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Journal of the American College of... Jul 1995This study was designed to compare exercise, dipyridamole and dobutamine echocardiography in the same patients and to evaluate, by measuring physiologic and... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
OBJECTIVES
This study was designed to compare exercise, dipyridamole and dobutamine echocardiography in the same patients and to evaluate, by measuring physiologic and echocardiographic variables, the mechanisms by which exercise and dobutamine induce ischemia.
BACKGROUND
The diagnostic value of stress echocardiography has been widely reported, but the specific effects of exercise, dipyridamole and dobutamine have not been directly compared. Furthermore, no echocardiography study has evaluated left ventricular volume changes at ischemic threshold during exercise and dobutamine administration.
METHODS
One hundred patients with suspected (Group A, n = 60) or known (Group B, n = 40) coronary artery disease underwent all three tests in random order.
RESULTS
In Group A, the sensitivities of exercise (mean 76%, 95% confidence interval [CI] 58% to 94%) and of dobutamine echocardiography (72%, 95% CI 53% to 91%) were higher than that of dipyridamole (52%, 95% CI 31% to 73%; p = 0.01 and p = 0.02, respectively). Specificity did not differ significantly among tests (94% for exercise [95% CI 86% to 100%] and 97% for dipyridamole and dobutamine [95% CI 91% to 100%]). Accuracy was identical for exercise and dobutamine (87%) and higher than that for dipyridamole (78%, p = 0.06). In Group B, the accuracy in predicting coronary disease extent was 71% for exercise, 33% for dipyridamole and 75% for dobutamine. At ischemic threshold, end-systolic volume index and the ratio of systolic blood pressure to end-systolic volume, a variable related to myocardial contractility, were significantly lower and higher, respectively, with dobutamine than during exercise (p < 0.05).
CONCLUSIONS
In a clinical setting, exercise echocardiography should represent the first diagnostic approach because it has high diagnostic efficacy and provides additional information on exercise capacity; pharmacologic stress, particularly that of dobutamine, provides a pivotal diagnostic tool when exercise is not feasible or its results are nondiagnostic. Our preliminary data on echocardiographic evaluation at ischemic threshold support the view that myocardial contractility is a major factor in inducing ischemia during dobutamine infusion.
Topics: Coronary Disease; Dipyridamole; Dobutamine; Echocardiography; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Sensitivity and Specificity
PubMed: 7797748
DOI: 10.1016/0735-1097(95)00121-f -
Pediatric Transplantation May 2020Relative contraindications to adenosine use have included heart transplant and dipyridamole. We previously demonstrated the safety and efficacy of adenosine-induced... (Clinical Trial)
Clinical Trial
BACKGROUND
Relative contraindications to adenosine use have included heart transplant and dipyridamole. We previously demonstrated the safety and efficacy of adenosine-induced atrioventricular (AV) block in healthy young heart transplant recipients while suspending dipyridamole therapy (dual antiplatelet agent). This prospective follow-up study evaluated the safety and efficacy of adenosine use in the same cohort of heart transplant recipients while on dipyridamole.
METHODS
Adenosine was incrementally dosed until AV block occurred (maximum 200 mcg/kg up to 12 mg). The primary outcome was clinically significant asystole (≥12 seconds). Secondary outcomes included maximal adenosine dose, AV block duration, dysrhythmias, and clinical symptoms. Outcomes were compared to the parent study.
RESULTS
Thirty of 39 eligible patients (5-24 years) were tested. No patient (0%, CI 0%-8%) experienced clinically significant asystole. AV block occurred in 29/30 patients (97%, CI 86%-100%). The median dose causing AV block was 50mcg/kg (vs 100 mcg/kg off dipyridamole; P = .011). Seventeen patients (57%, CI 39%-72%) required less adenosine to achieve AV block on dipyridamole; six (20%) required more. AV block occurred at doses ≥25 mcg/kg in all patients. In pairwise comparison to prior testing off dipyridamole, no significant change occurred in AV block duration, frequency of cardiac ectopy, or incidence of reported symptoms. No atrial fibrillation/flutter occurred.
CONCLUSIONS
AV block often occurs at twofold lower adenosine doses in healthy young heart transplant recipients taking oral dipyridamole, compared with previous testing of this cohort off dipyridamole. Results suggest that initial dosing of 25 mcg/kg (maximum 0.8 mg) with stepwise escalation poses low risk of prolonged asystole on dipyridamole.
