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PubMed1984

Adenosine and prostacyclin independent electrophysiological effects of dipyridamole in guinea-pig papillary muscles and canine cardiac Purkinje fibers.

Dipyridamole was initially introduced as a coronary vasodilator. The exact mechanism of action of dipyridamole on the coronary vasculature is unknown, but proposed mechanisms of action include inhibition of adenosine uptake, increased myocardial prostacyclin production and inhibition of phosphodiesterase activity. The purpose of our study was to examine the electrophysiological effects of dipyridamole on guinea-pig papillary muscles and canine cardiac Purkinje fibers to determine whether similar mechanisms might account for the electrophysiological effects of this compound. Conventional microelectrode techniques were used to record transmembrane action potentials from either guinea-pig papillary muscles or canine cardiac Purkinje fibers. Dipyridamole produces a dose-dependent prolongation of action potential duration with a threshold concentration of approximately 5 X 10(-7) M in tissues from either species. Dipyridamole (10(-5) M) increases action potential amplitude (124 +/- 1 to 127 +/- 1 mV), increases action potential duration (119 +/- 6 to 146 +/- 5 msec) and produces hyperpolarization of the resting potential (-85 +/- 1 to -87 +/- 1 mV) in guinea-pig papillary muscles (n = 27, P less than .05). Dipyridamole (10(-5) M) increases action potential duration (276 +/- 5 to 293 +/- 5 msec) in canine cardiac Purkinje fibers (n = 21, P less than .05). The effects of dipyridamole (5 X 10(-7) M) are neither accentuated by adenosine (10(-4) M) nor attenuated by adenosine deaminase (1 U/ml) Pretreatment with indomethacin (10(-5) M) does not block these effects. Dipyridamole (10(-5) M) produces a negative chronotropic response in canine Purkinje fibers, increases mean escape intervals from 4.9 +/- 0.9 to 7.8 +/- 1.4 sec (n = 8, P less than .05) and fails to suppress slow response action potentials in 22 mM K+ depolarized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed1995

[Protection and "preconditioning" of the human heart during percutaneous transluminal coronary angioplasty (PTCA) by intracoronary dipyridamole administration].

BACKGROUND AND AIM: A brief episode of ischemia followed by reperfusion termed "ischemic preconditioning" has been identified as a mechanism rendering the myocardium more resistant to ischemia. Recently adenosine has been identified as an important mediator of ischemic preconditioning. Dipyridamole represents an important drug interfering with myocardial adenosine metabolism by inhibiting its degradation. The aim of this study was to investigate the effect of an intracoronary dipyridamole infusion on the extent and tolerance of myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA). PATIENTS AND METHODS: In the first study group 46 patients undergoing coronary angioplasty were randomised to receive dipyridamole or conventional treatment before PTCA. In the second study group 11 patients were investigated, receiving PTCA of restenosis following PTCA carried out 6 months earlier. RESULTS: In the first group as a striking result patients receiving pretreatment with dipyridamole tolerated longer times of balloon inflations (155.3 +/- 68.9 vs. 93.1 +/- 24.7 s), expressed lower severity of cardiac pain, demonstrated less pronounced ST-segment shifts on the surface ECG and showed a lower incidence of arrhythmias. In the second group the first dilatation had been performed conventionally, while pretreatment with dipyridamole had been performed prior to the dilatation of restenosis. Similar to the findings in the first patient group pretreatment with dipyridamole resulted in enhancement of balloon inflation times, regression in cardiac pain and lower extent of ST-segment shift and incidence of arrhythmias. In both study groups intracoronary application of dipyridamole showed no significant impact on heart rate and arterial blood pressure. CONCLUSION: Summarising our results indicate, that intracoronary application of dipyridamole renders the heart more resistant to ischemia.

Aged↗

PubMed1994

[Combination of transesophageal atrial pacing and echo-dipyridamole test in the diagnosis of coronary disease in patients with suspected angina pectoris and negative exercise test].

