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PubMed2000

Dipyridamole administration at the end of an insufficient exercise Tc-99m MIBI SPECT improves detection of multivessel coronary artery disease in patients with previous myocardial infarction.

To demonstrate that the administration of dipyridamole at the end of an insufficient maximal subjective exercise test can improve the diagnostic accuracy of single-photon emission computed tomography in patients with previous myocardial infarction, 209 consecutive patients were studied with technetium-99m methoxyisobutyl isonitrile single-photon emission computed tomography and coronary angiography. Patients were divided in 3 groups: group 1, 107 patients with sufficient exercise testing; group 2, 55 patients with insufficient exercise testing; group 3, 47 patients with insufficient exercise testing in whom intravenous dipyridamole (0.56 mg/kg over 4 minutes) was administered at the end of exercise. In groups 1 and 3 the sensitivity values for the diagnosis of multivessel disease were significantly higher (80% and 76%, respectively) than those in group 2 (59% [p = 0.009 and p = 0.02, respectively]). Specificity and predictive values were not different among the 3 groups. Thus, in patients with previous infarction in whom adequate levels of exercise could not be achieved, dipyridamole administration at the end of exercise significantly increased the sensitivity for diagnosing multivessel disease.

Cardiac Catheterization↗
PubMed1995

Symptom-limited arm exercise increases detection of ischemia during dipyridamole tomographic thallium stress testing in patients with coronary artery disease.

Exercise combined with dipyridamole during thallium stress testing in patients with coronary artery disease (CAD) increases the frequency of angina and ischemic ST changes in the electrocardiogram. Evidence for an increase in thallium abnormalities has been inconclusive. We prospectively examined 54 consecutive patients who underwent coronary angiography and tomographic thallium with dipyridamole (0.57 mg/kg) alone and combined with symptom-limited dynamic arm exercise. Most patients presented with a history of chest pain and 49 had angiographic evidence of significant coronary stenosis (50% diameter narrowing). Thallium abnormalities were scored blindly by consensus. The number of abnormal segments (total and ischemic) and indexes of left ventricular dysfunction, such as increased lung uptake or ischemic dilation, were compared in the 49 patients with CAD. During arm exercise more patients had evidence of ischemia (39 vs 30; p < 0.001), and the number of ischemic segments increased significantly from 1.3 +/- 1.5 to 2.5 +/- 2.2 (p < 0.001). There was also a significant increase in the indexes of left ventricular dysfunction, ischemic dilation (10 vs 4 patients; p < 0.03) and increased lung uptake (16 vs 5 patients; p < 0.001). Patients who exercised had increased thallium evidence of extent and severity of ischemia and more frequent indexes of left ventricular dysfunction. Thus, symptom-limited arm exercise improves detection of extent and severity of ischemia in patients with CAD undergoing dipyridamole thallium stress testing.

Aged↗
PubMed1987

Prevention of recurrent idiopathic fetal growth retardation by low-dose aspirin and dipyridamole.

In a controlled, nonrandomized trial a treatment group of 24 multigravid women with a history of at least two previous pregnancies, all complicated by idiopathic fetal growth retardation and placental infarction, received 1 to 1.6 mg/kg aspirin and 225 mg dipyridamole daily from 16 to 34 weeks' gestation in a total of 30 pregnancies. The end-point measure of the study was birth weight related to gestational age. Results obtained in the treatment group were compared with those in 27 pregnancies of a control group of 24 multigravid women with a similar history of recurrent fetal growth retardation who received comparable antenatal care without low dose aspirin and dipyridamole. Fetal growth retardation occurred in 61% of the control pregnancies and in only 13% of treated pregnancies; severe fetal growth retardation was not observed in treated pregnancies, but it occurred in 27% of the control group. In treated women, platelet cyclo-oxygenase activity was suppressed to 5% to 10% of its pretreatment level, but no effect on vascular prostacyclin production was demonstrated. Treatment did not produce adverse effects in mothers or infants. Low-dose aspirin and dipyridamole direct prostacyclin/thromboxane A2 balance in pregnancy to the dominance of prostacyclin and may thus prevent idiopathic uteroplacental insufficiency and fetal growth retardation in high-risk patients.

