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PubMedDate not supplied

Synthesis of a new photoreactive derivative of dipyridamole and its use in the manufacture of artificial surfaces with low thrombogenicity.

Photoimmobilization of dipyridamole (Persantin) was accomplished through the use of a new synthetic conjugate molecule, 1. Persantin is a powerful inhibitor of platelet activation and aggregation and is widely used as a vasodilator. Conjugate 1 consists of triply protected dipyridamole [three of the four hydroxyl groups carry a tert-butyldimethylsilyl (TBDMS) protective group) and the photoreactive 4-azidobenzoyl group. A short hydrophilic spacer chain, derived from triethylene glycol, separates the protected dipyridamole system and the photoreactive group. Compound 1 was immobilized on polyurethane sheets (Pellethane D-55) through irradiation with ultraviolet (UV) light, and the protective groups were removed afterward. The resulting modified polyurethane surfaces were characterized by different physicochemical techniques: UV extinction, contact angle measurements (captive bubble technique), and X-ray photoelectron spectroscopy (XPS). The UV extinction measurements showed the presence of 13 +/- 1 nmol of immobilized dipyridamole/cm2. The contact angle measurements revealed that the modified surface was markedly more hydrophilic than the control (i.e. unmodified polyurethane). XPS measurements clearly established the presence of immobilized dipyridamole in the outermost layers of the modified surface. This was especially clear from the XPS spectra recorded at a low take-off angle (approximately 6 degrees). Furthermore, the XPS spectra showed that the TBDMS protective groups had been quantitatively removed during the deprotection/washing treatment. The in vitro blood compatibility of the modified surface was studied with the thrombin generation assay as developed in our group, as well as with scanning electron microscopy. The thrombin generation test produced a lag time of 1275 s for the modified surface, as opposed to 569 s for the control. Scanning electron microscopy showed that far fewer platelets adhere to the modified surface (approximately 7 x 10(3)/mm2) as compared to the control (approximately 6 x 10(2)/mm2). Taken together, the experimental data reveal that the modified surface has excellent blood compatibility in vitro. It is discussed that the use of conjugate 1 leads to simultaneous exposure of dipyridamole at the modified surface and to a marked increase of the surface hydrophilicity, which is likely to hamper adsorption of plasma proteins. The combination of these effects is uniquely related to the molecular buildup of 1. Conjugate 1 will be used in future work that is aimed at preparing small-caliber polyurethane vascular grafts with a blood compatible lumenal surface.

Biocompatible Materials↗
PubMed1982

Central hemodynamic effects of dipyridamole in severe heart failure: comparison with hydralazine.

The effects of dipyridamole, a coronary and peripheral vasodilator drug, on cardiac performance were investigated in nine patients with severe chronic heart failure. Dipyridamole (30 to 80 mg IV) increased cardiac index (1.63 to 2.65 l/min/m2) and decreased systemic vascular resistance (2097 to 1124 dyn/sec/cm-5). Left ventricular filling pressure decreased (23.7 to 20.7 mm Hg) without significant changes in mean right atrial pressure or heart rate. These effects were similar to the hemodynamic responses after 100 mg hydralazine in the same patients, but they were of shorter duration (less than 90 min). In contrast, oral dipyridamole induced only modest responses in three of eight patients despite large single doses of the drug (150 to 300 mg). Dipyridamole is a rapid-acting short-lived vasodilator, which exerts predominantly arterial vasodilator actions similar to those of hydralazine. Due to inconsistent response after oral doses, however, the therapeutic application of dipyridamole in long-term management of chronic heart failure appears to be limited.

Administration, Oral↗
PubMed1984

Effects of diltiazem, dipyridamole, and their combination on hemostasis.

