Erectile dysfunction (ED) in diabetes is associated with autonomic neuropathy and endothelial dysfunction. Whereas the nonadrenergic-noncholinergic (NANC)/neurogenic nitric oxide pathway has received great attention in diabetes-associated ED, few studies have addressed sympathetic overactivity.
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Dipyridamole can improve the specificity of photodynamic sterilization of RBC concentrates, thereby increasing the practical applicability of this photodecontamination method.
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The oxidative modification of low density lipoprotein (LDL) is believed to play an important role in the initiation of the atherosclerotic lesion. Dipyridamole, which is used clinically as a coronary vasodilator and an antiplatelet agent, has antioxidant properties. Probucol is a lipid-lowering agent which inhibits the oxidative modification of LDL. We have compared the effect of pharmacological concentrations of dipyridamole and probucol on the oxidative modification of LDL by copper or endothelial cells in vitro. Dipyridamole protected LDL from oxidative modification by either copper ions or endothelial cells at concentrations as low as 2.5 microM while probucol had no effect at this concentration. LDL oxidized with copper in the presence of dipyridamole (20 microM) was less effective than LDL oxidized in the absence of dipyridamole at inhibiting [3H]acetyl-LDL binding to cultured human. THP-1 monocyte derived macrophages. The concentrations of dipyridamole found to inhibit the oxidative modification of LDL in vitro are achieved in vivo using clinically recommended doses.
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A literature search was performed on August 28, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 until August 21, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search.
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In this small retrospective study, men with positive stress tests had fewer adverse events with either preoperative coronary revascularization or perioperative administration of β-adrenergic blocking drugs, compared with men who received no intervention. There were no significant differences in adverse outcomes between women with positive stress tests who received either treatment compared with those who did not receive any treatment.
The Beers and McLeod criteria, developed internationally, required considerable modification for local prescribing. The three criteria differed in their focus and approaches, such that development and validation of national criteria, using the key features of these models, is recommended. There is potential to apply validated guidelines in clinical practice and review of prescribing, but only to supplement clinical judgement.
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Significant (> or = 70% diameter stenosis) coronary artery disease was found in 34 patients (17 hypertensives and 17 normotensives). Positive exercise electrocardiography (ST-segment shift > 1 mm at 80 ms after the J point in leads V5 and V6 or leads II and Vf) and dipyridamole stress echo (new wall motion abnormalities) were observed in 38 and 30 patients, respectively. The result of tests was concordant in 69% of hypertensives and 92% of normotensives. The two tests shared the same sensitivity in hypertensives (82%) and normotensives (71%). Of 37 patients without coronary artery disease, 12 had a false-positive result during exercise electrocardiography and four during stress echo. The specificity was lower for exercise electrocardiography than for stress echo in hypertensives (50 versus 89%, P = 0.0006), while no difference was evidenced in normotensives (84 versus 89%, P = 0.4). In hypertensives, the accuracy, positive, and negative predictive values were 66, 61, and 75% for exercise electrocardiography, and 86, 87, and 84% for stress echo. Corresponding figures in normotensives were 78, 80, and 76% for exercise electrocardiography, and 81, 86, and 77% for stress echo.
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To detect changes in vascular physiology associated with early atherosclerosis, we studied whether alterations in coronary flow reserve, as assessed by positron emission tomography imaging with intravenous dipyridamole, would be related to risk factor variables in healthy young men. The number of conventional risk variables correlated significantly with coronary flow reserve (r = -0.58, p = 0.0007), suggesting that alterations in functional vascular reactivity are related to the cardiovascular risk status already in healthy young men.
