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PubMed1982

Assessment of diagnostic value of dipyridamole testing in angina pectoris.

In order to assess the diagnostic value of dipyridamole (D) testing, we studied the responses of 34 patients with chest pain and 10 normal subjects. Blood pressure and 12-lead ECG were recorded during and after intravenous infusion of 0.6 mg/kg dipyridamole for 10 minutes. Coronary arteriography and maximal or symptom-limited exercise tests were performed in the 34 patients with chest pain. During infusion 13 patients presented ischemic ST changes and 5 with anginal pain only. The latter group had normal coronary arteries. Among the 13 patients with ischemic ST changes, 7 had at least two critical coronary stenoses and the remaining 6 had no coronary lesions. Dipyridamole tests showed poor sensitivity (44%) and specificity (39%) with respect to coronary arteriography. The relatively high number of positive responses in subjects with normal coronary arteries indicates that the coronary steal phenomenon is not the sole cause of "ischemic" response to the drug. Indirect indexes of myocardial oxygen consumption were higher in patients with a positive response to drug infusion than in those with a negative response; however the value of rate-pressure product at infusion end never reached that observed at ischemic threshold during exercise testing in the same patient. This suggests that neither can oxygen consumption increase be considered as entirely responsible for ischemic response to dipyridamole. In conclusion dipyridamole test cannot be proposed for predicting critical coronary stenoses.

Adult↗
PubMed1987

Does the combination with handgrip increase the sensitivity of dipyridamole-echocardiography test?

The aim of this study was to assess the possibility of increasing the sensitivity of dipyridamole-echocardiography testing (DET:2-D echo monitoring during dipyridamole infusion) by combining this procedure with handgrip testing. Dipyridamole-handgrip test (DHT) was therefore performed in 24 patients with rest/effort angina, negative DET, and negative handgrip-echo (without dipyridamole pretreatment). DHT consisted of 4.5 min of sustained 25% maximum grip strength, started 4 min after the end of dipyridamole infusion (0.56 mg/kg for 4 min). Interpretable studies were obtained in all patients. Of the 24 patients tested (10 without and 14 with significant coronary artery disease, CAD), only one CAD patient had a positive DHT, which indicates an increased sensitivity of 7% versus DET alone. In conclusion, DHT is feasible in all patients and--if compared to DET--has the same specificity. However, in spite of the theoretical premises, it provides only a modest step up in sensitivity.

Angina Pectoris↗
PubMed1991

Long-term prognostic value of a normal dipyridamole thallium-201 perfusion scan.

In a 4-year period, 84 patients who were referred for a dipyridamole thallium-201 stress test to rule out significant coronary artery disease had normal scans. A dipyridamole study was recommended instead of exercise because of arthritis, severe obesity, peripheral vascular disease, pulmonary disease, other chronic illnesses, or combinations of these problems. All patients had three-view (i.e., anterior, shallow left anterior oblique, and steep left anterior oblique) planar thallium-201 imaging 10 minutes and 3.5 hours after administration of 0.6 mg/kg of intravenous dipyridamole. The patients were followed for 42 +/- 13 (range 1-58) months to document the cardiac event rate. Of the 84 patients with normal results, 14 died during the follow-up period from noncardiac causes. Three other patients died 29-51 months after the test due to an acute myocardial infarction, a probable acute myocardial infarction, and sudden cardiac death, respectively. Of the survivors, 5 suffered an acute myocardial infarction 28-50 months after the dipyridamole thallium scan and 1 had coronary artery bypass grafting due to increasing angina pectoris 58 months after the scan (overall cardiac event rate of 0.4% per year). Of the remaining 61 patients, 39 (64%) were asymptomatic, 20 (33%) had the same symptoms they had at the time of testing without significant deterioration, while 2 patients (3%) had deterioration of their chest pains but no cardiac complication. Thus, in this group of patients, a normal dipyridamole thallium-201 perfusion scan predicted a good cardiovascular outcome for at least 24 months following the test.

Adult↗
PubMed1996

Prediction of in-hospital cardiac events using dipyridamole-thallium scintigraphy performed very early after acute myocardial infarction.