Adult↗
PubMed2000

Ecto-nucleotidase of cultured rat superior cervical ganglia: dipyridamole is a novel inhibitor.

Based on studies of agonist potencies on intact rat superior cervical ganglia, it has been suggested that this ganglion possesses distinct receptors for purine and pyrimidine nucleotides. However, the potency of an agonist is dependent upon whether it is susceptible to extracellular metabolism by the tissue. The aim of this investigation was to study the metabolism of uridine or adenosine nucleotides and nucleosides and the effects of dipyridamole and an ecto-ATPase inhibitor ARL 67156 (6-N, N-diethyl-D-beta-gamma-dibromomethylene-ATP) on their metabolism. Adenosine- and uridine-5'-triphosphates (ATP and UTP) were catabolised by cultured rat superior cervical ganglia, to their di- and monophosphates. Both ATP and UTP breakdown was significantly inhibited by dipyridamole (10 mcM), whereas ARL 67156 (100 mcM), was a weaker inhibitor of ATP degradation and inhibited UTP breakdown by approximately 40%. Metabolism of ATP and UTP by cultured rat superior cervical ganglia was reduced after treatment with cytosine-beta-arabinoside, suggesting that non-neuronal cells along with neuronal cells contribute to their breakdown. In conclusion, these results indicate that rat superior cervical ganglia possess ecto-nucleotidases capable of catabolising purine and pyrimidine nucleotides to their nucleosides, and that dipyridamole is a potent inhibitor of ecto-nucleotidase activity.

5'-Nucleotidase↗
PubMed2000

[Results of myocardial scintigraphy with 99mTc-tetrofosmin and dipyridamole administration in patients diagnosed of microvascular angina].

The objective of the study was to evaluate the results of the myocardial scintigraphy with 99mTc-tetrofosmin (Tc-Tf) and pharmacological stimulation with dipyridamole in patients diagnosed of microvascular angina. The study population is made up of 50 patients discharged with the diagnosis of microvascular angina who had undergone Tc-Tf-dipyridamole. Clinical and electrical positivity appeared in 40% and 12% of the patients, respectively. Myocardial perfusion defects were found in 35 patients (70%), and were reversible in 21 (60%), fixed in 11 (21%), and combined in 3 (9%). Abnormalities were inferior, anteroseptal and lateral in 21, 18, and 2 patients, respectively. Patients with a positive exercise treadmill test, compared with those with a negative one, had more frequent perfusion abnormalities (91% vs 50%, p = 0.0327) and myocardial ischemia (64% vs 20%, p = 0.392). Women, in comparison with men, had angina (56% vs 22%, p = 0.013), and anteroseptal perfusion abnormalities (26% vs 4%, p = 0.028) more frequently. On the contrary, men had inferior perfusion abnormalities more frequently (57% vs 30%, p = 0.057). Thus, Tc-Tf-dipyridamole shows perfusion abnormalities in 70% of patients with microvascular angina (91% in patients with a positive exercise treadmill test). Scintigraphic pattern may be partially conditioned by gender in these patients.

Coronary Circulation↗
PubMed1982

Is dipyridamole an angiogenic agent?

Dipyridamole, a potent inhibitor of the nucleoside transport into cells, has recently been reported to stimulate the proliferation of capillary endothelial cells in the heart and skeletal muscle of rats following long-term treatment. We tested this drug on cultured calf aortic endothelial cells and obtained no evidence that dipyridamole is able to stimulate directly the proliferation and migration of these cells. By using the chorioallantoic membrane model we observed that the pharmaceutical preparation Curantyl induces vascular responses almost regularly. This effect, however, was found to be dependent on the high concentration of hydrogen ions in this preparation and could be prevented by increasing the pH value. A direct angiogenic effect of dipyridamole could not be demonstrated on the CAM.