BACKGROUND: Echo-dipyridamole test is an useful tool for non-invasive demonstration of inducible myocardial ischemia in patients with coronary artery disease, its sensitivity being consistently higher as compared with classic exercise stress testing. However, in patients with single vessel who often perform a normal or borderline stress test, even the sensibility of echo-dipyridamole test is comparatively reduced. METHODS: In 19 patients with clinically suspected angina (effort-related in 4, at rest in 8, mixed in 7) and normal exercise stress test, standard echo-dipyridamole test was performed. Thereafter, rapid atrial pacing, a procedure associated with a sharp increase of myocardial oxygen consumption, was performed by means of a transoesophageal catheter during the proceeding 5 min and during 4 min of repeated dipyridamole 0.56 mg/kg infusion. RESULTS: Standard echo-dipyridamole test induced ventricular wall motion abnormalities in 3 patients (one with borderline exercise stress test), whereas repeated pacing-sensitized procedure obtained wall motion abnormalities (apical, septal and lateral) in the same and in 4 additional patients. Coronary angiography demonstrated > 70% stenosis in 8/19 patients (single vessel disease in 5), 7 of whom had been correctly recognized by pacing-dipyridamole test; therefore, sensitivity of the latter as compared with standard dipyridamole test was 87% and 37% respectively. The anatomic correlation of induced wall motion abnormalities with coronary arterial stenosis was demonstrated in all cases. Specificity was 100% with both methods. CONCLUSIONS: Although limited by its restricted patient population, this study suggests that atrial pacing, performed via transoesophageal catheter, can significantly improve the positive predictive value of echo-dipyridamole test in coronary artery disease. By means of this simple procedure, the possibility of non invasively diagnosing even single vessel stenosis in patients with inconclusive exercise stress testing can be significantly improved.

Adult↗

PubMed1994

Secondary prevention of stroke: does dipyridamole add to aspirin?

BACKGROUND AND PURPOSE: The purpose of this paper is to evaluate, in the light of all available evidence, the place of aspirin alone and of aspirin combined with dipyridamole in the secondary prevention of cerebrovascular accidents. METHODS: We performed a meta-analysis of all identified double blind, controlled, studies in secondary prevention of cerebrovascular accidents for the following categories: studies comparing aspirin with placebo; studies comparing aspirin plus dipyridamole with placebo; studies comparing aspirin plus dipyridamole with aspirin alone. An indirect comparison was carried out to compare the results obtained with aspirin alone and those obtained with aspirin combined with dipyridamole. RESULTS: The meta-analysis of trials involving aspirin alone against placebo showed a risk reduction on strokes (17% reduction, p = 0.02), "important vascular events", i.e. a combination of vascular deaths, non-fatal strokes and non-fatal myocardial infarction (18% reduction, p = 0.003). Fatal vascular events (vascular deaths and fatal strokes) did not seem to be reduced at all. The overall mortality was reduced by 10%, but this reduction failed to reach statistical significance (p = 0.23). The meta-analysis of trials involving aspirin combined with dipyridamole showed more important risk reductions on every outcome whether fatal or not. Strokes were reduced by 42% (p < 0.001), fatal strokes by 43% (p = 0.02) and vascular deaths by 24% (p = 0.07, not significant). The overall mortality was reduced by 30% (p = 0.004). Direct comparisons of aspirin with aspirin plus dipyridamole did not indicate differences between the two treatment regimens. However the sample sizes involved in these comparisons were far too small to be informative. Indirect comparisons yielded statistically significant results in favour of the combination in terms of "important vascular events" (p = 0.007), all strokes (p = 0.007) and fatal strokes (p = 0.03). The results were also in favour of the combination but not statistically significant in terms of all deaths (p = 0.10) and vascular deaths (p = 0.08). CONCLUSIONS: Aspirin used alone reduces secondary occurrence of vascular events in cerebrovascular patients. There is no evidence, however, of a reduction of fatal events (vascular deaths and fatal strokes). In contrast, aspirin in combination with dipyridamole reduces non-fatal as well as fatal events. These results as well as the indirect comparisons of the risk reductions suggest that the combination of aspirin with dipyridamole may be superior to aspirin alone; this hypothesis is presently tested in a large randomized trial.

Aspirin↗

PubMed1993

[Dobutamine versus dipyridamole magnetic resonance tomography: safety and sensitivity in the detection of coronary stenoses].

