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[Dipyridamole test in the early detection of cerebrovascular disorders?].

The diagnosis of transient ischaemic attack (TIA) is mainly based on the clinical symptoms presented by the patient. Professionals in nuclear medicine have made a successful attempt to detect TIA by single photon emission tomography (SPECT) imaging. Improved sensitivity of the examination using stress test (e.g. acetazolamide) is well known in the literature. The dipyridamole stress test combined with SPECT imaging was regularly performed in patients (n = 100) with ischaemic heart disease. After injecting dipyridamole intravenously it found various forms of transient neurological deficits in 23% of the patients with considerably higher incidence reported previously in the literature (1.22/10,000). The so called "TIA positive" patients were examined further using the combination of dipyridamole stress test and brain SPECT imaging. The aim of this study was to analyse the relationship between transient neurological symptoms provoked by DPD test and the change in regional cerebral blood flow indicated by brain SPECT imaging. It is emphasized, that perfusion abnormalities revealed by brain SPECT were topographically consistent with the neurological deficits. In this article the attention was drawn to advantages of this test which may be suitable to provoke TIA safely. Combined with brain SPECT it may have an important role in the neurologic diagnostic procedures and in the prevention of stroke.

Cerebrovascular Circulation↗

[Coronary-angiographic demonstration of the dilating effect of dipyridamole on coronary arteries and its inhibition by caffeine (author's transl)].

Selective coronary cineangiographies are performed repeatedly in 13 mongrel dogs. The contrast medium itself has no demonstrable dilating effect upon the vessels. After the first injection of 0.2 mg/kg of dipyridamole the left anterior coronary artery is significantly (p less than 0.001) dilated, which is in contrast to some results described in literature. Immediately after an injection of high doses of caffeine (10 mg/kg) the previously enlarged coronary diameter decreases significantly (p less than 0.001). During the action of caffeine subsequent infections of dipyridamole result in a very small, or no change in coronary diameter. The coronary-dilating effect of dipyridamole can be inhibited by high doses of caffeine (10 mg/kg).

Angiocardiography↗

Safety and diagnostic accuracy of intravenous accelerated high-dose dipyridamole-atropine stress echocardiography.

BACKGROUND: In the present study, the safety and diagnostic accuracy of a modified protocol with accelerated high-dose dipyridamole-atropine stress echocardiography, utilized in an attempt to significantly shorten the test imaging time with respect to the standard protocol, were evaluated. METHODS: Three hundred and thirty-seven patients (231 men, 106 women, mean age 63 +/- 9 years) with known or suspected coronary artery disease underwent 404 tests. The ECG and blood pressure were continuously monitored during constant infusion of 0.21 mg/kg/min of dipyridamole over 4 min; atropine (0.50 mg at 5 and 6 min) was given in order to reach > or = 85% of the age-predicated heart rate. The wall motion score index and the 16-segment model were used to evaluate contractility. Eighty-nine patients underwent selective coronary angiography. Coronary artery stenosis was considered significant if the vessel diameter was < 50% of the normal value. RESULTS: Eight-eight out of 404 tests were positive: 72 for echocardiographic criteria, 11 for ECG criteria, 2 for clinical symptoms, and 3 for combined criteria. Three hundred and sixteen tests were negative. In 303 tests atropine was administered and 380 tests were performed in pharmacological wash-out. The maximal heart rate was 105.8 +/- 9 b/min and the maximal blood pressure was 128 +/- 19/78 +/- 9 mmHg. No major side effects nor life-threatening complications were observed. In 24 tests (5.9%) only minor side effects occurred and in no case did these effects cause premature suspension of the test. The sensitivity, specificity and diagnostic accuracy of angiographically assessed coronary artery disease were 56, 86 and 73% respectively. CONCLUSIONS: Accelerated high-dose dipyridamole echocardiography is practical, feasible and safe and allows for a significant reduction in the imaging time, with an increased cost-effectiveness and tolerance of the patients. In our experience the diagnostic accuracy of this new protocol was quite good and similar to that of the standard test.

Atropine↗

Correlation of transthoracic Doppler echocardiography and magnetic resonance imaging in measuring left anterior descending artery flow velocity and time-course of dipyridamole-induced coronary flow increase.