Allantois↗
PubMed1983

The effects of dipyridamole on TXA2 formation by horse platelet microsomes.

The effects of dipyridamole on thromboxane A2 formation by horse platelet microsomes were studied in comparison with those of imidazole, a prototype inhibitor of TXA2 synthetase and nifedipine, a calcium antagonistic vasodilator. Thromboxane A2 was synthesized by incubating PGH2 with horse platelet microsomes and was assayed on the superfused rabbit aorta. Dipyridamole induced as strong an inhibition of TXA2 synthesis as imidazole, while nifedipine was without effects. The possible beneficial clinical outcomes of this effect of dipyridamole are discussed.

Animals↗
PubMed1980

High-performance liquid chromatographic analysis of dipyridamole in plasma and whole blood.

A rapid, sensitive, and specific high-performance liquid chromatographic method is described for the quantitative analysis of dipyridamole in plasma and whole blood. The method involves a single extraction of an alkalinized sample with diethyl ether followed by evaporation of the organic solvent and ion-pair chromatography using fluorescence detection. The lower limit of sensitivity for dipyridamole is 1 ng/ml. Concentrations of dipyridamole between 1 and 500 ng per sample are measured with an average coefficient of variation of 4.5% in plasma and 7.4% in whole blood.

Chromatography, High Pressure Liquid↗
PubMed2001

Development and characterization of cross-linked poly(malate) microspheres with dipyridamole.

Biodegradable cross-linked microspheres containing up to 63 wt.% of the active substance were obtained in a polycondensation process between D,L-malic acid and the tetrahydroxy compound dipyridamole. The in vitro release mechanism from biodegradable cross-linked microspheres has been studied. It was found that dipyridamole was released due to two-step hydrolysis of the ester bonds of the network. Initially, the only product of the hydrolytic degradation was found to be an oligomeric ester fraction with M(w)=1000 Da. The release of the free drug started after 8 days due to a further hydrolysis of the oligomers in solution. It was found that blood plasma enzymes in rats did not affect the hydrolytic processes. Biodegradable poly(malate) microspheres containing an anti-aggregating agent dipyridamole can be considered as a novel drug delivery system for a prolonged period of time implying a future parenteral application.

Animals↗
PubMed1997

Spectrofluorometric estimation of aspirin and dipyridamole in pure admixtures and in dosage forms.

Aspirin and dipyridamole in pure admixtures and in dosage forms have been estimated by spectrofluorometry. Aspirin (2-12 mcg ml-1) was estimated in 1% v/v glacial acetic acid in chloroform using 246 and 345 nm for excitation and emission respectively. Dipyridamole (2-12 mcg ml-1) has been estimated in chloroform using 420 nm for excitation and 475 nm for emission. The non-interference of the excipients as well as the drugs in the estimation of each other, as evidenced by the results, indicate that this method may be used for the routine estimation of aspirin and dipyridamole in tablet preparations.

Aspirin↗
PubMed2003

Acute beta-blockade reduces the extent and severity of myocardial perfusion defects with dipyridamole Tc-99m sestamibi SPECT imaging.

OBJECTIVES: The goal of this study was to examine the effect of acute beta-blockade on dipyridamole Tc-99m sestamibi myocardial perfusion imaging (DMPI). BACKGROUND: Studies suggest that antianginal drugs may reduce the presence and severity of myocardial perfusion defects with dipyridamole stress. However, there are no data regarding specific drugs. METHODS: Patients with catheterization-proven coronary artery disease (CAD) were enrolled in this prospective, double-blind, placebo-controlled study and randomly assigned to DMPI after placebo, low-dose metoprolol (up to 10 mg), and high-dose metoprolol (up to 20 mg). Patients underwent one Tc-99m sestamibi study at rest on a separate day. The interval between DMPI studies was <or=14 days. Images were interpreted by three observers blinded to clinical data using a 17-segment, five-point model. For each image, a summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were calculated (SDS = SSS - SRS). Images with an SSS <4 were considered normal. RESULTS: Twenty-one patients completed all four Tc-99m sestamibi studies. The sensitivity of DMPI for detection of CAD was 85.7% with placebo versus 71.4% with low- and high-dose metoprolol. In comparison with placebo, the SSS was significantly lower (p < 0.05) with low- and high-dose metoprolol (12.0 +/- 10.1 vs. 8.7 +/- 9.0 and 9.3 +/- 10.6, respectively). The SDS also was significantly lower (8.4 +/- 8.8 with placebo vs. 5.0 +/- 6.7 [p < 0.001] and 5.4 +/- 7.9 [p < 0.01] with low- and high-dose metoprolol, respectively). CONCLUSIONS: The presence and severity of CAD may be underestimated in patients receiving beta-blocker therapy undergoing dipyridamole stress myocardial perfusion imaging.

