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Dipyridamole thallium-201 scintigraphy for early risk stratification of patients after uncomplicated myocardial infarction.

OBJECTIVE: To determine the safety and prognostic value of dipyridamole thallium-201 scintigraphy performed in patients within three to five days of acute myocardial infarction, including those receiving thrombolytic treatment. DESIGN: A prospective study of dipyridamole thallium-201 scintigraphy in patients early after acute myocardial infarction. SETTING: University hospital. PATIENTS: 200 patients who were clinically uncomplicated at day 3 after infarction, 92 (46%) of whom had received thrombolysis. MAIN OUTCOME MEASURES: Incidence of cardiac death, non-fatal reinfarction, readmission to hospital for unstable angina, or non-elective revascularisation procedure within six months' follow up. RESULTS: No patient had a serious complication from the dipyridamole study. At six month follow up, 55 patients (28%) had suffered a defined cardiac event. Patients who received thrombolysis had the same extent of thallium-201 redistribution and the same occurrence of subsequent cardiac events as those not receiving thrombolysis. Patients who subsequently had an event had more myocardial segments showing thallium-201 redistribution than event free patients: 2.7 (SD 1.9) v 1.2 (1.4), respectively (p < 0.001). Among all clinical and scintigraphic variables, multivariate analysis identified the extent of thallium-201 redistribution as the only independent predictor of outcome (p < 0.001). Among 63 patients (32%) of the study cohort who showed more than two myocardial segments with thallium-201 redistribution, the adjusted risk ratio for a cardiac event was 7.5 (95% confidence interval 2.9 to 19.1) compared with patients without any redistribution. CONCLUSIONS: 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.

Aged↗

Intimal thickening in autogenous vein grafts in rabbits: influence of aspirin and dipyridamole.

The effects of three different platelet modifying regimens on the degree of intimal thickening of autogenous vein grafts in rabbits were measured one month after operation. Dipyridamole alone (2 mg/kg/6 h) had little effect on the intimal thickness of these rabbits compared with that of controls (mean (1 SEM) for treated animals: 72.0 (7.9) micron; controls: 63.6 (6.0) micron). High dose acetylsalicylic acid (40 mg/kg/24 h) plus dipyridamole (2 mg/kg/6 h) increased intimal thickening significantly (85.8 (6.0) v 63.6 (6.2) micron; p = 0.05, n = 17). Low dose acetylsalicylic acid (0.5 mg/kg/24 h) plus dipyridamole (2 mg/kg/6 h) also increased intimal thickening (79.0 (6.1) v 63.6 (6.0] micron but not to a significant degree. It has previously been shown in vitro that acetylsalicylic acid increases the area of an exposed subendothelial arterial surface covered by platelets. Such an effect may explain our finding of increased intimal thickening with high dose acetylsalicylic acid plus dipyridamole.

Animals↗

Effect of dipyridamole and 6-(2-hydroxy-5-nitro)-benzylthioguanosine on low-frequency-stimulated relaxation in the guinea pig taenia coli.

Isolated guinea pig taenia coli responded to electrical field stimulation at 0.3 s-1 with relaxation which was potentiated from 6 to 230% in the presence of 1-1.5 micron dipyridamole. However, no potentiation was seen in the presence of 10 micron 6-(2-hydroxy-5-nitro)-benzylthioguanosine (HNBTG), another more selective inhibitor of adenosine uptake. Both drugs effectively potentiated the relaxant response to low doses of added adenosine. When complete frequency-response curves were recorded in the range 0.1 to 5 s-1, neither dipyridamole nor HNBTG caused any shift of the curves, although a statistically significant increase in relaxation was again seen in the presence of dipyridamole at 0.3 s-1. Thus, the response of taenia coli to transmural stimulation is not modified by all concentrations of inhibitors of adenosine uptake and the limited effect seen with dipyridamole at 0.3 s-1 may be based on another unknown mechanism. No evidence for or against the purinergic nerve hypothesis can be derived from our experiments.

Adenosine↗

Tc-99m sestamibi cardiac SPECT imaging during coronary artery occlusion in humans: comparison with dipyridamole stress studies.