BACKGROUND AND HYPOTHESIS: Ischemic complications occur frequently during hospitalization after acute myocardial infarction. Dipyridamole-thallium scintigraphy performed early after admission can detect residual ischemia, may have additional prognostic value and be useful in the management of these patients. METHODS: Dipyridamole infusion and 201thallium imaging were performed on the third day of infarction in 114 consecutive patients. Coronary angiography was performed before hospital discharge in 90% of patients and exercise testing was performed at the time of discharge in patients without contraindications. RESULTS: Side effects occurred in 28 patients, but they were mild and transient or rapidly reversed with intravenous aminophylline. During hospitalization, three patients died and four had a nonfatal reinfarction. Patients with these major cardiac events had previously shown a higher prevalence of reversible perfusion defects during testing (71 vs. 31%, p < 0.05). In addition, 19 patients had early recurrent ischemia requiring early in-hospital revascularization. Overall, cardiac events defined as death, reinfarction, or early myocardial revascularization occurred in 22 patients. Of the patients with these events, 68% had thallium redistribution on initial myocardial scanning compared with 25% of patients without events (p = 0.0001). Patients with cardiac events also showed a higher number of myocardial segments with reversible perfusion defects (1.8 +/- 2.2 vs. 0.6 +/- 1.3, p = 0.001). Logistic regression analysis revealed that among all the other clinical, scintigraphic, and angiographic variables, the presence of thallium redistribution on the dipyridamole-thallium scan was the only independent predictor of cardiac events, increasing the risk by sixfold. Furthermore, during a 1-year follow-up, 14 other patients had ischemic events. Of these, 64% had previously shown thallium redistribution during early dipyridamole testing compared with 19% of patients without cardiac events (p < 0.001). CONCLUSIONS: Intravenous dipyridamole-thallium-scintigraphy performed very early after myocardial infarction is safe and useful to predict in-hospital ischemic events.

Aged↗
PubMed2000

Dipyridamole-induced reversible thallium-201 defect in patients with vasospastic angina and nearly normal coronary arteries.

BACKGROUND: Dipyridamole is a vasodilator of resistance vessels and has no vasoconstrictive effect on large coronary arteries. HYPOTHESIS: The present study used dipyridamole thallium-201 (201Tl) scintigraphy to clarify the role of microvasculature in coronary flow limitation in patients with vasospastic angina and normal coronary arteries. METHODS: Sixteen patients underwent dipyridamole and exercise 201Tl scintigraphy and provocative coronary angiography with acetylcholine. All patients showed coronary spasm (> 90% vasoconstriction concomitant with ST change) in at least one vessel. RESULTS: Dipyridamole or exercise caused only ST depression despite the ST elevation observed at spontaneous attack. Dipyridamole 201Tl scintigraphy demonstrated the reversible defects (11 cases), as did exercise 201Tl scintigraphy (13 cases). The region of 201Tl defect was not always consistent with the territories of angiographically depicted vasospastic arteries. Basal coronary tone, assessed by percentage of diameter change of epicardial arteries from baseline to isosorbide dinitrate administration, did not differ between the positive and the negative defect regions. CONCLUSION: These results support the hypothesis that, in addition to epicardial coronary spasm, the dysfunction of microvasculature is responsible for abnormal coronary perfusion in the subgroup of patients with vasospastic angina and normal coronary arteries.

Angina Pectoris↗
PubMed1994

Dipyridamole inhibits early wound healing in rat skin incisions.

