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Results for “DIPYRIDAMOLE”

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PubMed1987

Dipyridamole stimulates urokinase production and suppresses procoagulant activity of rabbit alveolar macrophages: a possible mechanism of antithrombotic action.

Dipyridamole, an inhibitor of platelet aggregation, has been shown to have beneficial effects in disorders characterized by extravascular fibrin deposition. Mononuclear phagocytes are present in extravascular sites and are capable of expressing both plasminogen activator and procoagulant activities, which suggests these cells play a central role in extravascular fibrin turnover. We therefore sought to determine whether dipyridamole affects the expression of plasminogen activator and procoagulant activities by rabbit alveolar macrophages cultured in vitro. We found that dipyridamole (10 to 100 mumol/L) caused increases in both cell-associated and released plasminogen activator activity, which reached levels of 240% (P less than .05) and 543% (P less than .01) of controls, respectively. In contrast, dipyridamole decreased the cell-associated procoagulant activity of alveolar macrophages to as little as 21.3% of controls (P less than .01). Similar effects were seen in cells cotreated with lymphokines. The procoagulant activity expressed by these cells functioned as a tissue thromboplastin. The plasminogen activator of control and treated cells was a urokinase as determined by molecular weight characteristics (50 kilodaltons) and by antibody neutralization profiles using polyclonal antibodies against human urokinase and tissue plasminogen activator. These effects of dipyridamole could not be duplicated by structurally dissimilar agents sharing some of the pharmacological actions of dipyridamole; however, two pyrimidopyrimidine compounds structurally similar to dipyridamole effectively mimicked the effects on both procoagulant and plasminogen activator activities. We conclude that dipyridamole may have antithrombotic effects by directly modulating the role of mononuclear phagocytes in fibrin turnover. Thus, dipyridamole may be useful in situations where extravascular fibrin deposition is important to the pathogenesis of tissue injury and repair.

Animals↗

PubMed1984

Effect of beta-blockade on thallium-201 dipyridamole myocardial scintigraphy.

The effect of beta-blockade on dipyridamole thallium-201 images was assessed in 8 patients with coronary artery disease and positive dipyridamole test. Three dipyridamole thallium-201 tests were performed, the first in basal conditions, the second 30' after propranolol and the third with propranolol and atrial pacing. After dipyridamole heart rate and double product increased respectively from 75 +/- 7 to 98 +/- 15 b/min (p less than 0.01 vs starting values) and from 10 551 +/- 1255 to 11 740 +/- 4542 mmHg X b/min (p less than 0.05 vs starting values). Propranolol reduced heart rate to 64 +/- 6 b/min (p less than 0.05 vs basal conditions), systolic blood pressure to 136 +/- 13 and double product to 8733 +/- 1248 (p less than 0.05 vs basal conditions). Dipyridamole when infused after propranolol, induced an increase in heart rate to 70 +/- 5 b/min (p less than 0.05 vs starting values) while double product was 9133 +/- 1189 mmHg X b/min (p = NS vs starting values). Atrial pacing prevented the fall in heart rate and double product induced by propranolol so during dipyridamole infusion double product increased to 13 271 +/- 1868 (p less than 0.05 vs propranolol treatment; p less than 0.05 vs starting values). Segmental score calculated after dipyridamole was 5.2 +/- 2.0 in basal conditions, 5.1 +/- 1.3 after propranolol (p = NS) and 4.8 +/- 1.3 after propranolol plus atrial pacing (p = NS). Thus the results of the study show that beta-blockade does not worsen dipyridamole thallium-201 images. Furthermore the steal phenomenon seems to be the main mechanism of the dipyridamole induced ischemia. In fact, also when the increase, oxygen consumption is blunted with beta-blockade the disparity in myocardial blood flow resulted unaffected.

Blood Pressure↗

PubMed1994

[The echo-dobutamine and echo-dipyridamole tests in assessing vital myocardium and residual ischemia in myocardial infarct after thrombolysis].

