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PubMed1993

Safety of intravenous dipyridamole thallium myocardial perfusion imaging: experience in 435 patients.

Dipyridamole stress 201Tl scintigraphy is widely used in the investigation of myocardial ischaemia. We report our experience of adverse effects observed during this diagnostic procedure. A prospective study was undertaken of 435 consecutive patients (mean age 59 years; 273 males) referred to two nuclear medicine departments for assessment of myocardial perfusion was undertaken. Patients were monitored prior to and following the infusion of dipyridamole. All symptomatic, haemodynamic and electrocardiographic changes were documented. No deaths occurred in this series. Adverse events were observed in 174 (40%) patients. Of these, three patients experienced 'major' adverse events (0.6%) requiring hospitalization (myocardial infarction = 1; chest pain = 1; simple partial seizure = 1). 'Moderate' adverse events occurred in 39 (8.9%) patients and required intravenous aminophylline to reverse effects (ST segment abnormalities = 26; nausea = 7 headache = 3; chest pain = 2; bronchospasm = 1; protracted vomiting = 1; diarrhoea = 1). 'Minor' adverse events were experienced by 132 (30.3%) patients and did not require aminophylline. Sixty per cent of our patients experienced no ill effects from dipyridamole given as an exercise substitute in conjunction with 201Tl imaging. The rest had symptoms which were mostly mild, although a few patients found the experience unpleasant. Only one patient experienced a life-threatening episode.

Adult↗
PubMed1994

99Tcm-sestamibi SPECT with combined dipyridamole and exercise stress in coronary artery disease.

In order to evaluate the clinical value of 99Tcm-methoxyisobutylisonitrile (sestamibi) single photon emission computed tomography (SPECT) after dipyridamole infusion in combination with low level bicycle exercise for the assessment of the presence, localization and extent of coronary artery disease (CAD), myocardial perfusion imaging was performed in 76 patients. Low level bicycle exercise was used to supplement the standard dipyridamole infusion protocol because of the lower incidence of non-cardiac side effects. The results were compared to arteriographic findings obtained within 3 months of the SPECT studies. The overall sensitivity of detection of coronary artery disease (i.e. a luminal stenosis > 50%) was 81%, specificity 80%, positive predictive value 96%, negative predictive value 40% and accuracy 82%. The diagnostic values for the detection of significant stenoses in the three major coronary arteries were: left anterior descending artery sensitivity 72%, specificity 87% and accuracy 76%; right coronary artery sensitivity 75%, specificity 90% and accuracy 80%; left circumflex coronary artery sensitivity 57%, specificity 85% and accuracy 71%. Scintigraphic evidence of multivessel disease was found in 31 (65%) patients with two- or three-vessel involvement assessed by arteriography. False negative test results were mainly found in patients with relatively mild CAD (one-vessel disease, branch and distal disease). 99Tcm-sestamibi SPECT after dipyridamole infusion in combination with low level bicycle exercise is shown to be a valuable diagnostic tool for the evaluation of CAD.

Adult↗
PubMed2004

Irbesartan has a masking effect on dipyridamole stress induced myocardial perfusion defects.