In an effort to investigate the significance of platelet aggregation on early wound healing, the inhibitory effects of an antiplatelet drug (dipyridamole) on tensile wound strength was assessed. The breaking strength of the dorsal incisional wounds in Donryu rats both with and without the administration of dipyridamole was measured. In experiment I, the intraperitoneal administration of dipyridamole (100 mg/kg/day, Group A; 50 mg/kg/day, Group B) and saline (3 ml/day; Group C) was performed during the periods between the day of incision and the excision of the healing wound specimen in a 2.0-cm width on the third and seventh postoperative days (POD). The wound breaking strength was 229 +/- 44, 256 +/- 39, and 352 +/- 38 g/cm2 on POD 3 and 477 +/- 67, 578 +/- 60, and 764 +/- 31.9 g/cm2 on POD 7, in Groups A, B, and C, respectively. In experiment II, we performed the intraperitoneal administration of either dipyridamole (100 mg/kg) or 3 ml of saline as a control just before incision (Group a) as well as at 4 hr (Group b), and 12 hr (Group c) after incision, and the percentages of tensile strength compared with the control were 72 +/- 8, 89 +/- 13, and 103 +/- 23% in Groups a, b, and c, respectively. The administration of dipyridamole significantly inhibited the wound healing and, therefore, platelet aggregation would appear to play an important role in the early phase of wound healing.

Animals↗
PubMedDate not supplied

Short-term effect of dipyridamole on blood flow velocities in the extraocular vessels.

Dipyridamole is known to inhibit platelet aggregation and to induce vasodilatation. It has been shown that dipyridamole increases blood flow in various tissues in humans as well as in the eyes of animals. We studied the influence of dipyridamole in a prospective open trial in 23 patients with impaired ocular circulation due to different causes, based on experienced clinical judgement, such as anterior ischemic optic neuropathy, vasospastic syndrome, glaucoma, or central retinal vein occlusion. Blood flow velocities in the ophthalmic artery, central retinal artery and vein, one lateral and one medical posterior ciliary artery were measured using a Siemens Quantum 2000 color Doppler device. Blood flow velocities were measured before and under treatment. Dipyridamole increased blood flow velocities significantly in all vessels measured. Therefore, it seems promising to evaluate the effect of dipyridamole over a longer period in patients with impaired ocular blood flow.

Adult↗
PubMed1982

Pharmacokinetics of oral dipyridamole (Persantine) and its effect on platelet adenosine uptake in man.

Two preparations of dipyridamole have been studied by oral administration to 11 normal volunteers. The plasma levels of dipyridamole and its glucuronide were determined simultaneously by high performance liquid chromatography. The instant form (I.F., 100 mg) was administered four times daily and the slow release preparation (SRP, 200 mg) twice daily, for 3 days. Multiple blood samples were collected on Days 1-4 to provide plasma for assay, and simultaneously, platelet rich plasma was prepared for ex vivo study of the effect of dipyridamole on platelet uptake of adenosine. The pharmacokinetics of absorption and distribution of dipyridamole were described using a two compartment model with lag time and prolonged absorption. Strong inhibition of the platelet adenosine uptake was observed at therapeutic plasma levels. The inhibition of platelet adenosine uptake may be related to some of the pharmacological properties of dipyridamole.

Absorption↗
PubMed1976

Release of noradrenaline proposed as a mechanisms for the positive inotropic action of dipyridamole.

In the arterially blood-perfused canine papillary muscle, i.a. injections of dipyridamole (10-300 mug) produced a dose-dependent increase in developed tension amounting to about 45% of the basal developed tension at 300 mug. The positive inotropic response to dipyridamole was greatly reduced by a prior i.a. injection of propranolol (10 mug) or by pretreatment with reserpine (0.2 mg/kg s.c. for 3 consecutive days) but not affected by a prior i.a. injection of tetrodotoxin (1 mug) or desmethylimipramine (3-10 mug). The positive inotropic response to dipyridamole reduced by pretreatment with reserpine was restored by i.a. infusion of noradrenaline (0.03 mug/min). Dipyridamole did not modify the positive inotropic responses to noradrenaline and tyramine. These results suggest that the positive inotropic response to dipyridamole is largely due to noradrenaline released from adrenergic nerve endings by a mechanism that differs from those operative in the action of tyramine or in liberation of noradrenaline upon excitation.

Animals↗
PubMed1989

Myocardial 201Tl washout after combined dipyridamole submaximal exercise stress: reference values from different patient groups.