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The aim of this study was to evaluate the accuracy of myocardial perfusion scintigraphy with technetium-99m tetrofosmin by single-photon emission computed tomography (SPECT), using one-day protocol in the identification and localization of individual stenosed coronary vessels. Sixty-eight patients with suspected coronary artery disease (CAD) were studied. In thirty of them coronary angiography showed significant stenosis (> or = 50%). Nine patients were with one-vessel disease, 11 were with two-vessel disease, and 10 were with three-vessel disease. All the patients were administered two i.v. injections of 99mTc tetrofosmin, one at peak pharmacologic exercise (1-3 min after i.v. administration of dipiridamol 0.56 mg per kg during 4 min) 370 MBq, and the other 740 MBq at rest 3 hrs after the exercise test (acquisition was obtained 15-30 min after injections for both studies). Overall sensitivity, specificity, and diagnostic accuracy in the identification of individual stenosed coronary vessels were 90%, 86%, and 88%, respectively. Sensitivity, specificity, and accuracy in each of the individual vascular territories were not significantly different: LAD (96%, 64%, and 75%), ACx (73%, 100%, and 94%), RCA (95%, 93%, and 94%). The results of this study demonstrated one-day 99mTc-tetrofosmin SPECT scintigraphy to be suitable and accurate technique for the identification and localization of individual stenosed coronary vessels, as well as a highly sensitive method in the recognition of one- and multiple-vessel diseases of coronary arteries.
To describe the pharmacology, pharmacokinetics, efficacy, and safety of a fixed-dose combination of aspirin and extended-release (ER) dipyridamole indicated for the secondary prevention of stroke.
A retrospective comparison of wall motion and myocardial perfusion with RTCSE was assessed in 481 obese and 961 nonobese patients matched for age and gender without known coronary artery disease referred for either dobutamine (n = 1,056) or dipyridamole (n = 386) stress echocardiography at two separate institutions. Outcomes (death or nonfatal infarction) were determined over a median follow-up period of 1,195 days.
Dipyridamole thallium-201 scintigraphy can be performed safely within a few days of the event in patients with uncomplicated myocardial infarction, including those who received thrombolysis, and can identify a subgroup of patients at high risk of future ischaemic events.
Ethanol can increase the solubility of poorly soluble and hence present a higher drug concentration in the gastrointestinal tract. This may produce a faster and more effective absorption resulting in variable and/or high drug plasma concentrations, both of which can lead to adverse drug reactions. In this work we therefore studied the solubility and absorption effects of nine diverse compounds when ethanol was present. The apparent solubility was measured using the μDiss Profiler Plus (pION, MA) in four media representing gastric conditions with and without ethanol. The solubility results were combined with in-house data on solubility in intestinal fluids (with and without ethanol) and pharmacokinetic parameters extracted from the literature and used as input in compartmental absorption simulations using the software GI-Sim. Apparent solubility increased more than 7-fold for non-ionized compounds in simulated gastric fluid containing 20% ethanol. Compounds with weak base functions (cinnarizine, dipyridamole and terfenadine) were completely ionized at the studied gastric pH and their solubility was therefore unaffected by ethanol. Compounds with low solubility in intestinal media and a pronounced solubility increase due to ethanol in the upper gastric compartments showed an increased absorption in the simulations. The rate of absorption of the acidic compounds indomethacin and indoprofen was slightly increased but the extent of absorption was unaffected as the complete doses were readily absorbed even without ethanol. This was likely due to a high apparent solubility in the intestinal compartment where the weak acids are ionized. The absorption of the studied non-ionizable compounds increased when ethanol was present in the gastric and intestinal media. These results indicate that concomitant intake of alcohol may significantly increase the solubility and hence, the plasma concentration for non-ionizable, lipophilic compounds with the potential of adverse drug reactions to occur.
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We evaluated the value of coronary artery calcification (CAC) score in coronary artery disease (CAD) detection in asymptomatic hemodialysis (HD) patients by evaluating the association among CAC score, exercise electrocardiography (EECG), and Thallium-201 dipyridamole scintigraphy. Correlation between aortic pulse wave velocity (PWV) and CAC score was also evaluated.