Adrenergic beta-Antagonists↗
PubMed1988

Clinical significance of perfusion defects by thallium-201 single photon emission tomography following oral dipyridamole early after coronary angioplasty.

The clinical significance of myocardial perfusion defects present early after angiographically successful percutaneous transluminal coronary angioplasty was assessed in 53 patients using thallium-201 single photon emission computed tomography combined with pharmacologic vasodilation induced by a large dose (300 mg) of orally administered dipyridamole. Myocardial tomographic images were obtained at a mean of 20 +/- 6 h (SD) before and 2.9 +/- 2.7 days after angioplasty. Before angioplasty, 15 (28%) of the 53 patients developed angina after dipyridamole administration, in contrast to only 3 (7.5%) of 40 patients after angioplasty (p less than 0.001). The mean percent luminal area stenosis decreased from 93 +/- 6% before angioplasty to 34 +/- 17% after angioplasty (p less than 0.001). Myocardial perfusion defects, present in 49 (93%) of the 53 patients before angioplasty, were reversible in 44 patients (83%), all of whom underwent dilation of arteries supplying the ischemic areas. After angioplasty, 26 (65%) of 40 patients had no ischemic defects, whereas 14 (35%) of the patients still had an ischemic defect in the vascular territory of the dilated artery. After a mean follow-up period of 21.7 months, 13 (33%) of 39 patients developed restenosis, 10 of whom had an ischemic defect early after angioplasty. Restenosis developed in 10 (71%) of 14 patients with an ischemic defect after angioplasty, but in only 3 (11.5%) of the patients without an ischemic defect (p = 0.007). In conclusion, thallium-201 tomography after oral dipyridamole affords convenient assessment of the physiologic significance of coronary stenosis present before angioplasty and the residual stenosis after angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1999

Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. Echo-Persantine International Cooperative (EPIC) and Echo-Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: The study compared the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease. BACKGROUND: Extensive information is available on the relative diagnostic accuracy of the two tests assessed in a head-to-head fashion, whereas comparative data on their prognostic yield are largely preliminary to date. METHODS: Dipyridamole (up to 0.84 mg/kg over 10 min) atropine (up to 1 mg over 4 min) (DIP) and dobutamine (up to 40 microg/kg/min)-atropine (1 mg over 4 min) (DOB) stress tests were performed in 460 patients with known or suspected coronary artery disease. Patients were followed up for 38+/-21 months. RESULTS: The DIP was negative in 253 and positive in 207 patients. The DOB was negative in 242 and positive in 218 patients. During the follow-up, there were 80 cardiac events. For all cardiac events, the negative and positive predictive value were 83% and 17% for DOB, 84% and 19% for DIP, respectively (p = NS). Considering only cardiac death, by univariate analysis Wall-Motion Score Index (WMSI) at DIP peak dose (chi-square 13.80, p<0.0002) was the strongest predictor, followed by WMSI DOB (chi2 = 8.02, p<0.004) and WMSI at rest (chi2 = 6.85, p<0.008). By stepwise analysis, WMSI at DIP peak dose was the most important predictor (RR [relative risk] 7.4, p<0.0001). CONCLUSIONS: In patients at low-to-moderate risk of cardiac events, pharmacological stress echocardiography with either dobutamine or dipyridamole allows effective and grossly comparable, risk stratification on the basis of the presence, severity and extension of the induced ischemia.