Calcium channel blockers and antiplatelet agents, alone and in combination, have been reported to induce bleeding in patients undergoing surgery. Since diltiazem and dipyridamole influence platelet function in vitro and in vivo, their influence on hemostasis was examined in five normal men given diltiazem, 90 mg by mouth, followed by 60 mg every 6 hr for 48 hr, or dipyridamole, 75 mg by mouth every 8 hr for 48 hr. At 24 hr, the alternate drug was added to the regimen to assess effects of the combination on hemostasis. Platelet aggregation, serum thromboxane B2 and 6-keto-PGF1 alpha concentrations (stable metabolites of thromboxane A2 and prostacyclin), bleeding time, prothrombin time, partial thromboplastin time, and serum diltiazem concentrations were measured. Diltiazem and dipyridamole alone and in combination had no significant effect on bleeding time, prothrombin time, or partial thromboplastin time. Platelet aggregation induced by threshold concentrations of adenosine diphosphate, epinephrine, and calcium ionophore A 23187 were inhibited by diltiazem and dipyridamole alone and in combination. The only change in prostaglandin concentrations was a slight increase in serum 6-keto-PGF1 alpha after diltiazem. Despite influences on platelet function, neither diltiazem nor dipyridamole alone or in combination induced clinically relevant changes in hemostasis.

6-Ketoprostaglandin F1 alpha↗
PubMed2006

Efficacy of local dipyridamole therapy in a porcine model of arteriovenous graft stenosis.

Perivascular delivery of antiproliferative drugs has been proposed as an approach to prevent neointimal hyperplasia associated with hemodialysis polytetrafluoroethylene (PTFE) grafts. We examined this approach to deliver dipyridamole in a porcine graft model. PTFE grafts were implanted between the carotid artery and external jugular vein bilaterally in pigs. During the surgery or 1 week post-graft placement, dipyridamole (0.26-52 mg) alone or incorporated in microspheres was mixed with an injectable polymeric gel and applied to the graft-arterial and graft-venous anastomoses on one side, whereas the contralateral control graft received no treatment. Three or four weeks after operation, the grafts and adjacent vessels were explanted en bloc and cross-sections of the anastomoses were examined histologically. The degree of neointimal hyperplasia was quantified by planimetry. In separate experiments, dipyridamole was extracted from the explanted tissues and assayed by spectrofluorometry. The normalized median hyperplasia areas of the treated and control graft-venous anastomoses were 0.45 (25th-75th percentile, 0.30-0.86) and 0.24 (0.21-0.30), respectively (N=7; P=0.08). The median hyperplasia areas of the treated and control graft-arterial anastomoses were 0.12 (0.07-0.39) and 0.11 (0.09-0.13), respectively (N=7; P=0.31). The dipyridamole levels in the vascular walls around the anastomoses were at or above the in vitro inhibitory concentrations for approximately 3 weeks. These results suggest that the local perivascular sustained delivery of dipyridamole, even at high dosages, was ineffective in inhibiting neointimal hyperplasia associated with PTFE grafts in a porcine model.

Animals↗
PubMed1983

[Value of the dipyridamole test in the diagnosis of coronary heart disease. Comparison with the stress ECG and coronary angiogram].

In 500 patients suffering from angina pectoris (454 males, 46 females) in whom coronary angiography had been performed a dipyridamole test was carried out. The test was positive in 319 of 396 patients with stenosing coronary heart disease (sensitivity 80%); ECG changes typical of ischaemia were demonstrated in 51%. The exercise ECG test was positive in only 68% of 229 patients with coronary heart disease. Among 104 patients without stenosing coronary heart disease the dipyridamole test was false-positive in 47, giving a specificity of 55%, while in 17 (16%) there were false-positive ECG-changes. The exercise test was falsely positive in 20 of 38 patients without stenosing coronary heart disease (specificity of 47%). Coronary blood flow was measured with the argon technique in 19 of 47 with a false-positive dipyridamole test and three with a false-positive exercise ECG. Maximal pharmacologically induced coronary blood flow was significantly reduced in all so that the diagnosis of "atypical coronary heart disease" or "small vessel disease" was made. The dipyridamole test or the exercise ECG test were falsely positive in these patients only with regard to the coronary arteriogram, correctly positive, however, in relation to angiographically non-demonstrable coronary blood flow abnormalities. The dipyridamole test is complementary to the exercise ECG test and has comparable accuracy. The same precautions must be observed for both tests.

