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PubMed2003

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

UNLABELLED: Much evidence suggests endothelial dysfunction to be present in non-insulin-dependent diabetes mellitus (NIDDM) and to be important for the development of myocardial ischemia. Endothelial function in the coronary vessels may be studied in various ways. We compared the effect of cold pressor testing (CPT) with that of dipyridamole, a pharmacologic vasodilator, on coronary blood flow (CBF) measured by PET in NIDDM patients and healthy volunteers. In addition, we studied the effect of acute angiotensin-converting enzyme (ACE) inhibition on the flow response. METHODS: Ten NIDDM patients and 10 control subjects participated. Myocardial perfusion was determined at baseline, during CPT, and after dipyridamole infusion by PET using intravenous (13)N-ammonia. RESULTS: Resting CBF was similar in NIDDM patients and in control subjects. CPT increased CBF by 20% in the control group, whereas no increase was observed in the patients. After dipyridamole infusion, CBF increased 2- to 3-fold in patients and 3- to 4-fold in control subjects. The increase and maximal CBF were significantly higher in control subjects than in patients. During ACE-inhibitor infusion, which had no influence on resting CBF in patients or control subjects (n = 5), CPT increased CBF by 14% in the NIDDM group. After dipyridamole, CBF increased 3- to 4-fold in both groups. The increase in CBF and maximal CBF in the 2 groups were not different during ACE-inhibitor infusion. CONCLUSION: In these NIDDM patients without evidence of epicardial coronary disease, endothelial dysfunction is strongly suggested by an impaired increase in CBF both to dipyridamole and to CPT. This dysfunction was reversed by infusion of an ACE inhibitor. Although ACE inhibition during CPT did induce significant increases in CBF in the patients, the changes during ACE inhibition were small compared with the dipyridamole response, and the absence of CBF increase during CPT in 3 of the 10 control subjects further limits the value of CPT for the study of coronary endothelial dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

[Echocardiographic test of dipyridamole in recognition of coronary artery disease].

To assess the feasibility, safety and usefulness of dipyridamole stress echocardiography for the detection of coronary artery disease we evaluated 194 patients (124 men, 70 women) with effort chest pain. All patients underwent electrocardiographic submaximal bicycle exercise testing and 2-dimensional echocardiography after dipyridamole injection. Echocardiographic test was considered positive when new wall motion abnormalities were observed after dipyridamole i.v. injection (0.56 mg/kg b.m.). Sensitivity and specificity of electrocardiographic exercise test and dipyridamole stress echocardiography were assessed in 37 persons who underwent selective coronary angiography. The sensitivity and specificity of dipyridamole stress echocardiography, were respectively 85.0% and 91.7% and were higher than those of exercise electrocardiography. 2-dimensional echocardiography after dipyridamole injection is a well tolerated, feasible and effective test in the diagnosis of coronary artery disease.

Adult↗
PubMed1992

Quantification of walking exercise required for improvement of dipyridamole thallium-201 image quality.

Dipyridamole 201Tl imaging is an accepted diagnostic procedure for the evaluation of patients unable to perform adequate treadmill exercise, but is limited by high infradiaphragmatic activity. While recent studies have shown that the addition of exercise reduces this activity, the amount of exercise needed to effect such an improvement is uncertain. To prospectively evaluate the amount of walking exercise required to produce improvement in image quality, 120 patients were randomized to either a control group receiving dipyridamole alone, or to dipyridamole supplemented with one of four exercise protocols. Ratios of heart-to-liver and heart-to-adjacent infradiaphragmatic activity were generated from anterior images acquired immediately following the test. Heart-to-total infradiaphragmatic activity was also graded semiquantitatively. Results showed improved target-to-background ratios as well as semiquantitative assessment of image quality for dipyridamole supplemented with exercise as compared to dipyridamole alone. No difference was seen between walking in place and Bruce treadmill exercise at Stage 0 or 0.5. A trend towards higher values was seen with Bruce Stage 1 exercise supplementation, but this did not reach statistical significance. No significant complications occurred during the study. We conclude that 3 min of walking exercise is a safe and effective means of improving the quality of dipyridamole 201Tl images.

Adult↗
PubMed1992

[Dipyridamole-thallium myocardial imaging in patients unable to exercise adequately: comparison with arm and bicycle ergometer].