PURPOSE: To compare the magnitude of change in regional myocardial perfusion during dipyridamole stress with that during coronary occlusion. MATERIALS AND METHODS: The authors prospectively studied 14 men with more than 50% diameter stenosis in at least one major coronary artery. Same-day rest and dipyridamole technetium-99m sestamibi single photon emission computed tomography (SPECT) was performed 24 hours before coronary angioplasty. During angioplasty, while the vessel was occluded, 15 mCi(555 MBq) of tracer was injected, and SPECT studies were obtained 60 minutes later. Extent of regional perfusion abnormalities was estimated. RESULTS: Regional perfusion defect was greater during stress and occlusion than during rest (20%, P = .001 and 14%, P = .009, respectively). SPECT defect during coronary occlusion was similar to that obtained during pharmacologic stress with dipyridamole (53% vs 47%, P = .02). CONCLUSION: Tc-99m sestamibi SPECT with dipyridamole stress is a good predictor of the extent of perfusion abnormalities that occur during coronary occlusion and may facilitate estimation of the total myocardium in jeopardy from a stenotic lesion.

Adult↗

Dipyridamole myocardial perfusion tomography in patients with severe aortic stenosis.

UNLABELLED: Patients with aortic stenosis (AS) may have classic angina pectoris. The safety of exercise testing in adults with AS is controversial and, in fact, exercise testing in such patients is considered to be contraindicated especially in severe aortic stenosis (SAS). Furthermore, exercise testing has low specificity in uncovering coronary artery disease (CAD) in patients with AS, because the baseline ECG is frequently abnormal. We wished to assess the safety and diagnostic accuracy of dipyridamole stress myocardial perfusion tomography (DMPT) in the detection of CAD in patients with SAS. METHODS: The study included 30 patients with SAS (mean aortic valve area 0.57 +/- 0.09 cm(2)). All patients underwent dipyridamole myocardial perfusion scintigraphy (SPECT), coronary arteriography and catheterization, as well as Doppler echocardiography. Myocardial perfusion tomography was applied with (99m)Tc hexakis-2-methoxyisobutyl isonitrile (MIBI) by a single day rest-dipyridamole infusion protocol. Hemodynamic, electrocardiographic and clinical responses were compared with those of 50 control patients without AS. RESULTS: Hemodynamic responses during dipyridamole stress tests demonstrated no significant differences between the controls and the AS patients in the following parameters: systolic blood pressure, heart rate, rate-pressure product or incidence of headache, chest pain, dyspnea, flushing and dizziness. A reversible perfusion defect was observed in 10 patients with DMPT. The existence of coronary lesions was determined by coronary arteriography in 8 of 10 patients (sensitivity 100%, specificity 91%). CONCLUSION: The results showed that DMPT is well tolerated, even by patients with SAS and is of high diagnostic value in assessing CAD.

Aged↗

Dipyridamole specifically decreases platelet-derived growth factor release from platelets.

We previously reported that dipyridamole decreased platelet-derived growth factor (PDGF) levels in human serum by lowering the release of PDGF during blood clotting. In this study, we have shown that this effect is specific for dipyridamole, and is not shown in other anti-platelet drugs such as aspirin, trapidil or ticlopidine. In addition, dipyridamole has been shown to decrease the PDGF level selectively, but not the levels of other factors from alpha-granules in platelets (beta-thromboglobulin and platelet factor IV). These data indicate that dipyridamole may be an effective drug for preventing PDGF-related disorders.

Adult↗

Comparison of digital dipyridamole stress echocardiography and upright bicycle stress echocardiography for identification of coronary artery stenosis.

This study compared the diagnostic accuracy of dipyridamole (0.84 mg i.v./10 min) and bicycle stress echocardiography in 37 patients with inconclusive standard bicycle electrocardiography (ECG) tests; all underwent coronary angiography. Sensitivity for detection of coronary stenosis with dipyridamole echocardiography was 68% (21 of 31 patients), and for 1-, 2- and 3-vessel disease 56, 69 and 83%, respectively. Overall bicycle echocardiography sensitivity was 84%, and 78, 88 and 83% for patients with 1-, 2- and 3-vessel disease, respectively. Dipyridamole echocardiography was negative in all 6 patients with negative coronary angiography (specificity 100%), bicycle echocardiography was positive in 2 (specificity 67%). We conclude that dipyridamole echocardiography tends to be less sensitive in patients with mild disease, but is more specific than bicycle echocardiography.

Adult↗

Plasma serotonin and platelet aggregation during ischemia-reperfusion in dogs: effect of dipyridamole and coenzyme Q10.

