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PubMed1991

[Inhibition of induced thrombocyte aggregation in the presence of endothelial cells by dipyridamole].

Dipyridamole is widely used as a platelet function inhibitory drug. Its effect on platelet aggregation was investigated in a newly developed system, in which platelet aggregation was carried out in the presence of a human endothelial cell monolayer (EC). After iv. injection of 20 mg Dipyridamole platelet aggregation (inducer ADP 5 microM, Collagen 5 micrograms) was totally inhibited. The EC dependent antiaggregatory effect of Dipyridamol could be abolished if EC's were pretreated with 1 mmol ASA for 30 min. Our results, carried out in PRP demonstrate that Dipyridamole inhibits platelet aggregation even in the absence of red blood cells which were supposed to enhance the antiplatelet effect by their reduced adenosine uptake. Anenhanced PGI2 production in the EC's may explain the aggregation inhibiting effect of Dipyridamole in this test system.

Culture Techniques↗
PubMed1991

Potentiation of pirarubicin cytotoxicity by dipyridamole in doxorubicin-resistant mouse P388 leukemia cells.

The activity of dipyridamole and its possible mechanisms which reverse the resistance of pirarubicin were studied in a P388 mouse leukemia cell lines. Dipyridamole alone was minimally cytotoxic in both of the doxorubicin-resistant cell line (P388/DOX) and the sensitive parent cell line (P388/S), but reversed pirarubicin-resistance in a dose-related manner in P388/DOX cells. A similar dose-response relationship was observed for dipyridamole by increasing net intracellular pirarubicin accumulation. The increase was a result of secondary blocking of enhanced pirarubicin efflux from P388/DOX cells. In contrast, dipyridamole did not affect cytotoxicity and transport in the drug-sensitive cell line. It is suggested that dipyridamole is a useful drug for modulation of the multidrug-resistance of cells.

Animals↗
PubMed1990

[Ischemic heart disease evaluated using dipyridamole-stress two-dimensional echocardiography].

Dipyridamole-stress two-dimensional echocardiography (2DE) was performed in 25 subjects, 14 with stenotic and 11 with normal coronary arteries by coronary angiography, to assess the sites and severity of coronary artery stenosis noninvasively. Dipyridamole was administered intravenously with a dose of 0.56 mg/kg for 4 min. 2DE was recorded at the lower papillary muscle level and the percent fractional area change (% FAC) of the left ventricular segments was computed (FV). In all cases with an echocardiographic regional wall motion abnormality in the interventricular septum, a significant stenosis (greater than or equal to 75%) was documented angiographically in the left anterior descending coronary artery (LAD). In seven of eight patients with a segmental abnormality in the inferolateral wall, a significant stenosis was observed in the left circumflex coronary artery (Cx). The sensitivity and specificity of dipyridamole-stress echocardiography were 100% and 92%, respectively, for an LAD stenosis, and and 87.5% and 71%, respectively, for a Cx stenosis. The segmental wall motion abnormality induced by dipyridamole resolved within four to five min after terminating the infusion in patients with coronary artery narrowing of 75%; whereas, it persisted up to six to seven min in patients with 90% narrowing. There was no improvement in the LV wall motion 15 min after the termination of the infusion in patients with severe narrowing (99%). In conclusion, dipyridamole-stress echocardiography proved to be one of the most useful methods, not only for detecting coronary artery disease, but for predicting the severity and for localizing the sites of lesions as well.

Analysis of Variance↗
PubMed1990

[Significance of 2-dimensional echocardiography for the diagnosis of dipyridamole-induced myocardial ischemia in patients with coronary heart disease].

In 24 patients with coronary heart disease (group 1) and in 16 control patients (group 2) dipyridamole test was performed in combination with two-dimensional echocardiography. The studies were aimed at the comparison of sensitivity, specificity and predictive values calculated during analysis of segmental contractility of the left ventricular wall and LVEDVI, LVESVI, SVI, CI and EF in relation to ecg examination. During analysis of changes in ST segment, dipyridamole test sensitivity was 0.37, specificity--0.94, predictive confirmatory value--0.90, and predictive excluding value--0.50. During analysis of LVEDVI, SVI and CI diagnostic value of the dipyridamole test did not change (p greater than 0.05). During analysis of LVESVI and EF dipyridamole test sensitivity increased to 0.75 and 0.83, respectively (p less than 0.05). Also during analysis of segmental contractility of the left ventricular wall sensitivity of the test increased to 0.75 (p less than 0.01), while its specificity and predictive value did not change (p greater than 0.05). Two-dimensional echocardiography augments diagnostic value of the dipyridamole test.

