow and left ventricular functional reserve in hypertrophic cardiomyopathy: a {sup 13}NH{sub 3} gated PET study

    Sciagra, Roberto; Calabretta, Raffaella; Passeri, Alessandro; Castello, Angelo; Pupi, Alberto [University of Florence, Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences ' ' Mario Serio' ' , Florence (Italy); Cipollini, Fabrizio [University of Florence, Department of Statistics, Florence (Italy); Cecchi, Franco; Olivotto, Iacopo [Careggi University Hospital, Referral Centre for Myocardial Diseases, Florence (Italy)


    Ischemia in hypertrophic cardiomyopathy (HCM) is caused by coronary microvascular dysfunction (CMD), which is detected by measuring myocardial blood flow (MBF) with PET. Whether CMD may be associated with ischemic left ventricular (LV) dysfunction is unclear. We therefore assessed LV ejection fraction (EF) reserve in HCM patients undergoing dipyridamole (Dip) PET. Resting and stress {sup 13}NH{sub 3} dynamic as well as gated PET were performed in 34 HCM patients. Segmental MBF and transmural perfusion gradient (TPG = subendocardial / subepicardial MBF) were assessed. LVEF reserve was considered abnormal if Dip LVEF decreased more than 5 units as compared to rest. Eighteen patients had preserved (group A) and 16 abnormal LVEF reserve (group B; range -7 to -32). Group B patients had greater wall thickness than group A, but resting volumes, LVEF, resting and Dip MBF, and myocardial flow reserve were similar. Group B had slightly higher summed stress score and summed difference score in visual analysis than group A, and a significantly higher summed stress wall motion score. In group B, resting TPG was slightly lower (1.31 ± 0.29 vs. 1.37 ± 0.34, p <0.05), and further decreased after Dip, whilst in group A it increased (B = 1.20 ± 0.39, p < 0.0001 vs. rest and vs. A = 1.40 ± 0.43). The number of segments per patient with TPG <1 was higher than in group A (p < 0.001) and was a significant predictor of impaired LVEF reserve (OR 1.86, p < 0.02), together with wall thickness (OR 1.3, p < 0.02). Abnormal LVEF response is common in HCM patients following Dip, and is related to abnormal TPG, suggesting that subendocardial ischemia might occur under Dip and cause transient LV dysfunction. Although in vivo this effect may be hindered by the adrenergic drive associated with effort, these findings may have relevance in understanding exercise limitation and heart failure symptoms in HCM. (orig.)

  19. Validation of pixel-wise parametric mapping of myocardial blood flow with {sup 13}NH{sub 3} PET in patients with hypertrophic cardiomyopathy

    Sciagra, Roberto; Passeri, Alessandro; Castagnoli, Helga; Pupi, Alberto [University of Florence, Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences, Florence (Italy); Cipollini, Fabrizio [University of Florence, Department of Statistics, Florence (Italy); Olivotto, Iacopo; Cecchi, Franco [University of Florence, Department of Clinical and Experimental Medicine, Florence (Italy); Burger, Cyrill [Pmod Technologies Ltd, Zurich (Switzerland)


    Transmural abnormalities in myocardial blood flow (MBF) are important causes of ischaemia in patients with left ventricular (LV) hypertrophy. The study aimed to test whether pixel-wise parametric mapping of {sup 13}NH{sub 3} MBF can reveal transmural abnormalities in patients with hypertrophic cardiomyopathy (HCM). We submitted 11 HCM patients and 9 age-matched controls with physiological LV hypertrophy to rest and stress (dipyridamole) {sup 13}NH{sub 3} PET. We measured MBF using a compartmental model, and obtained rest and stress parametric maps. Pixel MBF values were reorganized to obtain subendocardial and subepicardial MBF of LV segments. MBF at rest was higher in the subendocardial than in the subepicardial layer: 0.78 ± 0.19 vs. 0.60 ± 0.18 mL/min/g in HCM patients; 0.92 ± 0.24 vs. 0.75 ± 0.24 mL/min/g in controls (both p < 0.0001). Transmural perfusion gradient (TPG = subendocardial MBF/subepicardial MBF) at rest was similar: 1.35 ± 0.31 in HCM patients; 1.28 ± 0.27 in controls (NS). During stress, controls maintained higher subendocardial MBF: 2.44 ± 0.54 vs. 1.96 ± 0.67 mL/min/g tissue (p < 0.0001), with a TPG of 1.33 ± 0.35 (NS vs. rest). In HCM patients, the difference between subendocardial and subepicardial MBF was reduced (1.46 ± 0.48 vs. 1.36 ± 0.48 mL/min/g tissue, p < 0.01) and TPG decreased to 1.11 ± 0.34 (p < 0.0001 vs. rest and vs. controls). In HCM patients 8 of 176 segments had subendocardial MBF less than -2 x SD of the mean, versus none of 144 segments in controls (p < 0.01). Pixel-wise parametric mapping of {sup 13}NH{sub 3} MBF enables the identification of transmural abnormalities in patients with HCM. (orig.)

  20. In vitro-in vivo correlation of the effect of supersaturation on the intestinal absorption of BCS Class 2 drugs.

    Higashino, Haruki; Hasegawa, Tsubasa; Yamamoto, Mari; Matsui, Rie; Masaoka, Yoshie; Kataoka, Makoto; Sakuma, Shinji; Yamashita, Shinji


    The aim of this study was to establish an in vitro method for evaluating the effect of supersaturation on oral absorption of poorly water-soluble drugs in vivo. Albendazole, dipyridamole, gefitinib, and ketoconazole were used as model drugs. Supersaturation of each drug was induced by diluting its stock solution by fasted state simulated intestinal fluid (FaSSIF) (solvent-shift method), then dissolution and precipitation profile of the drug was observed in vitro. The crystalline form of the precipitate was checked by differential scanning calorimetry (DSC). For comparison, control suspension was prepared by suspending a drug powder directly into FaSSIF (powder-suspending method). In vivo intestinal absorption of the drug was observed in rats by determined the plasma concentration after intraduodenal administration of drug suspensions. For all drugs, suspensions prepared by solvent-shift method showed significantly higher dissolved concentration in vitro than that prepared by powder-suspending method, clearly indicated the induction of supersaturation. DSC analysis revealed that crystalline form of the precipitate profoundly affects the extent and the duration of supersaturation. A rat in vivo study confirmed that the supersaturation of these drugs increased the fraction absorbed from the intestine, which corresponded well to the in vitro dissolution and precipitation profile of drugs except for ketoconazole. For ketoconazole, an in vivo absorption study was performed in rats pretreated with 1-aminobenzotriazole, a potent inhibitor of CYP mediated metabolism. CYP inhibition study suggested that the high luminal concentration of ketoconazole caused by supersaturation saturated the metabolic enzymes and further increased the systemic exposure of the absorbed drug. The additional effects of supersaturation on the absorption of ketoconazole are consistent with previous studies in humans under differing gastric pH conditions. In conclusion, effects of supersaturation on

  1. Advances in noninvasive cardiovascular imaging: implications for the anesthesiologist.

    Cahalan, M K; Litt, L; Botvinick, E H; Schiller, N B


    We have presented a review of recent advances in medical imaging which are relevant to the practice of anesthesia and associated research. The appropriate interpretation and use of the information derived from these noninvasive technologies can prevent unnecessary morbidity and mortality. Echocardiography remains the most advanced tool for noninvasive cardiac imaging because of its applicability for most cardiac disorders and its exquisite spatial resolution. Two-dimensional systems produce real time, dynamic, qualitative assessments of cardiac chamber morphology, size, thickness, and performance. The development of transesophageal echocardiography has brought this imaging power into the operating room for use by anesthesiologists. Recently developed quantitative and color-coded Doppler techniques will reveal intracardiac flow patterns and their alterations by anesthetics and surgery. These advantages are partially offset by inherent difficulties in quantifying echocardiographic data, and the need for highly trained operators for image reproduction. Nuclear cardiology and echocardiology are highly complementary. The scintigraphic methods identify myocardium at risk for infarction, confirm infarction when present, and produce quantitative, highly reproducible estimates of ventricular filling and performance. Time required to obtain data can be very brief for first-pass techniques, and these data are ideally suited for computer processing. Equilibrium studies require a larger dose of radioactive material, but provide excellent assessment of segmental wall motion. Preoperative studies with dipyridamole and Tl can indicate the patients truly at high risk for perioperative myocardial infarction. Monitoring and intensive care efforts may be better allocated with this information. No new technology in the past decade has stirred as much interest among clinicians as magnetic resonance imaging. Like echocardiography, it uses no ionizing radiation and is entirely noninvasive

  2. Effect observation of application of low molecular heparin in the treatment of children with primary nephrotic syndrome and hypercoagulative state%应用低分子肝素治疗儿童原发性肾病综合征高凝状态的效果观察



    Objective:To explore the treatment effect of low molecular heparin in the treatment of children with primary nephrotic syndrome and hypercoagulative state.Methods:38 patients with primary nephrotic syndrome and hypercoagulative state were selected.They were randomly divided into the control group and the treatment group with 19 cases in each group.The control group was treated with oral dipyridamole,and the treatment group was given subcutaneous injection of low molecular weight heparin on the basis of the control group,then we compared the effect of two groups.Results:At 1 week and 2 weeks after treatment, compared with before treatment,the plasma levels of FB and DD of the two groups were significantly decreased(P<0.05);complete remission time of urinary protein in the treatment group was significantly lower than that of the control group(P<0.05).Conclusion:The treatment effect of low molecular heparin in the treatment of children with primary nephrotic syndrome and hypercoagulative state was significant.%目的:探讨低分子肝素对儿童原发性肾病综合征并发高凝状态时的治疗效果。方法:收治合并高凝状态的原发性肾病综合征患儿38例,随机分为对照组和治疗组,各19例。对照组口服双嘧达莫,治疗组在对照组基础上加皮下注射低分子肝素钙,比较两组效果。结果:治疗1周及2周时两组血浆FB和DD均较治疗前有明显下降(P<0.05),治疗组患儿尿蛋白完全缓解时间明显低于对照组(P<0.05)。结论:低分子肝素对儿童原发性肾病综合征并发高凝状态时的治疗效果显著。

  3. Theoretical and experimental investigation of drug-polymer interaction and miscibility and its impact on drug supersaturation in aqueous medium.

    Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J


    Amorphous solid dispersions (ASDs) have the potential to offer higher apparent solubility and bioavailability of BCS class II drugs. Knowledge of the solid state drug-polymer solubility/miscibility and their mutual interaction are fundamental requirements for the effective design and development of such systems. To this end, we have carried out a comprehensive investigation of various ASD systems of dipyridamole and cinnarizine in polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) at different drug loadings. Theoretical and experimental examinations (by implementing binary and ternary Flory-Huggins (F-H) theory) related to drug-polymer interaction/miscibility including solubility parameter approach, melting point depression method, phase diagram, drug-polymer interaction in the presence of moisture and the effect of drug loading on interaction parameter were performed. The information obtained from this study was used to predict the stability of ASDs at different drug loadings and under different thermal and moisture conditions. Thermal and moisture sorption analysis not only provided the composition-dependent interaction parameter but also predicted the composition dependent miscibility. DPM-PVP, DPM-PAA and CNZ-PAA systems have shown molecular level mixing over the complete range of drug loading. For CNZ-PVP, the presence of a single Tg at lower drug loadings (10, 20 and 35%w/w) indicates the formation of solid solution. However, drug recrystallization was observed for samples with higher drug weight fractions (50 and 65%w/w). Finally, the role of polymer in maintaining drug supersaturation has also been explored. It has been found that drug-polymer combinations capable of hydrogen-bonding in the solution state (DPM-PVP, DPM-PAA and CNZ-PAA) are more effective in preventing drug crystallization compared to the drug-polymer systems without such interaction (CNZ-PVP). The DPM-PAA system outperformed all other ASDs in various stability conditions (dry-state, in

  4. A Case Report of Renal Sympathetic Denervation for the Treatment of Polymorphic Ventricular Premature Complexes

    Kiuchi, Márcio Galindo; Vitorio, Frederico Puppim; da Silva, Gustavo Ramalho; Paz, Luis Marcelo Rodrigues; Souto, Gladyston Luiz Lima


    Abstract Premature ventricular complexes are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Recently, Armaganijan et al reported the relevance of sympathetic activation in patients with ventricular arrhythmias and suggested a potential role for catheter-based renal sympathetic denervation in reducing the arrhythmic burden. In this report, we describe a 32-year-old hypertensive male patient presenting with a high incidence of polymorphic premature ventricular complexes on a 24 hour Holter monitor. Beginning 1 year prior, the patient experienced episodes of presyncope, syncope, and tachycardia palpitations. The patient was taking losartan 100 mg/day, which kept his blood pressure (BP) under control, and sotalol 160 mg twice daily. Bisoprolol 10 mg/day was used previously but was not successful for controlling the episodes. The 24 hour Holter performed after the onset of sotalol 160 mg twice daily showed a heart rate ranging between 48 (minimum)–78 (average)–119 (maximum) bpm; 14,286 polymorphic premature ventricular complexes; 3 episodes of nonsustained ventricular tachycardia, the largest composed of 4 beats at a rate of 197 bpm; and 14 isolated atrial ectopic beats. Cardiac magnetic resonance imaging with gadolinium perfusion performed at rest and under pharmacological stress with dipyridamole showed increased left atrial internal volume, preserved systolic global biventricular function, and an absence of infarcted or ischemic areas. The patient underwent bilateral renal sympathetic denervation. The only drug used postprocedure was losartan 25 mg/day. Three months after the patient underwent renal sympathetic denervation, the mean BP value dropped to 132/86 mmHg, the mean systolic/diastolic 24 hour ambulatory BP measurement was reduced to 128/83

  5. Myocardial stress perfusion magnetic resonance: initial experience in a pediatric and young adult population using regadenoson

    Noel, Cory V. [Baylor College of Medicine, Department of Pediatric Cardiology, Houston, TX (United States); Texas Children' s Hospital, Department of Pediatric Cardiology, Houston, TX (United States); Krishnamurthy, Ramkumar; Krishnamurthy, Rajesh [Texas Children' s Hospital, Department of Radiology, Houston, TX (United States); Moffett, Brady [Texas Children' s Hospital, Department of Pharmacology, Houston, TX (United States)


    Dipyridamole and adenosine are traditional pharmacological stressors for myocardial perfusion. Regadenoson, a selective adenosine A2A agonist, has a lower side effect profile with lower incidence of bronchospasm and bradycardia. There is a growing need for myocardial perfusion assessment within pediatrics. There is no report on the utility of regadenoson as a stress agent in children. To observe the safety and feasibility of regadenoson as a pharmacologic stressor for perfusion cardiac MR in a pilot cohort of pediatric patients weighing more than 40 kg who have congenital heart disease and pediatric acquired heart disease. We reviewed our initial experience with regadenoson stress cardiac MR in 31 pediatric patients 15.8 ± 1.7 years (range 12-22 years) with congenital heart disease and acquired heart disease. Mean patient weight was 60 ± 15 kg (range of 40-93 kg). All patients underwent cardiac MR because of concern for ischemia. The cohort included a heterogeneous group of patients at a pediatric institution with potential risk for ischemia. Subjects' heart rate and blood pressure were monitored and pharmacologic stress was induced by injection of 400 mcg of regadenoson. We evaluated their hemodynamic response and adverse effects using changes in vital signs and onset of symptoms. A pediatric cardiologist and radiologist qualitatively assessed myocardial perfusion and viability images. One child was unable to complete the stress perfusion portion of the examination, but did complete the remaining portion of the CMR. Resting heart rate was 72 ± 14 beats per minute (bpm) and rose to peak of 124 ± 17 bpm (95 ± 50% increase, P < 0.005) with regadenoson. Image quality was considered good or diagnostic in all cases. Three patients had irreversible perfusion defects. Four patients had reversible perfusion defects. Nine of the patients underwent cardiac catheterization with angiography and the findings showed excellent agreement. Regadenoson might be a safe and

  6. The effect of location and configuration on forearm and upper arm hemodialysis arteriovenous grafts.

    Farber, Alik; Tan, Tze-Woei; Hu, Bo; Dember, Laura M; Beck, Gerald J; Dixon, Bradley S; Kusek, John W; Feldman, Harold I


    The arteriovenous graft (AVG) is most often used in hemodialysis patients when an autogenous fistula is not feasible. The optimal location (forearm or upper arm) and configuration (loop or straight) of AVGs are not known. To evaluate relationships of AVG location and configuration with patency, we conducted a secondary analysis using data from a randomized, placebo-controlled trial of dipyridamole plus aspirin for newly placed AVG. Participants of the Dialysis Access Consortium (DAC) Graft Study with newly placed upper extremity prosthetic grafts involving the brachial artery were studied. Multivariable analyses adjusting for trial treatment group, center, gender, race, body mass index, diabetes, current treatment with chronic dialysis, and prior arteriovenous vascular access or central venous catheter were performed to compare outcomes of forearm (fAVG) and upper arm (uAVG) grafts, including loss of primary unassisted patency (LPUP) and cumulative primary graft failure (CGF). Subgroup analyses of graft configuration and outflow vein used were also conducted. A total of 508 of the 649 participants (78%) enrolled in the trial had an upper extremity brachial artery graft placed, 255 with fAVG and 253 with uAVG. Participants with fAVG were less often male (33% vs 43%; P = .03), African American (62% vs 78%; P location (uAVG vs fAVG) was not associated with LPUP (hazard ratio, 1.21; 95% confidence interval, 0.90-1.63; P = .20) or CGF (hazard ratio, 1.36; 95% confidence interval, 0.94-1.97; P = .10). LPUP did not differ significantly between fAVG and uAVG among subgroups based on AVG configuration (P = 1.00) or outflow vein used (P = .16). Patency was comparable between fAVG and uAVG despite the larger caliber veins often encountered in the upper arm in carefully selected patients. Our findings support the traditional view that, in order to preserve a maximal number of access sites, the forearm location should be considered first before resorting to an upper arm

  7. Regadenoson in the detection of coronary artery disease

    Christiane Buhr


    Full Text Available Christiane Buhr1, Mario Gössl2, Raimund Erbel1, Holger Eggebrecht11Department of Cardiology, West-German Heart Center Essen, University of Duisburg-Essen, Essen, Germany; 2Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USAAbstract: Myocardial perfusion studies use either physical exercise or pharmacologic vasodilator stress to induce maximum myocardial hyperemia. Adenosine and dipyridamole are the most commonly used agents to induce coronary arterial vasodilation for myocardial perfusion imaging. Both cause frequent undesirable side-effects. Because of its ultrashort half-life, adenosine must be administered by constant intravenous infusion during the examination. A key feature of an ideal A2A agonist for myocardial perfusion imaging studies would be an optimal level and duration of hyperemic response. Drugs with a longer half-time and more selective A2A adenosine receptor agonism, such as regadenoson, should theoretically result in a similar degree of coronary vasodilation with fewer or less severe side-effects than non-selective, ultrashort-lasting adenosine receptor stimulation. The available preclinical and clinical data suggest that regadenoson is a highly subtype-selective, potent, low-affinity A2A adenosine receptor agonist that holds promise for future use as a coronary vasodilator in myocardial perfusion imaging studies. Infusion of regadenoson achieves maximum coronary hyperemia that is equivalent to adenosine. After a single bolus infusion over 10 s, hyperemia is maintained significantly longer (approximately 2–5 min than with adenosine, which should facilitate radionuclide distribution for myocardial perfusion imaging studies. In comparison with the clinically competitive A2A adenosine receptor agonist binodenoson, regadenoson has a several-fold shorter duration of action, although the magnitude of hyperemic response is comparable between the two. The more rapid termination of action of regadenoson