Dipyridamole stress is favorable in patients unable to exercise maximally for 201Tl myocardial scintigraphy. Aside from an analysis of uptake defects, proper washout analysis can be limited by heart rate variations when isolated dipyridamole stress is used. Heart rate standardized 201Tl washout kinetics after a combined dipyridamole and submaximal exercise stress protocol (CDSE), feasible in elderly patients as well as in patients with peripheral artery disease, were therefore studied to investigate the 201Tl washout after CDSE in differently defined patient groups: Group I comprised 19 patients with documented heart disease and angiographically excluded coronary artery disease (CAD); group II contained 17 patients with a very low likelihood of CAD determined by both normal exercise radionuclide ventriculography and normal 201Tl uptake. Group III comprised 56 patients with a 50% pretest likelihood of CAD but normal 201Tl uptake. Mean washout values were nearly identical in all groups. Despite similar uptake patterns, however, washout standardized by CDSE was significantly lower than the normal washout values after maximal treadmill exercise. Thus an obviously lower 201Tl washout after CDSE than after maximal treadmill exercise must be considered if washout analysis criteria after dipyridamole are applied to evaluate ischemic heart disease. Nevertheless, heart rate elevation achieved by additional submaximal exercise stress seems necessary, adequate and clinically safe for standardisation of washout analysis in dipyridamole 201Tl scintigraphy.

Adult↗
PubMedDate not supplied

Effect of dipyridamole on the blood flow in coronary aneurysms resulting from Kawasaki disease.

Dipyridamole has been widely used in Japan to treat patients with a coronary aneurysm resulting from Kawasaki disease, but its effect in these patients has not been established. In the present study we assessed the effect of dipyridamole on the coronary arteries of patients with a history of Kawasaki disease by measuring the diameter of the coronary arteries and by quantifying the disappearance time of contrast medium (runoff time) on coronary angiography. Intravenous injection of dipyridamole increased the diameter of nondilated arteries by 7.9%. Its effect on the diameter of dilated coronary arteries (coronary aneurysm) was less than 3% (p < 0.01). Runoff time of dilated coronary arteries was significantly (p < 0.01) greater than that of nondilated coronary arteries. Dipyridamole accelerated runoff time not only in nondilated coronary arteries (p < 0.01) but also in coronary arteries with various degrees of dilatation (p < 0.01). We conclude that dipyridamole increases blood flow in coronary arteries without dilating the proximal aneurysm in children with a history of Kawasaki disease.

Child↗
PubMed1990

Dipyridamole combined with symptom-limited exercise for myocardial perfusion scintigraphy: image characteristics and clinical role.

Although dipyridamole can be used with myocardial scintigraphy to demonstrate reversible perfusion defects, combining exercise with the pharmacologic tool could improve image quality and information yield. The incidence of perfusion defects and the quality of thallium 201 images were reviewed in a series of 820 patients who had been assigned to a specific stress-test mode. Supine bicycle exercise alone was used (group I) where no pharmacologic or physical factors (e.g., beta-blockers, arthritis) limited performance; otherwise, intravenous dipyridamole was followed by symptom-limited exercise (group II). Angiographic correlation was available in 57 patients in group I, and in 158 in group II; of these, 109 performed significant exercise (greater than or equal to 3 min at increasing workloads) following dipyridamole (group IIA), whereas in 49 (group IIB) the exercise phase following dipyridamole was truncated. All test-mode groups were similar with respect to the incidence of ST segment depression during testing, patient throughput, and the sensitivity of perfusion defects. Chest pain and reversible defects were induced more frequently in group II than in group I. In group IIA, splanchnic background activity was lower (P less than 0.001) than in group IIB, and the false-positive rate tended to be lower. Thus, combining exercise with dipyridamole in patients with non-cardiac limitations to exercise enabled the achievement of optimal results for perfusion scintigraphy.

Cardiac Catheterization↗
PubMed1995

Does dyspnoea during dipyridamole cardiac stress testing indicate bronchospasm and is the pretest clinical history predictive of this side-effect?

