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PubMed1986

Usefulness of oral dipyridamole suspension for stress thallium imaging without exercise in the detection of coronary artery disease.

Stress thallium imaging with intravenous dipyridamole permits assessment of coronary artery disease (CAD) without the need for exercise. However, intravenous dipyridamole is available in the United States only on an experimental basis. To study the use of oral dipyridamole as a clinically available alternative to intravenous dipyridamole for this purpose, 100 patients underwent thallium imaging with oral dipyridamole. Each patient received 300 mg of pulverized tablets in a 30-ml suspension. Maximal increase in mean heart rate and decrease in mean blood pressure occurred 30 minutes after ingestion. At 45 minutes, 2 mCi of thallium was given intravenously and serial imaging was begun within 7 minutes. The serum dipyridamole level (mean +/- standard deviation) 45 minutes after 300 mg was administered orally (3.7 +/- 2.2 micrograms/ml) was similar to that 5 minutes after 0.56 mg/kg was given intravenously (4.6 +/- 1.3 micrograms/ml). Fifty-five patients had some adverse effects between 15 and 75 minutes after oral ingestion, including nausea, headache, dizziness, chest pain (25 patients) and electrocardiographic changes (14 patients). Intravenous aminophylline was used to resolve these adverse effects in 21 patients. There were no severe arrhythmias, myocardial infarctions or deaths. Of the 43 patients with angiographically documented CAD, 39 had an initial perfusion defect that redistributed on the delayed images. When the results in patients who had undergone catheterization were analyzed by individual segment, the presence of thallium redistribution was associated with normal or hypokinetic contrast left ventriculographic wall motion of that segment, whereas the presence of a persistent defect was associated with akinesia or dyskinesia (Fisher's standardized Z = 9.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Comparison of dipyridamole-handgrip test and bicycle exercise test for thallium tomographic imaging.

Seventy-three patients with angina pectoris and 20 with atypical chest pain, who underwent coronary angiography, were examined by single-photon emission computed thallium tomography (TI-SPECT) using a combined dipyridamole-handgrip stress test. Perfusion defects were detected in 78 of 81 patients with angiographically significant coronary artery disease (CAD) (sensitivity 96%). In 9 of 12 patients without CAD, the thallium images were normal (specificity 75%). Thirty-five patients with CAD were reexamined by TI-SPECT using a dynamic bicycle exercise stress test. The sensitivity of the dipyridamole-handgrip test did not differ from the bicycle exercise test in diagnosing the CAD (97% vs 94%). Multiple thallium defects were seen in 19 of 22 (86%) patients with multivessel CAD by the dipyridamole-handgrip test but only in 14 of 22 (64%) by the bicycle exercise test. Noncardiac side-effects occurred in 17 of 93 (18%) patients after dipyridamole infusion. Cardiac symptoms were less common during the dipyridamole-handgrip test than during the bicycle exercise (15% vs 76%, p less than 0.01). These data suggest that the dipyridamole-handgrip test is a useful alternative stress method for thallium perfusion imaging, particularly in detecting multivessel CAD.

Angina Pectoris↗
PubMed1988

Aminophylline termination of dipyridamole stress as a trigger of coronary vasospasm in variant angina.

Dipyridamole testing represents an alternative to exercise stress testing for documentation of ischemia related to coronary artery disease (CAD). In such a case, ischemia is attributed to maldistribution of coronary flow during dipyridamole-induced vasodilation. The present study evaluated the potential role of dipyridamole testing in producing ischemia through a vasospastic mechanism, following rapid withdrawal of vasodilation induced by aminophylline. The possibility was tested in 36 in-hospital patients with variant angina pectoris who underwent dipyridamole infusion (up to 0.84 mg/kg over 10 minutes) with continuous 12-lead electrocardiographic and 2-dimensional echo monitoring. Medications were withdrawn from all patients. The test was pharmacologically stopped with the dipyridamole antidote (aminophylline, 80 to 240 mg intravenously over 1 to 3 minutes) in all patients. Two to 6 minutes after starting aminophylline infusion, 10 patients (28%) developed (greater than 0.10 mV) ST-segment elevation (2.9 +/- 0.8 mm from baseline), always accompanied by obvious asynergy detected by echocardiography, in the same electrocardiographic leads showing spontaneous or ergonovine-induced ST-segment elevation. Nitrates promptly resolved ischemia in all patients. At coronary angiography, 5 of these 10 patients showed significant CAD (greater than 70% lumen diameter reduction of at least 1 major coronary artery), whereas 5 had nonsignificant CAD. The rate pressure product at the onset of ST-segment elevation (after dipyridamole plus aminophylline) was considerably less than that recorded at peak exercise stress test in these patients (9,600 +/- 2,200 vs 18,400 +/- 4,900, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Simultaneous low level treadmill exercise and intravenous dipyridamole stress thallium imaging.