We assessed the usefulness of dipyridamole-thallium myocardial imaging in patients unable to exercise adequately, compared with arm-ergometer and standard (bicycle) ergometer. Fifty-six patients with arteriosclerosis obliterans, aortic aneurysm, aortic dissection and so on, who were revealed normal imaging, were studied. Only one of 13 cases with arm-ergometer and two of 14 with bicycle ergometer reached target heart rate. Lung thallium uptake in the cases with arm-ergometer (37 +/- 9%) is higher than that with dipyridamole (29 +/- 5%). This elevation may be confused with pectoralis muscle uptake. Washout rate is 45 +/- 9% with dipyridamole and 46 +/- 12% with bicycle ergometer, respectively, though there was no significant differences. Myocardial/background counts ratio with dipyridamole (4.6 +/- 0.8%) is significantly higher than that with arm and bicycle ergometer (arm-ergometer; 3.5 +/- 0.7, bicycle ergometer; 4.2 +/- 0.9). Then, myocardial image with dipyridamole have superior quality. We concluded that dipyridamole-thallium myocardial imaging is very useful in the patients who have suboptimal exercise efforts.

Aged↗
PubMed2004

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

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

Adrenergic Antagonists↗
PubMed1991

Dipyridamole potentiates platelet inhibition by nitric oxide.

In a placebo-controlled double blind cross-over experiment the adenosine uptake inhibitor dipyridamole (400 mg/day) did not affect ex vivo platelet aggregation induced by collagen or adenosine-diphosphate (ADP) in an electronic whole blood aggregometer (WBA). Dipyridamole was also inactive in vitro, unless red blood cell injury was deliberately enhanced, thereby increasing the level of free adenine nucleotides. Since dipyridamole also inhibits cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE), we used platelet rich plasma (PRP) to study its interaction with authentic and endothelium-derived nitric oxide (NO). The latter inhibits platelets by increasing cyclic GMP. Dipyridamole (1 to 30 microM), either alone or in combination with a subthreshold concentration of prostacyclin (PGI2), was inactive. However, when combined with a subthreshold concentration of NO, dipyridamole caused a concentration-dependent platelet suppression, which became more pronounced when PGI2 was present as well. It is concluded that dipyridamole could reduce the threshold for platelet suppression by NO through inhibition of cyclic GMP PDE.

Adult↗
PubMed1991

Dipyridamole 201Tl scintigraphy in the evaluation of prognosis after myocardial infarction.

Dipyridamole 201Tl imaging has been proposed as an alternative to exercise ECG testing for the prehospital discharge evaluation of patients recovering from myocardial infarction. The rationale is that many postinfarction patients with exercise-induced ischemia experience later cardiac events, and the sensitivity of predischarge exercise ECG testing in patients with multivessel disease ranges from only 45% to 62%. In addition, several groups of investigators have shown the sensitivity of submaximum exercise 201Tl imaging to be less than ideal. This report summarizes the current status of dipyridamole 201Tl imaging in the period of 1-13 days after myocardial infarction. Although the number of studies performed to date is limited, the following conclusions can be drawn: dipyridamole 201Tl imaging after myocardial infarction was associated with no serious side effects, and those present could be quickly reversed with aminophylline; redistribution with dipyridamole 201Tl images definitely correlates with prognosis after uncomplicated myocardial infarction; dipyridamole 201Tl imaging is definitely useful in patients unable to exercise for a variety of reasons; and future studies are definitely indicated to further define the role of dipyridamole 201Tl imaging for assessing prognosis, especially in those patients undergoing interventional therapy after acute myocardial infarction.

Aged↗
PubMed1990

[Cineventriculography with radionuclides and intravenous dipyridamole in the prognostic evaluation after acute myocardial infarction].

PURPOSE: To evaluate safety and usefulness of dipyridamole-radionuclide ventriculography (D-RVG), soon after acute myocardial infarction (MI), in the prediction of future cardiac events. Traditionally performed tests were also compared. PATIENTS AND METHODS: Forty-one patients (4 females) with recent MI underwent rest and dipyridamole (0.58 mg/kg of body weight) radionuclide ventriculography. The criteria for a positive test for ischemia was failure to increase left ventricular ejection fraction in 0.05 from baseline value. All patients had also coronary angiography and 36 patients underwent thallium-201 scintigraphy for comparison. The mean follow-up was 16 +/- 3 months. The following findings were considered future for events: cardiac death, reinfarction, significant angina or heart failure. RESULTS: During the follow-up 18 of the 20 patients who had cardiac events had shown positive dipyridamole-RVG, as opposed to 5 of 21 event-free patients (p less than 0.01). The ventriculographic criteria for a positive test and dipyridamole left ventricular ejection fraction were the strongest predictors of those medical events (p less than 0.01 and p less than 0.001). Among the 36 patients who had thallium-201 imaging, 16 subsequently had cardiac events and the scans were positive in 82% (p less than 0.01). Twelve (29%) patients experienced reactions during dipyridamole infusion although no fatal complications were noted. CONCLUSION: Dipyridamole-RVG is relatively safe and a sensitive predictor of future cardiac events soon after acute MI, although additional experience is required before this new technique should be routinely recommended as an alternative approach.