Adult↗
PubMedDate not supplied

Pharmacokinetics of dipyridamole-beta-cyclodextrin complex in dogs.

Plasma concentrations and urinary and fecal excretion of intact dipyridamole were followed in dogs after oral administration of dipyridamole-beta-cyclodextrin complex (dip-beta-CD) (capsules containing 37.5 and 75 mg of active principle), of commercial dipyridamole and of dipyridamole. HCl (tablets and capsules of 75 mg of active principle, respectively), according to a crossover design. Dip-beta-CD afforded significantly shorter lag-times, higher Cmax, smaller interindividual variations of plasma concentrations and greater urinary excretion than the other two preparations, as a consequence of a better bioavailability of the former one. This amelioration seems to be due not only to an increased wettability and water solubility of the product, but also to a finer molecular dispersion in the gastrointestinal fluids which favors the contact of dipyridamole with a greater absorption surface.

Administration, Oral↗
PubMed1989

Effects of dipyridamole on the cardiovascular response to +Gz stress in miniature swine.

Eight conscious female miniature swine experienced acceleration levels of 3, 5, and 7 +Gz before and after infusion of dipyridamole (1-2 mg.kg-1). Each animal was instrumented to measure ECG, heart level arterial pressure (AP), eye level arterial pressure (ELBP), left arterial pressure (LAP), heart rate (HR), and regional tissue blood flows. Each was also fitted with an abdominal anti-G suit which automatically inflated. Dipyridamole infusion had no direct effect on HR or LAP but AP was significantly reduced. All cardiovascular responses to +Gz were qualitatively similar before and after dipyridamole. Tachycardia always occurred. AP and CNS blood flow were maintained better prior to dipyridamole and AP always fell in proportion to acceleration intensity. +Gz was generally associated with increased blood flow to respiratory muscles and heart, decreased blood flow throughout the viscera and to the eyes. ELBP paralleled AP, but was always lower in direct proportion to the +Gz level. We conclude that dipyridamole reduces arterial pressure thus compromising the ability of the animal to sustain cerebral perfusion pressure (ELBP) during +Gz.

Animals↗
PubMed1989

[Evaluation of antiplatelet drugs on platelet functions--comparison between ticlopidine and dipyridamole after prosthetic valve replacement].

We examined the efficacy of antiplatelet drugs after prosthetic valve replacement. As an early postoperative group (group E), 49 patients were divided into four groups. In group A only warfarin was given. In group B warfarin and dipyridamole 300 mg/day, in group C warfarin and ticlopidine 300 mg/day, in group D warfarin and ticlopidine 600 mg/day were administered respectively. As a late postoperative group (group L), 45 patients with prosthetic valves were divided into two groups. In group I dipyridamole 300 mg/day in group II ticlopidine 300 mg/day were administered. Both group I and II received warfarin. In group E platelet counts and platelet aggregability were examined to 22 POD. In group L starting two years after valve replacement, platelet counts were examined eight times by three-month intervals, and platelet aggregability, platelet adhesiveness were investigated 36 months in group I and 27 months in group II postoperatively. Results are the following. 1) Neither ticlopidine nor dipyridamole had any effects on the platelet counts through the postoperative period. 2) In the early postoperative period, the administration of antiplatelet drugs to groups B, C, and D suppressed platelet aggregability more than group A. 3) Ticlopidine (groups C and II) reduced ADP and collagen aggregabilities compared with dipyridamole (group B and I) both in the early and late postoperative period. 4) Ticlopidine 300 mg/day (group C) and ticlopidine 600 mg/day (group D) had no difference in ADP and Collagen aggregabilities. 5) No significant difference was shown between dipyridamole (group I) and ticlopidine (group II) in platelet adhesiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Comparison of exercise and dipyridamole equilibrium blood pool scintigraphy (EBPS) in angina pectoris.