Intravenous dipyridamole-thallium imaging unmasks ischemia in patients unable to exercise adequately. However, some of these patients can perform limited exercise, which, if added, may provide useful information. Treadmill exercise combined with dipyridamole-thallium imaging was performed in 100 patients and results compared with those of 100 other blindly age- and sex-matched patients who received dipyridamole alone. Exercise began after completion of the dipyridamole infusion. Mean +/- 1 standard deviation peak heart rate (109 +/- 19 vs 83 +/- 12 beats/min, p less than 0.0001) and peak systolic and diastolic blood pressure (146 +/- 28/77 +/- 14 vs 125 +/- 24/68 +/- 11 mm Hg, p less than 0.0001) were higher in the exercise group compared with the nonexercise group. There was no difference in the occurrence of chest pain, but more patients in the exercise group developed ST-segment depression (26 vs 12%, p less than 0.0001). The exercise group had fewer noncardiac side effects (4 vs 12%, p less than 0.01) and a higher target (heart) to background (liver) count ratio (2.1 +/- 0.7 vs 1.2 +/- 0.3; p less than 0.01), due to fewer liver counts. There were no deaths, myocardial infarctions or sustained arrhythmias in either group. Combined treadmill exercise and dipyridamole testing is safe, associated with fewer noncardiac side effects, a higher target to background ratio and a higher incidence of clinical electrocardiographic ischemia than dipyridamole alone. Therefore, it is recommended whenever possible.

Aged↗
PubMed1989

A trial of dipyridamole and aspirin in the prevention of smoking-induced changes in platelets and endothelium in men with coronary artery disease.

A random-order, double-blind crossover study compared the effects of placebo, dipyridamole and dipyridamole plus aspirin on smoking-induced changes in endothelium and platelets. Each of 12 male habitual smokers with coronary artery disease was given dipyridamole (75 mg) and aspirin (324 mg), dipyridamole (75 mg) and placebo for aspirin, or a placebo for each drug 3 times daily for 1 week before each of three 20-minute periods (separated by 2 weeks) of smoking 2 cigarettes after a 12-hour period of abstinence. During each period of smoking there were increases in the mean values of the plasma concentrations of beta-thromboglobulin, platelet factor 4 and nicotine, the endothelial cell count and the blood level of carboxyhemoglobin. In addition, the mean platelet aggregate ratio decreased during each period. After administration of placebos for both dipyridamole and aspirin, the respective mean values +/- standard deviations before and after smoking were 28 +/- 8 and 30 +/- 7 ng/ml (beta-thromboglobulin), 7.4 +/- 1.0 and 8.2 +/- 1.4 ng/ml (platelet factor 4), 3.7 +/- 0.6 and 15.7 +/- 3.5 ng/ml (nicotine), 4.2 +/- 1.4 and 5.4 +/- 1.7/counting chamber (endothelial cell count), 5.0 +/- 2.2 and 6.6 +/- 2.2% (carboxyhemoglobin) and 0.80 +/- 0.07 and 0.68 +/- 0.10 (platelet aggregate ratio). Each of the differences between the means before and after smoking was statistically significant (p less than or equal to 0.02). Neither dipyridamole alone nor in combination with aspiring significantly affected the mean smoking-induced change in any of these variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Prognostic utility of predischarge dipyridamole-thallium imaging compared to predischarge submaximal exercise electrocardiography and maximal exercise thallium imaging after uncomplicated acute myocardial infarction.