Coronary Angiography↗
PubMed1990

Increased prostacyclin production from human veins by dipyridamole: an in vitro and ex vivo study.

The effect of dipyridamole on prostacyclin (PGI2) production in the presence or in the absence of sodium arachidonate was examined in human veins collected from otherwise normal subjects undergoing saphenous vein removal. Vein segments, maintained in ex vivo culture, that were removed from subjects treated with dipyridamole for two days prior to surgery synthesized 2.5 times more PGI2 (p less than 0.05) than veins that were removed from placebo-treated subjects when incubated in the presence of arachidonate. This difference decreased progressively when vein segments were washed repeatedly and then re-incubated in the presence of arachidonate. Direct addition of dipyridamole to vein segments incubated in vitro resulted in a dose-dependent increase in PGI2 production when the incubation was carried out in the presence of arachidonic acid. No effect of dipyridamole was observed in experiments performed in the absence of arachidonic acid. A mathematical analysis based on both ex vivo and in vitro experiments of the rate of decline of endothelial cell PGI2 biosynthesis suggested that the elevation of PGI2 with dipyridamole treatment resulted from increased PGI2 synthesis rather than decreased PGI2 catabolism. These data support the hypothesis that dipyridamole both ex vivo and in vitro enhances and prolongs PGI2 production by human vessels.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Adenosine deaminase and porcine meat quality. I. Effect of dipyridamole on plasma free fatty acids, glucose, lactate and c-AMP in pigs representing high and low red cell adenosine deaminase activity.

The effect of dipyridamole--an adenosine uptake inhibitor--on the plasma concentration of free fatty acids (FFA), glucose, lactate and cyclic adenosine monophosphate (cAMP) has been examined in 2 groups of Landrace pigs representing low (Ada 0) and high (Ada A) red cell adenosine deaminase (Ada) activity. Pigs fitted with a jugular vein catheter were given dipyridamole (0.16 mg/kg/min) over a period of 30 min. The infusions were performed 22 h after the last meal at a time where pigs were found to show steady increase and decline in rates of lipolysis and glycogenolysis, respectively. The results showed that lipid mobilization as identified by the plasma FFA concentration was markedly depressed. During the infusion of dipyridamole similar degree of inhibition was seen in Ada 0 and Ada A pigs, however, in the period following the infusion, a significantly stronger suppression persisted in the Ada 0 pigs. Both the blood glucose and lactate level rose distinctly as a result of the dipyridamole treatment. This stimulation of the glycolysis rate was significantly more expressed in Ada 0 pigs compared to that of the Ada A pigs. When theophylline, an antagonist of adenosine, was given together with dipyridamole, the rise in the lactate level was considerably diminished. Dipyridamole also produced a distinct rise in the plasma cAMP levels.

Adenosine Deaminase↗
PubMed1990

Phase I trial of 5-fluorouracil and dipyridamole administered by seventy-two-hour concurrent continuous infusion.