  8. Feasibility and diagnostic accuracy of Ecg-gated SPECT myocardial perfusion imaging by a two-hour protocol: The Myofast study;Faisabilite et precision diagnostique d'un protocole de scintigraphie myocardique synchronisee a l'ECG en deux heures: l'etude Myofast

    Dunet, V.; Costo, S.; Sabatier, R.; Grollier, G.; Bouvard, G.; Agostini, D. [CHU Cote-de-Nacre, Service de medecine nucleaire, 14 - Caen (France)


    Aim of the study: To assess the feasibility of early stress and rest myocardial perfusion and function study using a fast {sup 99m}Tc-tetrofosmin gated-SPECT protocol in patients with known coronary artery disease. Materials and methods: Forty-three patients (pts) (37 M, 6 F, mean age 63.8 +- 9.8 years) underwent a {sup 99m}Tc-Tetrofosmin gated-SPECT (Axis Picker-Philips) myocardial study and a coronary angiography (C.A.) within 3 months. Images were acquired (LEHR, eight bins, 40 sec per image) after injection of {sup 99m}Tc-tetrofosmin (200 to 380 MBq) early (15 min) post-stress (36 dipyridamole, two dobutamine and five ergo-metric stress), and at rest after {sup 99m}Tc-tetrofosmin reinjection (600 to 1150 MBq), in a total time not exceeding 2 hours. Processing was performed with Q.G.S. software using the 17-segment model. Pathological study was defined as a summed difference score (SDS) greater than or equal to 4 4, a fixed defect with summed rest score greater than or equal to 4 and/or L.V. dysfunction defined as myocardial stunning (variation between stress and rest L.V.E.F. greater than or equal to 4 5%), stress L.V.E.F. less than or equal to 45% or rest L.V.E.F. less than or equal to 40%. Results were compared with C.A., and stenosis greater than or equal to 4 50% was considered as significant. Results: For 100% the quality of SPECT imaging was good or excellent. For six patients gating was impossible because of arrhythmia. The overall sensitivity, specificity and accuracy were 95%, 50%, and 91%, respectively. The concordance between gated SPECT and C.A. was moderate (kappa = 0.45, S.E. = 0.15). Interestingly, early-gated acquisition permitted to underline left ventricular dysfunction in 11 cases (30%), of whom eight had poly vascular disease. Stunning was detected in six of 37 cases (16%), of whom six had poly vascular disease. Conclusion: A one-day two-hour {sup 99m}Tc-tetrofosmin gated-SPECT protocol to assess left ventricular perfusion and function is

  9. ABC gene-ranking for prediction of drug-induced cholestasis in rats

    Yauheniya Cherkas


    drugs that behaved very differently, and were distinct from both non-cholestatic and cholestatic drugs (ketoconazole, dipyridamole, cyproheptadine and aniline, and many postulated human cholestatic drugs that in rat showed no evidence of cholestasis (chlorpromazine, erythromycin, niacin, captopril, dapsone, rifampicin, glibenclamide, simvastatin, furosemide, tamoxifen, and sulfamethoxazole. Most of these latter drugs were noted previously by other groups as showing cholestasis only in humans. The results of this work suggest that the ABC procedure and similar statistical approaches can be instrumental in combining data to compare toxicants across toxicogenomics databases, extract similarities among responses and reduce unexplained data varation.

  10. Reactivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation.

    María F Montenegro

    Full Text Available BACKGROUND: Tumour suppressor genes are often transcriptionally silenced by promoter hypermethylation, and recent research has implicated alterations in chromatin structure as the mechanistic basis for this repression. In addition to DNA methylation, other epigenetic post-translational modifications that modulate the stability and binding of specific transcription factors to gene promoters have emerged as important mechanisms for controlling gene expression. The aim of this study was to analyse the implications of these mechanisms and their molecular connections in the reactivation of RASSF1A in breast cancer. METHODS: Compounds that modulate the intracellular concentration of adenosine, such as dipyridamole (DIPY, greatly increase the antiproliferative effects of 3-O-(3,4,5-trimethoxybenzoyl-(--catechin (TMCG, a synthetic antifolate derived from the structure of tea catechins. Quantitative real-time PCR arrays and MALDI-TOF mass spectrometry indicated that this combination (TMCG/DIPY induced apoptosis in breast cancer cells by modulating the methylation levels of DNA and proteins (such as E2F1, respectively. Chromatin immunoprecipitation (ChIP assays were employed to confirm that this combination induced chromatin remodelling of the RASSF1A promoter and increased the occupancy of E2F1 at the promoter of this tumour suppressor gene. RESULTS: The TMCG/DIPY combination acted as an epigenetic treatment that reactivated RASSF1A expression and induced apoptosis in breast cancer cells. In addition to modulating DNA methylation and chromatin remodelling, this combination also induced demethylation of the E2F1 transcription factor. The ChIP assay showed enhancement of E2F1 occupancy at the unmethylated RASSF1A promoter after TMCG/DIPY treatment. Interestingly, inhibition of E2F1 demethylation using an irreversible inhibitor of lysine-specific demethylase 1 reduced both TMCG/DIPY-mediated RASSF1A expression and apoptosis in MDA-MB-231 cells, suggesting

  11. Effects of gastric pH on oral drug absorption: In vitro assessment using a dissolution/permeation system reflecting the gastric dissolution process.

    Kataoka, Makoto; Fukahori, Miho; Ikemura, Atsumi; Kubota, Ayaka; Higashino, Haruki; Sakuma, Shinji; Yamashita, Shinji


    The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of

  12. Transport of eicosapentaenoic acid-derived PGE₃, PGF(3α, and TXB₃ by ABCC4.

    Nobuaki Tanaka

    Full Text Available Eicosapentaenoic acid-derived prostaglandin (PG E3, PGF(3α, and thromboxane (TX B3 are bioactive lipid mediators which have anti-cancer and anti-inflammatory effects. To exert their effects, PGE3, PGF(3α, and TXB3 must be released to the extracellular space from cells, but the release mechanism has been unclear. We therefore investigated the contribution of ATP-binding cassette transporter C4 (ABCC4, which has been known as a prostanoids efflux transporter, to the release of PGE3, PGF(3α, and TXB3.ATP-dependent transport of PGE3, PGF(3α, and TXB3 via ABCC4 was investigated by using inside-out membrane vesicles prepared from ABCC4-overexpressing HEK293 cells. To evaluate the contribution of ABCC4 to the release of PGE3, PGF(3α, and TXB3, we measured the extracellular and intracellular levels of PGE3, PGF(3α, and TXB3 in A549 cells when we used ABCC4 inhibitors (dipyridamole, MK571, and probenecid or ABCC4 siRNAs. The quantification of PGE3, PGF(3α, and TXB3 was performed by using liquid chromatography-tandem mass spectrometry.The apparent Km values for ABCC4-mediated transport were 2.9±0.1 µM for PGE3, 12.1±1.3 µM for PGF(3α, and 11.9±1.4 µM for TXB3 and the ATP-dependent accumulation of PGE3, PGF(3α, and TXB3 into vesicles was decreased by using typical substrates and inhibitors of ABCC4. ABCC4 inhibitors and ABCC4 knockdown showed the reduction of extracellular/intracellular ratio of PGE3 (40-60% of control and PGF(3α (60-80% of control in A549 cells.Our results suggest that PGE3, PGF(3α, and TXB3 are substrates of ABCC4 and ABCC4 partially contributes to the release of PGE3 and PGF(3α.

  13. Growth inhibitory effect and apoptosis induced by extracellular ATP and adenosine on human gastric carcinoma cells: involvement of intracellular uptake of adenosine

    Ming-xia WANG; Lei-ming REN


    Aim: To study the growth inhibitory and apoptotic effects of adenosine triphosphate (ATP) and adenosine (ADO) on human gastric carcinoma (HGC)-27 cells in vitro and the mechanisms related to the actions of ATP and ADO. Methods: MTT assay was used to determine the reduction of cell viability. The morphological changes of HGC-27 cells induced by ATP or ADO were observed under fluorescence light microscope by acridine orange/ethidium bromide double-stained cells. The internucleosomal fragmentation of genomic DNA was detected by agarose gel electrophoresis. The apoptotic rate and cell-cycle analysis after treatment with ATP or ADO was determined by flow cytometry. Results: ATP, ADO and the intermediate metabolites, ADP and AMP, and the agonist of purinergic receptors, reduced cell viability of HGC-27 cells at doses of 0.3 and 1.0 mmol·L-1. The distribution of cell cycle phase and proliferation index (PI) value of HGC-27 cells changed when exposed to ATP or ADO at the concentrations of 0.1,0.3 and 1 mmol/L for 48 h. ATP and ADO both altered the distribution of cell cycle phase via Go/G1-phase arrest and significantly decreased PI value. Under light microscope, the tumor cells exposed to 0.3 mmol·L-1 ATP or ADO displayed morphological changes of apoptosis; a ladder-like pattern of DNA fragmentation obtained from HGC-27 cells treated with 0.1-1 mmol·L-1 ATP or ADO appeared in agarose gel electrophoresis; ATP and ADO induced the apoptosis of HGC-27 cells in a dose-dependent manner at concentrations between 0.03-1 mmol·L-1. The maximum apoptotic rate of HGC-27 cells exposed to ATP or ADO for 48 h was 13.53% or 15.9%, respectively. HGC-27 cell death induced by ATP or ADO was significantly inhibited by dipy-ridamole (10 mmol·L-1), an inhibitor of adenosine transporter, but was not affected by aminophylline, a broad inhibitor of PI receptors and pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetrasodium salt (30 nmol·L-1), a non-selective antagonist of P2