Safety and sensitivity of gradient-echo magnetic resonance imaging (MRI) for the identification of significant coronary artery stenoses using pharmacologic stress testing was assessed in 61 patients with > or = 70% stenosis of a major coronary artery and a normal left ventricle. After MRI at rest 28 patients underwent dobutamine-MRI during steady-state dobutamine infusion (5, 10, 15 and 20 micrograms/kg/min) and 33 patients had dipyridamole-MRI after high-dose dipyridamole infusion (0.75 mg/kg over 10 min). All patients additionally performed standard ECG exercise stress testing (EST). Segmental wall motion analysis was performed in basal and midventricular short axis tomograms by two observers. A segment was graded pathologic if transient dobutamine or dipyridamole induced wall motion abnormalities could be detected. For comparison to coronary angiography findings, each segment was assigned to one of the coronary artery perfusion territories. There were no serious side-effects during dobutamine and dipyridamole infusion leading to termination of the study protocol. Peak double product during dobutamine infusion was significantly higher (p < 0.001) than after dipyridamole infusion (18.493 +/- 4.311 versus 12.799 +/- 2.694 mm Hg/min). Overall sensitivity of dobutamine and dipyridamole-MRI for coronary artery disease (CAD) was 85% and 84%. Regional asynergy by dobutamine and dipyridamole-MRI was observed in 73% versus 79% patients with single- and 100% versus 92% with multi-vessel disease. Individual coronary artery stenoses were correctly identified by segmental wall motion abnormalities in 87% versus 81% for left anterior descending, 62% versus 86% for left circumflex and 78% versus 92% for right coronary artery stenoses. In conclusion, dobutamine and dipyridamole-MRI are well tolerated and safe non-exercise dependent tests for detection and localization of hemodynamically significant coronary artery stenoses with a similar diagnostic accuracy but with a better control of stress intensity and duration provided by dobutamine.

Adult↗

PubMed1995

Reduced red cell deformability associated with blood flow and platelet activation: improved by dipyridamole alone or combined with aspirin.

OBJECTIVES: To explore the role of blood flow in red blood cell deformability and determine whether it is associated with the release of ATP by red cells. METHODS: A perfusion system was employed to mimic the blood flow conditions. Red cell treatment in vitro with dipyridamole or aspirin, either alone or combined, was performed either on red cells alone prior to blood reconstitution or on already reconstituted blood. Blood viscosity at shear rates of 90 and 450 s-1 was measured, before and after perfusion, by means of a cone/plate viscometer. Red cell deformability was estimated as the magnitude of the slope between these two values of viscosity. ATP level in platelet-free plasma was measured by the firefly luciferase assay, and was used to monitor dipyridamole-induced blockade of ATP efflux by red cells. RESULTS: In control experiments, red cells became more rigid after perfusion (slope values: 0.62 +/- 0.09 vs 0.40 +/- 0.04; P < 0.05). Absence of platelets or treatment of red cells with aspirin and/or dipyridamole prevented dipyridamole prevented the increased stiffness of red cells observed after exposure of blood to flow conditions. Moreover, a significant increase in red cell deformability was observed when blood was treated with dipyridamole alone or combined with aspirin (0.69 +/- 0.07 and 0.65 +/- 0.05 respectively vs. 0.40 +/- 0.04; P < 0.05). Treatment with dipyridamole alone or combined with aspirin caused a decrease in ATP levels. Statistical significance was reached when red cells alone were treated with dipyridamole alone (45.8 +/- 2.8 vs. 173.3 +/- 47.6 ng ATP/ml; P < 0.05). CONCLUSIONS: Flow stress induced a decrease in red cell deformability probably linked to platelet activation. Treatment with dipyridamole alone or associated with aspirin eliminated the effect of flow, increasing red cell deformability. Under our experimental conditions, modifications could not be ascribed to red cell-released ATP. Our results emphasize the importance of blood flow conditions to evaluate RBC deformability.

Adenosine Triphosphate↗

PubMed1996

Brain SPECT with dipyridamole stress to evaluate cerebral blood flow reserve in carotid artery disease.