There is an increasing need for new, functional and more quantitative parameters to assess coronary arterial function, for the purposes of evidence-based medicine. Coronary arterial function has been widely studied using pharmacological stimulation induced by dipyridamole or adenosine. Coronary flow reserve (CFR), defined as the ratio of pharmacologically induced hyperemic flow divided by basal flow, has been found to be an important functional index in both the clinical and subclinical stages of cardiovascular diseases. Ten healthy male volunteers were studied to compare transthoracic Doppler echocardiography (TTE) and MRI for measuring left anterior descending coronary artery (LAD) flow velocity and CFR. Additionally, the time-response curve of dipyridamole infusion was studied in five healthy males using TTE. Assessment of blood flow velocity, measured as MDV, PDV and VTI indicated Pearson's correlation coefficients of 0.88, 0.85 and 0.70, respectively, between flow velocity measurements performed using TTE and MRI. The results indicate that, despite minor differences in LAD diastolic velocities measured by TTE and MRI, the correlation of the LAD diastolic velocities measured using both methods are good and both methods are feasible for measuring CFR. Moreover, TTE has the unique capability of continuous measurement of LAD flow velocity, which allowed assessment of the time-response curve for dipyridamole-induced increase in LAD flow velocity in this study. This study indicates that the TTE method may be used in sequential or on-line monitoring of LAD blood flow velocity and therefore can be applied to evaluate the time- or dose-response effects of infused drugs in the coronary circulation of humans.

Adult↗

[Prognostic value of thallium 201 myocardial scintigraphy with dipyridamole before peripheral arterial surgery].

The evaluation of patients who are candidates for peripheral arterial surgery is difficult. The aim of this study was to show that dipyridamole stress scintigraphy could be a prognostic aid for patient selection. Between 1991 and 2000, 275 patients underwent dipyridamole stress myocardial scintigraphy before peripheral arterial surgery of the lower limbs (49%), the aortic (33%) or carotid arteries (18%). A perfusion defect was observed in 145 patients suggesting myocardial ischaemia in 79 cases and myocardial infarction in 66 cases. Twenty-seven of the 79 ischaemic patients underwent a preoperative coronary revascularisation. The operative adverse coronary events (5%) were: 7 non-fatal myocardial infarctions and 7 acute coronary syndromes. The 79 ischaemic patients had a higher risk of adverse coronary events: 11% (ischaemia) versus 3% (no ischaemia) (p < 0.01). Myocardial scintigraphy allowed stratification of patients with an intermediate risk of Eagle's score into high coronary risk (15%, ischaemia) or low coronary risk (2%, no ischaemia) (p < 0.01). The extent of the ischaemia was associated with a higher risk of adverse coronary events: 4 zones (20%) versus 1 zone (5%) (p = 0.02). Preoperative coronary revascularisation tended to reduce the risk of adverse coronary events from 15% to 4% (p = NS). Myocardial ischaemia (p < 0.0001) and left bundle branch block (p = 0.002) were the two predictive factors of an adverse operative coronary event. Thallium-dipyridamole myocardial scintigraphy with a high negative predictive value (97%) is a useful tool for the identification of high risk patients for whom an aggressive preoperative therapeutic strategy may be beneficial.

Aged↗

[The action of dipyridamole on megakaryocytopoiesis in regenerating and stationary bone marrow cell populations].

The effect of dipyridamole on megakaryocytopoiesis in regenerating and stationary populations of mouse bone marrow cells has been studied by heterotopic transplantation of the bone marrow using histological, electron microscopic and biochemical techniques. It is shown that drug administration induced destruction of megakaryocytes. In megakaryocytic cytoplasm giant lipid granules were found whose growth and number increase resulted in megakaryocytes kill. Gas-liquid chromatography was used to evaluate the effect of dipyridamole on distribution of lipid fatty acids of the stationary and regenerating populations of the bone marrow cells. A marked increase of the percentage of docosahexaenoic acid was found in lipids of the stationary population. Chronic dipyridamole administration caused an increase of percentage of myristic, palmitic oleic acids, and decrease of percentage of arachidonic and eicosapentaenoic acids in lipids of regenerating bone marrow cells population.

Animals↗

[Variation of mechanical and biochemical parameters of pressure-loaded rabbit hearts following chronic administration of dipyridamole].

After constricting the aorta ascendens of rabbits, the influence of chronic administration of dipyridamole (8 mg/kg i.m. on 6 out of 7 days of the week for 3 months) upon heart hypertrophy, hemodynamics and the hydroxyproline content in the right and left ventricles, the incorporation rate of 2-[14C]-glycine into the actomyosin and soluble protein of the left ventricle was studied. The dipyridamole treatment had no effect on the increase in systolic pressure, the contractility index of the aorta-stenosed animals and heart rate. In contrast, the hypertrophic development, and consequently the increase in hydroxyproline concentration and the increased incorporation rate of 2-[14C]-glycine into the soluble protein were inhibited. The possible mechanism of action of dipyridamole on the development of heart hypertrophy in the rabbit is discussed.