Twelve patients with exertional angina underwent exercise treadmill testing, exercise equilibrium blood pool scintigraphy (Ex EBPS). Dipyridamole equilibrium blood pool scintigraphy (Dip EBPS) and coronary angiography by the Judkin's technique. Dipyridamole was infused through a venous cannula placed in the antecubital vein, in a dose of 0.56 mg/kg over four minutes. Four patients had single vessel disease, three double vessel disease, four triple vessel disease, and one had normal coronary arteries. Exercise equilibrium blood pool scintigraphy was found to have a sensitivity of 81%, and a positive predictive value for significant coronary artery disease of 100%. Dipyridamole EBPS had a sensitivity of 72% with a positive predictive value of 100%. The occurrence of regional wall motion abnormalities, following dipyridamole infusion, occurs up to fifteen minutes after exercise, and, therefore, serial acquisition for up to 20 minutes after the infusion is recommended. In patients with angina, who are unable to exercise because of orthopaedic disabilities or peripheral vascular disease, dipyridamole stress blood pool scintigraphy is a feasible alternative.

Adult↗
PubMed1986

Clinical effect of dipyridamole in patients with IgA nephropathy.

Clinical effects of dipyridamole and carbazochrome sodium sulfonate in patients with IgA nephropathy are described. Oral administration of 300 mg of dipyridamole and 180 mg of carbazochrome sodium sulfonate per day was employed in the present study. Urinalysis and renal function tests, i.e. serum creatinine (s-Cr), blood urea nitrogen (BUN), glomerular filtration rate (GFR) and phenolsulfonphtalein (PSP) tests, were performed before and after the administration of dipyridamole. It was demonstrated that the administration of dipyridamole was effective in reducing the level of proteinuria in the patients. The administration of carbazochrome sodium sulfonate was not effective in reducing the proteinuria level. It was concluded that the administration of dipyridamole may be useful for treatment of patients with IgA nephropathy.

Adrenochrome↗
PubMed1986

Reduction of intimal hyperplasia in canine autologous vein grafts with cod-liver oil and dipyridamole.

To determine the effects of cod-liver oil and a combination of cod-liver oil and dipyridamole on vein-graft intimal hyperplasia, 76 segments of undistended jugular vein were interposed between bilaterally divided femoral arteries in 38 mongrel dogs who received a 2% cholesterol diet. Ten control animals received the diet alone, 8 received cod-liver oil containing 1.8 g of eicosapentaenoic acid daily 1 week before and for 6 weeks after operation, and 20 dogs received 1.8 g of eicosapentaenoic acid and 75 mg of dipyridamole daily 1 week before and for 6 weeks after operation. A similar and significant (p less than 0.01) increase in serum cholesterol was observed in all three groups. Prothrombin, partial thromboplastin and clotting times and the platelet count were unchanged in the controls and in those receiving cod-liver oil. Clotting time increased in the animals receiving a combination of cod-liver oil and dipyridamole (p less than 0.001). Measurements (406 +/- 27) of intimal thickness were made from each graft. Intimal thickness was 3.7 +/- 0.1 micron before implantation and increased to 78 +/- 8 micron after in the controls. Cod-liver oil limited the increase in intimal thickening, to 24 +/- 3 micron (p less than 0.001); cod-liver oil and dipyridamole further reduced the increase in intimal thickening, to 17 +/- 1.4 micron (p less than 0.001). The data indicate that a combination of cod-liver oil and dipyridamole is more effective than cod-liver oil alone in reducing canine vein-graft intimal hyperplasia (p less than 0.03).

Animals↗
PubMed1986

Time dependence of dipyridamole-induced increase in skeletal muscle capillarization.

40 young Sprague-Dawley rats in groups of 10 were subjected to treatment with dipyridamole for 1, 2, 4 and 8 weeks. Another 40 sham-treated rats served as controls. The medial portion of the quadriceps femoris muscle was evaluated for total capillarization, fiber area and fiber type composition. Capillary/fiber ratio and mean number of capillaries in contact with each fiber were significantly increased in the rats treated with dipyridamole for 2 weeks and longer. The capillary density, however, did not increase until after 4 weeks of dipyridamole treatment. The fiber area increased gradually with age and was significantly enlarged by dipyridamole treatment after 2 and 4 weeks. All fibers in the examined muscles were of the low oxidative (white) type and no change was recorded in this respect after dipyridamole treatment.

Animals↗
PubMed1986

[Coronary artery disease detected noninvasively by dipyridamole-loading 201T1 myocardial scintigraphy in elderly patients].