BACKGROUND AND AIM: The angiotensin II type 1 (AT1) receptor antagonist irbesartan is used for the treatment of hypertension, but its anti-ischaemic effect is not yet known. Our aim was to assess the effect of irbesartan administration on the diagnostic yield of 99mTc sestamibi single photon emission computed tomography (SPECT) in patients with coronary artery disease (CAD) after dipyridamole stress. METHODS: Our study group consisted of 13 patients (11 men and two women; mean age, 53.3 +/- 10.6 years; body mass index, 26.9 +/- 3.3 kg x m(-2)) with angiographically documented CAD. All patients underwent SmTc sestamibi SPECT studies at rest, before (STRESS-1) and 2 weeks after irbesartan (150 mg daily) administration (STRESS-2) at dipyridamole stress. The extent and severity of defects were analysed by using visual and quantitative 99mTc sestamibi SPECT. RESULTS: The mean summed stress score was significantly higher during the STRESS-1 study than the STRESS-2 study (13.2 +/- 7.4 vs. 11 +/- 7.4, P=0.003). The mean size of perfusion defects at stress was significantly larger for the STRESS-1 group than the STRESS-2 group (17.8% +/- 2.85% vs. 15.3% +/- 2.95%, P=0.01). CONCLUSION: Our study showed that the AT1 receptor blocker irbesartan reduces the extent and severity of 99mTc sestamibi perfusion defects after dipyridamole stress in patients with CAD. Irbesartan may alter coronary blood flow reserve. The continued use of irbesartan before stress myocardial perfusion SPECT has a masking effect on stress induced myocardial perfusion defects. For this reason AT1 receptor blockers must be stopped before stress myocardial perfusion scintigraphic examinations.

Adult↗
PubMed1990

Ineffectiveness of dipyridamole SPECT thallium imaging as a screening technique for coronary artery disease in patients with end-stage renal failure.

The efficacy of dipyridamole single photon emission computed tomography (SPECT) thallium as a screening test for coronary artery disease (CAD), was studied in 45 patients with end-stage renal failure undergoing evaluation for renal transplantation. Coronary arteriography, dipyridamole SPECT thallium imaging and clinical follow-up were performed in all patients. Nineteen patients (42%) had an obstruction of 50% or more in at least one coronary artery. Fourteen patients had a positive thallium scan, but 7 of these were false-positives (sensitivity 37%, specificity 73%). The sensitivity was considerably lower than that quoted for non-ESRF patients in the literature, and significantly lower than a control group of 19 patients without ESRF having comparable severity and distribution of CAD. Five of the 6 patients who died of cardiac causes over a mean follow-up period of 25 months had normal thallium imaging, but all had significant coronary artery disease at cardiac catheterization. Dipyridamole SPECT thallium imaging has not proved a useful screening test for angiographically significant CAD, and does not predict cardiac prognosis in this population.

Adult↗
PubMed1996

Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein.

Human alpha 1-acid glycoprotein (AAG), a plasma drug transport protein, has three main genetic variants, the A variant and the F1 and S variants, which are encoded by two different genes. The binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main gene products of AAG-the A variant and a mixture of the F1 and S variants (60% F1 and 40% S)-separated by chromatography from native commercial AAG, a mixture of almost equal proportions of the F1, S and A variants, was studied by equilibrium dialysis. A selective binding of disopyramide and methadone to the A variant and a preferential binding of dipyridamole to the F1S variant mixture were found. Lignocaine and chlorpromazine had a slight preference for binding to the A variant and to the F1S mixture, respectively, but progesterone showed no selectivity with regard to any of the variants of AAG. The differences in drug-binding demonstrated between the A variant and the F1S mixture confirmed those of a previous study, in which a selective binding of imipramine to the A variant and of warfarin and mifepristone to the F1S mixture have been found. These results indicate specific drug transport roles for each AAG variant, according to its separate genetic origin. The results of control binding experiments performed with (unfractionated) commercial AAG and the series of tested ligands concurred with that for the separate AAG variants, with respect to the proportion of the A variant (27%) and that of the F1 and S variants (73%) in the commercial protein. In addition, disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone were used in equilibrium dialysis displacement experiments to study interactions on binding sites labelled with imipramine for the A variant and with warfarin for the F1S variant mixture. The four latter ligands were found to competitively inhibit the binding of warfarin to the F1S variant mixture and all of them that of imipramine to the A variant. The ligands association constants to each AAG variant obtained from such inhibitory experiments were comparable to those determined in the direct binding studies. As the stochlometry of the interactions of the A variant and the F1S variants, respectively, with their specific ligands was approximately one (1), it was concluded that these ligands bind to each of these variants via a single common binding site. These results indicate that the AAG molecule would have for its ligands at least two separate binding sites, showing different specificity and localization, and not one site, as it is generally assumed. The possible pharmacological and clinical consequences of the binding results with the separate AAG variants are discussed.