Topics: Adenosine; Adolescent; Anti-Arrhythmia Agents; Atrioventricular Block; Child; Child, Preschool; Dipyridamole; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Heart Transplantation; Humans; Male; Postoperative Complications; Prospective Studies; Tachycardia, Supraventricular; Young Adult
PubMed: 32157785
DOI: 10.1111/petr.13689 -
Clinical Cardiology Jan 1990Intravenous dipyridamole is a relative selective coronary vasodilator which, when combined with thallium-201, provides a useful technique to assess myocardial perfusion.... (Review)
Review
Intravenous dipyridamole is a relative selective coronary vasodilator which, when combined with thallium-201, provides a useful technique to assess myocardial perfusion. The intravenous dipyridamole is administered as an infusion at a rate of 0.14 mg/kg/min for 4 minutes. In the presence of significant coronary artery disease the increase of coronary blood flow is disproportionate between vessels with and without significant coronary lesions, providing the basis for detecting regional differences in flow using thallium-201. The test can be used alone or combined with low level exercise to increase test sensitivity. The test is safe when performed under medical supervision and when patient selection is done appropriately. Most of the side effects induced by dipyridamole infusion are well tolerated by patients and readily reversed with intravenous aminophylline and sublingual nitroglycerin. The average sensitivity and specificity of the dipyridamole thallium scintigraphy test from the major studies are 76% and 70%, respectively. The test is very useful in providing prognostic information in patients who are unable to exercise. A reversible thallium defect after dipyridamole infusion has been shown to be associated with significant mortality and morbidity in patients with documented or suspected coronary artery disease. The use of intravenous dipyridamole has been extended into other modalities of imaging, including 2-dimensional and Doppler echocardiography, to study functional changes in the left ventricular induced by the infusion of intravenous dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Coronary Disease; Dipyridamole; Drug Administration Schedule; Hemodynamics; Humans; Prognosis; Radionuclide Imaging; Thallium Radioisotopes
PubMed: 2404645
DOI: 10.1002/clc.4960130103 -
Journal of Medicinal Chemistry Aug 2007Dipyridamole (Persantine) is a clinically used vasodilator with equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2) inhibitory activity albeit less potent than...
Dipyridamole (Persantine) is a clinically used vasodilator with equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2) inhibitory activity albeit less potent than the prototype ENT1 inhibitor nitrobenzylmercaptopurine riboside (NBMPR). Dipyridamole is a good candidate for further exploration because it is a non-nucleoside and has a proven record of safe use in humans. A series of dipyridamole analogues were synthesized with systematic modification and evaluated as ENT1 inhibitors by flow cytometry. Compounds with much higher potency were identified, the best being 2,6-bis(diethanolamino)-4,8-diheptamethyleneiminopyrimido[5,4-d]pyrimidine (13) with a K(i) of 0.49 nM compared to a K(i) of 308 nM for dipyridamole. Compound 13 is similar in potency to the prototype potent ENT1 inhibitor NBMPR (0.43 nM). For the first time, a dipyridamole analogue has been identified that is equipotent with NBMPR. The SAR indicated that diethanolamine substituted analogues were more active than monoethanolamine compounds. Also, free hydroxyl groups are not essential for activity.
Topics: Cell Line, Tumor; Dipyridamole; Equilibrative Nucleoside Transporter 1; Flow Cytometry; Heterocyclic Compounds, 1-Ring; Humans; Pyrimidines; Structure-Activity Relationship
PubMed: 17636949
DOI: 10.1021/jm070311l -
Plastic and Reconstructive Surgery Feb 2020Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial...
Bone Tissue Engineering in the Growing Calvaria Using Dipyridamole-Coated, Three-Dimensionally-Printed Bioceramic Scaffolds: Construct Optimization and Effects on Cranial Suture Patency.
BACKGROUND
Three-dimensionally-printed bioceramic scaffolds composed of β-tricalcium phosphate delivering the osteogenic agent dipyridamole can heal critically sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, the authors implanted three-dimensionally-printed bioceramic/dipyridamole scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and dipyridamole concentration. Potential adverse effects on the growing suture were also evaluated.
METHODS
Bilateral calvarial defects (10 mm) were created in 5-week-old (approximately 1.1 kg) New Zealand White rabbits (n = 16 analyzed). Three-dimensionally-printed bioceramic scaffolds were constructed in quadrant form composed of varying pore dimensions (220, 330, and 500 μm). Each scaffold was coated with collagen and soaked in varying concentrations of dipyridamole (100, 1000, and 10,000 μM). Controls consisted of empty defects. Animals were killed 8 weeks postoperatively. Calvariae were analyzed using micro-computed tomography, three-dimensional reconstruction, and nondecalcified histologic sectioning.
RESULTS
Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p = 0.02). Large scaffold pores, 500 μm, coated in 1000 μM dipyridamole yielded the most bone growth and lowest degree of scaffold presence within the defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. Micro-computed tomographic and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all dipyridamole concentrations.