  14. Targeting the Plasmodium vivax equilibrative nucleoside transporter 1 (PvENT1) for antimalarial drug development.

    Deniskin, Roman; Frame, I J; Sosa, Yvett; Akabas, Myles H


    Infection with Plasmodium falciparum and vivax cause most cases of malaria. Emerging resistance to current antimalarial medications makes new drug development imperative. Ideally a new antimalarial drug should treat both falciparum and vivax malaria. Because malaria parasites are purine auxotrophic, they rely on purines imported from the host erythrocyte via Equilibrative Nucleoside Transporters (ENTs). Thus, the purine import transporters represent a potential target for antimalarial drug development. For falciparum parasites the primary purine transporter is the P. falciparum Equilibrative Nucleoside Transporter Type 1 (PfENT1). Recently we identified potent PfENT1 inhibitors with nanomolar IC50 values using a robust, yeast-based high throughput screening assay. In the current work we characterized the Plasmodium vivax ENT1 (PvENT1) homologue and its sensitivity to the PfENT1 inhibitors. We expressed a yeast codon-optimized PvENT1 gene in Saccharomyces cerevisiae. PvENT1-expressing yeast imported both purines ([(3)H]adenosine) and pyrimidines ([(3)H]uridine), whereas wild type (fui1Δ) yeast did not. Based on radiolabel substrate uptake inhibition experiments, inosine had the lowest IC50 (3.8 μM), compared to guanosine (14.9 μM) and adenosine (142 μM). For pyrimidines, thymidine had an IC50 of 183 μM (vs. cytidine and uridine; mM range). IC50 values were higher for nucleobases compared to the corresponding nucleosides; hypoxanthine had a 25-fold higher IC50 than inosine. The archetypal human ENT1 inhibitor 4-nitrobenzylthioinosine (NBMPR) had no effect on PvENT1, whereas dipyridamole inhibited PvENT1, albeit with a 40 μM IC50, a 1000-fold less sensitive than human ENT1 (hENT1). The PfENT1 inhibitors blocked transport activity of PvENT1 and the five known naturally occurring non-synonymous single nucleotide polymorphisms (SNPs) with similar IC50 values. Thus, the PfENT1 inhibitors also target PvENT1. This implies that development of novel antimalarial drugs

  15. Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening

    Penfornis Alfred


    Full Text Available Abstract Background Most guidelines recommend a systematic screening of asymptomatic high risk patients with diabetes for silent ischemia, but the clinical benefit of this strategy has not been demonstrated compared with the simple control of cardiovascular risk factors. We sought to determine whether referring asymptomatic diabetic patients for screening of silent ischemia decreases the risk of cardiovascular events compared with usual care. Methods DYNAMIT was a prospective, randomized, open, blinded end-point multicenter trial run between 2000 and 2005, with a 3.5 year mean follow-up in ambulatory care in 45 French hospitals. The study included 631 male and female with diabetes aged 63.9 ± 5.1 years, with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors, receiving appropriate medical treatment. The patients were randomized centrally to either screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography (N = 316, or follow-up without screening (N = 315. The main study end point was time to death from all causes, non-fatal myocardial infarction, non-fatal stroke, or heart failure requiring hospitalization or emergency service intervention. The results of a meta-analysis of DYNAMIT and DIAD, a similar study, are also presented. Results The study was discontinued prematurely because of difficulties in recruitment and a lower-than expected event rate. Follow-up was complete for 98.9% patients regarding mortality and for 97.5% regarding the main study end point. Silent ischemia detection procedure was positive or uncertain in 68 (21.5% patients of the screening group. There was no significant difference between the screening and the usual care group for the main outcome (hazard ratio = 1.00 95%CI 0.59 to 1.71. The meta-analysis of these and DIAD results gave similar results, with narrower confidence intervals for each endpoint. Conclusions These

  16. Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin.

    Klimt, C R; Knatterud, G L; Stamler, J; Meier, P


    In the Persantine-Aspirin Reinfarction Study, Part II (PARIS II), 3,128 persons who had recovered from myocardial infarction, suffered from 4 weeks to 4 months previously, were randomized into two groups: dipyridamole (Persantine) plus aspirin (n = 1,563) and placebo (n = 1,565). The average length of follow-up was 23.4 months. Prespecified primary end points were coronary incidence (definite nonfatal myocardial infarction plus death due to recent or acute cardiac event), coronary mortality (death due to recent or acute cardiac event) and total mortality, each at 1 year of patient follow-up and at the end of the study. Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group, both at 1 year (30% reduction) and at the end of the study (24% reduction). The statistically significant differences in coronary incidence, at 1 year and at the end of the study, in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing (three end points for two time periods). Although there were reductions for other end points, these differences were not statistically significant. Coronary mortality was 20% lower in the Persantine plus aspirin group compared with the placebo group at 1 year, and 6% lower overall. Total mortality in the treated group compared with the placebo group was 11% lower at 1 year and 3% lower overall. The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infarction in the Persantine plus aspirin group. Several subgroups were defined a priori and at the end of the study. The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients: those who had a non-Q wave infarct; those who were not taking digitalis; those who were receiving beta-receptor blocking drugs at baseline; those who were in New York Heart

  17. Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A₁ and A2A receptor activation.

    Cunha, Mauricio P; Pazini, Francis L; Rosa, Julia M; Ramos-Hryb, Ana B; Oliveira, Ágatha; Kaster, Manuella P; Rodrigues, Ana Lúcia S


    The benefits of creatine supplementation have been reported in a broad range of central nervous systems diseases, including depression. A previous study from our group demonstrated that creatine produces an antidepressant-like effect in the tail suspension test (TST), a predictive model of antidepressant activity. Since depression is associated with a dysfunction of the adenosinergic system, we investigated the involvement of adenosine A1 and A2A receptors in the antidepressant-like effect of creatine in the TST. The anti-immobility effect of creatine (1 mg/kg, po) or ketamine (a fast-acting antidepressant, 1 mg/kg, ip) in the TST was prevented by pretreatment of mice with caffeine (3 mg/kg, ip, nonselective adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (2 mg/kg, ip, selective adenosine A1 receptor antagonist), and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)-phenol (ZM241385) (1 mg/kg, ip, selective adenosine A2A receptor antagonist). In addition, the combined administration of subeffective doses of creatine and adenosine (0.1 mg/kg, ip, nonselective adenosine receptor agonist) or inosine (0.1 mg/kg, ip, nucleoside formed by the breakdown of adenosine) reduced immobility time in the TST. Moreover, the administration of subeffective doses of creatine or ketamine combined with N-6-cyclohexyladenosine (CHA) (0.05 mg/kg, ip, selective adenosine A1 receptor agonist), N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA) (0.1 mg/kg, ip, selective adenosine A2A receptor agonist), or dipyridamole (0.1 μg/mouse, icv, adenosine transporter inhibitor) produced a synergistic antidepressant-like effect in the TST. These results indicate that creatine, similarly to ketamine, exhibits antidepressant-like effect in the TST probably mediated by the activation of both adenosine A1 and A2A receptors, further reinforcing the potential of targeting the purinergic system to the management of mood disorders.

  18. Significant regional heterogeneity of coronary flow reserve in paediatric hypertrophic cardiomyopathy

    Tadamura, E.; Kudoh, T.; Kubo, S.; Konishi, J. [Kyoto Univ. (Japan). School of Medicine; Yoshibayashi, M.; Yonemura, T. [Dept. of Pediatrics, Kyoto Univ. Graduate School of Medicine, Kyoto (Japan); Motooka, M.; Nohara, R.; Matsumori, A.; Sasayama, S. [Third Div., Dept. of Internal Medicine, Kyoto Univ. Graduate School of Medicine, Kyoto (Japan); Matsuda, T. [Dept. of Medical Informatics, Kyoto Univ. Graduate School of Medicine, Kyoto (Japan); Tamaki, N. [Dept. of Nuclear Medicine, Hokkaido Univ. School of Medicine, Sapporo (Japan)


    Previous studies have indicated that cardiac events in young patients with hypertrophic cardiomyopathy (HCM) are related to ischaemia rather than to arrhythmia. We measured coronary flow reserve in paediatric HCM and compared the values with those in adult HCM. We studied 12 patients with HCM including six paediatric (<20 years old; mean 13 years) and six adult patients (>20 years old: mean 62 years), and six healthy young adults (mean 29 years) as controls. Every patient underwent magnetic resonance imaging (MRI) for anatomical assessment. Myocardial blood flow at rest and after dipyridamole infusion was measured with dynamic nitrogen-13 ammonia positron emission tomography (PET). Partial volume effect was corrected for using the anatomical data obtained with MRI. In adult patients with HCM, coronary flow reserve in the hypertrophied septal region was not significantly different from that in the non-hypertrophied lateral wall (1.38{+-}0.29 vs 1.77{+-}0.39, respectively). In the paediatric patients, coronary flow reserve in the hypertrophied septal region was significantly lower than in the non-hypertrophied lateral wall (0.84{+-}0.33 vs 2.74{+-}0.90, respectively, P<0.01). In addition, coronary flow reserve in adult patients was lower than in control subjects both in the septal wall (1.38{+-}0.29 vs 2.94{+-}0.35, respectively, P<0.0001) and in the lateral wall (1.77{+-}0.39 vs 2.85{+-}0.69, respectively, P<0.05). In contrast, coronary flow reserve in paediatric patients was not significantly different from that in control subjects in the lateral wall (2.74{+-}0.90 vs 2.85{+-}0.69, respectively), while absolute reduction of myocardial blood flow was noted after pharmacological vasodilatation in the hypertrophied septal region. In conclusion, significant regional differences of coronary flow reserve were present in the paediatric patients with HCM. These results suggest that paediatric patients with HCM intrinsically have the potential to experience significant