Binding, Competitive↗
PubMed1997

Left ventricular diastolic filling changes during dipyridamole-induced ischaemia. An echo-Doppler study.

OBJECTIVE: To evaluate the usefulness of the Doppler assessment of left ventricular diastolic functioning during dipyridamole-induced ischaemia in patients with coronary artery disease (CAD). METHODS: We studied 28 patients with angiographically proven CAD [18 men, aged 62 +/- 7 years (mean +/- SD)] and 18 normal subjects (12 men, aged 59 +/- 7.5 years). Two-dimensional and transmitral flow Doppler echocardiography studies were performed at baseline and after intravenous administration of a high dose of dipyridamole (0.84 mg/kg during 10 min). Left ventricular wall motion was evaluated by two-dimensional Doppler echocardiography, with the left ventricle divided into a 16-segment model, whereas peak velocities of early and late diastolic flow, the early:late diastolic flow ratio and the deceleration rate of early diastolic flow were determined from transmitral flow Doppler echocardiography. RESULTS: Sixteen patients developed new wall-motion abnormalities (WMA), whereas the remaining 12 patients and the controls did not. Multivariate logistic regression analysis was performed to identify which of the parameters had independent diagnostic value for revealing CAD. WMA was entered at the first step and yielded a 57% sensitivity and 100% specificity; the changes in deceleration rate were entered as the second step, which improved the sensitivity to 85.5%, and reduced the specificity to 83% and raised the overall accuracy to 85% from 70% for WMA alone. More specifically, the sensitivity improved from 37.5, 63.5 and 65.5% to 62.5, 91 and 100%, respectively, for patients with one-, two- and three-vessel disease. The cut-off value of the change in deceleration rate was 7%. CONCLUSIONS: Patients could be classified as having CAD either if they developed new WMA or if the deceleration rate of early diastolic flow during dipyridamole-stress echocardiography increased by more than 7% compared with the rest value.

Case-Control Studies↗
PubMed1998

Indobufen compared with aspirin and dipyridamole on graft patency after coronary artery bypass surgery: results of a combined analysis.

BACKGROUND: Two prospective, randomized, double-blind clinical trials, performed in the UK and Italy, showed that indobufen, a reversible cyclo-oxygenase inhibitor, is as effective as, and safer than, a combination of aspirin with dipyridamole in preventing occlusion of saphenous vein coronary artery bypass grafts (CABG) 1 year after surgery. OBJECTIVE: To obtain, in a larger patient population, a more precise estimate of the possible differences in efficacy and safety between the two treatments. METHODS: We performed a combined analysis of the results of the two studies, based on the 1-year angiography data, on a total of 934 patients with 2258 saphenous vein distal anastomoses. RESULTS: Patients in the UK and Italy had similar baseline clinical characteristics. The analysis confirmed that there were no significant differences between the two treatment groups in the proportion of patients with one or more occluded grafts and in the proportion of occluded distal anastomoses. The combined analysis showed that the difference in response frequency (indobufen compared with aspirin and dipyridamole) was close to 0: 2.0% (95% confidence interval (CI) -4.2 to 8.2) in terms of patients, and 0.8% (95% CI -2.5 to 4.2) in terms of distal anastomoses. The 1-year incidence of postoperative major cardiovascular events was not statistically different between the treatment groups (19/694 indobufen compared with 25/678 aspirin and dipyridamole). CONCLUSIONS: Two multicentre CABG studies performed in different countries in patients with similar characteristics showed similar results in terms of graft patency. On the basis of the combined analysis, the two treatments can reasonably be considered to be equally effective in the prevention of graft occlusion.

Aspirin↗
PubMed1977

The effect of dipyridamole on platelet function: correlation with blood levels in man.