Animals↗

[Double-blind study of the effect of dipyridamole in patients with intermittent claudication].

32 patients (mean age 65 years, range 51-75 years) were included in this controlled, double blind study to evaluate the effect of dipyridamole in patients with intermittent claudication. Following a run-in phase of one month, 15 patients received 400 mg dipyridamole per day and 17 patients placebo. Patient characteristics (risk factors, age, clinical and apparative tests) of both groups did not differ significantly before and during the study period. Mean pain free und absolute walking distance on the treadmill (3.2 km/h, 12.5 degrees gradient) increased significantly in both groups during study period (p < 0.001 and p < 0.01). Explanations are more intensive physical activity and increasing adaptation to treadmill exercise. However, dipyridamole did not induce a significantly longer walking distance in comparison with placebo. The working hypothesis that the drug with inhibiting properties of thrombocyte function prolongs walking distance in intermittent claudication, could not be confirmed.

Aged↗

[Chemiluminescence method for determination of dipyridamole].

A new system for the determination of dipyridamole with flow injection chemiluminescence was described. It is based on the chemiluminescence reaction of dipyridamole-potassium permanganate with rhodamine B. Tween-80 was found to be an enhancer of the chemiluminescence reaction. A method based on the enhanced chemiluminescence for dipyridamole determination has been developed. The method has high sensitivity, selectivity and good repeatability with a linear concentration range of 5.0 x 10(-8) - 5.0 x 10(-5) g x mL(-1), a detection limit of 1.7 x 10(-8) g x mL(-1) and a RSD of 1.1% (n = 11, cs = 1.0 x 10(-6) g x mL(-1)).

Dipyridamole↗

Differentiation of erythrocyte-(GLUT1), liver-(GLUT2), and adipocyte-type (GLUT4) glucose transporters by binding of the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and isobutylmethylxanthine.

The binding affinities of the glucose transporter isoforms GLUT1, GLUT2, and GLUT4 for the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and isobutylmethylxanthine (IBMX) were compared in membranes from human erythrocytes and rat brain containing the erythrocyte-type glucose transporter (GLUT1), in membranes from rat liver containing the liver-type glucose transporter (GLUT2), and in membranes from adipocytes and heart containing predominantly the adipose/muscle-type glucose transporter (GLUT4). The binding affinities of cytochalasin B for GLUT1 and GLUT4 were virtually identical (KD) in membranes from erythrocytes, 190 nM; in brain, 130 nM; in adipocytes, 160 nM; and in heart, 170 nM). In contrast, no specific glucose-inhibitable binding of cytochalasin B was detected in liver membranes. The binding affinity for forskolin of GLUT1 was significantly lower than that of GLUT4 (KD in erythrocytes, 2360 nM; Kl in brain, 4360 nM; and KD in adipocytes, 200 nM; and in heart, 210 nM); specific glucose-inhibitable binding to GLUT2 was not detectable. Like forskolin, the glucose transport inhibitors dipyridamole (Kl in adipocyte membranes, 1.2 microM; in erythrocytes, greater than 40 microM) and IMBX (Kl in adipocyte membranes, 60 microM; and in erythrocytes, greater than 500 microM) bound with higher affinity to GLUT4 than to GLUT1. These data demonstrate striking differences of GLUT1, GLUT2, and GLUT4 with respect to their binding affinity for the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and IBMX. It is suggested that the complex differences result from interaction of more than one heterogeneous binding site at the glucose transporters with the inhibitory ligand.

1-Methyl-3-isobutylxanthine↗

[The diagnostic and prognostic value of echo-dipyridamole in patients with suspected coronary disease: a comparison with the stress test].