  19. Myocardial blood flow assessment with {sup 82}rubidium-PET imaging in patients with left bundle branch block

    Falcao, Andrea; Chalela, William; Giorgi, Maria Clementina; Imada, Rodrigo; Soares Junior, Jose; Do Val, Renata; Oliveira, Marco Antonio; Izaki, Marisa; Kalil Filho, Roberto; Meneghetti, Jose C., E-mail: [Universidade de Sao Paulo (InCor/USP), Sao Paulo, SP (Brazil). Hospital das Clinicas. Instituto do Coracao


    Objectives: Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease. Objective: we sought to investigate rubidium-82 ({sup 82}Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block. Methods: thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress {sup 82}Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal {sup 82}Rb-positron emission tomography studies and without left bundle branch block (GII). Results: stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p>0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001). Conclusion: the data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by {sup 82}Rb-positron emission tomography imaging may be useful in identifying coronary artery

  20. Quantitation of myocardial blood flow and myocardial flow reserve with {sup 99m}Tc-sestamibi dynamic SPECT/CT to enhance detection of coronary artery disease

    Hsu, Bailing [University of Missouri-Columbia, Nuclear Science and Engineering Institute, Columbia, MO (United States); Chen, Fu-Chung; Chen, Chien-Cheng [Show Chwan Memorial Hospital, Section of Cardiology, Department of Internal Medicine, Changhua (China); Wu, Tao-Cheng [Taipei Veterans General Hospital, Section of Cardiology, Department of Internal Medicine, Taipei (China); Huang, Wen-Sheng [Changhua Christian Hospital, Department of Medical Research and Department of Nuclear Medicine, Changhua (China); Hou, Po-Nien [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Lukong Town, Changhua Shien (China); Hung, Guang-Uei [Chang Bing Show Chwan Memorial Hospital, Department of Nuclear Medicine, Lukong Town, Changhua Shien (China); Central Taiwan University of Science and Technology, Department of Medical Imaging and Radiological Science, Taichung (China); China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China)


    Conventional dual-head single photon emission computed tomography (SPECT)/CT systems capable of fast dynamic SPECT (DySPECT) imaging have a potential for flow quantitation. This study introduced a new method to quantify myocardial blood flow (MBF) and myocardial flow reserve (MFR) with DySPECT scan and evaluated the diagnostic performance of detecting coronary artery disease (CAD) compared with perfusion using invasive coronary angiography (CAG) as the reference standard. This study included 21 patients with suspected or known CAD who had received DySPECT, ECG-gated SPECT (GSPECT), and CAG (13 with ≥50 % stenosis in any vessel; non-CAD group: 8 with patent arteries or <50 % stenosis). DySPECT and GSPECT scans were performed on a widely used dual-head SPECT/CT scanner. The DySPECT imaging protocol utilized 12-min multiple back-and-forth gantry rotations during injections of {sup 99m}Tc-sestamibi (MIBI) tracer at rest or dipyridamole-stress stages. DySPECT images were reconstructed with full physical corrections and converted to the physical unit of becquerels per milliliter. Stress MBF (SMBF), rest MBF (RMBF), and MFR were quantified by a one-tissue compartment flow model using time-activity curves derived from DySPECT images. Perfusion images were processed for GSPECT scan and interpreted to obtain summed stress score (SSS) and summed difference score (SDS). Receiver-operating characteristic (ROC) analyses were conducted to evaluate the diagnostic performance of flow and perfusion. Using the criteria of ≥50 % stenosis as positive CAD, areas under the ROC curve (AUCs) of flow assessment were overall significantly greater than those of perfusion. For patient-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.91 ± 0.07, 0.86 ± 0.09, 0.64 ± 0.12, and 0.59 ± 0.13. For vessel-based analysis, AUCs for MFR, SMBF, SSS, and SDS were 0.81 ± 0.05, 0.76 ± 0.06, 0.62 ± 0.07, and 0.56 ± 0.08, respectively. The preliminary data suggest that MBF quantitation with a

  1. 葡甲胺环腺苷酸对血小板功能的影响%Study of the effect of meglumine cyclic adenyl ate on platelet function of rats

    刘桂兰; 徐志华


    目的:研究葡甲胺环腺苷酸(MCA)对鼠血小板功能的 影响。方法:大鼠50只,随机分5组。对照组:尾静脉注射生理盐水( NS)共3 d;双嘧达莫组:静脉注射双嘧达莫5mg/kg共3d,MCA 3组:分别于尾静脉注射MCA 1 0,20,40mg/kg共3d。用二磷酸腺苷(ADP)和胶原诱导血小板聚集,测定凝集率。同时用小 鼠20只,腹腔注射MCA 10mg/kg共3d,测定其尾动脉出血时间。结果:MCA可抑制ADP和胶原引起的血小板聚集;且延长小鼠尾动脉出血时间。结论[ HT5”F〗:MCA可抑制鼠血小板功能。%Objectives:As stated in the title.Methods:50 rats were randomly and equally divided to receive tail venous injection o f saline for 3d;dipyridamole in regimen of 5 mg/kg×3d;MCA in 3 different regime n of 10 mg/kg×3d;20 mg/kg×3 d;and 40 mg/kg×3 d.The platelet aggregation was d etermined using ADP and collagen as inducing agents.The tail artery blooding tim e was also determined using another 20 rats receiving 10 mg/kg×3d given by peri toneal injection.Results:The platelet aggregation induced by ADP a nd collagen can be inhibited by MCA and the rats'tail artery blooding time can b e prolonged by it.Conclusions:The platelet function of rats can be inhibited by MCA.

  2. Respostas cardiorrespiratórias durante exercício em portadores de transplante cardíaco. Análise ergoespirométrica comparativa com indivíduos normais Cardiorespiratory response during exercise in heart transplant recipients comparated to normal healthy subjects

    Ana Fátima Salles


    Full Text Available OBJETIVO: Avaliar as respostas cardiorrespiratórias dos portadores de transplante cardíaco (TxC. MÉTODOS: Submeteram-se a testes ergoespirométricos 9 portadores de TxC (GI, pareados por sexo, idade, peso e altura, com 9 indivíduos sedentários, aparentemente sadios (GII. Os pacientes eram do sexo masculino, com idade de 48±12 anos, com TFI (NYHA após 23±21 meses TxC. Faziam uso regular de ciclosporina, azatioprina, prednisona, dipiridamol e anti-hipertensivos. Os testes foram limitados por sintomas e interrompidos por exaustão. RESULTADOS: No pico do exercício, o GI apresentou desempenho significativamente inferior ao GII quanto ao VO2, VE, VEO2, FC, tempo de endurance e potência. No limiar anaeróbio, o GI apresentou VO2, tempo de endurance e potência significativamente inferior a do GII. Na potência de 40W o desempenho dos dois grupos foi similar. CONCLUSÃO: O GI apresentou desempenho cardiorrespiratório significativamente inferior no pico do exercício e similar na potência de 40W em relação ao GII, evidenciando os benefícios do TxC para cardiopatas em atividades habituaisPURPOSE: To evaluate the cardiorespiratory response of heart transplant (HT recipients. METHODS: Nine HT recipients (GI underwent ergospirometric tests and were compared to 9 apparently healthy, sedentary subjects with similar sex, age, weight and height (GII. All were male patients aging 48±12 years, in functional class I (NYHA an average of 23±21 months after HT. They were receiving cyclosporin, azathioprine, prednisone, dipyridamole and antihypertensive drugs. The tests were symptom-limited and they were interrupted due to exhaustion. RESULTS: During peak exercise, GI had a significantly lower physical performance related to lower VO2, VE, VEO2, HR, endurance time and work load. At the anaerobic threshold, VO2, endurance time and work load levels were also significantly lower in GI. The physical performance was similar between the groups in the 40W

  3. Recruitment of aged donor heart with pharmacological stress echo. A case report

    Bombardini Tonino


    Full Text Available Abstract Background The heart transplant is a treatment of the heart failure, which is not responding to medications, and its efficiency is already proved: unfortunately, organ donation is a limiting step of this life-saving procedure. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease. Donors with a history of cardiac disease are generally excluded. Coronary angiography is recommended for most male donors older than 45 years and female donors older than 50 years to evaluate coronary artery stenoses. A simpler way to screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease should be stress echocardiography. Case report A marginal donor (A 57 year old woman meeting legal requirements for brain death underwent a transesophageal (TE Dipyridamole stress echo (6 minutes accelerated protocol to rule out moderate or severe heart and coronary artery disease. Wall motion was normal at baseline and at peak stress (WMSI = 1 at baseline and peak stress, without signs of stress inducible ischemia. The pressure/volume ratio was 9.6 mmHg/ml/m2 at baseline, increasing to 14 mmHg/ml/m2 at peak stress, demonstrating absence of latent myocardial dysfunction. The marginal donor heart was transplanted to a recipient "marginal" for co-morbidity ( a 63 year old man with multiple myeloma and cardiac amyloidosis , chronic severe heart failure, NYHA class IV. Postoperative treatment and early immunosuppressant regimen were performed according to standard protocols. The transplanted heart was assessed normal for dimensions and ventricular function at transthoracic (TT echocardiography on post-transplant day 7. Coronary artery disease was ruled out at coronary angiography one month after transplant; left ventriculography showed normal global and segmental LV function of the transplanted heart. Conclusion For

  4. 心肌造影超声心动图对糖尿病大鼠心肌微循环的评价%Assessment of myocardial microcirculation in diabetic rats using myocardial contrast echocardiography