Angiography↗
PubMedDate not supplied

Dipyridamole-induced increased glucose uptake in patients with single-vessel coronary artery disease assessed with PET.

BACKGROUND: The aim of this study was to determine the relationship between vasodilatation-induced ischemia and poststress glucose uptake. Coronary vasodilators may induce myocardial ischemia due to coronary steal through collateral circulation or transmural blood flow redistribution with diminished subendocardial perfusion. Myocardial ischemia can be demonstrated by increased glucose uptake as previously shown in patients with exercise-induced ischemia. METHODS AND RESULTS: We studied 11 patients with single-vessel disease and no history of myocardial infarction. Five patients had no collateral circulation, and 6 had angiographic evidence of collateral vessels. We measured myocardial blood flow (MBF) and glucose uptake at baseline and after the administration of dipyridamole (0.56 mg/kg) with positron emission tomography, using O-15 water and fluorine 18 deoxyglucose (FDG) as perfusion and glucose tracers. MBF at baseline was 0.82 +/- 0.13 mL/g/min in normal areas and 0.80 +/- 0.15 mL/g/min in areas supplied by stenotic arteries. MBF during dipyridamole was 2.05 +/- 0.66 and 1.19 +/- 0.66 mL/g/min in normal areas and areas with stenotic arteries, respectively (P < or = .001). FDG uptake at baseline was 1.36 +/- 0.55 in normal areas and 1.57 +/- 0.62 in areas supplied by stenotic arteries. FDG uptake after dipyridamole infusion was 1.79 +/- 1.1 and 4.04 +/- 0.84 in normal areas and areas with stenotic arteries, respectively (P < or =.001). MBF and FDG uptake were not different between patients with collateral circulation and those without collateral circulation. CONCLUSIONS: Increased myocardial glucose uptake was consistently observed after dipyridamole administration in those areas with diminished coronary vasodilatory capacity. The similar MBF and FDG findings in patients with and without collateral circulation may indicate that transmural blood flow redistribution appears to be a possible mechanism of dipyridamole-induced myocardial ischemia.

Blood Glucose↗
PubMed2001

Mutation of residue 33 of human equilibrative nucleoside transporters 1 and 2 alters sensitivity to inhibition of transport by dilazep and dipyridamole.

Human equilibrative nucleoside transporters (hENT) 1 and 2 differ in that hENT1 is inhibited by nanomolar concentrations of dipyridamole and dilazep, whereas hENT2 is 2 and 3 orders of magnitude less sensitive, respectively. When a yeast expression plasmid containing the hENT1 cDNA was randomly mutated and screened by phenotypic complementation in Saccharomyces cerevisiae to identify mutants with reduced sensitivity to dilazep, clones with a point mutation that converted Met33 to Ile (hENT1-M33I) were obtained. Characterization of the mutant protein in S. cerevisiae and Xenopus laevis oocytes revealed that the mutant had less than one-tenth the sensitivity to dilazep and dipyridamole than wild type hENT1, with no change in nitrobenzylmercaptopurine ribonucleoside (NBMPR) sensitivity or apparent uridine affinity. To determine whether the reciprocal mutation in hENT2 (Ile33 to Met) also altered sensitivity to dilazep and dipyridamole, hENT2-I33M was created by site-directed mutagenesis. Although the resulting mutant (hENT2-I33M) displayed >10-fold higher dilazep and dipyridamole sensitivity and >8-fold higher uridine affinity compared with wild type hENT2, it retained insensitivity to NBMPR. These data established that mutation of residue 33 (Met versus Ile) of hENT1 and hENT2 altered the dilazep and dipyridamole sensitivities in both proteins, suggesting that a common region of inhibitor interaction has been identified.

Amino Acid Sequence↗
PubMed2006

Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke.