The aim of the study was to assess the relative diagnostic and prognostic accuracy of high-dose dipyridamole echocardiography test (DET: 2D-echo monitoring during dipyridamole infusion up to 0.84 mg/kg over 10') vs maximal symptom limited bicycle exercise electrocardiography test (EET) in patients with chest pain addressed to coronary angiography. We initially considered 477 consecutive patients, meeting the following inclusion criteria: 1) history of chest pain; 2) off antianginal therapy; 3) no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction. All patients were submitted to a DET and EET--on different days and in random order--within 1 week of coronary angiography (which was performed independently of test results). DET could not be performed in 32 patients for a poor acoustic window in resting conditions (n = 31) or for asthmatic disease requiring xanthine therapy (n = 1); EET could not be performed in 54 patients for inability to exercise, or resting electrocardiographic abnormalities making the EET interpretable. The overall feasibility was of 445/477 for DET and 423/477 for EET (93 vs 89%, p = ns). Criteria for positivity were: transient regional dyssynergy absent in the baseline examination for DET; ST segment shift greater than .15 m V from baseline for EET. Angiographically assessed coronary artery disease (CAD) was considered present when a luminal reduction greater than or equal to 50% occurred in at least 1 major coronary vessel. There were 135 pts with no significant CAD and 256 with CAD; 137 had single, 70 double, 49 triple and/or left main (15) vessel disease. The specificity was higher in DET vs EET (96 vs 59%, p less than .01). The overall sensitivity of DET was similar to EET (67 vs 69%, p = ns), with no significant differences in the subset with single (56 vs 63%, p = ns), double (74 vs 69%, p = ns) or triple (88 vs 86%, p = ns) vessel disease. Patients were followed-up for 26 +/- 22 (range 1 to 73) months considering only death and myocardial infarction as end-points. A Cox stepwise survival analysis identified the Wall Motion Score Index (an integrated semiquantitative measure of extent and severity of the dyssynergy) at peak dipyridamole as the most powerful prognostic predictor (X2 = 18.5, p less than 0001) of all invasive (number of stenotic coronary vessels, X2 = 5.8, p less than .05) and noninvasive (exercise electrocardiography positivity, p = ns) parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary Angiography↗

[Use of isometric exercise to enhance the diagnostic value of dipyridamole testing in patients with angina pectoris].

A dipyridamole test was performed in 40 patients with coronary heart disease who were divided into 2 groups, each consisting of 20 subjects. The dipyridamole test alone was performed in the patients from Group 1, while the agent was given by using manual dynamometry and increasing venous return in those from Group 2. Positive results were obtained in 55 and 85%, respectively (p less than 0.05). The mean dipyridamole dose was 0.64 mg/kg for Group 1 patients and 0.48 mg/kg for Group 2 patients (p less than 0.05).

Adult↗

Dipyridamole echocardiography stress testing in hypertensive patients. Targets and tools.

Arterial hypertension can provoke a reduction in coronary flow reserve through several mechanisms that are not mutually exclusive, namely, coronary artery disease, left ventricular hypertrophy, and microvascular disease. These different targets of arterial hypertension should be explored with different diagnostic markers. The transient dyssynergy detected by two-dimensional echocardiography and evoked during dipyridamole infusion is a marker of coronary disease that is equally reliable in normotensive and hypertensive individuals. On the contrary, dipyridamole-induced ST segment depression is frequently elicited in hypertensive patients when angiographically assessed coronary disease is absent. This ischemiclike electrocardiographic response can be found in echocardiographically assessed left ventricular hypertrophy. However, even when left ventricular mass is normal, dipyridamole-induced ST segment depression is associated with an impaired coronary flow response to pacing, which is consistent with microvascular disease. Whether echocardiographically silent electrocardiographic changes are simply diagnostic noises transmitting a misleading false positive response or a potentially important clinical marker of early myocardial damage remains a pivotal though still unanswered question.

Cardiomegaly↗

Exercise supplementation of dipyridamole for myocardial perfusion imaging.

The substitution of intravenous dipyridamole for symptom-limited treadmill exercise has provided a non-invasive means to diagnose coronary artery disease with 201Tl scintigraphy in patients unable to adequately exercise. Limitations of dipyridamole/thallium imaging are primarily due to suboptimal image quality secondary to hepatic tracer concentration and decreased test sensitivity in patients who are dipyridamole "non-responders." Low-level treadmill exercise supplementation improves image quality, whereas handgrip has little, if any, benefit. The effect of low-level exercise in augmenting coronary blood flow is unknown and reports regarding the effect of handgrip are conflicting. The diagnostic benefit of these maneuvers in improving test sensitivity and decreasing the number of "non-responders" has not been documented. The combination of maximal, symptom-limited treadmill exercise and intravenous dipyridamole is a theoretically attractive option to improve overall test sensitivity, but the physiologic consequences and potential side effects should be more thoroughly investigated.

Coronary Disease↗

Dipyridamole echocardiography. A new diagnostic window on coronary artery disease.