CONCLUSION
The authors present an effective pediatric bone tissue-engineering scaffold design and dipyridamole concentration that is effective in augmentation of calvarial bone generation while preserving cranial suture patency.
Topics: Animals; Bone Regeneration; Calcium Phosphates; Dipyridamole; Disease Models, Animal; Rabbits; Skull; Skull Fractures; Tissue Engineering; Tissue Scaffolds
PubMed: 31985634
DOI: 10.1097/PRS.0000000000006483 -
Cerebrovascular Diseases (Basel,... Aug 2010Increasing evidence suggests that beyond its antiplatelet properties, dipyridamole may have pleiotropic effects on other cells within the neurovascular elements of the...
BACKGROUND
Increasing evidence suggests that beyond its antiplatelet properties, dipyridamole may have pleiotropic effects on other cells within the neurovascular elements of the brain. In this experimental cellular study, we asked whether dipyridamole can ameliorate brain endothelial injury after exposure to inflammatory and metabolic insults.
METHODS
Human brain endothelial cells were grown in culture, and exposed to TNFalpha (continuously for 20 h) or subjected to oxygen-glucose deprivation (OGD; 6 h of insult followed by 18 h recovery). Expression of ICAM-1, VCAM-1 and PECAM-1 were measured by immunoblotting. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the conditioned media were quantified via zymography. MTT mitochondrial activity was measured to assess endothelial cell viability.
RESULTS
Exposure of human brain endothelial cells to TNFalpha (12.5-50 ng/ml) induced a clear increase in protein levels of ICAM-1, VCAM-1 and MMP-9. TNFalpha did not alter PECAM-1. Dipyridamole (1-5 muM) significantly attenuated ICAM-1 and MMP-9 levels after this inflammatory insult. No significant effects of dipyridamole were noted for VCAM-1. Six-hour OGD induced moderate endothelial cell death accompanied by a release of MMP-9. Dipyridamole significantly decreased MMP-9 levels and cell death after this metabolic insult.
CONCLUSIONS
These results suggest that dipyridamole may ameliorate brain endothelial injury after inflammation and/or metabolic insults. How these putative cellular mechanisms may relate to clinical outcomes and conditions in stroke patients remains to be elucidated.
Topics: Brain; Cell Hypoxia; Cell Line; Cell Survival; Cytotoxins; Dipyridamole; Endothelium, Vascular; Humans; Inflammation; Intercellular Adhesion Molecule-1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Phosphodiesterase Inhibitors; Platelet Endothelial Cell Adhesion Molecule-1; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1
PubMed: 20664263
DOI: 10.1159/000319072 -
Medicine Feb 2019Acute cerebral infarction (ACI) is one of the most commonly seen cerebral vascular disease and the current therapy options are not satisfied. Ginkgo leaf extract and...
Ginkgo leaf extract and dipyridamole injection as adjuvant treatment for acute cerebral infarction: Protocol for systemic review and meta-analysis of randomized controlled trials.
BACKGROUND
Acute cerebral infarction (ACI) is one of the most commonly seen cerebral vascular disease and the current therapy options are not satisfied. Ginkgo leaf extract and dipyridamole injection (GDI) is widely used as adjuvant therapy for ACI. However, there is no systemic review and meta-analysis published regarding the efficacy and safety of GDI. Herein, we describe the protocol of a proposed study aims to systemically evaluate the efficacy and safety of GDI in ACI patients.
METHODS
Five electronic databases (Medline, EMBase, Cochrane database, China National Knowledge Infrastructure, and Wanfang database) will be searched up to February 28, 2018. Randomized controlled trials (RCTs) meet the eligibility criteria will be identified and included. Data synthesis will be run using RevMan software after the data extraction and risk of bias assessment of included studies. The primary outcomes of this study are effective rate and adverse event rate.
RESULTS
This study will provide a high-quality synthesis of RCTs on the efficacy and safety of GDI as an adjuvant therapy in the treatment of ACI.
CONCLUSION
This systemic review and meta-analysis will provide high quality evidence to evaluate GDI as adjuvant therapy in patients with ACI.Registration: PEROSPERO CRD42018107112.
Topics: Acute Disease; Adjuvants, Pharmaceutic; Cardiovascular Agents; Cerebral Infarction; Clinical Protocols; Dipyridamole; Ginkgo biloba; Humans; Plant Extracts; Randomized Controlled Trials as Topic; Treatment Outcome; Meta-Analysis as Topic; Systematic Review as Topic
PubMed: 30813204
DOI: 10.1097/MD.0000000000014643 -
Arthritis Research & Therapy 2009Glucocorticoids are a mainstay of anti-inflammatory therapy, but significant adverse effects ultimately limit their utility. Previous efforts to design glucocorticoid...