1 The effect on platelet functions of dipyridamole (a pyrimido-pyrimidine compound) was compared with a control group of patients taking warfarin. 2 Adhesion, aggregation and platelet factor 4 availability showed a significant decrease in the dypyridamole group. 3 Aggregation and platelet factor 4 showed a significant correlation with blood dipyridamole level. 4 Adhesion, aggregation and platelet factor 4 were reduced below the lower limit of normal at blood dipyridamole levels above 3.5 micronmol/1.

Blood Platelets↗
PubMed1989

Interferon response to dipyridamole in lupus erythematosus patients.

Studies in patients with autoimmune disorders strongly support a role for interferon (IFN) in the disease process. In the present study we investigated the in vivo production of alpha-IFN in lupus erythematosus patients after stimulation with dipyridamole, recently characterized as an alpha-IFN inducer in mice and humans. Levels of IFN were measured in serum samples from 22 patients with systemic lupus erythematosus (SLE) and 12 patients with discoid lupus erythematosus (DLE) before and 24 h after dipyridamole administration. IFN activity was assayed on human and bovine cells in parallel. Initial serum concentrations of alpha-IFN in SLE patients were markedly elevated. The percentage of DLE positive responders to dipyridamole induction was about twice as high as that found for SLE. Studies of factors responsible for IFN production in lupus erythematosus might result in better understanding of the relationship between DLE and SLE.

Dipyridamole↗
PubMed1993

Dipyridamole-provoked chest pain implies severe coronary artery disease in children.

The diagnostic significance of dipyridamole-provoked chest pain was studied in 17 children with severe coronary arterial stenotic lesions (CAL) complicated with Kawasaki disease. Although dipyridamole induced chest pain in seven patients (symptomatic group), 10 reported no pain (asymptomatic group). In the asymptomatic group, seven children had one vessel disease (1 VD) of right coronary artery (RCA) and the other three had two vessel disease (2 VD) involving the RCA and left anterior descending artery (LAD). Four multivessel disease patients, one three vessel disease (3VD) and three 2VD of LAD and RCA, and three 1VD of LAD, were symptomatic. In the thallium scans, all patients, except two of the asymptomatic group, showed perfusion abnormalities. In addition, the extent score of the symptomatic group was significantly worse than that of the asymptomatic group (P = 0.01). While only one in six of the asymptomatic group showed abnormal ST depression on treadmill exercise electrocardiography, all patients in the symptomatic group (P = 0.02) showed ischemic ST depression. These findings suggest that the occurrence of chest pain after medication with dipyridamole closely correlates with the severity of CAL in children.

Adolescent↗
PubMed1987

Effects of dipyridamole and theophylline on reactive hyperaemia in subcutaneous adipose tissue in humans.

The importance of adenosine for reactive hyperaemia in subcutaneous adipose tissue was studied in healthy volunteers, using the adenosine uptake inhibitor dipyridamole (bolus 0.1 mg/kg i.v. followed by infusion of 0.7 microgram/kg/min) and the adenosine receptor antagonist theophylline (4 or 6 mg/kg i.v.). Basal blood flow, total blood flow and hyperaemia (total minus basal flow) after a 20-min arterial occlusion were measured in the distal femoral region by the 133Xe washout technique with and without drug treatment. Basal blood flow (mean +/- SEM) was 2.4 +/- 0.3 ml/min/100 g, while total post-occlusive flow and total reactive hyperaemia were 97.3 +/- 8.4 and 61.8 +/- 6.5 ml/100 g, respectively, without drug treatment. Basal blood flow was unaffected by dipyridamole but the total flow and hyperaemia were enhanced by 49 +/- 24 and 60 +/- 31%, respectively (P less than 0.05 for both). This enhancement was due to increases in both amplitude and duration of the hyperaemia. Neither basal blood flow, total post-occlusive flow nor hyperaemia were significantly altered by theophylline. The amplitude of the enhanced hyperaemia during dipyridamole was not significantly counteracted by simultaneous theophylline treatment (6 mg/kg) but the duration of hyperaemia was reduced from 13 +/- 1 to 8 +/- 1 min (P less than 0.01). The results suggest that endogenous adenosine does not regulate basal blood flow or reactive hyperaemia of limited duration in human adipose tissue. However, reactive hyperaemia may be enhanced by pharmacological elevation of endogenous adenosine levels.