Platelet aggregation and plasma serotonin were studied during ischemia-reperfusion of the small intestine in dogs. Blood was withdrawn from the superior mesenteric vein before and 1 h after ischemia, then 5, 30 and 60 min after reperfusion. Dipyridamole (5 mg/kg body weight) and coenzyme Q10 (CoQ10; 10 mg/kg body weight) were administered intravenously 5 min before reperfusion, following 1 h ischemia, in order to investigate their effects on platelet function and free serotonin. Ischemia-reperfusion resulted in an increased local free serotonin concentration together with an enhanced platelet response to ADP, collagen and arachidonic acid. Administration of dipyridamole and CoQ10 prior to reperfusion prevented, at least in part, augmented platelet activation and serotonin release. It appeared that dipyridamole was more potent than CoQ10. Our results may indicate a possible protective effect of dipyridamole on enhanced platelet activation during ischemia-reperfusion in dogs.

Animals↗

Dipyridamole therapy in the nephrotic syndrome.

Dipyridamole was used in 30 cases of nephrotic syndrome, mostly of intractable type. The results indicate that the drug therapy proved to be effective in decreasing urinary protein and controlling nephrotic condition in 40% of the cases after an initial period of treatment. Long-term results of the drug on urinary protein and on nephrotic condition were rated as good in 36.7 and 53.3%, respectively, of the cases treated. The exact mechanism of action of dipyridamole in the nephrotic syndrome is still obscure in many respects. However, the fact that the drug shares its anti-platelet action with the non-steroid anti-inflammatory drugs, e.g. aspirin and indomethacin, and the rapidity with which it produces its urinary protein-decreasing effect, strongly suggests that it inhibits the release of vasoactive amines and other chemical mediators from blood platelets. As far as the present study is concerned, adverse side effects of dipyridamole were few or minimal, even when the drug used in large doses over a prolonged period of time. From these results it is considered that dipyridamole provides a new remedy which is worthy of trying in nephrotic syndrome as a means of reducing the requirement of steroids and immunosuppressive drugs.

Adolescent↗

Reduction of indium-111 platelet deposition on Dacron vascular grafts in humans by aspirin plus dipyridamole.

Aspirin plus dipyridamole reduces platelet accumulation on short-term Dacron vascular grafts in man. To determine whether drug inhibition of platelet deposition is sustained on older grafts, we studied 18 men aged 41 to 87 years who had Dacron aortic bifurcation grafts in place a mean of 43.4 months (range 9.8 to 121.0) before and during short-term therapy with aspirin (325 mg tid) plus dipyridamole (75 mg tid). During both the baseline and drug studies, indium-111 (111In) platelet deposition was quantitated by two techniques, standard planar imaging performed at 24, 48, and 72 hr after injection of platelets and single photon emission computed tomographic imaging performed at 24 and 72 hr after injection. All analyses were performed in a blinded fashion. On both the planar and tomographic images, platelet accumulation on the graft was quantitated by a graft/blood ratio that compared activity in the graft to simultaneously collected whole blood 111In platelet activity. Aspirin plus dipyridamole reduced the tomographic graft/blood ratio at 24 hr (20.6 +/- 3.5 vs 17.3 +/- 2.5) (+/-SEM) and at 72 hr (29.0 +/- 4.8 vs 25.0 +/- 4.1) after injection of platelets (p = .02). Dacron vascular grafts. Similarly, the planar graft/blood ratio was reduced at 24 hr (2.7 +/- 0.5 vs 2.4 +/- 0.5), 48 hr (3.7 +/- 0.9 vs 3.1 +/- 0.7), and 72 hr (4.0 +/- 0.9 vs 3.6 +/- 0.8) (p = .04). We conclude that aspirin (325 mg tid) plus dipyridamole (75 mg tid) reduces platelet accumulation on long-term Dacron vascular grafts.

Adult↗

Usefulness of high-dose dipyridamole echocardiography test in coronary angioplasty.

Seventy-four consecutive patients with angina undergoing single-lesion percutaneous transluminal coronary angioplasty were evaluated with high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiography test (DET) before angioplasty and when possible, afterward. Angioplasty was clinically or angiographically successful in 63 patients and unsuccessful in 11. Before the procedure, 69 patients had a positive DET. Of these 69 patients, six with clinicall unsuccessful angioplasty had a dipyridamole time (i.e., the time from the onset of dipyridamole infusion to development of asynergy) lower than the 63 patients with clinically successfully angioplasty (4.2 +/- 2.9 vs. 7.0 +/- 2.9 minutes, mean +/- SD, p less than 0.01). In the five patients with angiographically unsuccessful angioplasty (residual stenosis diameter, greater than 50%), coronary stenosis decreased from 89 +/- 10 to 69 +/- 22 (p = NS); DET was positive in all five before and in four of the five after the procedure (100% vs. 80%, p = NS). In the 63 patients with angiographically successful angioplasty, coronary stenosis diameter was reduced from 85 +/- 9% to 30 +/- 10% (p less than 0.01). DET was positive in 58 patients before and in only 16 after the procedure (92% vs. 25%, p less than 0.01). In the 16 patients with positive DET, before and after angioplasty, dipyridamole time increased from 5.6 +/- 2.2 before to 7.3 +/- 2.4 minutes immediately after the procedure (p less than 0.05). After an average follow-up time of 10.8 +/- 5.9 months, angina recurred in eight of 47 patients with negative DET after angioplasty and in 11 of 16 patients with positive DET (17% vs. 69%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group.