This study investigates the acute effects of intravenous dipyridamole (0.7mg/kg) on pulmonary airflow in relation to clinical parameters suggestive of chronic obstructive pulmonary disease (COPD) in order to assess predictive and causative factors of dyspnoea during cardiac stress testing. Mild pulmonary airflow obstruction was noted in all patients, but reached statistical significance only in small airways (FEF75-85%: -7%; P=0.034). The changes in pulmonary function parameters were independent of the clinical history. Dyspnoea under dipyridamole stress testing occurred in parallel with angina, yet was not associated with ischaemic or non-ischaemic left ventricular dysfunction. These data do not support the use of dipyridamole stress testing in asthmatics, but show that (1) the acute effects of a diagnostic dose of dipyridamole on pulmonary airflow are mild even in patients with a history suggestive of COPD and (2) dyspnoea during dipyridamole testing is not necessarily indicative of bronchospasm.

Adult↗
PubMed1976

[The effect of antiaggregating agents - acetylsalicylic acid (ASA) and dipyridamol - on the rejection of allotransplanted canine kidneys in presensitized animals (author's transl)].

The effect of antiaggregating agents - acetylsalicyclic acid (ASA) and dipyridamol - on the rejection of allotransplanted canine kidneys in presensitized animals were studied. Blood flow dropped more markedly in the control group than in the group treated with ASA and dipyridamol. 24 hours after transplantation the blood flow in this group was significantly higher than in the control group (p 2,5 %) and in the third group treated with dipyridamol alone. The cellular rejection started earlier and was more pronounced in the control group. Only in this group vascular rejection and microthrombi were demonstrated. Urine output ceased 24 to 60 hours after transplantation. The immunosuppressive, antiphlogistic and platelet antiaggregating effect of the combined ASA and dipyridamol therapy is thought to be responsible for the better results in this group. In this experimental model the combined treatment of ASA and dipyridamol results in a later onset of cellular rejection, in better blood-flow of the kidney and later onset of anuria.

Animals↗
PubMedDate not supplied

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog.

The effects of 3 different doses (0.02, 0.1, 0.5 mg/kg/h) of dipyridamole on myocardial infarct size were evaluated in pentobarbital anesthetized open-chest dogs following sequential coronary occlusion of two medium sized coronary arteries in the same heart. The first coronary occlusion produced a control infarct, the other a test infarct under the influence of the drug. Dipyridamole infusion was started 10 min before the second occlusion at a rate of 0.02 (group A, n = 9), 0.1 (group B, n = 10) or 0.5 (group C, n = 9) mg/kg/h respectively and continued to the end of reperfusion (90 min). Biopsy samples were obtained at the end of each occlusion period and at the end of the second reflow period. Infarct size was determined using post mortem angiography and pNBT staining. Control and treated infarct sizes, expressed as a percentage of the perfusion area, were 21.9 +/- 5.4% vs. 25.2 +/- 7.7% in group A (n = 9), 21.8 +/- 7.3% vs. 18.3 +/- 5.2% in group B (n = 9), and 22.3 +/- 7.7% vs. 16.2 +/- 4.8% in group C (n = 8). There were no significant differences between control and treated infarct sizes in the 3 groups. After 90 min coronary occlusion tissue adenosine contents in the ischemic myocardium were significantly higher (42 +/- 7 nmol/gww in group C and 40 +/- 5 nmol/gww in group B) than those in the nonischemic myocardium, and dipyridamole enhanced these levels (395 +/- 6 nmol/gww in group C: p less than 0.01, 55 +/- 10 nmol/gww in group B). Dipyridamole did not affect the tissue inosine levels in the ischemic myocardium after 90 min coronary occlusion. ATP and creatine phosphate levels were not affected by dipyridamole during ischemia or during reflow. The accumulated adenosine was not phosphorylated to AMP and on to ATP upon reperfusion.

Adenosine↗
PubMedDate not supplied

Comparison of exercise, dipyridamole, and adenosine by use of technetium 99m sestamibi tomographic imaging.