Adenosine↗
PubMed1993

Comparison between reference values for 201thallium uptake and washout from the myocardium after exercise and after dipyridamole.

A slow washout of 201Thallium has a high diagnostic and prognostic value for coronary artery disease. The aim of the present work was to contribute with reference data on 201Tl uptake and washout from the myocardium. With a quantitative method using circumferential profiles and interpolative background subtraction we performed 201Tl myocardial imaging in two groups of subjects with a low probability of coronary artery disease. Washout in per cent is defined as (1-D/I).100, where D is the delayed uptake rate and I the initial uptake rate. In group A (n = 16) myocardial hyperaemia was induced by maximal exercise, in group B (n = 15) by intravenous infusion of dipyridamole. In group A, the mean washout was 52%, and in group B it was 34% (P < 0.001). The delayed uptake rate D was significantly higher after dipyridamole, 58.4 cps, than after exercise, 44.5 cps (P < 0.05). There was no significant differences in I between the two groups. The findings regarding D and I explain that the washout is slower after dipyridamole than after exercise, as the mean D/I ratio was 0.48 in group A and 0.66 in group B (P < 0.001).

Adult↗
PubMed1972

The effects of dipyridamole on coronary post-occlusion hyperaemia and on myocardial vasodilatation induced by systemic hypoxia.

1. The arterial pO(2) of anaesthetized cats was reduced to 33 mmHg by supplying a mixture of oxygen and nitrogen as the respiratory gas. This produced vasodilatation in the myocardial bed which was not increased after the injection of dipyridamole (1 mg/kg).2. Reactive hyperaemia was observed following occlusion of the left anterior descending coronary artery for 10-120 seconds. The duration of the period of reactive hyperaemia was increased after the injection of dipyridamole. This effect of dipyridamole was most pronounced when the longest periods of occlusion were used.3. These results support the hypothesis that myocardial reactive hyperaemia is at least partly caused by adenosine released from hypoxic myocardial cells. The vasodilatation occurring during systemic hypoxia, on the other hand, is probably mediated via a different mechanism.

Animals↗
PubMed1973

The effects of dipyridamole on blood flow and oxygen handling in the acutely ischaemic and normal canine myocardium.

1. The effects of the intravenous administration of dipyridamole (0.25 mg/kg) were examined in a canine preparation that enabled simultaneous measurements to be made of blood flow in ischaemic and in essentially normal areas of the myocardium and also of oxygen handling (availability, consumption and extraction) in both these regions.2. When administered to dogs anaesthetized with trichlorethylene 2-3 h after acute ligation of the descending branch of the left coronary artery, dipyridamole markedly increased blood flow in essentially normal regions (left circumflex flow) but failed to increase flow in the area supplied by the ligated vessel (measured by (133)xenon clearance and by retrograde flow). In five of the six animals definite decreases in flow (; stealing ') were observed in the ischaemic region. These flow changes were related to the decreased trans-ventricular perfusion pressure (diastolic peripheral coronary pressure minus left ventricular end-diastolic pressure) and were accompanied by electrocardiographic evidence of increasingly severe myocardial ischaemia. The results support the suggestion that only increasing the perfusion gradient will usefully improve blood flow (and hence oxygen availability) to the acutely ischaemic myocardium.3. Despite these effects on ischaemic muscle blood flow, the oxygen tension of the blood draining the infarcting muscle was markedly elevated. The conclusion is drawn that dipyridamole decreases the efficiency of the myocardial circulation by opening up vessels that do not take part in tissue exchange.