BACKGROUND: This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS: A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group. CONCLUSIONS: We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function.

Administration, Oral↗

The effect of combined aspirin and dipyridamole therapy on thrombus formation in an arterial thrombogenic lesion in the dog.

We investigated the potential of aspirin and dipyridamole in combination to inhibit thrombus formation by comparing endarterectomized segments of 20 dog carotid arteries in animals treated with pre- and post-operative aspirin and dipyridamole to 20 arteries from untreated animals and 20 arteries from animals receiving intra-operative heparin. The temporal profile of thrombus formation was assessed by means of angiography, light microscopy, and scanning electron microscopy at time intervals ranging from 30 minutes to three months from the time of surgery. All of the aspirin-dipyridamole vessels remained patent and only one had significant gross thrombus formation. This contrasted to six occlusions and six significant gross thrombi in the control group and one occlusion and six significant gross thrombi in the heparin group. The combination of oral aspirin and dipyridamole minimizes thrombus formation in the highly thrombogenic lesion created by carotid endarterectomy in the dog.

Animals↗

Dipyridamole increases oxygen-glucose deprivation-induced injury in cortical cell culture.

BACKGROUND AND PURPOSE: Adenosine transport inhibitors attenuate ischemic central neuronal damage in vivo, but the locus of this protective action is presently unknown. To help address the question of whether adenosine transport inhibitors have a protective effect directly on brain parenchyma, we tested the effect of the adenosine transport inhibitor dipyridamole on neuronal loss induced by oxygen-glucose deprivation in vitro. METHODS: Murine cortical cultures were exposed to combined oxygen and glucose deprivation, N-methyl-D-aspartate, or kainate. The extracellular concentrations of glutamate and adenosine were measured by high-performance liquid chromatography; neuronal cell death was assessed by morphological examination and measurement of lactate dehydrogenase release. RESULTS: Cultures exposed to oxygen-glucose deprivation for 30 to 75 minutes exhibited an insult-dependent increase in extracellular adenosine, followed shortly by an increase in extracellular glutamate and 24 hours later by neuronal death. Addition of the A1 receptor antagonist 8-cyclopentyltheophylline during oxygen-glucose deprivation enhanced both glutamate release and neuronal damage. Addition of 10 mumol/L dipyridamole decreased extracellular adenosine and also enhanced extracellular glutamate and neuronal death. In contrast, dipyridamole increased the levels of extracellular adenosine stimulated by N-methyl-D-aspartate or kainate. CONCLUSIONS: These results are consistent with the idea that endogenous adenosine has a neuroprotective effect directly on cortical cells exposed to oxygen-glucose deprivation. However, inhibition of adenosine transport with dipyridamole was surprisingly not an effective strategy for enhancing this protective effect. The beneficial effects of adenosine transport inhibitors observed in vivo may be mediated indirectly--for example, by effects on the vasculature.

Adenosine↗

Safety of echo-dipyridamole test in elderly patients with coronary artery disease.

The authors prospectively studied the feasibility and safety of high-dose dipyridamole echocardiography in 166 patients (77 younger and 89 elderly patients) referred for clinical evaluation of coronary artery disease. Echocardiographic examinations were adequate for analysis of parameters considered in 135 of the 166 patients (81.3%; 73 elderly, 62 younger patients). The feasibility of dipyridamole echocardiography test was 80.5% in young and 82% in elderly patients (P = ns). The incidence of side effects during dipyridamole echocardiography was similar in the two groups, except for dyspnea, which was observed in 20.5% of older and 3.2% of younger patients (p < 0.05). These data demonstrate that the dipyridamole test combined with echocardiographic monitoring of regional myocardial contractility may be considered a valid noninvasive method of evaluating coronary artery disease in the elderly.

Adult↗

Experimental retinopathy of prematurity: angiostatic inhibition by nimodipine, ginkgo-biloba, and dipyridamole, and response to different growth factors.