    卫张蕊; 张军; 苏海砾; 张海滨; 施红; 朱霆


    目的 研究心肌造影超声心动图(MCE)技术结合潘生丁负荷试验是否能够早期检测糖尿病(DM)大鼠左室心肌微循环的功能障碍.方法 雄性SD大鼠18只,腹腔注射链脲菌素复制DM模型,另12只体质量匹配的雄性SD大鼠腹腔注射生理盐水作为对照.分别在静息状态和潘生丁负荷后,对两组大鼠(12周)乳头肌水平左室短轴行MCE检查,测定各室壁感兴趣区域峰值声学强度(PI)、造影剂灌注速率(β)及声学强度达峰时间(TTP)等指标,计算心肌血流量(MBF)和心肌血流储备(MFR).MCE检查完毕后,对心肌组织分别行~(99m)Tc-MIBI核素摄取量及毛细血管密度测定.结果 无论静息状态还是负荷后,同组大鼠后壁的MBF较前壁、侧壁和室间隔的MBF显著减低(P<0.05);取前壁心肌进行组间比较,静息状态和负荷后,DM组的PI、MBF和MFR均较对照组显著减低(P<0.05).潘生丁负荷后,DM组β也较对照组显著减低,TTP显著延长(P<0.05).DM组各室壁的核素摄取量和毛细血管密度均显著减低(P<0.05).结论 MCE检测的PI、β、TTP、MBF及MFR等指标可以敏感地检测出DM早期的心肌微循环功能障碍.%Objective To investigate whether myocardial contrast echocardiography(MCE)combined with stress echocardiography could detect myocardial microcirculation disturbance of left ventricular(LV)in diabetic rats.Methods MCE were performed at rest and after dipyridamole infusion from parasternal shortaxis views at the papillary muscle level in DM rats(n=18,12 weeks later after STZ administration)and control rats(n=12).Regions of interest(ROI)were positioned with the anterior, lateral, posterior and septum walls.Plateau intensity(PI), initial slope of the curve(β)and time to PI(TTP)were obtained from the curve and myocardial blood flow(MBF)and myocardial flow reserve(MFR)was estimated.After the performance of MCE, myocardium was prepared for γ Well counting with ~(99m)Tc-MIBI and CD31

  5. Initial and delayed stress phase imaging in a single-injection double-acquisition SPECT. The potential value of early {sup 99m}Tc-MIBI redistribution in assessment of myocardial perfusion reversibility in patients with coronary artery disease

    Beiki, D. [Research Inst. for Nuclear Medicine, Tehran Univ. of Medical Sciences, Tehran (Iran); Dept. of Nuclear Pharmacy, Tehran Univ. of Medical Sciences, Tehran (Iran); Fallahi, B.; Fard-Esfahani, A.; Eftekhari, M. [Research Inst. for Nuclear Medicine, Tehran Univ. of Medical Sciences, Tehran (Iran); Mohseni, Z.; Khalaj, A. [Dept. of Nuclear Pharmacy, Tehran Univ. of Medical Sciences, Tehran (Iran)


    Some studies reported that {sup 99m}Tc-MIBI may redistribute in ischaemic myocardium and this phenomenon may have potential role for better assessment of viability by delayed {sup 99m}Tc-MIBI imaging. Some studies also suggested that infusion of low dose dobutamine during delayed imaging may enhance the value of {sup 99m}Tc-MIBI imaging for evaluation of viability. The aim of this study is to determine whether the observed changes of perfusion defects on delayed images are caused by early radiotracer redistribution or as a result of reversal partial volume effect secondary to inotropic stimulation. Patients, methods: 89 patients with angiographically proven coronary artery disease (CAD) were enrolled in this randomized clinical trial study. In all cases, gated-SPECT images were obtained 60 minutes after stress with dipyridamole injection. Subsequently the patients were randomly allocated in two groups and the second imaging was performed at 120{sup th} minute during low dose dobutamine (dobutamine group; 45 cases) or placebo infusion (placebo group; 44 cases). Difference between summed stress score of the first (SSS{sub 1}) and second (SSS{sub 2}) stress images ({delta}SSS) was considered as a marker of reversibility in single-injection double-acquisition (SIDA) protocol. Also summed difference score (SDS) was recorded as a marker of reversibility in standard stress/rest, double-injection double-acquisition (DIDA) protocol. {delta}SSS of the two studied groups were compared. Also the correlation and agreement between {delta}SSS and SDS were analyzed. Results: A significant difference was found between SSS{sub 1} (median 15, range 0-48) and SSS{sub 2} (median 11, range 0-42) in total patients (p < 0.0001). A significant correlation was noted between {delta}SSS and SDS in dobutamine group (r = 0.58, p = 0.002) as well as in placebo group (r = 0.57, p < 0.0001). Considering DIDA protocol as a standard reference method, the influence of dobutamine infusion was not

  6. Observation on Curative Effect of Modified Xiaoji Zhixue Decoction in Treatment of Simple Hematuria IgA Kidney Disease%小蓟止血汤加减治疗IgA肾病单纯血尿疗效分析



    Objective To observe the clinical curative effect of modified xiaoji zhixue decoction in treatment of simple hematuria IgA kidney disease. Methods 70 cases of patients with simple hematuria IgA kidney disease admitted and treated in our hospital from September 2013 to October 2015 were selected and randomly divided into two groups with 35 cases in each, the control group were treated with prednisone tablet and dipyridamole tablet, the observation group were treated with additional modified xiaoji zhixue decoction on the basis of the control group, and the curative effects of the two groups were observed and analyzed. Results The total effective rate in the observation group was obviously higher that in the control group, and the difference had statistical significance, (91.43%vs 65.71%), P<0.01, and the curative effect in the observation group was better than that in the control group. Conclusion The curative effect of modified xiaoji zhixue decoction in treat-ment of simple hematuria IgA kidney disease is obvious, which can effectively relieve the hematuria symptoms, and the clinical cure rate is much higher than the simple western medicine treatment with high safety and without side and toxic ef-fects, and it is of higher clinical application value.%目的:探讨小蓟止血汤加减治疗IgA肾病单纯血尿的临床疗效。方法随机选取2013年9月—2015年10月该院收治IgA肾病单纯血尿患者70例,随机分为对照组和观察组。对照组35例患者,给予泼尼松龙片和双嘧达莫片治疗;观察组35例患者则在对照组的基础上,加用小蓟止血汤加减治疗。观察分析两组疗效。结果观察组的总有效率为91.43%,明显高于对照组的65.71%,差异有统计学意义(P<0.01),可见观察组疗效优于对照组。结论小蓟止血汤加减对于单纯血尿型IgA肾病疗效显著,可有效缓解血尿症状,临床治愈率远高于单纯的西药治疗,且安全性高,无毒副作用

  7. Effect of tripterygium glycosides on serum ion and β2-GPI/ox-LDL in patients with IgA nephropathy%雷公藤多苷对IgAN患者血清离子及β2-GPI/ox-LDL影响

    彭健韫; 苏震


    目的:探讨雷公藤多苷对IgA肾病(IgA nephropathy,IgAN)患者血清离子及β2糖蛋白I(β2-glycoprotein,β2-GPI)/氧化低密度脂蛋白( oxidized low density lipoprotein ,ox-LDL)的影响。方法收集丽水市人民医院肾内科2014年1月~2015年4月收治的原发性IgAN患者54例,随机分为对照组和实验组,每组27例,对照组患者常规给予盐酸贝那普利片10 mg,1次/天口服;给予双嘧达莫片50 mg,3次/天口服,实验组在对照组基础上给予雷公藤多苷片20 mg,3次/天口服。2组患者均治疗6个月。治疗结束后,对所有患者的血清Ca、P、β2-GPI/ox-LDL水平及肾功能相关指标进行检测。结果与对照组治疗后比较,实验组患者血清Ca水平较高,血清P水平较低(P<0.05);实验组患者的血清β2-GPI/ox-LDL水平较低(P<0.05);实验组患者的血清Scr、BUN水平较低(P<0.05)。结论雷公藤多苷能够显著降低IgAN患者血清P、β2-GPI/ox-LDL、Scr及BUN水平,提高血清Ca水平,改善肾功能。%Objective To analyse effect of tripterygium glycosides on serum ion and β2-GPI/ox-LDL in patients with IgA nephropathy. Methods 54 patients who were diagnosed with primary IgA nephropathy in our hospital were collected.All patients were randomly divided into experimental group and control group, 27 cases in each group.Control group was given conventional Benazepri1 Hydrochloride Tablets 10 mg, 1 times per day orally;given Dipyridamole Tablets 50 mg, 3 times per day orally, patients in experimental group were given tripterygium glycosides 20 mg on the basis of control group treatment orally,3 times per day.All the patients were treated for 6 month.After the treatment, the serum levels of Ca,P,β2-GPI/ox-LDL and renal function related index were detected in all patients.Results Compared with control group post-treatment, the serum level of Ca was higher(P<0.05); and the serum level of P

  8. Influence of Neck-napex Needle Combined with Transcranial Magnetic Stimulation on Balance Function of Cervical Proprioception Vertigo%枕-项针配合经颅磁刺激对颈本体感觉性眩晕平衡功能的影响

    李旗; 田福玲; 王凤玲; 郑德松; 陈金铭; 马树祥; 崔建美; 王洪彬; 李雪青


    Objective:To explore neck-napex needle combined with transcranial magnetic stimulation (TMS) on balance function of cervical proprioception vertigo. Methods:One hundred patients were allocated to the control group and the test group according to random numble table. The patients of the control group were given with gink-go leaf extract and dipyridamole injection, vinpocetine injection, intravenous dripping; the ones of the test group were treated by neck-napex needle and TMS, once each day. After treating for 21 days, the length of locus, peripher-al area, the length in unit area, deviation, rectangle area, weight distribution coefficient and stability coefficient were detected by B-PHY type balance function testing and training system. Results:The length of locus, peripheral area, the length in unit area, deviation, rectangle area, weight distribution coefficient and stability coefficient in both groups were improved after treating compared with before treating (P0.05), the test group was superior to the control group in the length of locus, peripheral area, the length in unit area, deviation, weight distribution coefficient and stability coefficient (P<0.05). Conclusion:neck-napex needle combined with TMS could improve the symptoms of the pa-tients with cervical proprioception vertigo and balance function.%目的:探讨枕-项针配合经颅磁刺激对本体感觉性眩晕平衡功能的影响。方法:将颈本体感觉性眩晕患者100例按随机数字表法随机分为对照组与试验组各50例。对照组应用银杏达莫注射液和长春西汀注射液静脉滴注;试验组在对照组治疗的基础上使用项针配合经颅磁刺激进行治疗,1次/d。治疗21天后应用B-PHY型平衡功能检测训练系统检测轨迹长、外周面积、单位面积轨迹长、左右偏移、矩形面积、体重分布系数和稳定性系数。结果:2组患者治疗后轨迹长、外周面积、单位面积轨迹长、左右偏移、矩形面积