Although the mechanisms of action by which aspirin, clopidogrel and dipyridamole inhibit platelets are well characterised, their effects on soluble modulators of thrombosis, inflammation, and endothelial function have yet to assessed systematically. In this investigation aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in combination (A, C, D, AC, AD, CD, ACD) in random order for 2 weeks (without washout) to 11 healthy subjects and 11 patients with previous ischaemic stroke. At the end of each treatment period plasma cyclic guanosine monophosphate (cGMP), monocyte chemoattractant pertide-1 (MCP-1), nitric oxide metabolites (NO(x)), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWf); and serum C-reactive protein (CRP) and platelet derived growth factor (PDGF); were measured blinded to treatment. Dipyridamole reduced plasma vWf levels (%) in both volunteers, -10.0 (4.95), and patients, -10.11 (4.34) (p < 0.05). Dipyridamole also lowered CRP (mg/l) in patients, -0.96 (0.47), but not volunteers. Clopidogrel reduced PAI-1 (ng/ml) in volunteers, -5.30 (2.20) (p < 0.05), and patients, -3.61 (2.75) (non-significant trend). Aspirin lowered PDGF (ng/ml) in volunteers, -3.46 (1.55), but not patients. Triple antiplatelet therapy was superior to dual and mono therapy in reducing vWf levels. In conclusion, antiplatelet agents have non-platelet-related effects on soluble modulators of thrombosis, inflammation, and endothelial function. In particular, dipyridamole reduces plasma vWf and clopidogrel lowers plasma PAI-1 levels. These effects may explain, in part, their roles in preventing atherothrombogenesis.

Adult↗
PubMed1976

Influence of long-term treatment with dipyridamole on the aorta-stenosed rabbit heart: morphometric and functional investigations.

The well-known effects of dipyridamole on the increase of the coronary vessel system and on cardiac metabolism suggest that dipyridamole may have a favourable influence on the chronic pressure loaded heart. In the model of the aorta-stenosed growing rabbit the cardiomegaly was diminished after a 3-month treatment using high doses of dipyridamole. Histometrically a marked decrease of the enlargement of the cross-sectional area of muscle fibres was found. It is assumed that dipyridamole retards myocardial hypertrophy and stimulates hyperplasia. Simultaneously the impairment of distinct parameters of cardiac contractility in the aorta-stenosed heart was prevented in growing rabbits by long-term dipyridamole treatment.

Animals↗
PubMed1987

Collateral function modified by glyceryl trinitrate and dipyridamole during coronary occlusion in conscious dogs.

The effects of glyceryl trinitrate and dipyridamole on induced ischaemia were studied in awake dogs during transient coronary occlusion before and after collateral development. Seventeen dogs were instrumented under sterile conditions with a miniature pressure gauge to measure left ventricular pressure, a cannula for aortic pressure, and pairs of piezoelectric crystals towards the subendocardium of the left ventricle for regional segment length measurements. A hydraulic cuff occluder and Doppler flow probe were placed around the left circumflex coronary artery. Collateral function was increased by repeated 2 min coronary occlusions at 32 min intervals for 2-9 days until regional wall motion returned to preocclusive values, despite the persistence of coronary occlusion. The effects of glyceryl trinitrate and dipyridamole were studied after the initial haemodynamic changes had subsided. Collateral function was quantified by integrating changes in end systolic length of the ischaemic area during coronary occlusion. Before collateral development the end systolic length area was 29.4(2.4) cm X s and was unchanged by glyceryl trinitrate or dipyridamole. After the development of collaterals the end systolic length area decreased from 4.1(1.1) to 2.2(1.0) cm X s (p less than 0.01) after glyceryl trinitrate and increased to 14.9(1.7) cm X s (p less than 0.01) after dipyridamole. Therefore, glyceryl trinitrate acted directly on collaterals and improved the induced ischaemia, whereas dipyridamole exaggerated the regional wall motion abnormality.

Animals↗
PubMed1993

Enhanced sensitivity for detection of coronary artery disease by addition of atropine to dipyridamole echocardiography.