INTRODUCTION
Glucocorticoids are a mainstay of anti-inflammatory therapy, but significant adverse effects ultimately limit their utility. Previous efforts to design glucocorticoid structures with an increased therapeutic window have focused on dissociating anti-inflammatory transcriptional repression from adverse effects primarily driven by transcriptional activation. An alternative to this medicinal chemistry approach is a systems biology based strategy that seeks to amplify selectively the anti-inflammatory activity of very low dose glucocorticoid in immune cells without modulating alternative cellular networks that mediate glucocorticoid toxicity.
METHODS
The combination of prednisolone and the antithrombotic drug dipyridamole was profiled using in vitro and in vivo models of anti-inflammatory activity and glucocorticoid-induced adverse effects to demonstrate a dissociated activity profile.
RESULTS
The combination synergistically suppresses release of proinflammatory mediators, including tumour necrosis factor-alpha, IL-6, chemokine (C-C motif) ligand 5 (RANTES), matrix metalloproteinase-9, and others, from human peripheral blood mononuclear cells and mouse macrophages. In rat models of acute lipopolysaccharide-induced endotoxemia and delayed-type hypersensitivity, and in chronic models of collagen-induced and adjuvant-induced arthritis, the combination produced anti-inflammatory activity that required only a subtherapeutic dose of prednisolone. The immune-specific amplification of prednisolone anti-inflammatory activity by dipyridamole did not extend to glucocorticoid-mediated adverse effects, including corticosterone suppression or increased expression of tyrosine aminotransferase, in vivo after repeat dosing in rats. After 8 weeks of oral dosing in mice, treatment with the combination did not alter prednisolone-induced reduction in osteocalcin and mid-femur bone density, which are markers of steroid-induced osteoporosis. Additionally, amplification was not observed in the cellular network of corticotroph AtT-20/D16v-F2 cells in vitro, as measured by pro-opiomelanocortin expression and adrenocorticotropic hormone secretion.
CONCLUSIONS
These data suggest that the multi-target mechanism of low-dose prednisolone and dipyridamole creates a dissociated activity profile with an increased therapeutic window through cellular network selective amplification of glucocorticoid-mediated anti-inflammatory signaling.
Topics: Animals; Anti-Inflammatory Agents; Dipyridamole; Drug Therapy, Combination; Glucocorticoids; Humans; Inflammation; Inflammation Mediators; Mice; Prednisolone; Rats; Rats, Inbred Lew
PubMed: 19171052
DOI: 10.1186/ar2602 -
Biochemistry. Biokhimiia Oct 2022Effect of dipyridamole (DIP) at concentrations up to 1 mM on fluorescent characteristics of light-harvesting complexes LH2 and LH1, as well as on conditions of...
Effect of dipyridamole (DIP) at concentrations up to 1 mM on fluorescent characteristics of light-harvesting complexes LH2 and LH1, as well as on conditions of photosynthetic electron transport chain in the bacterial chromatophores of Rba. sphaeroides was investigated. DIP was found to affect efficiency of energy transfer from the light-harvesting complex LH2 to the LH1-reaction center core complex and to produce the long-wavelength ("red") shift of the absorption band of light-harvesting bacteriochlorophyll molecules in the IR spectral region at 840-900 nm. This shift is associated with the membrane transition to the energized state. It was shown that DIP is able to reduce the photooxidized bacteriochlorophyll of the reaction center, which accelerated electron flow along the electron transport chain, thereby stimulating generation of the transmembrane potential on the chromatophore membrane. The results are important for clarifying possible mechanisms of DIP influence on the activity of membrane-bound functional proteins. In particular, they might be significant for interpreting numerous therapeutic effects of DIP.
Topics: Rhodobacter sphaeroides; Light-Harvesting Protein Complexes; Bacteriochlorophylls; Dipyridamole; Energy Transfer; Membrane Proteins; Chromatophores; Bacterial Proteins
PubMed: 36273882
DOI: 10.1134/S0006297922100078 -
Journal of Pharmacological Sciences Feb 2018Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs... (Comparative Study)
Comparative Study
Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs.
Topics: Anesthesia; Animals; Collateral Circulation; Coronary Circulation; Dipyridamole; Dogs; Dose-Response Relationship, Drug; Electrocardiography; Female; Hemodynamics; Infusions, Intravenous; Male; Models, Animal; Swine; Swine, Miniature
PubMed: 29398450
DOI: 10.1016/j.jphs.2018.01.002