  9. A Clinical review of thirteen cases of atrophie blanche%白色萎缩13例临床分析

    叶庭路; 陆春; 钟绮丽; 于波; 顾有守; 潘慧清


    Objective: To promote the understanding of atrophie blanche and improve the diagnosis and treatment. Methods: Thirteen cases of atrophie blanche were retrospectively studied, by reviewing the clinical manifestations, laboratory examination results, therapeutic regimens and the follow-up data. Results: The symptoms of all the patients, most of them were young female, were more severe in the summer than those in the winter. The main skin lesions were red or mauve macules, patches, papules, or vesicles on both lower limbs, especially on the ankles and dorsa of the feet, which gradually became ulcerated, exudative and crusted. These lesions eventually became ivory atrophie scars, surrounded by telangiectasia or small glomus tumor-like appearance. Livedo reticularis on the lower extremities were seen in some patients. There were no specific laboratory findings. The histopathology of the skin specimens were consistent with the changes of livedo vasculitis. The patients were effectively treated with oral danazol, dipyridamole, low dose of aspirin, or DANSHEN dripping pills, and topical application of sodium heparin cream or mucopolysaccharide polysulfate cream. But the relapses were seen in most cases after stopping of the treatment. Conclusion: The diagnosis of atrophie blanche is mainly based on clinical manifestations and histopathologic findings. The remission could be successfully achieved by the medications but the relapses are often seen.%目的:提高对白色萎缩的临床认识,探讨其诊治方法.方法:回顾分析13例白色萎缩患者的临床表现、实验室检查、治疗及随访情况.结果:患者以青年女性居多,病情夏重冬轻.主要表现为双下肢,尤其双踝关节及足背部对称性红色或紫红色斑疹、斑片、丘疹及水疱,逐渐出现溃疡、渗出物及结痂,愈后遗留象牙白色萎缩性瘢痕,周围有毛细血管扩张和(或)形成小血管球瘤样外观.部分患者双下肢还有网状青斑样改变.实

  10. 药物负荷核素心肌灌注显影对冠心病的诊断价值%Diagnostic value of drug stress nuclide myocardial perfusion imaging to coronary heart disease

    张海英; 郭月玲; 李菲; 蔡丽; 蒲朝煜


    Objective To explore the diagnostic value of drug stress nuclide myocardial perfusion imaging ( MPI ) to coronary heart disease ( CHD ). Methods The patients ( n = 88 ) with suspected CHD were simultaneously given coronary angiography ( CAG ) and dipyridamole or adenosine stress nuclide MPI, and then they were given retrospective analysis. The difference was less than 14 days between CAG date and MPI date. Taking CAG results as golden criterion of CHD diagnosis, the sensitivity and specificity of drug stress nuclide MPI were compared and analyzed. Results The sensitivity, specificity and accuracy of drug stress nuclide MPI were, respectively, 91. 4% ,73. 3% and 85. 2% in the diagnosis of CHD. Among 5 false negative cases ,4 with single vessel lesion, 1 with double vessel lesion and all of them had good compensatory circulation. Among 8 false positive cases, 3 with syndrome X and 4 with slow coronary flow. Conclusion Drug stress nuclide MPI is an effective pathway for non-invasive diagnosis of CHD and myocardial ischemia. Most of patients with false positive or false negative have corresponding pathophysiological bases of coronary artery or cardial myodium.%目的 探讨药物负荷核素心肌灌注显像(MPI)对冠心病的诊断价值.方法 回顾性分析88例疑有冠心病且同时行冠状动脉造影(CAG)和双嘧达莫或腺苷药物负荷核素MPI患者,CAG与MPI检查日期相差不超过14 d,以CAG检查结果作为诊断冠心病的金标准,对比分析药物负荷核素MPI敏感度、特异性等指标.结果 药物负荷核素MPI诊断冠心病的敏感度、特异性、准确率分别为91.4%、73.3%、85.2%;在5例假阴性患者中,4例为单支病变,1例为双支病变,侧支循环均良好;8例假阳性患者中,3例为X综合征,4例为冠状动脉血流缓慢.结论 药物负荷核素心肌灌注显像是无创诊断冠心病及心肌缺血的有效途径,其假阳性和假阴性患者多有相应的冠状动脉或心肌的病理生理基础.

  11. Management of Membranoproliferative Glomerulonephritis: Evidence-Based Recommendations%膜增生性肾小球肾炎患者的循证治疗

    沈昊; 张玲; 刘修恒; 匡幼林


    Objective:Make the management of the individualized membranoproliferative glomerulonephritis with evidencebased recommendations.Methods:Based on the clinical questions we raised, evidence was collected and evaluated critically. Patient's will was also taken into consideration in the treatment. Results:Finally 12 randomized controlled trials,5 systematic reviews/metaanalysis and 2 clinical guidelines were considered eligible and collected. The evidence indicated that the first step in management of patients with membranoproliferative glomerulonephritis should aim to control blood pressure stably which can effectively relieve renal failure.Glucocorticoid can reduce glomerular filtration rate and improve renal function. Immunosuppressant was not recommended in the treatment of membranoproliferative glomerulonephritis.There was effective resume renal function by combining aspirin with dipyridamole. Tripterysium Glycosides might reduce the proteinuria and relieve renal failure. The individualized treatment plans were developed based on the levels of evidence of the supporting studies. After 2 months of treatment, the patient's blood pressure was controlled well and the proteinuria and the serum creatinine were reduced apparently. Conclusion:The management based on evidence recommendations was profit for the individualized membranoproliferative glomerulonephritis.%目的:针对一例膜增生性肾小球肾炎患者,检索当前最佳证据,为患者选择药物治疗方案提供依据.方法:根据循证临床实践的方法,提出问题,检索证据,对所获证据进行评价,并结合患者意愿制定治疗方案.结果:共纳入12个随机对照试验,5个系统评价/Meta分析和2个临床指南.证据结果表明:(1)稳定而良好的血压控制能有效延缓肾功能衰竭;(2)糖皮质激素能减少肾小球率过滤,改善肾功能;(3)不推荐免疫抑制剂治疗膜增生性肾小球肾炎;(4)阿司匹林与双嘧达莫连用能有效保护肾功能;(5)

  12. MR angiography and determination of the flow reserve after minimal invasive direct coronary artery bypass (MIDCAB) surgery of the left internal mammary arteria in comparison to the multidetector-row CT; MR-Angiographie und Flussreservenbestimmung nach minimalinvasiver direkter Koronararterien-Bypass(MIDCAB)-Operation der linken Arteria mammaria interna im Vergleich zur Mehrzeilen-CT

    Stauder, N.I.; Fenchel, M.; Kuettner, A.; Kramer, U.; Claussen, C.D.; Miller, S. [Abt. Radiologische Diagnostik, Universitaetsklinik Tuebingen (Germany); Stauder, H.; Scheule, A.M. [Abt. Thorax-, Herz- und Gefaesschirurgie, Universitaetsklinik Tuebingen (Germany)


    Purpose: To evaluate graft patency, flow and flow reserve in patients with minimal invasive direct coronary artery bypass (MIDCAB) of internal mammary artery (IMA) grafts using a combined MR protocol with phase-contrast technique and MR angiography. Material and methods: At a 1.5T Magnetom Sonata (SIEMENS), 19 symptomatic (angina CCS I-III, intermittent thoracic discomfort, scar disorders) patients (59.9{+-}7.9 years old) with 19 left internal mammary artery (LIMA) grafts implanted in minimal invasive technique were examined 6.9{+-}1.5 years post surgery. Contrast enhanced MR angiography (TR 2.5 ms, TE 1 ms, flip angle 20 , spatial resolution 1.4 x 0.9 x 1.0 mm{sup 3}, breath hold technique, no ECG-triggering, 25 ml Gd-DTPA) was performed to assess bypass patency. Phase-contrast flow measurements with retrospective gating (TR 41 msec, TE 3.2 msec, flip angle 30 , spatial resolution 1.1 x 1.1 x 5 mm{sup 3}, temporal resolution 42 msec, venc 90 cm/sec) were applied in the IMA grafts at rest and after stress induction with dipyridamole (0.56 mg/kg/BW). For comparison, graft patency was evaluated by multidetector-row computed tomography (16-row CT). In 9 patients a selective catheter angiography was performed. Results: MIDCAB grafts were occluded in 4/19 patients. In 4 patients the anastomosis to LAD was highly stenotic (>70%) at MDCT (2 experienced investigators in consensus reading). In MRA 9 grafts could be delineated completely including the distal anastomosis to LAD (47%). In 9 patients the distal part could not be evaluated. In patients with patent grafts (MDCT), a significant improvement of graft flow (at rest 75.4{+-}33.3 ml/min; after stress 202.7{+-}49.6; P<0.002) and flow reserve (patent grafts 3.0{+-}1.1; stenotic grafts 1.5{+-}0.2, P<0.02; occluded grafts 0.9{+-}0.2, P<0.01) after stress induction was detected. Diastolic-to-systolic peak velocity ratios (D/S-PVR) at baseline were not significant between patent and stenotic grafts. Mean flow at baseline and

  13. 克罗恩病合并红斑肢痛症1例报告及文献复习%Crohn’s disease complicated with erythromelalgia:report of 1 case and literature review