The prognostic value of predischarge dipyridamole-thallium scanning after uncomplicated myocardial infarction was determined by comparison with submaximal exercise electrocardiography and 6-week maximal exercise thallium imaging and by correlation with clinical events. Two endpoints were defined: cardiac events and severe ischemic potential. Of the 40 patients studied, 8 had cardiac events within 6 months (1 died, 3 had myocardial infarction and 4 had unstable angina requiring hospitalization). The finding of any redistribution on dipyridamole-thallium scanning was common (77%) in these patients and had poor specificity (29%). Redistribution outside of the infarct zone, however, had equivalent sensitivity (63%) and better specificity (75%) for events (p less than 0.05). Both predischarge dipyridamole-thallium and submaximal exercise electrocardiography identified 5 of the 8 events (p = 0.04 and 0.07, respectively). The negative predictive accuracy for events for both dipyridamole-thallium and submaximal exercise electrocardiography was 88%. In addition to the 8 patients with events, 16 other patients had severe ischemic potential (6 had coronary bypass surgery, 1 had inoperable 3-vessel disease and 9 had markedly abnormal 6-week maximal exercise tests). Predischarge dipyridamole-thallium and submaximal exercise testing also identified 8 and 7 of these 16 patients with severe ischemic potential, respectively. Six of the 8 cardiac events occurred before 6-week follow-up. A maximal exercise thallium test at 6 weeks identified 1 of the 2 additional events within 6 months correctly. Thallium redistribution after dipyridamole in coronary territories outside the infarct zone is a sensitive and specific predictor of subsequent cardiac events and identifies patients with severe ischemic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole↗
PubMed1991

Prediction of major cardiac events after peripheral vascular surgery using dipyridamole echocardiography.

Patients undergoing peripheral vascular surgery are at increased risk of postoperative cardiac complications. To evaluate the role of dipyridamole echocardiography in predicting major cardiac events, 109 unselected patients undergoing elective peripheral vascular surgery were prospectively studied. Preoperative dipyridamole echocardiograms were interpreted by an echocardiographer unaware of all clinical data. Patients were followed up until hospital discharge by research physicians without knowledge of dipyridamole echocardiography results. Outcomes were classified using strict predefined criteria by reviewers unaware of other clinical and echocardiographic data. Of the 109 patients, 9 (8%) had positive studies defined as development of new regional wall motion abnormalities or worsening of preexistent wall motion abnormalities. Of these 9 patients, 7 had postoperative events, including 3 cardiac deaths, 1 nonfatal myocardial infarction, 2 with unstable angina, and 1 with pulmonary edema. Only 1 event occurred among the 100 patients with negative studies. The sensitivity and specificity of dipyridamole echocardiography for predicting cardiac events after vascular surgery were 88 and 98%, respectively; the positive and negative predictive values were 78 and 99%. The relative risk of having a cardiac event if dipyridamole echocardiography was abnormal was 78 (95% confidence interval, 11 to 564; p less than 0.0001). If these results are extended and confirmed by other investigators, preoperative dipyridamole echocardiography may be an important screening test for patients undergoing elective peripheral vascular surgery.

Aged↗
PubMed1991

Comparison of usefulness of high-dose dipyridamole echocardiography and exercise electrocardiography for detection of asymptomatic restenosis after coronary angioplasty.

The present study compares the relative usefulness of the maximal treadmill exercise electrocardiography test with the high-dose dipyridamole echocardiography test (echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg in 10 minutes) in detecting severe restenosis or coronary artery disease progression (greater than 70% stenosis) in asymptomatic patients 12 months after a primary successful coronary angioplasty. Criteria of positivity were: for the exercise electrocardiography test, an ST-segment shift greater than or equal to 0.1 mV from baseline, 0.08 second from the J point; for the dipyridamole echocardiography test, a transient dyssynergy of contraction, absent or of a lesser degree than that in the baseline examination. The exercise electrocardiography and dipyridamole echocardiography tests revealed a similar feasibility (91 vs 87%, difference not significant). Both tests could be performed in 75 patients. For detection of restenosis or disease progression, or both, the exercise electrocardiography test revealed a sensitivity similar to the dipyridamole echocardiography test (71 vs 71%, difference not significant), but a lower specificity (61 vs 90%). It is concluded that the high-dose dipyridamole echocardiography test is equally feasible but more accurate than the exercise electrocardiography test for noninvasive detection of severe asymptomatic restenosis or disease progression at 1 year after successful coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1991

Evaluation of dipyridamole-Doppler echocardiography for detection of myocardial ischemia and coronary artery disease.