To evaluate the usefulness in diagnosing coronary artery disease (CAD), dipyridamole-loading 201T1 myocardial scintigraphy was performed for 52 elderly patients (65-92 years, mean: 72 years), and the results were compared with data from the treadmill exercise tests. Thirty-five patients could not tolerate adequate exercise tests. Seven of them had reversible defects; six, fixed (irreversible) ones. Dipyridamole scintigraphy is therefore applicable in detecting CAD among patients with suspected CAD who are unable to perform adequate exercise tests. Four of 16 patients with positive exercise tests had no reversible defects; the exercise results in three were regarded as false positives. Seventeen patients experienced chest pain; 12 had ST depression during dipyridamole loading. There were no serious complications, but seven patients required aminophylline. We demonstrated previously that the sensitivity and specificity of dipyridamole scintigraphy in detecting CAD were 90% and 92%, respectively, in patients with chest pain undergoing coronary angiography. These results were superior to those of conventional exercise myocardial scintigraphy. Therefore, dipyridamole scintigraphy is regarded as a safe and useful method for detecting CAD, particularly in elderly patients who have ST and T wave abnormalities but cannot tolerate exercise test adequately.

Aged↗
PubMed1985

[201T1 computed tomography using dipyridamole for assessing dilated cardiomyopathy].

The value of redistribution thallium-201 (T1-20(1] emission computed tomography (ECT) using dipyridamole for evaluating coronary circulation was analyzed in 18 patients with dilated cardiomyopathy (DCM). After maximal inducible coronary vasodilation (dipyridamole, 0.56 mg/kg), 2 mCi T1-201 was administered, and dipyridamole ECT data at 10 minutes and delayed ECT data at 3 hours after the injection were collected. Image interpretation was made visually. The results were as follows: In all cases, perfusion defects were observed on the dipyridamole images, and eight (45%) had redistribution on their delayed images. Patients with redistribution had better left ventricular function (% fractional shortening 24.7 +/- 7.0 versus 18.0 +/- 5.0) by two-dimensional echocardiography. Segments with redistribution showed less severe wall motion abnormalities compared with segments without redistribution. It is concluded that redistribution thallium ECT imaging using dipyridamole is a useful tool for the evaluation of coronary circulation of patients with DCM.

Cardiomyopathy, Dilated↗
PubMed1979

Effect of dipyridamole on prostaglandin-induced ocular hypertension in rabbits.

The effect of intraperitoneal injections of dipyridamole on the elevations of intraocular pressure and anterior chamber aqueous humor protein produced by topical application of prostaglandin E2 was studied in rabbits. Pretreatment with 100 mg/kg dipyridamole inhibited the prostaglandin E2--induced ocular hypertension and rise of aqueous humor protein. Systemic administration of dipyridamole did not alter the responses of the eye to instilled nitrogen mustard. Topical instillation of dipyridamole was ineffective. Dipyridamole, a clinically available drug, may be useful in the treatment of ocular inflammatory disease.

Administration, Topical↗
PubMed1979

[The diagnostic accuracy of the dipyridamole test in coronary heart disease (author's transl)].

The diagnostic accuracy of the dipyridamole test in provoking coronary insufficiency was investigated in 79 patients with chest pain and the results were compared with the findings on angiography and exercise electrocardiogram. 58 patients had documented severe coronary artery stenosis, 21 had patent coronary vessels (cardiomyopathy 8, aortic stenosis 1, ectopic origin of coronary artery 1, normal 11). Anginal pain after dipyridamole was a non-specific finding. Approximately half the subjects in whom coronary insufficiency would be expected according to the coronary angiographic and ventriculographic findings evidenced ischaemic ST-segment depression after dipyridamole, which was comparable to the number of positive exercise electrocardiograms. In 23 patients, most of whom had shown an inadequate frequency response during the initial exercise test, ergometry was repeated after the administration of dipyridamole. This resulted in an increase in ischaemic ECG response from 26 to 70%. It is concluded that a stress test combining dipyridamole and submaximum exercise increases the incidence of ischaemic ST-segment depression in comparison with ergometry alone. Anginal pain without ST-segment depression proved to be without diagnostic value.

Adult↗
PubMed1979

Effects of aspirin and dipyridamole on platelet function, hematology, and blood chemistry of saturation divers.