UNLABELLED: This is a preliminary study of SPECT brain scan using dipyridamole as a stress agent to assess cerebral blood flow reserve in six patients with severe carotid artery disease. METHODS: We performed SPECT scanning of the brain, with and without dipyridamole stress. Dipyridamole (0.57 mg/kg) was given intravenously 3 min before infusion of 99mTc-HMPAO. Patients were studied 30 min later using a rotating head gamma camera. The scans were analyzed qualitatively and semiquantitatively. An acetazolamide stress SPECT image was also obtained in two patients. RESULTS: All patients had at least 80% stenosis in one internal carotid artery, three of them also had contralateral carotid stenosis. The dipyridamole SPECT showed an increased region of hypoperfusion in the hemisphere ipsilateral to the severe carotid disease in four patients. That suggests poor perfusion reserve and the potential risk of regional ischemia. In four of six patients, side-to-side asymmetry increased from the baseline condition after injection of dipyridamole. The asymmetry index increased more after dipyridamole than after acetazolamide injection in two patients. CONCLUSION: This study suggests that dipyridamole stress SPECT is useful in assessing cerebral blood flow reserve. It demonstrates the region of poor vascular reserve in patients with severe carotid artery disease. Dipyridamole SPECT scans show more extensive hypoperfusion than acetazolamide in the two cases.

Acetazolamide↗

PubMed1998

Neuroprotective actions of dipyridamole on cultured CNS neurons.

We report that dipyridamole is neuroprotective for a variety of rat embryonic CNS neurons cultured in serum-free basal medium lacking trophic factors or other additives. We also describe the mechanism underlying this action. Neurons died rapidly in basal medium but were rescued in large measure by 10 microM dipyridamole. The protective action of dipyridamole seems to be attributable to its antioxidant property. Vitamin E and N-acetylcysteine provided comparable neuroprotection in basal medium, whereas an array of compounds that mimic other actions of dipyridamole (inhibition of phosphodiesterases, blockade of nucleoside and chloride transport, interference with the multidrug resistance protein, and enhancement of prostacyclin synthesis) failed to promote survival. Thus, a major cause of neuronal death in this system seems to be oxidative stress that is relieved by dipyridamole. Iron plays a significant role in generation of such stress, as indicated by the observations that addition of apotransferrin or iron chelators to basal medium or use of iron-free medium also afforded protection. Although oxidative stress was a major determinant of neuronal death, it was not the only factor. Dipyridamole or other antioxidant measures did not provide sustained neuroprotection. However, provision of insulin, which was not protective alone in basal medium, along with dipyridamole significantly enhanced long-term neuronal survival. Hence, optimal protection requires both trophic support and relief from oxidative stress. These findings lend credence to the potential use of dipyridamole or its derivatives in prevention and/or treatment of CNS injuries and degenerative disorders in which oxidative stress is a significant component.

Animals↗

PubMed1980

Comparative effect of intravenous dipyridamole and sublingual nitroglycerin on coronary hemodynamics and myocardial metabolism at rest and during atrial pacing in patients with coronary artery disease.

The effects of intravenous dipyridamole (20 mg) and sublingual nitroglycerin (0.6 mg) were compared at rest and during rapid atrial pacing in patients with significant coronary obstruction. Dipyridamole, which had no significant effect on resting systolic blood pressure, caused a significant increase in coronary sinus flow (CSF) and reduction of coronary vascular resistance (CVR) and arterial-coronary sinus oxygen difference (AO2CSO2 delta), whereas nitroglycerin reduced resting systolic pressure but had no significant effect on CSF, CVR, or AO2-CSO2 delta. Although theses effects of dipyridamole and nitroglycerin on resting systolic pressure, CSF, CVR, and AO2-CSO2 delta were qualitatively similar during rapid atrial pacing, the onset of chest pain and ischemic ECG changes occurred at a lower heart rate following dipyridamole (136 +/- 5 beats/min) than following nitroglycerin (149 +/- 6 beats/min, p less than 0.01). However, maximal double product and myocardial oxygen consumption achieved during pacing were similar following both dipyridamole and nitroglycerin and were less than control pacing values. Coronary dilatation following dipyridamole appears to reduce tolerance to pacing-induced ischemia probably by maldistribution of coronary flow away from ischemic myocardium. Nitroglycerin differs from dipyridamole by improving tolerance to pacing; however, this difference appears to be due to systemic vasodilator effects of nitroglycerin rather than to enhancement of flow to ischemic myocardium.

Aged↗

PubMed1990

Update on intravenous dipyridamole cardiac imaging in the assessment of ischemic heart disease.