Aged↗
PubMed1999

Medium effects on the antioxidant activity of dipyridamole.

Very strong medium effects have been observed when testing the antioxidant activity of dipyridamole (DP) in different media such as benzene, tert-butanol, methanol solutions and egg yolk lecithin unilamellar and multilamellar vesicles. Actually, dipyridamole behaves as a very poor antioxidant in benzene while its ability to inhibit the lipid peroxidation reaction increases with increasing solvent polarity, being the highest in lipid vesicles. This behavior can not be rationalized on the basis of the classical chain breaking mechanism which operates in the case of phenolic and amine antioxidants and involving the transfer of a hydrogen atom to peroxyl radicals. An explanation is instead given in terms of an electron transfer reaction which leads to the oxidation of DP by the chain carrying peroxyl radical to give the dipyridamole cation radical, DP+*, and the peroxyl anion LOO-, and whose rate constant is expected to increase in strongly polar media. EPR and electrochemical data supporting this interpretation have been collected.

Antioxidants↗
PubMed2001

A flow-through optosensing device with fluorimetric transduction for rapid and sensitive determination of dipyridamole in pharmaceuticals and human plasma.

A flow-through optosensor with fluorimetric transduction has been prepared for the sensitive and selective determination of dipyridamole in aqueous solutions and biological fluids. The method is based on a monochannel flow-injection analysis system using Sephadex QAE A-25 resin, placed into a Hellma 176-QS fluorimetric flow-through cell, as an active sorbing substrate. The native fluorescence of dipyridamole fixed on the solid sorbent is continuously monitored at wavelengths of 305 and 490 nm for excitation and emission, respectively. After obtaining the maximum fluorescence intensity, the eluent solution (KH(2)PO(4)/NaOH buffer solution, c(T)=0.05 mol l(-1), pH 6.0) is allowed to reach the flow cell, the analyte is removed, and the resin support is regenerated. When an NaOH (10(-4) mol l(-1))/NaCl (0.1 mol l(-1)) solution is used as carrier solution, at a flow-rate of 1.56 ml min(-1), the sensor responds linearly in the measuring range of 10-500 microg l(-1) with a detection limit of 0.94 microg l(-1) and a throughput of 22 samples per hour (300 microl of sample volume). The relative standard deviation for ten independent determinations (200 microg l(-1)) is less than 0.82%. The method was satisfactorily applied to the determination of dipyridamole in pharmaceutical preparations and human plasma.

Chemistry, Pharmaceutical↗
PubMed2000

Doppler monitoring of the vascular resistance in the lower limbs during dipyridamole test in preparation for myocardial tomoscintigraphy.

OBJECTIVE: the aim of this work was to quantify the intensity of the vasodilation induced by dipyridamole used to simulate a stress test during a myocardial tomoscintigraphy. METHODS: Doppler measurements of the femoral artery and the thoracic aorta were made on 26 patients (11 men, 15 women), using transducers attached to the skin, measurements being performed every 2 min during the 10 min of the stress test. The following parameters were measured: (a) the vascular resistance index of the lower limbs defined as R(fa)=D/S with S and D, respectively, the maximum amplitude of the systolic wave and the maximum amplitude of the diastolic reflux measured on the Doppler femoral spectrogram; (b) the aortic and femoral blood flows obtained from the mean velocity on the Doppler spectrogram. RESULTS: 14 of the 26 patients (54%) showed a significant vasodilation (i.e. a decrease of R(fa) of more than 10%). Eighty-seven percent of the patients with a positive myocardial scintigraphy showed a vasodilation. Sixty-six percent of patients who had prior vasodilator treatment showed no vasodilation. A slight decrease in blood pressure was observed for vasodilated patients but also for non-vasodilated patients. The aortic flow increased slightly for all patients. CONCLUSIONS: Doppler monitoring of femoral vascular resistance is a useful method for quantifying the dipyridamole-induced vasodilation, and hence the stress level upon which the diagnostic efficiency of myocardial scintigraphy is depending. Our study demonstrates that testing with dipyridamole was inconclusive in 66% of patients who had already vasodilator treatment.