Dipyridamole echocardiography test (DET) has gained acceptance due to its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the test is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. Atropine with dipyridamole might theoretically combine to become a synergistic ischaemic stress test, by increasing myocardial oxygen demand through chronotropic stress and by reducing flow supply through a shortening of the diastolic interval under maximal coronary vasodilation. The aim of this study was to assess the effects of the addition of atropine to DET. Three hundred and twenty-one patients (age = 58 +/- 9 years), referred for testing in the echo lab, were initially studied by DET. Of these, 151 were stopped during or within the 2 min following dipyridamole infusion because of achievement of a predetermined end-point: obvious echocardiographic positivity (n = 137), severe chest pain (n = 3), diagnostic ST segment changes (n = 7) or limited side effects (n = 4). In another three cases, atropine was not given due to a history of glaucoma or severe prostatic hypertrophy. In the remaining 167 patients with a negative DET test, atropine (0.25 mg intravenously, repeated every min up to a maximum of 1 mg, if necessary) was added, starting 3 min after the end of the dipyridamole infusion. The dipyridamole-atropine echo test (DETA) was positive in 32 and negative in 135 patients, and no major side effects occurred in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Impact of culprit lesion morphology on prevalence of provoked myocardial ischaemia in patients with old myocardial infarction. A dipyridamole stress echocardiography, exercise electrocardiography and angiographic study.

We have recently shown that in patients with single vessel disease and no myocardial infarction, a complex plaque morphology makes myocardium more vulnerable to ischaemia during dipyridamole echocardiography testing. Whether coronary lesion morphology in the infarct-related artery in a chronic phase may also modulate prevalence of ischaemia in the same territory remains unknown. In order to determine the possible relationship between culprit lesion morphology in the infarct-related artery and the prevalence of homotopic ischaemia during stress tests, data from high dose dipyridamole echocardiography tests (up to 0.84 mg.kg-1 over 10 min), exercise electrocardiography and coronary angiography from 73 in-hospital patients with a previous myocardial infarction and patent infarct-related single-vessel disease (> or = 50% diameter reduction) were analysed. An angiographic culprit lesion was considered complex (Ambrose classification) when irregular borders, ulcers, thrombus and/or intraluminal lucencies were present. According to angiographic lesion morphology, two groups were identified: Group I, with simple-type culprit lesions; Group II, with complex type culprit lesions. Number of patients (I = 36; II = 37), age (I = 57 +/- II vs II = 55 +/- 9 years), ejection fraction (I = 58.8 +/- II 3 vs II = 56.5 +/- 10.2%), number of Q or non-Q wave myocardial infarctions, prevalence of rest angina (I = 9; II = II) or effort angina (I = 10; II = 10), culprit lesion stenosis severity (I = 57.9 +/- 7.2% vs II = 57.7 +/- 6.2% by computer analysis) and degree of infarct artery anterograde flow (I = 2.64 +/- 0.48 vs II = 2.56 +/- 0.50 by Thrombolysis in Myocardial Infarction definition) did not differ between the two groups (P = ns for all intergroup differences). Dipyridamole echocardiography test-induced ischaemia (considered as new or worsening abnormal wall motion) in the infarct-related artery territory was 25% in Group I and 59% in Group II (P < 0.01). Among positive dipyridamole echocardiography tests, low dose (0.56 mg.kg-1 over the 4 min) positivity occurred in two out of nine Group I patients and in 16 out of 22 Group II patients (22 vs 73%, P < 0.05). Exercise electrocardiography was positive in seven out of 32 Group I patients, and in 16 out of 35 Group II patients (22 vs 46%, P < 0.05). The peak rate pressure product tended to be higher in Group I than in Group II patients (282 +/- 65 vs 257 +/- 65 mmHg x beats.min x 10(2), P = 0.07). Thus, in patients with previous myocardial infarction and a patent infarct-related artery, complex culprit lesion morphology is associated with a higher prevalence of ischaemia and a lower ischaemic threshold during both exercise and dipyridamole stress testing. The morphology of culprit stenosis is important in modulating different stress responses in the chronic phase of myocardial infarction.

Adult↗
PubMedDate not supplied

Intravenous dipyridamole thallium imaging V combined arm-leg cycle stress testing of patients unable to exercise on the treadmill.