Forty-seven patients with advanced malignancies were treated with a concurrent 72-h continuous infusion of 5-fluorouracil (FUra) and dipyridamole. The FUra dose was escalated over the dose range of 185 to 3600 mg/m2/day for 3 days. Dipyridamole was administered in a fixed dose of 7.7 mg/kg/day for 3 days. A total of 155 courses of therapy were completed of which there were 31 paired courses of the combination and FUra alone, at the same dose of FUra and in the same patient. This was for purposes of analysis of pharmacokinetics and modulation of FUra toxicity by dipyridamole. Stomatitis was the dose-limiting toxicity experienced by patients entered into this trial. Myelosuppression was not a serious problem. Increasing FUra plasma concentration was associated with greater leukopenia and stomatitis. Dipyridamole did not appear to modulate the systemic toxicity of FUra. The pharmacokinetics of FUra were altered by the concurrent administration of dipyridamole. Dipyridamole promoted the total body clearance of FUra which resulted in lower mean steady-state FUra plasma concentrations when compared with courses of FUra alone administered at the same dose level. These differences were statistically significant over the course of the trial. For courses of the combination, FUra exhibited linear pharmacokinetics over the dose range studied. Total body clearance of FUra declined slightly at the higher dose levels, but the differences were not significant. For courses of FUra alone, total body clearance was significantly decreased above the dose level of 2300 mg/m2/day. At the maximal tolerated dose of FUra, 2300 mg/m2/day x3, mean steady-state FUra plasma concentration and total body clearance were 6.6 microM and 122 liters/h/m2, respectively, for courses of the combination. The corresponding pharmacokinetic parameters were 7.4 microM and 103 liters/h/m2 for courses when FUra was given alone. Further evaluation of the utility of this regimen and basis of these pharmacokinetic observations appear warranted.

Adult↗
PubMed1989

[Prognostic meaning of the echo-dipyridamole test in recent non-Q myocardial infarct].

The aim of this study was to evaluate the usefulness of the dipyridamole-echocardiography test soon after non Q wave myocardial infarction. Forty-two consecutive patients admitted to the Coronary Care Unit for a first episode of a non Q wave myocardial infarction were enrolled. Dipyridamole-echocardiography test and exercise stress test were performed on 29/42 patients without clinical or electrocardiographic evidence of residual ischaemia, before hospital discharge (from 7 to 15 days after admission). They were followed-up for 1 to 15 months (mean 11.9) or until one of the following clinical end points occurred: recurrence of myocardial infarction, angina or cardiac death. Over a period of 4 minutes, 0.56 mg/kg of dipyridamole was infused intravenously. The test was considered positive when a new transient wall motion abnormality was confirmed by two independent observers. According to these criteria a positive test was observed in 7/29 patients (24%) and a negative one in 22/29 (76%). The exercise stress test was positive in 12/27 patients (44%). Subsequent coronary events occurred in all the patients (100%) with positive dipyridamole-echocardiography test and in 7/22 patients (32%) with negative dipyridamole-echocardiography test (p less than 0.001). Five out of the 7 patients with positive test who underwent coronary angiography showed multivessel coronary artery disease. The sensitivity, specificity and positive predictive value of dipyridamole-echocardiography test for the identification of patients at risk for subsequent coronary events were respectively 50%, 100%, 100%, while for exercise stress test these values were 83%, 86% and 75%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

[The bioavailability of dipyridamole in the form of liposomes].

Liposomes containing dipyridamole have been prepared by evaporating-shaking method. Phospholipid bilayer consisted of lecithin and cholesterol in three varying molar rations: 5:2, 7:2, 10:2. According to lipid layer composition the obtained liposomes varied in size and amount of dipyridamole entrapped. The suspension of liposomes in 0.9% sodium chloride prepared with lecithin and cholesterol in molar ratio 7:2 was chosen to the study in vivo. A suspension of dipyridamole in 0.9% sodium chloride was used comparatively. Particle size of dipyridamole was similar to that of liposomes with entrapped substance. Both suspensions were administrated to guinea pigs orally or intraperitoneally. The study has shown that liposomally-entrapped dipyridamole has essential and advantageous effect on its absorption after oral or intraperitoneal administration when compared with dipyridamole itself. The best bioavailability has been demonstrated by the suspension of liposomes after intraperitoneal administration.

Animals↗
PubMed1985

The effect of dipyridamole on histamine- and adenosine-induced bronchoconstriction in normal and asthmatic subjects.

The effect of intravenous infusion of dipyridamole on histamine- and adenosine-induced bronchoconstriction was studied in 6 normal and 6 allergic asthmatic subjects. Dipyridamole in a single dose of 50 mg over 50 min had no effect upon baseline airway calibre measured as specific airways conductance (sGaw) and the forced expiratory volume in 1 s (FEV1). In the asthmatic subjects adenosine-induced bronchoconstriction was potentiated to a small extent by dipyridamole as indicated by a decrease in the concentration of adenosine required to produce falls from baseline of 40% for sGaw (PCs40) and 20% for FEV (PCf20) from 0.48 mg/ml to 0.32 and 0.37 mg/ml respectively. Dipyridamole had a small protective effect on histamine-induced bronchoconstriction with PCs40 and PCf20 increasing from 0.08 mg/ml to 0.11 and 0.17 mg/ml. In normal subjects dipyridamole failed to reveal a bronchoconstrictor effect of adenosine. These studies demonstrate the complex interaction between dipyridamole and bronchoconstrictor stimuli on the airways.