Doppler assessment of left ventricular filling and ejection during dipyridamole stress may supplement wall motion analysis for detection of myocardial ischemia and coronary artery disease (CAD). Thirty-four patients taking no cardioactive therapy were studied using intravenous dipyridamole (0.6 mg/kg) during 2-dimensional and pulsed Doppler echocardiography. Twelve patients had normal coronary arteries (group 1) and the remainder, who had significant CAD, were divided into groups 2 (n = 11) and 3 (n = 11). Only subjects in group 2 developed myocardial ischemia manifest as reversible regional asynergy and ST-segment depression. Heart rate increased (16 +/- 9 beats/min, p less than 0.01) and mean blood pressure decreased (-5 +/- 8 mm Hg, p = not significant) uniformly across groups. Exaggerated hyperkinesia of normally contracting wall segments was the common response to dipyridamole infusion in patients with CAD. The respective mean percent changes in peak early diastolic velocity, peak atrial velocity, their ratio and ejection peak velocity, and mean acceleration for groups 1 (20, 42, -13, 20 and 23%), 2 (22, 32, -2, 10 and 14%) and 3 (23, 33, -6, 16 and 18%) were similar. Comparisons between normal patients and those with CAD and between groups 2 and 3 revealed no significant differences in the effect of dipyridamole on any variable. However, a decrease in both peak velocity and mean acceleration of left ventricular ejection was seen in 3 of 4 group 2 patients who developed severe ischemia. Dipyridamole-Doppler echocardiography is insensitive for detection of CAD and appears unable to identify myocardial ischemia unless this is severe. Hemodynamic changes and compensatory wall motion induced by dipyridamole may explain these findings.

Adult↗
PubMed1992

Assessment of left ventricular function in Kawasaki disease by dipyridamole-loading cineventriculography.

Dipyridamole-loading cineventriculography was performed to evaluate left ventricular (LV) function in 76 patients with Kawasaki disease. Forty-five of 76 patients underwent the procedure within 6 months from the onset of illness (group 1A, normal findings on coronary angiogram; group 1B, maximal diameter of coronary lesions less than 4 mm; group 1C, maximal diameter of coronary lesions greater than 4 mm). Thirty-one of 76 patients underwent the procedure greater than 6 months after onset (group 2A, coronary lesions improved to normal or less than 4 mm; group 2B, remaining coronary lesions greater than 4 mm; group 2C, stenosis or obstruction of the coronary artery). Global LV ejection fraction increased in groups 1A, 1B and 2A after infusion of dipyridamole, but there was no significant change in groups 1C, 2B and 2C. In analyzing LV excursion, the pattern of LV wall motion with dipyridamole in groups 1B and 2A were similar to that in group 1A, but in 38% (5 of 13) of group 2A patients, abnormal regional LV wall motion after administration of dipyridamole was detected. Abnormal LV wall motion after dipyridamole infusion was detected in 42% (5 of 12) of group 1C patients, 38% (3 of 8 cases) of group 2B patients and 70% (7 of 10 cases) of group 2C patients. In conclusion, analysis of LV wall motion with dipyridamole is useful in evaluating cardiac involvement in Kawasaki disease.

Child↗
PubMed1992

ST-segment depression during dipyridamole infusion, and its clinical, scintigraphic and hemodynamic correlates.

The goal of this study was to determine whether dipyridamole-induced ST-segment depression reflects more severe or extensive myocardial hypoperfusion than the absence of this electrocardiographic finding. The clinical, hemodynamic and scintigraphic correlates of ST-segment depression during intravenous dipyridamole infusion were studied in 204 consecutive patients undergoing dipyridamole stress thallium-201 (Tl-201) imaging for evaluation of coronary artery disease. Of 182 patients with a diagnostic baseline electrocardiogram, 28 (15%) developed ST depression after dipyridamole. Patients with ST depression, compared with those without, were older (64 +/- 1 vs 60 +/- 1 years; p less than 0.03) and had a higher frequency of chest pain (57 vs 23%; p less than 0.001) and a higher heart rate-blood pressure product (12.7 +/- 0.6 vs 11.2 +/- 0.2 x 10(3); p less than 0.008) after dipyridamole. Patients with ST depression were more likely to have Tl-201 redistribution (64 vs 38%; p less than 0.02) and a greater number of redistribution defects (2.3 +/- 0.04 vs 0.9 +/- 0.1, p less than 0.001) than were those without ST depression. By multivariate logistic regression analysis, the most powerful correlate of ST depression was the number of segments having Tl-201 redistribution (p less than 0.001). Other independent correlates were presence of chest pain, heart rate at Tl-201 injection, and age. Thus, the determinants of dipyridamole-induced ST-segment depression include the scintigraphic extent of reversible hypoperfusion, as well as indexes of myocardial oxygen demand.