UNLABELLED: Rehabilitation patients who will undergo noncardiac surgery or strenuous rehabilitation programs often cannot exercise to greater than 85% of predicted maximal heart rate as required for valid treadmill testing. Because many patients have known or suspected coronary artery disease, greatly increasing their risk for a cardiac event, dipyridamole thallium scans are usually performed, despite a cost of approximately $1400, patient radiation exposure, and the need for a gamma camera. Instead, arm-leg cycle stress testing can be continued to an appropriately high heart rate, is done in the physician's office with an electrocardiograph machine and a blood pressure cuff, and costs $250. This study describes nine patients who had both dipyridamole thallium scans and arm-leg cycle ergometry. Four awaited peripheral vascular surgery, one needed bilateral knee replacements, one was an amputee, and three had claudication. Six had documented and three had suspected coronary disease. RESULTS: In eight of nine patients, the electrocardiograms during both dipyridamole thallium imaging and ergometry were in agreement as to the presence or absence of ischemia (kappa statistic, 0.7273; P = 0.0117). In seven of nine patients, thallium images and ergometry agreed (78% concurrence). To achieve 90% agreement between dipyridamole thallium scans and cycle results, however, 68 patients would have to be studied. CONCLUSION: In this preliminary study, arm-leg ergometry was feasible in all patients and seemed cost-effective and useful for detecting myocardial ischemia. Clinically, if the ergometry were inconclusive, dipyridamole thallium scans could be performed subsequently to obtain the needed information.

Aged↗
PubMed1988

Dipyridamole thallium-201 myocardial imaging. Complications associated with oral and intravenous routes of administration.

Previous reports have shown that TI-201 myocardial imaging with either an oral or intravenous administration of dipyridamole is a suitable diagnostic examination for patients at risk for coronary artery disease who cannot perform treadmill exercise. To compare the incidence of complications associated with these two routes of drug administration, the records of 78 oral and 97 intravenous dipyridamole TI-201 imaging studies were reviewed. The oral administration is associated with a significantly higher incidence of nausea (15% vs. 4%). Despite the higher incidence of nausea, the percentage of patients having one or more dipyridamole-induced symptoms was no greater for the oral (29%) than for the intravenous (37%) administration. Intravenous administration produced both a significantly higher incidence of atypical angina (14% vs. 4%) and a significantly greater increase in heart rate (16.6 vs. 10.2 beats per minute). No patient in either the oral or intravenous dipyridamole protocols had life-threatening arrhythmias or myocardial infarctions. In clinical practice, the difference in complications associated with the oral and intravenous administration of dipyridamole for TI-201 imaging is not significant.

Administration, Oral↗
PubMed1992

Significance of increased Tl-201 uptake by the lungs in patients undergoing oral dipyridamole-thallium myocardial imaging.

The purpose of this study was to evaluate the significance of increased Tl-201 uptake by the lungs after oral dipyridamole testing. In conjunction with myocardial perfusion scintigraphy, intravenous dipyridamole has been recently approved as an alternative to exercise for the evaluation of coronary artery disease in patients who cannot adequately exercise, and it will largely replace oral dipyridamole testing. This study contributes to the understanding of the significance of increased lung thallium uptake during pharmacologic stress testing. Oral dipyridamole, 400 mg, was administered to 192 patients undergoing Tl-201 imaging for clinical indications. Mild adverse effects occurred in 31% of patients (chest pain, nausea, headache, or flushing). Dipyridamole had minimal hemodynamic effects. The lung/heart thallium activity ratio was determined in 152 patients. These were subdivided into four groups according to the presence or absence of ischemia, transient myocardial perfusion defect, or scar as indicated by a fixed myocardial perfusion defect. In 61 patients without transient myocardial perfusion defect or fixed myocardial perfusion defect (group 1), the lung/heart thallium activity ratio was 0.39 +/- 0.01 (mean +/- SEM). In 31 patients without transient myocardial perfusion defect but with fixed myocardial perfusion defect (group 2), the lung/heart thallium activity ratio was higher, 0.44 +/- 0.02 (P less than 0.05). In 27 patients with transient myocardial perfusion defect but no fixed myocardial perfusion defect (group 3) and in 33 patients with both transient myocardial perfusion defect and fixed myocardial perfusion defect (group 4), the lung/heart thallium activity ratio was 0.51 +/- 0.03 and 0.52 +/- 0.03, respectively, both significantly higher than either group 1 or group 2 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Inhibition of dipyridamole-induced myocardial ischemia by diltiazem in patients with coronary artery disease.