Adenosine↗
PubMed1984

[Stress studies with dipyridamole in patients with coronary heart disease in comparison to coronary angiography, myocardial scintigraphy and ergometry findings].

In 102 patients with typical symptoms of angina pectoris who underwent a coronary angiography a Dipyridamol test was performed. The result was a sensitivity of about 84% concerning the coronary heart disease and a specifity of about 93%. In the same test persons the ECG after work showed a sensitivity of about 84% and a specifity of about 57%. Dipyridamol test and bicycle ergometry are methods of the same value for the preinvasive diagnostics of the coronary heart disease which should supplement each other. The higher specifity of the ECG changes in the Dipyridamol test was evident in comparison to the bicycle ergometry. In 85 of our patients the Tl-201-scintigraphy was carried out under Dipyridamol and ergometer stress. For the Tl-201-scintigraphy under Dipyridamol a sensitivity of about 70% and a specifity of about 81,5% was the result. In the Tl-201-scintigraphy under ergometer load a sensitity ob about 84% and a specifity of about 57% was the result. The proportion of exactly positive findings increased with the number of the stenosed vessels under ergometer as well as Dipyridamol intervention. A negative load scintigraphy does not exclude a coronary heart disease, but renders a three-vessel-disease very improbable.

Angina Pectoris↗
PubMed1983

Dipyridamole inhibits platelet aggregation in whole blood.

Dipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine-5'-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p less than 0.001). A statistically significant inhibition of both collagen (p less than 0.0025) and ADP-induced (p less than 0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37 degrees C with dipyridamole (3.9 microM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood. Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.

Adenosine↗
PubMed1982

Dipyridamole: an antioxidant that promotes the proliferation of aorta smooth muscle cells.

Smooth muscle cells from guinea pig aorta were grown in tissue culture. Dipyridamole enhanced the proliferation of these cells in culture and dipyridamole overcame the inhibitory effect of arachidonic acid on cell proliferation. Dipyridamole and the antioxidant vitamin E both increased the cloning potential and the number of population doublings for smooth muscle cells in culture. Lipid peroxidation was measured in cultured cells with thiobarbituric acid. Dipyridamole, vitamin E and butylated hydroxytoluene inhibited lipid peroxidation both in cultures treated with media alone and in cultures treated with arachidonic acid. Dipyridamole enhanced PGI2 biosynthesis while vitamin E and butylated hydroxytoluene had no effect on PGI2 biosynthesis. These data show that cell proliferation is related to lipid peroxidation rather than PGI2 biosynthesis. Dipyridamole functions as an antioxidant that stimulates the proliferation of aorta smooth muscle cells.

Animals↗
PubMed1983

Effects of acivicin and dipyridamole on hepatoma 3924A cells.

Dipyridamole inhibited the incorporation of cytidine, thymidine, uridine, and guanosine in rat hepatoma 3924A cells with 50% inhibitory concentrations of 0.2 to 0.5 microM. For deoxycytidine, the 50% inhibitory concentration was about 100 times higher (23.8 microM). Addition of a combination of cytidine, deoxycytidine, and guanosine, at an optimal concentration of 80 microM each, protected the hepatoma cells from the growth-inhibitory action of the antiglutamine drug, acivicin. The protection provided by the nucleosides was blocked by dipyridamole (6 microM), but not by nitrobenzylthionosine (30 microM). The effect on cell survival of graded concentrations of 0.25 to 1.75 microM acivicin plus dipyridamole (5 microM) and 80 microM concentrations each of cytidine, deoxycytidine, and guanosine was investigated. At an acivicin concentration of 1.75 microM, survivals in the different groups were: (a) acivicin alone, 1%; (b) acivicin plus dipyridamole, 1%; (c) acivicin plus nucleosides, 78%; and (d) acivicin plus nucleosides plus dipyridamole, 3%. Acivicin and dipyridamole were cytotoxic for hepatoma 3924A cells with 50% inhibitory concentrations of 0.5 and 20.3 microM, respectively, as measured by clonogenic assay.

Animals↗