Dipyridamole echocardiography testing is a highly feasible, inexpensive, and safe diagnostic tool, with excellent specificity and good sensitivity--especially in patients with multivessel disease and/or resting dyssynergy--for the diagnosis of coronary artery disease. The test does not offer an "all or none" binary result but rather a complex stratification of the ischemic response along the coordinates of time and space, accurately identifying the degree of physiological impairment of coronary reserve, the severity and extent of coronary disease, the geographic location of the area at risk, and the prognostic outlook. It offers highly competitive diagnostic information versus more sophisticated, time-consuming, and costly radionuclide techniques; in comparison with other stress echocardiography techniques, it is more feasible than exercise and less invasive and better tolerated than pacing. The electrocardiogram usefully integrates the information provided by the mechanical marker of ischemia during dipyridamole testing. The finding of echocardiographically silent ST segment depression represents a clue to the identification of angiographically normal coronary arteries. On the basis of this evidence, dipyridamole testing with two-dimensional echocardiography and 12-lead electrocardiography can be considered a reasonable choice for the exercise-independent diagnosis of coronary artery disease.

Coronary Disease↗

[Dipyridamole echocardiography test during the acute phase of lower myocardial infarction].

Two-dimensional echocardiography with intravenous injection of dipyridamole (0.56 mg/kg) was performed in 33 consecutive patients with acute (2 +/- 2 days) postero-inferior myocardial infarction for semiquantitative segmental wall motion analysis. The results were compared with those of coronary angiography which was carried out during the hospital period. After a second evaluation of the recordings the following results were obtained: feasibility: 94 per cent with 85 per cent of segments analysed. Residual ischaemia in the first days of myocardial necrosis was common (70%). The ischaemia was often clinically silent including during the investigation (61%). When pain occurred, it always followed changes in regional wall motion. The dipyridamole test suggested multivessel disease with a sensitivity of 72 per cent and a specificity of 90 per cent, and residual arterial stenosis with a sensitivity of 75 per cent ans specificity of 80 per cent the secondary effects were minor. The main limitation of the test is related to the distinction between pharmacological and physiologic ischaemia. A positive test was associated with lesions justifying myocardial revascularisation (coronary bypass or angioplasty) in 19 out of 23 cases but with a very poor correlation with the topography of the coronary lesions. A negative test indicated arterial occlusion, residual stenosis with extensive myocardial damage or a normal coronary angiogram. Therefore, the dipyridamole echocardiography test may help identify a group of patients with little or no myocardial ischaemia in whom invasive investigations could be deferred; these patients contrast with the group with a positive test indicating residual ischaemia in which the coronary lesions should be documented by coronary angiography.

Aged↗

[The effect of dipyridamole on the results of allogenic kidney transplantation].

In a prospective randomized trial the anti-thrombotic effect of dipyridamole was studied in 64 patients after cadaveric kidney allotransplantation. The frequency of early graft function was significantly higher in the control group, whereas the incidence of arterial and venous thromboses were not different. One-year graft survival could not be improved by dipyridamole. Therefore, dipyridamole should not be recommended in cadaveric kidney allotransplantation.

Cadaver↗

[Regional myocardial blood flow measurements in resting and dipyridamole induced vasodilative state by Xenon-133 clearance method].

Myocardial imaging with Xenon-133 and a gamma camera was employed to evaluate the relationship between angiographically demonstrated coronary artery stenosis and regional myocardial blood flow (r-MBF) in 22 patients with ischemic heart disease and 9 control subjects. After a left anterior oblique cineangiogram was obtained, the cinecamera was replaced by the mobile gamma camera in the same plane and location over the pericardium of patients. Then, 370 MBq (10 mCi) of 133Xe was injected into the left coronary artery as a bolus. After the first measurement of r-MBF in resting state, a second injection was made 3 minutes after intravenous injection of 0.56 mg/kg of dipyridamole for 4 minutes. The r-MBF in different regions of the heart was calculated by Kety formula. Coronary flow reserve (CFR) was defined the rMBF ratio between resting and dipyridamole induced vasodilative state. In the resting state, good correlation (r = 0.711) was observed between pressure rate product and the r-MBF at the areas perfused by non stenotic vessels. The r-MBF of the areas perfused by severe stenotic vessels (greater than 90%) was smaller than that of the areas perfused by non stenotic vessels, however there was overlapping of flow. In the dipyridamole induced vasodilative state, the r-MBF of the areas perfused by intact vessels increased approximately 2.4 times of the resting state, and showed good correlation with pressure rate product. In contrast, the r-MBF of the areas perfused by stenotic vessels did not correlate with pressure rate product, but depended on the degrees of coronary stenosis (50-75% stenosis; 1.9 times, greater than 90% stenosis; 1.3 times, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