Intravenous dipyridamole is a relative selective coronary vasodilator which, when combined with thallium-201, provides a useful technique to assess myocardial perfusion. The intravenous dipyridamole is administered as an infusion at a rate of 0.14 mg/kg/min for 4 minutes. In the presence of significant coronary artery disease the increase of coronary blood flow is disproportionate between vessels with and without significant coronary lesions, providing the basis for detecting regional differences in flow using thallium-201. The test can be used alone or combined with low level exercise to increase test sensitivity. The test is safe when performed under medical supervision and when patient selection is done appropriately. Most of the side effects induced by dipyridamole infusion are well tolerated by patients and readily reversed with intravenous aminophylline and sublingual nitroglycerin. The average sensitivity and specificity of the dipyridamole thallium scintigraphy test from the major studies are 76% and 70%, respectively. The test is very useful in providing prognostic information in patients who are unable to exercise. A reversible thallium defect after dipyridamole infusion has been shown to be associated with significant mortality and morbidity in patients with documented or suspected coronary artery disease. The use of intravenous dipyridamole has been extended into other modalities of imaging, including 2-dimensional and Doppler echocardiography, to study functional changes in the left ventricular induced by the infusion of intravenous dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

PubMed1998

Association of ventricular ectopy with nuclear scintigraphic perfusion defects during dipyridamole stress testing.

BACKGROUND AND HYPOTHESIS: No information is available regarding the significance of ventricular ectopic activity induced during dipyridamole nuclear scintigraphic stress testing. This study tested the hypothesis that dipyridamole-induced ventricular ectopy predicts a thallium-201 or technetium-99m sestamibi perfusion defect. METHODS: A group of 186 consecutive patients with premature ventricular contractions and/or couplets occurring during dipyridamole stress testing (ventricular tachycardia did not occur) was compared with a control group of 194 patients without ventricular ectopy during dipyridamole stress testing. RESULTS: The results indicated that ventricular ectopy induced during dipyridamole infusion occurred more frequently in patients demonstrating either a fixed or reversible perfusion defect on scintigraphic imaging (p < 0.01). The higher frequency of perfusion defects in this group of patients was attributable to a higher frequency of "fixed" compared with "reversible" defects (p < 0.05). This finding is consistent with the additional observation that ventricular ectopy induced by dipyridamole was associated with the presence of Q waves on the resting ECG (p < 0.05). The positive and negative predictive values of the presence of ventricular ectopy in predicting a fixed myocardial perfusion defect were 59 and 54%, respectively. CONCLUSIONS: Ventricular ectopy induced during dipyridamole infusion suggests the presence of a fixed myocardial perfusion defect.

Aged↗

PubMed1992

Dipyridamole enhances an anti-proliferative effect of interferon in various types of human tumor cells.

The anti-proliferative activity of human interferon (HuIFN) was enhanced by dipyridamole, 2,6-bis-(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-py rimidine, when tested against various human tumor cell lines, including KT (breast carcinoma), PLC/PRF/5 (hepatoma), MGC-I, U251-SP and T98 (glioma), HAC-2 and SHIN-3 (ovarian carcinoma), and MM-ICB (melanoma). The enhancement occurred irrespective of the kind of HuIFN used (alpha, beta or gamma) and the original degree of susceptibility of the cells to HuIFN. Even low doses down to 0.01 microM of dipyridamole that had no intrinsic anti-proliferative activity could enhance the effect of HuIFN. The enhancement of HuIFN effects seems not to be caused by induction of HuIFN production, because neither anti-viral activity nor HuIFN antigens were detected in culture medium in cells treated with dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine residue, produced little enhancement of the effects of HuIFN. Among ovarian cancer cell lines tested, the enhancement of the activity of HuIFN by dipyridamole for HAC-2 and SHIN-3 cells was equivalent to or greater than that for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin derivative). However, neither HOC-21 ovarian cancer cells nor HEC-1 endometrial adenocarcinoma cells were susceptible to any combinations. When MGC-1, U251-SP, and HAC-2 cells were injected into nude mice, the growth of tumors was more markedly inhibited by the subcutaneous administration of HuIFN in combination with oral administration of dipyridamole than by the HuIFN alone. Thus, this combination therapy seems to be worth trying for human cancer, although the enhancement of the effects of HuIFN by dipyridamole varied among the cell lines examined.

Animals↗

PubMed2002

Regional changes in human cerebral blood flow during dipyridamole stress: neural activation in the thalamus and prefrontal cortex.