PURPOSE: To investigate whether commonly used vasodilating drugs ameliorate angiogenesis in experimental retinopathy of prematurity (ROP), and to study the response of these drugs to different growth factors. METHODS: We used a rat and mouse model of oxygen-induced ischemic retinopathy. Animals were treated with nimodipine, gingko-biloba and dipyridamole intraperitoneally starting the day before exposure to room air (day 1). Controls were injected with vehicle solution only. Eyes were processed histopathologically with serial sections and neovascularization was measured by counting the nuclei within the retinal internal limiting membrane, by a masked observer. Retinal and vitreous tissues were assayed by ELISA for VEGF, PDGF and TGFbeta2. RESULTS: Nimodipine significantly inhibited the growth of new vessels in rats. The number of nuclei was 310 +/- 69 in the control group (n:14) and 121 +/- 53 in the treated ones (n:14), (p<0.0005). Similar results were found with ginkgo-biloba extracts: 344 +/- 53 (n:15) in controls, and 136 +/- 29 (n:11) in treated ones (p<0.0005), and with dipyridamole: 303 +/- 69 (n:13) in controls, and 131 +/- 48.5 in treated rats (p<0.0005). Results were similar in mice. 186 +/- 45 (n:7) nuclei counted in controls against 90 +/- 25 (n:6) for dipyridamole treated (p<0.0005); and 81 +/- 21 for ginkgo-biloba treated animals (p<0.0005). A gradual, very significant increase in VEGF values in response to relative hypoxia (room air) contrasted with the significant inhibition noted both with ginkgo-biloba extracts and dipyridamole. TGFbeta2 and PDGF both showed a gradual increase in relative hypoxia at days 2 and 4 of room air (p<0.0005). Treated animals showed marked inhibition of the three growth factors. CONCLUSIONS: All three drugs markedly inhibited angiogenesis in experimental ROP. Growth factors were elevated in hypoxic conditions. Treated animals showed significant decreases of PDGF, VEGF, and TGFbeta2 in retinal and vitreous tissues.

Animals↗

Portable-type signal-averaged electrocardiography with dipyridamole to detect patients with coronary artery disease.

BACKGROUND: In a retrospective study portable-type signal-averaged electrocardiography (SAECG) with dipyridamole stress was found to identify patients with coronary artery disease (CAD) at their bedside with high sensitivity and specificity, so the utility of this method was prospectively investigated in the present study. METHODS AND RESULTS: Standard 12-lead QRS wave SAECG was performed before and after dipyridamole stress at the bedside in 71 patients with chest pain (43 males, mean age 63 +/-9 years). The filtered QRS duration (fQRSd) before and after dipyridamole stress was determined by multiphasic oscillation method for each of the standard 12 leads, and the maximal value of changes in fQRSd (MAX DeltafQRSd) among the 12 leads was determined. The positive test was defined as MAX DeltafQRSd >or=5 ms, and negative as MAX DeltafQRSd <5 ms based on the previous study. Selective coronary arteriography was performed next. In the positive group (n=31), 25 patients had significant stenosis of the coronary artery and 6 did not. In the negative group (n=40), 5 patients had significant stenosis and 35 did not. The sensitivity, specificity, positive predictive accuracy and negative predictive accuracy for CAD detection by SAECG was 83%, 85%, 81% and 88%, respectively. CONCLUSIONS: Dipyridamole-stress portable SAECG is useful for detecting CAD at the patient's bedside with high sensitivity and specificity.

Adult↗

Detection of coronary artery stenosis by dipyridamole radionuclide ventriculography.

We assessed the usefulness of dipyridamole radionuclide ventriculography for detecting significant coronary artery stenosis in 89 patients who were undergoing cardiac catheterization. Radionuclide ventriculography was performed before and after the infusion of dipyridamole (0.56 mg/kg). The end-diastolic regions of interest of the left ventricle were divided into 5 sectors for calculation of the regional ejection fractions. Results were considered to be positive when the regional ejection fraction decreased by more than 5% after the infusion of dipyridamole. The presence of significant coronary artery stenosis (> 75%) was demonstrated by arteriography in 49 patients and was absent in 40 patients. A decrease in the regional ejection fraction greater than 5% was observed in 41 (84%) of the 49 patients with significant coronary artery stenosis and in 2 of the 40 without significant coronary stenosis. The sensitivity and specificity of this method for detecting significant coronary artery stenosis were 84% and 95%, respectively. We conclude that a decrease in the radionuclide-determined regional ejection fraction after the infusion of dipyridamole reflects left ventricular dysfunction and is a sensitive and specific indicator of significant coronary artery stenosis.

Adult↗