We investigated the effect of diltiazem on dipyridamole-induced myocardial ischemia in eight patients with coronary artery disease. Dipyridamole was infused at a rate of 0.142 mg/kg/min for 4 min, and 87-lead mapping was performed to determine the number of leads with ischemic ST-segment depression greater than or equal to 0.05 mV (nST). The range of nST was 8-24 (mean, 13.8) in the control study. Of eight patients studied, a single dose of 90 mg diltiazem administered 3 h before dipyridamole infusion inhibited dipyridamole-induced ST-segment depression completely in seven (nST = 0) and incompletely in one (nST = from 24 to 5). It was concluded that diltiazem could suppress the myocardial ischemia following dipyridamole infusion.

Aged↗
PubMed2004

Cilostazol and dipyridamole synergistically inhibit human platelet aggregation.

It has been previously shown that cilostazol (Pletal), a drug for relief of symptoms of intermittent claudication, potently inhibits cyclic nucleotide phosphodiesterase type 3 (PDE3) and moderately inhibits adenosine uptake. It elevates extracellular adenosine concentration, by inhibiting adenosine uptake, and combines with PDE3 inhibition to augment inhibition of platelet aggregation and vasodilation while attenuating positive chronotropic and inotropic effects on the heart. In the present study, we tested the hypothesis that cilostazol combined with a more potent adenosine uptake inhibitor, dipyridamole, synergistically inhibited platelet aggregation in human blood. In the presence of exogenous adenosine (1 microM), the combination of cilostazol and dipyridamole synergistically increased intra-platelet cAMP. Furthermore, cilostazol inhibited platelet aggregation in a washed platelet assay concentration-dependently with IC50s of 0.17 +/- 0.04 microM (P < 0.05 versus plus adenosine alone of 0.38 +/- 0.05 microM), 0.11 +/- 0.06 microM (P < 0.05), and 0.01 +/- 0.01 microM (P < 0.005) when combined with 1, 3, or 10 microM dipyridamole, respectively (n = 5). In whole blood, cilostazol (0.3 to 3 microM) and dipyridamole (1 or 3 microM) synergistically inhibited collagen- and ADP-induced platelet aggregation in vitro. Furthermore, the synergism was confirmed in an open-label, sequential study in healthy human subjects using ex vivo whole-blood collagen-induced platelet aggregation. Four hours after oral co-administration of cilostazol (100 mg) and dipyridamole (200 mg), platelet aggregation was inhibited by 45 +/- 17%, while no significant inhibition was observed from subjects treated with either drug alone. The combination may provide a potential treatment of arterial thrombotic disorders.

Adenosine↗
PubMed1993

Sensitivity and specificity of radionuclide ventriculography with dipyridamole infusion in patients with severe coronary artery disease.

Noninvasive first-pass radionuclide ventriculography may permit the assessment of global and regional left ventricular function during dipyridamole infusion. Twenty patients with > or = 75% stenosis of at least one coronary artery were studied to assess the sensitivity of the technique in detecting coronary artery disease. Seven (35%) had regional dysfunction after dipyridamole infusion, and 16 (80%) developed lower than normal response in left ventricular ejection fraction (an increase of less than 5%) after dipyridamole infusion. When both regional dysfunction and subnormal rejection fraction were considered together, the sensitivity was 80%. Eight normal subjects were studied to assess specificity. None developed regional dysfunction, and left ventricular ejection fraction invariably increased after dipyridamole infusion in all normal subjects, with an increase of less than 5% in only one subject; therefore, the specificity was 88%. It is concluded that the assessment of regional dysfunction with dipyridamole infusion itself is not sensitive, whereas the assessment of changes in left ventricular ejection fraction is sensitive and specific in detecting coronary artery disease.

Coronary Disease↗