Intravenous dipyridamole increases the concentration of circulating adenosine and produces coronary vasodilation. However, it decreases global cerebral blood flow (CBF) due to hyperventilation side effect of adenosine. In the present study, changes in regional CBF during dipyridamole stress were identified in detail. In 11 healthy men (51-71 years of age), CBF was measured by positron emission tomography with oxygen-15-labeled water at rest (baseline) and during dipyridamole stress. All images were normalized to global CBF and transformed to standard brain anatomy. A t map between baseline and dipyridamole stress conditions was then created on a pixel-by-pixel basis. CBF was globally decreased during dipyridamole stress. However, a significant relative increase in CBF was observed bilaterally in the thalamus and prefrontal cortex, indicating neural activation in these regions. Adenosine plays an important role in the production of anginal pain by stimulation of A(1) adenosine receptors. Neural activation in the thalamus and prefrontal cortex during angina pectoris has been reported. Although no subject felt chest pain during dipyridamole stress, neural activation in the thalamus and prefrontal cortex indicates that stimulation of A(1) adenosine receptors during dipyridamole stress may produce input from the heart to the thalamus through the vagal fiber.

Blood Pressure↗

PubMed1994

Effect of dipyridamole on glomerular mesangial cell ecto-5'-nucleotidase expression.

Although dipyridamole has been extensively studied as an anti-aggregating agent, its mechanism of action has not been elucidated. Cultured mesangial cells were treated with dipyridamole 1-100 microM from 6-72 h. Ecto-5'-nucleotidase activity approximately doubled (from 115 +/- 11 to 226 +/- 14 nmol/min/mg) after treatment with 100 microM dipyridamole for 72 h. This effect was concentration- and time-dependent. Cycloheximide, an inhibitor of protein synthesis, did not alter basal 5'-nucleotidase activity. However, it prevented stimulation by 5 microM dipyridamole. Adenosine availability at the receptor sites was increased by dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), which inhibit adenosine uptake into the cell. Addition of dipyridamole or NBTI to the adenosine-treated mesangial cells produced an additive increase in ecto-5'-nucleotidase activity. Dipyridamole, through its effect on extracellular adenosine and ecto-5'-nucleotidase, may have an influence upon regulation of the glomerular microcirculation.

5'-Nucleotidase↗

PubMed1992

Effect of dipyridamole with or without aspirin on urine protein excretion in patients with membranous glomerulonephritis.

The antiproteinuric effect of the antiplatelet agent dipyridamole has been assessed after inhibition of thromboxane B2 (TxB2) synthesis in 8 patients with confirmed membranous glomerulonephritis. There were three study periods, each of 30 days, and 45 days apart, namely a washout period, treatment with dipyridamole 300 mg/d, and dipyridamole 225 mg/d plus aspirin 150 mg/d. On Days 1 and 30 of each study period serum and urine creatinine, 24-h excretion of protein, creatinine clearance, platelet aggregometry on whole blood and serum TxB2 were measured. Treatment with dipyridamole alone or with aspirin produced significant inhibition of platelet aggregation and a fall in 24-h protein excretion; the latter amounted to 54% with dipyridamole alone and 56% with dipyridamole plus aspirin (NS). Dipyridamole plus aspirin caused an 82% reduction in serum TxB2.

Adult↗

PubMed1997

ECG-manifest and ECG-silent dipyridamole technetium-99m sestamibi SPET perfusion defects in patients with ischaemic heart disease.