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Thrombotic thrombocytopenic purpura is an uncommon disease with a high mortality rate even with current treatment. The cause of the syndrome and its optimal treatment are unknown. Although both plasma exchange and plasma infusion have been useful treatments, it is not clear which is superior. In this report we describe a prospective randomized trial comparing plasma exchange with plasma infusion for the treatment of thrombotic thrombocytopenic purpura.
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From April 2005 to April 2010, 39 "marginal" candidate donors (mean age, 56 ± 6 years; 21 men) were initially enrolled. After legal declaration of brain death, marginal donors underwent rest echocardiography, and if the results were normal, dipyridamole (0.84 mg/kg over 6 min, n = 25) or dobutamine (up to 40 μg/kg/min, n = 3) stress echocardiography.
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In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect of antihypertensive treatment by 12-month administration of the angiotensin converting enzyme (ACE) inhibitor captopril (50 mg twice a day orally). In essential hypertensives with dipypridamole echocardiography stress test (DET) (DET+, n = 8) and without (DET-, n = 8) ST segment depression greater than 0.1 mV during intravenous dipyridamole infusion (0.84 mg/kg over 10 min), we studied the forearm blood flow (FBF, venous plethysmography, mL/100) modifications induced by intrabrachial acetylcholine (Ach) (0.15, 0.45, 1.5, 4.5, 15 micrograms/100 mL/min x 5 min each), an endothelium-dependent vasodilator, and by sodium nitroprusside (SNP) (1, 2, 4 micrograms/100 mL/min x 5 min each), a smooth muscle cell relaxant compound. Minimal forearm vascular resistances (MFVR), an index of arteriolar structural changes, were also calculated. Both Ach and SNP caused greater vasodilation in DET- as compared to DET+ while MFVRs were lower in DET- compared to DET+. After treatment, both DET+ and DET- patients showed a significant and similar reduction in blood pressure and left ventricular mass index, while vasodilation to acetylcholine and sodium nitroprusside was increased only in the DET+ group. In addition, forearm minimal vascular resistances were significantly reduced only in DET+ patients, who showed disappearance of dipyridamole-induced ischemic-like ST segment depression. In conclusion, these data confirm that essential hypertensive patients with microvascular coronary disease are characterized by the presence of structural changes in the forearm vascular bed. Our results also indicate that both cardiac and forearm vascular abnormalities can be reversed by antihypertensive treatment with an ACE inhibitor.
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Twenty patients suffering from transient attacks of ischaemia were studied. Seven received acetylsalicylic acid, six dipyridamole and seven a combination of the two drugs. No significant difference in platelet aggregation was shown in the acute phase between the three treatment groups using an adenosine diphosphate test method. Using Thrombofax platelet substitute, however, a significant difference was seen in all measures. On the seventh day following the ischaemic attack the Thrombofax values returned to normal but, in contrast, Platelet Factor 4 release was increased. Monthly testing of platelet activity during treatment shows that the combination of acetylsalicylic acid with dipyridamole was more effective in bringing about an early inhibition of Platelet Factor 4 release than either agent alone.
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Changes in regional myocardial perfusion throughout the entire coronary vascular tree, as opposed to changes in the worst regional perfusion defect, have not been described during long-term regression or progression of coronary artery disease (CAD) or related to clinical outcomes.
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Inhalation of aerosolized prostacyclin (PGI(2)) exerts selective pulmonary vasodilation, but its effect is rapidly lost after termination of nebulization. Amplification of the vasodilatory response to inhaled PGI(2) might be achieved by phosphodiesterase (PDE) inhibitors to stabilize its second messenger, cAMP. We established stable pulmonary hypertension in perfused rabbit lungs by continuous infusion of U-46619. Short-term (10-min) aerosolization maneuvers of PGI(2) effected a rapid, moderate decrease in pulmonary arterial pressure, with post-PGI(2) vasorelaxation being lost within 10-15 min, accompanied by a marginal reduction in shunt flow. Preceding administration of subthreshold doses of the PDE inhibitors theophylline, dipyridamole, and pentoxifylline via the intravascular or inhalational route, which per se did not influence pulmonary hemodynamics, caused more than doubling of the immediate pulmonary arterial pressure drop in response to PGI(2) and marked prolongation of the post-PGI(2) vasorelaxation to >60 min (all PDE inhibitors via both routes of application). This was accompanied by a reduction in shunt flow in the case of aerosolized theophylline (27.5%), pentoxifylline (30.5%), and dipyridamole (33.4%). Coaerosolization of PGI(2) and PDE inhibitors may be considered as a therapeutic strategy in pulmonary hypertension.