    徐亚珍; 储波; 蒋丽蓉; 殷蕾; 应大明; 陈惠金


    Objectives To explore the clinical features, diagnosis and treatment of Crohn’s disease complicated by erythromelalgia (EM) in a pediatric case. Methods The clinical manifestation, results of laboratory testing and endoscopy, mutational analysis of the SCN9A gene, and the follow-up record were collected and analyzed based on review of literature to a thirteen-year-old girl with Crohn’s disease complicated by erythromelalgia. Results The patient experienced symptoms of anorexia, fatigue, diarrhea, dark red and swelling skin, increased skin temperature and burning pain in her both lower extremities during the course of disease. The endoscopic ifndings included multiple ulcerations and polypoid protrusion lesion in colon, and the pathological examination showed the local abscess formation in colonic mucosa. The mutation in SCN9A gene of the child was excluded by gene analysis. The symptoms were gradually ameliorated after treatment using prednisone and mesalazine combined with dipyridamole and low-molecular-weight heparin calcium. Conclusions Crohn’s disease complicated by erythromelalgia is rare. The pathogenesis may relate to immune factors, thrombocytosis, and hyper-coagulable states, etc. The combination of glucocorticoids, 5-aminosalicylic acid and anticoagulants may lead to a better therapeutic effect.%  目的探讨克罗恩病(Crohn’s disease,CD)合并红斑肢痛症(erythromelalgia,EM)的临床特点及其诊断和治疗。方法整理分析1例克罗恩病合并红斑肢痛症的13岁女童的临床表现、实验室和内镜检查结果、SCN9A基因分析和随访资料,并进行相关文献复习。结果患儿临床表现为食欲减退、乏力伴腹泻,双下肢端皮肤肿胀呈暗红色,肤温高并伴烧灼样疼痛。内镜检查见结肠呈多发性溃疡和息肉样隆起,病理检查提示为结肠黏膜局部脓肿形成。基因分析排除SCN9A基因突变。经口服泼尼松和美沙拉嗪,并联合双嘧

  14. 川崎病冠状动脉血栓患儿8例药物治疗分析%Analysis of drug treatment of the coronary embolism in Kawasaki disease

    俞惠娟; 朱卫华


    目的:观察川崎病(KD)冠状动脉瘤并发血栓药物治疗的效果。方法回顾性分析8例KD冠状动脉瘤合并血栓患儿的临床资料。结果8例KD患儿年龄0.2~5.2岁;男6例,女2例。冠状动脉瘤瘤体内径8.3~13.8 mm,血栓发生时间在冠状动脉瘤形成后19 d至5月余。初发症状为突发胸痛1例,有心肌梗死伴心力衰竭症状;休克样症状1例;无症状6例。心脏超声检查发现瘤内血栓最大径2.8 mm×15.4 mm,呈长段条索状。冠状动脉血栓右侧4例,左侧2例,双侧2例。使用肝素、尿激酶溶栓,华法林、阿司匹林及潘生丁抗凝,抗血小板治疗。7例消溶成功,完全消溶所需要时间7d至4月余。1例4个月后血栓复发;1例发病12 h死亡。结论 KD冠状动脉瘤合并血栓好发于KD发病半年内,药物溶栓治疗需要时间较长,血栓脱落不多见。%Objective To observe the efficacy of drug treatment of coronary aneurysm complicated with embolism in Kawasaki disease (KD). Methods The clinical data of eight KD children with coronary aneurysm and embolism were retrospectively analyzed. Results Eight KD children (six males and two females) at age of 0.25-5.2 years (mean=2.89) ,were diagnosed with gigantic coronary artery aneurysms. The diameter of aneurysm was around 8.3-13.8mm. Thrombosis appeared from 19 days to five months after coronary aneurysms formation. The onset manifestations included sudden chest pain and myocardial infarction with symptoms of heart failure in one case, shock in one case and no symptom in six cases. The maximum diameter of the thrombus was 2.8 mm×15.4 mm in the shape of funicular. Four cases had thrombus in the right coronary artery, two cases in the left coronary artery, and two cases in both sides. The patients underwent anticoagulant therapy taking heparin, urokinase, warfarin, aspirin and dipyridamole. Anticoagulant therapy was successful in 7 cases and the thrombus was completely

  15. O teste ergométrico é factível, eficaz e custo-efetivo na predição de eventos cardiovasculares no paciente muito idoso, quando comparado à cintilografia de perfusão miocárdica In comparison to the myocardial perfusion scintigraphy, a treadmill stress test is a viable, efficient and cost effective option to predict cardiovascular events in elderly patients

    Luciano Janussi Vacanti


    Full Text Available OBJETIVO: Definir o valor prognóstico e a custo-efetividade do teste ergométrico (TE em comparação à cintilografia de perfusão miocárdica com dipiridamol (DIP em indivíduos com > 75 anos de idade. MÉTODOS: Foram avaliados, consecutiva e prospectivamente, 66 pacientes (40% homens, com média de idade de 81 ± 5 anos. Desses pacientes, 57% eram hipertensos, 38% eram dislipidêmicos e 28%, diabéticos. O protocolo de Bruce para rampa foi adaptado, obtendo-se o valor prognóstico do TE pelo escore de Duke. RESULTADOS: A duração do TE, o porcentual da freqüência cardíaca máxima preconizada e o duplo produto no pico do exercício foram, respectivamente, de 7 ± 3 minutos, 95 ± 9% e 24.946 ± 4.576 (bpm x mmHg. O TE e a DIP apresentaram resultados positivos para isquemia miocárdica similares (21% vs 15%, respectivamente. A concordância entre os testes foi de 88% (Kappa 0,63, p OBJECTIVE: To define the prognostic value and cost-effectiveness of the treadmill stress test (TST in comparison to the dipyridamole myocardial perfusion scintigraphy (DIP, in individuals >75 years of age. METHODS: Consecutive and prospective assessment of 66 patients (40% male aged 81 ± 5 years of which 57% were hypertensive, 38% had dyslipidemia and 28% were diabetics. The Bruce protocol was adapted for a tilt treadmill and the TST prognostic value was obtained using the Duke treadmill score. RESULTS: The TST duration, recommended maximum heart rate percentage and double product at peak exercise were respectively: 7 ± 3 minutes, 95 ± 9% and 24,946 ± 4,576 (bpm x mmHg. The TST and DIP presented similar positive results for myocardial ischemia (21% vs 15%, respectively. The correlation between the tests was 88% (Kappa 0.63, p<0.01. During 685 ± 120 days of follow-up, nine major events occurred: 6 deaths, 2 acute coronary syndromes and 1 myocardial revascularization. The variables associated with the major events were: age (83 ± 6 vs 80 ± 4 years; p=0

  16. Stress echocardiography for the diagnosis of coronary artery disease: an evidence-based analysis.


    CARDIAC MAGNETIC RESONANCE IMAGING FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisPease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website:POSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: An Evidence-Based AnalysisMAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY: an Evidence-Based AnalysisThe Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled:The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from: OBJECTIVE: The objective of the analysis is to determine the diagnostic accuracy of stress echocardiography (ECHO) in the diagnosis of patients with suspected coronary artery disease (CAD) compared to coronary angiography (CA). STRESS ECHOCARDIOGRAPHY: Stress ECHO is a non-invasive technology that images the heart using ultrasound. It is one of the most commonly employed imaging techniques for investigating a variety of cardiac abnormalities in both community and hospital settings. A complete ECHO exam includes M-mode, 2-dimensional (2-D) images and Doppler imaging. In order to diagnosis CAD and assess whether myocardial ischemia is present, images obtained at rest are compared to those obtained during or immediately after stress. The most commonly used agents used to induce stress are exercise and pharmacological agents such as dobutamine and dipyridamole. The hallmark of stress-induced myocardial ischemia is worsening of wall motion abnormalities or the development of new wall motion abnormalities. A major challenge for stress ECHO is that the interpretation of wall motion contractility and function is subjective. This leads to inter-observer variability and reduced reproducibility

  17. 我院肾病综合征超说明书用药分析%Analysis of Off-label Drug Use in Nephrotic Syndrome in Our Hospital

    黄婧; 于西全; 陈威


    Objective:To analyze the rationality of off-label drug use in nephritic syndrome prescriptions to provide scientific basis for clinical rational drug use and further regulate the off-label drug use in our hospital. Methods:Totally 1 908 outpatient prescriptions of nephritic syndrome selected from our hospital during November 2014 to April 2015 were analyzed, and all the off-label drugs were listed . The rationality of the off-label drug use was analyzed and evaluated by searching the related kidney disease guidelines and litera-tures. Results:The off-label drug use of tacrolimus capsules, mycophenolate mofetil capsules, cyclophosphamide for injection, ciclos-porin soft capsules, dipyridamole tablets, hydroxychloroquine sulfate tablets and warfarin sodium tablets were recommended by domes-tic and overseas guidelines with better evidence of evidence-based medicines. Tripterygium glycosides tablets and leflunomide tablets were supported by the literatures on clinical studies at home and abroad. The above 9 kinds of off-label drugs were rational drug use. Lumbrokinase enteric-coated capsules, salvia miltiorrhiza and ligustrazine injection and pidotimod dispersible tablets were reported only by a handful of journals. Bacteria lysate capsules and boric acid powder had no related information support, which belonged to the em-pirical prescriptions of physicians. The above 5 kinds of off-label drugs were not rational drug use. Conclusion:It is a widely existing phenomenon that the medication in nephrotic syndrome is beyond the instruction, the most of off-label drug use are reasonable, and cli-nicians should prescribe medicines carefully. Our hospital needs to further standardize the management of off-label drug use supported by higher evidence in order to improve the level of clinical rational drug use and the reasonable rate of prescriptions.%目的::分析我院治疗肾病综合征超说明书用药的合理性,为临床合理用药提供科学依据,并进一