Aged↗
PubMed1992

Effect of dipyridamole therapy on myocardial ischemia in patients with stable angina pectoris receiving concurrent anti-ischemic therapy.

The effects of oral dipyridamole on exercise performance and anginal symptoms were evaluated in 15 men with stable angina pectoris. In a double-blind, randomized, crossover design, patients received 75 mg of dipyridamole or placebo every 8 hours for 2 weeks in addition to their previously prescribed cardiac medications. Graded exercise tolerance testing was performed twice before randomization, at the end of each treatment period, and after single-blind placebo washout. When compared with baseline tests, the time to onset of 0.1 mV ST-segment depression was similar between dipyridamole and placebo treatments (316 +/- 89 vs 345 +/- 102 seconds, respectively, p = not significant). No significant differences existed between treatments in the peak systolic blood pressure-heart rate product or in the duration of exercise. Angina pectoris occurred during all 3 baseline exercise tests in 7 of the 15 subjects; the time to onset of angina was unchanged by either treatment. Analysis of symptom diaries conducted in 13 patients revealed no significant alteration in reported anginal symptoms during dipyridamole treatment compared with placebo treatment (0.6 +/- 0.9 vs 0.3 +/- 0.4 episodes per week). Ambulatory electrocardiographic monitoring in 12 patients revealed few episodes of ischemia during daily activities with no alteration in frequency of episodes during treatment periods. Plasma concentrations of dipyridamole did not correspond with the outcomes of exercise testing. It is concluded that chronic oral dipyridamole therapy given in its usual clinical dose does not adversely affect exercise performance, daily anginal episodes or ambulatory ischemia in patients receiving concurrent anti-ischemic medication.

Aged↗
PubMed1992

Effects of the dipyridamole test on left ventricular function in coronary artery disease.

The dipyridamole stress test is used with thallium-201 to detect areas of inhomogeneity of blood flow that point to coronary artery disease (CAD). It is unclear whether dipyridamole produces inhomogeneous perfusion only or whether it actually decreases net flow in the obstructed vessels and produces true ischemia. It is also unclear what effect dipyridamole has on global and segmental left ventricular function. Therefore, ejection fraction, segmental wall motion and ventricular volume equivalents were measured before and after dipyridamole in 113 patients and 32 normal subjects. Ejection fraction responded in an abnormal fashion in 98 patients (87%), decreasing from 49 +/- 11% to 43 +/- 13% (p less than 0.0001), whereas it increased in 29 normal subjects (90%) from 57 +/- 6% to 64 +/- 10% (p less than 0.0001). Wall motion worsened distinctly in 75 patients (66%), and pressure/volume ratio deteriorated in 72%. The effect of dipyridamole lasted between 10 and 25 minutes, but was promptly reversed by aminophylline. These findings indicate that dipyridamole generally induces true ischemia in CAD. Furthermore, the degree of dysfunction is related to the angiographically assessed severity of CAD. The shortness of breath (seen in 10% of patients) may be partially explained by the findings, and it seems advisable to give aminophylline to every patient in order to promptly correct left ventricular dysfunction.

Adult↗
PubMed1993

Digital dipyridamole stress echocardiography in silent ischemia after coronary artery bypass grafting and/or after healing of acute myocardial infarction.

This study evaluates dipyridamole stress echocardiography in silent ischemia. Fourteen patients with previous coronary artery bypass grafting (group A) and 16 patients with healed myocardial infarction (group B) were studied. All had > or = 1 mm ST depression without chest pain during bicycle exercise testing. Left ventricular wall motion was analyzed using a computerized display of digital systolic cineloops with a high frame rate. Test results were compared with coronary angiography. Dipyridamole echocardiography accurately identified patients with significant coronary artery stenosis in both groups (3 of 4 in group A, 11 of 14 in group B). Retrograde flow to the occluded native artery was associated with positive results on dipyridamole testing in 6 of 7 patients in group A and all 3 in group B. Sensitivity, specificity and diagnostic accuracy for detecting significant coronary stenosis or occlusions with retrograde flow was 78, 100 and 83%, respectively. Patients with angiographic multivessel disease had a significantly larger increase in wall motion score index during dipyridamole stress than patients with 0- or 1-vessel disease, 0.18 +/- 0.11 versus 0.05 +/- 0.18 (p < 0.05). Two patients developed symptomatic bradycardia and hypotension during dipyridamole infusion. It is concluded that dipyridamole echocardiography accurately identifies myocardial regions with restricted coronary flow. Stress echocardiography is a valuable tool for assessing coronary flow in silent ischemia.