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This study extends our earlier work (Abumrad, N. A., Perkins, R.C., Park, J.H., and Park, C.R. J. Biol. Chem. 256, 9183-9191) which showed that oleate permeates the plasma membrane of the rat adipocyte principally by a transport process with the characteristics of facilitated diffusion. In the present study, fatty acid (FA) transport is characterized with regard to its specificity and susceptibility to inhibition by protein modifiers. The kinetics of competitive inhibition for transport of oleate and stearate are shown under conditions where complications due to competition for binding of FAs to the albumin in the medium are minimized. Stearate inhibits influx of tracer oleate with a Ki that closely approximates its Km and, conversely, oleate inhibits similarly the influx of tracer stearate. Specificity of the FA transport system is shown in studies using a variety of natural FAs of different chain length, or FA analogues. Oleate (Km = 0.06 microM), stearate (Km = 0.16 microM), linoleate (Km = 0.22 microM), palmitate, (Km = 0.2 microM), and laurate (Km = 1.5 microM) are good substrates, but octanoate is not transported. An oxazolidine ring on C-5 but not on C-16 of stearate blocks binding to the transporter. Methylation of the carboxyl function but not alpha-bromination inhibits transport. These studies suggest that a FA must have a hydrocarbon chain of at least nine carbons and a free carboxyl function to be recognized by the transporter. FA transport does not require Na or ATP. Pronase but not trypsin treatment of intact cells reduces fatty acid influx. Transport is insensitive to maleimides. It is strongly and irreversibly blocked by pretreatment of the cells with the stilbene compounds, 4,4'-diisothiocyanostilbene-2,2'-disulfonate and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, but only slightly inhibited by dipyridamole. Polyacrylamide gel electrophoresis of plasma membrane proteins from cells treated with [3H] 4,4'-diisothiocyanostilbene-2,2'-disulfonate shows a peak of radioactivity at about Mr = 85,000. When cells are incubated in various concentrations of this agent, the counts recovered in the peak reach a maximum coincident with maximum inhibition of transport. We conclude that permeation of the plasma membrane of the adipocyte by long-chain FAs at physiological concentrations is mediated by a protein transporter with distinct specificity requirements.
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Myocardial perfusion can be analyzed by the first pass of Doppler intensity (DI) signals in the myocardium by myocardial contrast echocardiography with triggered power Doppler harmonic imaging (PDHI).
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Dipyridamole, an inhibitor of adenosine uptake as well as a cGMP phosphodiesterase inhibitor, is commonly used in prophylactic therapy for patients with angina pectoris. However, the effects of dipyridamole on systemic blood vessels, especially on the peripheral vascular system, are not well understood. Therefore, the effect of dipyridamole on ATP-induced arteriole contraction was examined with special reference to intracellular Ca(2+) concentration ([Ca(2+)](i)) using real-time confocal microscopy. In cases of 0.1-10microM range, dipyridamole induced only slight [Ca(2+)](i) decreases in smooth muscle cells of both testicular and cerebral arterioles. However, 100microM dipyridamole induced substantial [Ca(2+)](i) decreases in the cells. In the presence of 10microM dipyridamole, changes in ATP-induced [Ca(2+)](i) were found to be inhibited in smooth muscle cells of testicular arterioles but not in those of cerebral arterioles. In addition, alpha, beta-methylene ATP-induced [Ca(2+)](i) increases in testicular arteriole smooth muscle cells were also partially inhibited in the presence of dipyridamole. When testicular arterioles were perfused with dipyridamole, no increases in nitric oxide levels were detected. High levels of K(+) induced a [Ca(2+)](i) increase in testicular arterioles that was also partially inhibited by dipyridamole. In the presence of substances that affect protein kinase A or G, ATP-induced [Ca(2+)](i) was not completely inhibited. These findings suggest that dipyridamole may act not only as an inhibitor of adenosine uptake and as a cGMP phosphodiesterase inhibitor, but also as a calcium channel blocker in arteriole smooth muscle cells.