At dipyridamole myocardial scintigraphy, perfusion defects are seldom backed up by significant ECG changes. This would suggest myocardial blood flow heterogeneity, rather than true ischaemia, as the cause of the scintigraphic abnormalities. Electrocardiographic surface mapping has been documented to be more accurate than standard 12-lead ECG in the detection of provoked ischaemia. Thus, to investigate the relationship between ECG changes and perfusion abnormalities, body surface maps were recorded during dipyridamole infusion in 55 subjects (11 normals and 44 patients with ischaemic heart disease) undergoing dipyridamole technetium-99m sestamibi single-photon emission tomography (SPET). All had a normal resting ECG. The extent and severity of the sestamibi defect were quantified. New negative areas in the isointegral maps and rest-dipyridamole map differences >2 SD from normal limits were considered abnormal. After dipyridamole in normals, neither perfusion defects nor >/=1 mm ST segment depression on 12-lead ECG nor new negative areas in isointegral maps occurred. In patients, dipyridamole induced new perfusion defects in 35 (80%) but ST segment depression in only 18 (41%, P<0.001). Of the 35 patients with perfusion defects, 17 (49%, group 1) showed ST segment depression, while the other 18 (51%, group 2) did not. Abnormal body surface maps were found in 100% of group 1 and 88% of group 2 patients (NS). In group 1, the provoked hypoperfusion was of greater extent (P=0.007) and severity (P=0.01) and the onset of map abnormalities was significantly earlier (P<0. 001) than in group 2; time to map abnormalities was also significantly shorter than time to ST segment depression (P=0.01). In the 35 patients with complete scintigraphic, body map and angiographic data, the severity of reversible perfusion defect proved to be the strongest correlate of ST segment depression upon logistic regression analysis. Thus, sestamibi SPET abnormalities after dipyridamole are almost always associated with electrical changes on body surface maps, suggesting myocardial ischaemia as their cause. The much less common 12-lead ECG changes are slower to appear and reflect a more severe hypoperfusion.

Body Surface Potential Mapping↗

PubMed1998

[Effect of intracoronary dipyridamole administration on the incidence of restenosis after PTCA. A prospective randomized study].

BACKGROUND: Restenosis after PTCA remains a serious long-term complication of balloon angioplasty occurring in 30 to 50% of patients. Platelets play a crucial role in the pathogenesis of restenosis following PTCA. Dipyridamole has been shown to inhibit platelet aggregation in humans. Its action as an antithrombotic drug can be attributed to different mechanisms including inhibition of platelet phosphodiesterase and inhibition of the cellular uptake of adenosine. PATIENTS AND METHODS: The purpose of the following study was to investigate the effect of an intracoronary infusion of dipyridamole on the incidence of angiographic and clinical restenosis. In 763 balloon angioplasties patients were randomly allocated to receive either conventional pretreatment (heparin 15000 IE, aspirin 500 mg i.v.) or an additional intracoronary infusion of dipyridamole (0.5 mg/kg body weight). Conventional pretreatment was performed in 388 interventions (61 interventions in women, age 60.5 +/- 8.7 years; 47 interventions for acute coronary syndromes); in 375 interventions additional intracoronary dipyridamole was infused (58 interventions in women, age = 59.6 +/- 9.6 years; 57 interventions for acute coronary syndromes). RESULTS: As compared to conventional pretreatment intracoronary dipyridamole application was associated with a reduction in angiographic restenosis from 43.0% to 36.8% and a reduction of target vessel revascularisation by 15.5% but failed to reach statistical significance. These results were due to an increase in net gain following dipyridamole application. CONCLUSION: Intracoronary pretreatment with dipyridamole prior to PTCA fails to reduce the incidence of angiographic restenosis and target vessel revascularisation significantly. However, a moderate improvement of long-term follow-up can be achieved.

Aged↗

PubMedDate not supplied

Pharmacokinetics of dipyridamole-beta-cyclodextrin complex in healthy volunteers after single and multiple doses.

Dipyridamole is a well known anti-aggregating agent characterized by poor water solubility as well as scant and variable bioavailability. Recently, the compound was complexed with beta-cyclodextrin forming a molecular encapsulation resulting in better oral absorption and stronger biological activities in animals. In the present study, a randomized double blind cross-over comparison between dipyridamole-beta-cyclodextrin complex (dip-beta-CD) and dipyridamole was performed in 12 healthy subjects after single (75mg) and multiple oral treatments (75mg TID). Dip-beta-CD showed better bioavailability and less interindividual variability than dipyridamole either after single or multiple doses. In particular, dip-beta-CD had a greater AUC and Cmax, and a smaller Tmax even at the steady state. In addition, 100% of the subjects receiving a single dose of dip-beta-CD, as compared to 66.7% of those treated with dipyridamole, had plasma levels superior to 1 microgram/ml (which is the supposed anti-aggregating threshold level). In contrast, 0 and 33.03% of the subjects showed plasma levels superior to 2.5 micrograms/ml (which might cause the appearance of side-effects) on the 7th day of the multiple treatment with dip-beta-CD and dipyridamole, respectively. In fact, the subjects presenting higher levels after uncomplexed dipyridamole also complained of headache and/or dizziness on occasion. No adverse side effects were reported for dip-beta-CD.

Administration, Oral↗