Adult↗
PubMed1986

Amphotericin B renders stationary phase hepatoma cells sensitive to dipyridamole.

This study provides evidence that the dipyridamole inhibitory effect on nucleoside incorporation changed with culture time. Lag and log phase hepatoma 3924A cells were highly sensitive to dipyridamole with IC50 values for thymidine incorporation of 0.20 and 0.31 microM, respectively. In contrast, stationary phase cells were comparatively insensitive to dipyridamole with an IC50 of 38.9 microM. Amphotericin B (10 microM) restored the sensitivity of stationary phase cells to dipyridamole, lowering the IC50 value for thymidine incorporation to 0.25 microM. Amphotericin B also enhanced the cytotoxicity of dipyridamole to hepatoma 3924A cells. The combination of amphotericin B and dipyridamole may be useful in cancer chemotherapy.

Amphotericin B↗
PubMed1986

Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole. The role of methotrexate polyglutamates.

MTX and dipyridamole are synergistic in their toxicity towards the MDA.MB.436 human breast cancer cell line. Dipyridamole increases net MTX uptake into the cells and increases the intracellular levels of MTXG7 to G10, the highest molecular weight polyglutamyl derivatives of MTX detected. During a recovery period, after completion of exposure to MTX with and without dipyridamole, levels of MTXG7 to G10 remained elevated in dipyridamole treated cells by comparison with controls. Dipyridamole, which has no intrinsic effect on cell growth, transforms a cytostatic response of MDA.MB.436 cells towards MTX into a cytotoxic response. The effect of dipyridamole is not mediated through an increase in prostacyclin biosynthesis.

Arachidonic Acid↗
PubMed1994

Dipyridamole inhibits the oxidative modification of low density lipoprotein.

The oxidative modification of low density lipoprotein (LDL) is believed to play an important role in the initiation of the atherosclerotic lesion. Dipyridamole, which is used clinically as a coronary vasodilator and an antiplatelet agent, has antioxidant properties. Probucol is a lipid-lowering agent which inhibits the oxidative modification of LDL. We have compared the effect of pharmacological concentrations of dipyridamole and probucol on the oxidative modification of LDL by copper or endothelial cells in vitro. Dipyridamole protected LDL from oxidative modification by either copper ions or endothelial cells at concentrations as low as 2.5 microM while probucol had no effect at this concentration. LDL oxidized with copper in the presence of dipyridamole (20 microM) was less effective than LDL oxidized in the absence of dipyridamole at inhibiting [3H]acetyl-LDL binding to cultured human. THP-1 monocyte derived macrophages. The concentrations of dipyridamole found to inhibit the oxidative modification of LDL in vitro are achieved in vivo using clinically recommended doses.

Cells, Cultured↗
PubMed1982

A study of the stimulation of human venous prostacyclin synthesis by dipyridamole.

The synthesis of prostacyclin by human venous tissue in vitro and the effects of aspirin and dipyridamole thereon were investigated. Dipyridamole significantly stimulated prostacyclin production in a concentration range of 25 to 100 microM. Dipyridamole significantly attenuated the inhibitory effect of 0.1 mM aspirin in a concentration range of 12.5 to 100 microM. Isobutylmethylxanthine 0.1 mM, an unrelated inhibitor of phosphodiesterase, had similar effects to dipyridamole. Cyclic AMP 3.0 mM had an inhibitory effect on prostacyclin synthesis in the presence of dipyridamole. Adenosine 0.1 mM and nitrobenzylthioguanosine 0.1 mM, an inhibitor of adenosine uptake, did not significantly influence prostacyclin synthesis in this system. We conclude that the stimulation of prostacyclin synthesis by dipyridamole is unrelated to the ability of this drug to block the high-affinity uptake of adenosine by endothelial cells and that the effect may also be independent of changes in the concentration of cAMP induced by the drug.

Aspirin↗