The effects of the phosphodiesterase (PDE) inhibitors milrinone and dipyridamole were studied in an in situ perfused rabbit lung model in which the pulmonary vascular resistance (PVR) was elevated by infusion of the thromboxane-A2 mimetic U46619. Dose-response curves for reduction of elevated PVR were generated for each of these drugs. The EC50 for milrinone was approximately 2 microM. The EC50 for dipyridamole was approximately 0.2 microM. In separate experiments, 0.1 microM milrinone was found to reduce elevated PVR by 4.6 +/- 2.4%, 0.06 microM dipyridamole reduced elevated PVR by 8.2 +/- 2.8%, whereas the combination of 0.1 microM milrinone and 0.06 microM dipyridamole reduced elevated PVR by 41.9 +/- 7.3%. In more limited experiments, it was determined that the PDE type V inhibitor zaprinast also caused a synergistic reduction of PVR when used with milrinone. We concluded that both the type III PDE inhibitor milrinone and the type V PDE inhibitors dipyridamole or zaprinast are effectively able to reduce elevated PVR and that the combination of PDE type III and type V inhibitors is synergistic in the ability to reduce elevated PVR. We speculate that type V PDE may play a more important role than type III PDE in the regulation of pulmonary vascular tone. It is proposed that the combination of milrinone and dipyridamole has the potential to be useful in the clinical treatment of elevated PVR.
The aim of this study was to investigate a case of EDTA-induced polymorphonuclear leukocyte (PMN) agglutination in vitro on Bayer Technicon H*1. Coulter Counter STKS and STKR analyzers.
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To assess the prognostic value of CFR in patients with known or suspected coronary artery disease (CAD) and negative stress echo.
Quantitative dynamic (82)Rb PET using generalized factor analysis of dynamic sequences and compartmental modeling yields estimates of parameters of absolute myocardial perfusion and kinetics with errors of <9%.
To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients.
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Endothelial function has been shown to be a highly sensitive marker for the overall cardiovascular risk of an individual. Furthermore, there is evidence of important sex differences in endothelial function that may underlie the differential presentation of cardiovascular disease (CVD) in women relative to men. As such, measuring endothelial function may have sex-specific prognostic value for the prediction of CVD events, thus improving risk stratification for the overall prediction of CVD in both men and women. The primary objective of this study is to assess the clinical utility of the forearm hyperaemic reactivity (FHR) test (a proxy measure of endothelial function) for the prediction of CVD events in men vs. women using a novel, noninvasive nuclear medicine -based approach. It is hypothesised that: 1) endothelial dysfunction will be a significant predictor of 5-year CVD events independent of baseline stress test results, clinical, demographic, and psychological variables in both men and women; and 2) endothelial dysfunction will be a better predictor of 5-year CVD events in women compared to men.
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Maximum MBF (intravenous dipyridamole, 0.56 mg/kg; Dip-MBF) was measured using (13)N-labeled ammonia in 61 patients with HCM (age 38 ± 14 years), genotyped by automatic DNA sequencing of 8 myofilament-encoding genes (myosin-binding protein C, beta-myosin heavy chain, regulatory and essential light chains, troponin T, troponin I, troponin C, alpha-tropomyosin, and alpha-actin). In 35 patients, cardiac magnetic resonance imaging was performed.