Twenty-four young male divers were assigned randomly to 4 treatment groups: Group I received aspirin (325 mg) three times daily; II received dipyridamole (75 mg) three times daily; III received both drug regimens; and IV received matching placebo. Double-blind procedures were followed. Treatment began 24 h prior to a 48-h saturation dive (inclusive of 17 h decompression) at a simulated depth of 18.3 m and continued throughout and for 3 days after the dive. A post-dive reduction in circulating platelet count was observed in all groups, except the group that received aspirin only. Platelet survival was shortened in all treatment groups. Five cases of Type I decompression sickness occurred and were treated by recompression, two in the aspirin plus dipyridamole group, two in the dipyridamole group, and one in the placebo group. Blood chemistry and hematology profiles showed that divers with decompression sickness had more elevated GOT, GPT, CPK, cholesterol and triglyceride levels, and greater reductions in platelet count, Platelet Factor 4 and Thrombin Clotting Time than most other subjects. Subjects receiving either aspirin or aspirin plus dipyridamole had fewer changes in these parameters. Failure of aspirin to potentiate, or add to, dipyridamole may be due to other actions of aspirin such as inhibition of prostacyclin synthesis. Further studies of the role of antiplatelet drugs in decompression sickness are warranted.

Adult↗
PubMed1984

[Diagnosis of myocardial ischemia in Kawasaki disease: thallium-201 myocardial imagings at rest, with exercise and with dipyridamole administration].

Thallium-201 myocardial imaging was performed at rest in 131 children with coronary arterial lesions due to Kawasaki disease. The coronary arterial lesions were assessed by selective coronary angiography within a few days of the isotope study. Twenty-one children had occlusive lesions, and segmental stenotic lesions were seen in 16 children. Perfusion defects of the myocardial images were detected in nine of the former and in three of the latter. The locations of the perfusion defects coincided with the perfusion areas of the affected vessels on coronary angiography. Twelve patients with initial perfusion defects at rest had a follow-up study and the defects disappeared in five. These patients had re-establishment of coronary blood flow in the initially affected areas by either development of collateral vessels or recanalization. Myocardial imaging with exercise was performed in 27 patients including four with coronary arterial occlusion and two with segmental stenosis on coronary angiography. All with coronary artery lesions showed perfusion defects on the imaging with exercise, while the resting study showed the defects only in one patient, in whom more extensive perfusion defects were observed after exercise. Myocardial imaging following intravenous injection of dipyridamole was carried out in 43 patients. Perfusion defects after the injection were noted in 15 of 17 patients with coronary occlusion and in nine of 13 patients with segmental stenosis. In four patients with perfusion defects at rest, additional or more extensive defects were revealed by this drug in the areas of additional coronary arterial involvements. In 20 patients with perfusion defects only after dipyridamole injection, the perfusion defects coincided with the angiographic findings very well. A perfusion defect was documented following dipyridamole injection in one exceptional patient who had no stenotic lesions, but had three giant coronary aneurysms of the right coronary artery. Thus the dilated coronary lesions seemed to give a perfusion defect. In some of the patients whose perfusion defects disappeared at rest on a follow-up study, the defects were disclosed by exercise and/or dipyridamole administration. Thus, thallium-201 myocardial imagings combining resting and exercise or dipyridamole studies were valuable for the detection and assessment of coronary arterial lesions of Kawasaki disease.

Adolescent↗
PubMed1984

Potentiation of methotrexate toxicity by dipyridamole.

Dipyridamole, an inhibitor of facilitated transport systems for purines and pyrimidines, was shown to enhance the toxicity of methotrexate (MTX) against cells in culture and in mice. Under certain incubation conditions, the availability of performed purines and pyrimidines in undialyzed serum appeared to render Chinese hamster ovary cells insensitive to MTX. Addition to the culture of nontoxic levels of dipyridamole conferred sensitivity to MTX. Inhibition of [3H]thymidine uptake by dipyridamole paralleled the enhanced MTX toxicity in a comparison of the dose-effect relationships. Inhibition of [3H]hypoxanthine uptake also occurred, although approximately 10-fold higher levels of dipyridamole were required. In vivo dipyridamole enhanced MTX toxicity in mice; however, the antitumor activity of MTX toward Ridgway osteogenic sarcoma and L1210 leukemia was not dramatically improved.

Animals↗