Acute Disease↗
PubMed1994

Sustained left ventricular tachycardia terminated by dipyridamole: cyclic AMP-mediated triggered activity as a possible mechanism.

Sustained VT in two patients was terminated by intravenous administration of dipyridamole, an adenosine transport inhibitor. VT was induced by rapid atrial or ventricular pacing, isoproterenol, or dibutyryl cyclic AMP infusion, or exercise. VT also was aborted by adenosine triphosphate or acetylcholine injection, or by vagal stimulation. VT was terminated or prevented by verapamil or propranolol. In addition, arrhythmias were prevented by oral administration of dipyridamole. These results suggest that VT is due to cyclic AMP-mediated triggered activity and that inhibition by dipyridamole may be due to a reduction in the intracellular concentration of cyclic AMP.

Acetylcholine↗
PubMed1992

Dipyridamole-echocardiography: clinical usefulness following interventions.

Dipyridamole-echocardiography test response can be expressed not only in a black or white (positive vs negative) code but also, in positive tests, by a gray scale integrating the severity and extent of the dyssynergy as well as the ischemia-free stress time. The recognition of the dyssynergy is important to establish the diagnosis; however, the evaluation of the degree of the induced ischemia, stratified according to spatiotemporal coordinates, is even more important because it accurately predicts the coronary anatomical and functional situation, as well as the prognosis of the individual patient. Furthermore, the "shades of gray" in a positive response have proved useful in assessing the beneficial effects of several interventions: coronary angioplasty; coronary artery bypass surgery; thrombolysis; and medical antianginal therapy. Due to its excellent reproducibility, dipyridamole-echocardiography can play a pivotal role for simple, safe, fast, accurate, and objective assessment of therapeutic interventions, either mechanical or pharmacological, based upon the presence, timing, severity, and extent of dipyridamole-induced dyssynergy.

Angina Pectoris↗
PubMed1993

Prognostic value of the dipyridamole echocardiography test performed early after aortocoronary bypass surgery.

It has been demonstrated that high dose (up to 0.84 mg/kg over 10 min) dipyridamole echocardiography stress testing is feasible even in the first few hours after coronary artery bypass graft surgery and can be used to assess the beneficial physiological effects of coronary revascularization as well as graft patency. The aim of this study was to assess the role of dipyridamole echocardiography testing performed shortly after myocardial revascularization in the stratification of prognosis during follow-up. We studied 49 consecutive patients (45 males and 4 females; mean age 56 +/- 8 years) referred to our institute for elective myocardial revascularization. Six patients had single, 14 double, and 29 triple vessel disease. Forty-two left internal mammary artery grafts, 16 sequential venous grafts, and 45 single venous grafts were performed. All patients were submitted to dipyridamole echocardiography testing before (range 1-3 days) and shortly after (range 5-7 days) myocardial revascularization, always with the patients off antianginal medication. An arbitrary wall-motion score grading from 0 to 3 (normal, hypokinesia, akinesia, and dyskinesia) was applied to the seven regions into which the left ventricle was divided. Before surgery 48 patients showed wall-motion abnormalities during the test (47 patients also presented ECG changes). Angina occurred in 48 patients. One patient had ischemic ECG changes and angina. The mean wall-motion score was 3.11 per patient before and 6.5 per patient after the test (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Location and clinical implications of high-degree atrioventricular block during dipyridamole infusion: a case report.

We describe a patient with bifascicular block, who developed transient high-degree atrioventricular block during dipyridamole infusion. This patient was subsequently found to have significant His-Purkinje disease at electrophysiology study, and underwent permanent pacemaker implantation. Spontaneous atrioventricular block was documented during follow-up. This case report raises the issue of dipyridamole safety in patients with intraventricular conduction defects, and contributes an additional mechanism to the possible explanation of dipyridamole-induced atrioventricular block.

Aged↗