BACKGROUND: Pharmacologic stress has been shown in animal studies to induce high degrees of myocardial hyperemia. At these levels of myocardial blood flow, the myocardial uptake of technetium 99m sestamibi may plateau and may affect the diagnostic accuracy. This study compared the effects of myocardial hyperemia induced by exercise, dipyridamole, and adenosine on 99mTc sestamibi tomographic imaging in normal subjects and patients with ischemic coronary artery disease. METHODS AND RESULTS: Twenty subjects (group I, 10 normal subjects; group II, 10 patients with known coronary artery disease) underwent 99mTc sestamibi tomographic imaging after rest, exercise, dipyridamole infusion, and adenosine infusions on separate occasions. Total and background-corrected myocardial counts of the resulting images were calculated. Visual and computer-generated quantitative myocardial perfusion defect analysis was performed in subjects in group II. For subjects in both groups I and II, there were no significant differences in the background-corrected myocardial counts obtained with exercise, dipyridamole, and adenosine stress. There were no significant differences in the myocardial perfusion defects obtained after the three different modes of stress, including percentage defect size, stress deficit percentage, percentage of ischemia, count deficit index, and defect nadir. CONCLUSIONS: The myocardial uptake of 99mTc sestamibi in normal subjects and patients with coronary artery disease is comparable after exercise, dipyridamole, and adenosine stress. In addition, the defect sizes and intensities with 99mTc sestamibi after all forms of stress were equivalent. Thus 99mTc sestamibi, in combination with either adenosine or dipyridamole infusions, provides imaging data equivalent to those with exercise and may be considered an alternative in patients unable to undergo adequate exercise.

Adenosine↗
PubMed2006

Adenosine and cytokine levels following treatment of rheumatoid arthritis with dipyridamole.

Adenosine can suppress the release of tumour necrosis factor-alpha (TNF-alpha) from activated monocytes and macrophages, and may contribute to the anti-inflammatory activities of methotrexate and sulphasalazine. Dipyridamole inhibits the cellular uptake and metabolism of adenosine and we have, therefore, examined the effects of dipyridamole in patients with rheumatoid arthritis in an attempt to alleviate their symptoms. Forty patients aged 18-75 years were randomised to receive dipyridamole 400 mg/day or placebo. Blood samples were taken at baseline and at monthly intervals for 6 months. Purines were determined by HPLC and cytokines by ELISA. After 3 months of treatment there were significant reductions in neopterin levels and in the modified Health Assessment Questionnaire score, but these were not maintained. Dipyridamole had no effect on disease severity or the levels of purine metabolites, interleukin-1beta (IL-1beta), IL-6, TNF-alpha, lipid peroxidation products, erythrocyte sedimentation rate or C-reactive protein. In conclusion, rheumatoid arthritis patients showed no clinical improvement following treatment with dipyridamole for 6 months.

Adenosine↗
PubMed1984

Effect of intravenous dipyridamole on regional coronary blood flow with 1-vessel coronary artery disease: evidence against coronary steal.

The effects of i.v. dipyridamole were studied in 9 patients with isolated total left anterior descending coronary artery (LAD) obstruction, in 6 patients with isolated 90 to 99% diameter reduction of the LAD and in 10 patients with normal coronary arteries and normal left ventricular function. Coronary sinus and great cardiac vein flows were determined by continuous thermodilution. Flows were measured at rest and 1, 3, 5 and 10 minutes after i.v. dipyridamole. Great cardiac vein flow represents the venous outflow from the LAD territory. In the presence of coronary steal from the LAD territory, great cardiac vein flow is expected to decrease while coronary sinus flow increases. Intravenous dipyridamole induced a similar flow increase in the coronary sinus and the great cardiac vein in all 3 groups (p less than 0.001 between rest and dipyridamole, difference not significant among groups), suggesting that no coronary steal was induced. The maximal increase in great cardiac vein flow was 118 +/- 74% in the control group, 86 +/- 74% in the group with 90 to 99% LAD obstruction and 102 +/- 29% in the group with total LAD obstruction (difference not significant). These data show that i.v. dipyridamole produces a similar increase in coronary flow in ischemic and nonischemic areas and suggests that an increase in collateral flow is the underlying mechanism for increased flow to the ischemic area.

Adult↗