Aorta, Thoracic↗
PubMed1993

Cardiac risk stratification using dipyridamole myocardial perfusion imaging and ambulatory ECG monitoring prior to vascular surgery.

Both dipyridamole myocardial perfusion imaging (cardiolite) and ambulatory ECG monitoring (Holter) for silent ischaemia have been found to be useful for stratification of cardiac risk in patients undergoing vascular surgery. The purpose of this study was to compare the diagnostic accuracy of these two non-invasive tests for prediction of perioperative cardiac events. One hundred patients (86 males, 14 females; mean age 67 +/- 8 years) underwent out-patient 48 h Holter monitoring and cardiolite imaging prior to vascular surgery (70 abdominal aortic aneurysm, 21 aortobifemoral, nine femoralpopliteal grafts). Ischaemia on Holter was defined as one or more episodes of ST segment depression 1 mm or greater, lasting 1 min or longer. Myocardial perfusion imaging was carried out with the high dose dipyridamole protocol (0.84 mg/kg), cardiolite and planar imaging. Ischaemia was defined as a segmental perfusion abnormality following dipyridamole with improved perfusion on rest imaging. Holter was positive for ischaemia in 34/100 patients (34%). Cardiolite scans were positive for ischaemia in 30/100 patients (30%). Perioperative myocardial infarction occurred in nine patients (two cardiac deaths). [table: see text] The diagnostic accuracy of the two tests was similar, with a low positive predictive value of 15-20%, and an extremely high negative predictive value of 94-96%. The event rate in patients with both tests negative was 2/48 (4.2%), with only one test positive 3/40 (7.5%) and with both tests positive 4/12 (33%). A reasonable approach to risk stratification would be to obtain either a Holter or cardiolite scan initially.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The value of perioperative clinical indexes and dipyridamole thallium scintigraphy for the prediction of myocardial infarction and cardiac death in patients undergoing vascular surgery.

BACKGROUND: Dipyridamole thallium scintigraphy has previously been shown to have predictive value for both perioperative and late cardiac events in patients undergoing vascular surgery. However, despite the prognostic utility of this technique, the relative importance of clinical factors and scintigraphic information is not well known. The purpose of this study was to evaluate the value of commonly used clinical risk indexes, composed of historic variables, and dipyridamole thallium scintigraphy for predicting perioperative cardiac event-free survival rates. METHODS AND RESULTS: Clinical and scintigraphic variables in 360 patients undergoing vascular surgery were analyzed for their predictive utility for perioperative and late (up to 5 years) cardiac events (nonfatal myocardial infarction or cardiac death) by means of chart review and telephone contact. Patients were correctly categorized as being at low, moderate, or high risk for perioperative cardiac events based on two clinical indexes. Thallium redistribution, however, was a more powerful predictor of cardiac events than these indexes. Even in a clinically low-risk patient cohort, the odds ratio for an event increased by 6- to 8-fold (p < 0.05) if thallium redistribution was noted. These indexes also demonstrated prognostic utility for late cardiac event-free survival rates by life-table analysis (p < 0.001). The presence of a fixed thallium defect was associated with an increased risk of late cardiac events (p < 0.01). When stratified by risk index, in those patients at moderate to high risk who had a fixed defect the odds ratio increased by 3.9- to 5.4-fold (p < 0.001). Likewise, the low-risk subgroup had a 3.9- to 8.2-fold increase in the risk of a late cardiac event when a fixed perfusion defect was present. CONCLUSIONS: Preoperative clinical indexes are predictive of both perioperative and late cardiac events in patients undergoing vascular surgery. However, dipyridamole thallium scintigraphy is more powerful prognostically than these clinical indexes and provides supplemental value to clinical risk stratification.

Adult↗