The aim of the study was to compare the ability of dobutamine and dipyridamole echocardiography to detect stunned but viable myocardium early after acute myocardial infarction, to predict spontaneous functional recovery of the reperfused myocardium at 2 months and to detect myocardial ischemia in the infarcted area. Within 10 days from acute myocardial infarction, 47 patients, 29 anterior and 18 inferior, 41 Q-wave and 6 non Q-wave infarctions, underwent dobutamine echocardiography test at low-dose (5-10 mcg/kg/min over 5 min) and high-dose (20-40 mgc/kg/min over 3 min) and to dipyridamole echocardiography test (0.56 mg/kg over 4 min + 0.28 mg/kg over 2 min) in different days and in random order, after interruption of any vasoactive drug. Resting echocardiography was repeated at 2 months in 38/47 patients. Regional wall motion analysis was performed in a qualitative manner on a 14-segment model; viability was defined as improvement of 1 grade or more of at least 2 basally asynergic segments in the infarcted area. Ischemia was defined as an improvement followed by significant deterioration of contractility of the infarcted segments or deterioration of the infarcted area. All patients underwent coronary arteriography within 1 month from admission. Viability was detected by low-dose dobutamine in 34/47 patients (72%) and in 131/297 (44%) of basally asynergic segments compared to only 21/47 patients (45%) and in 66/297 segments (22%) detected by dipyridamole; myocardial ischemia was induced by dobutamine in 64% of patients compared to 36% by dipyridamole. Late spontaneous functional recovery was detected in 21/38 patients (57%) and in 70/244 (29%) of asynergic segments. Sensitivity of dobutamine and dipyridamole echocardiography for predicting spontaneous functional recovery was 70% and 46% specificity 69% and 83%, positive predictive value 48% and 52%, negative predictive value 85% and 79% respectively. Dobutamine correctly identified the presence of a significant stenosis of the infarct-related artery in 74% of cases compared with 43% of dipyridamole; specificity for detecting stenosis was 67% for dobutamine and 83% for dipyridamole. In conclusion, in patients with thrombolyzed myocardial infarction dobutamine echocardiography detects viable myocardium with late spontaneous recovery in a greater proportion of patients and segments than dipyridamole; dobutamine has a higher sensitivity but a lower specificity compared to dipyridamole for identifying a residual stenosis of the infarct-related artery that may jeopardize myocardium in the area at risk.

Adult↗

PubMed1997

Lack of pharmacokinetic interaction between dipyridamole and zalcitabine in rats.

Resistance usually manifests following long-term dideoxynucleoside therapy of HIV-1 infection. This period appears to coincide with reduced dosage regimens. Resistance that is associated with long-term monotherapy may, in part, be due to decreased intracellular drug concentrations. It has been reported that intracellular uptake of the dideoxynucleosides is enhanced by dipyridamole. Hence, dipyridamole may potentially be used to optimize the effects of zalcitabine in HIV-1 antiretroviral "cocktail". The purpose of this study was to characterize the pharmacokinetics of zalcitabine when administered alone and concomitantly with dipyridamole. Also, we determined, indirectly, whether dipyridamole modulated the intracellular uptake of zalcitabine. Rats were intravenously administered either zalcitabine 100 mg/kg alone or with dipyridamole 15 mg/kg. Except renal clearance (CIR), there were no statistically significant differences in the pharmacokinetic parameters including the steady-state volume of distribution and distribution coefficient. Zalcitabine plasma concentrations declined rapidly in a bi-exponential fashion, with a terminal half-life of 1.03 +/- 0.18 hr. alone versus 1.08 +/- 0.22 hr. with dipyridamole. The area under the concentration-time curve was not significantly different with or without dipyridamole. ClR, was 1.42 +/- 0.37 l/hr./kg for zalcitabine alone versus 1.09 +/- 0.28 l/hr./kg with dipyridamole. Our single dose study show that zalcitabine disposition kinetics were not significantly modulated by dipyridamole.

Animals↗

PubMed2000

Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dipyridamole.

BACKGROUND: Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. METHODS: The study group consisted of 20 consecutive patients (52 +/- 10 years, 17 male, 3 female) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for > 5% (inferoapical and posterolateral regions) or > 10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the followup period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. RESULTS: Out of the 180 analyzed segments (20 x 9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34 +/- 12% to 42 +/- 14% in the follow-up period (p = 0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51%), whereas 32 segments were responders (36%, p = 0.05 vs. dobutamine) during low dose dipyridamole. Positive predictive value of dobutamine and dipyridamole for predicting functional recovery was 72% and 75% (p = ns), respectively. Negative predictive value of dobutamine and dipyridamole was 48% and 69% (p = 0.05), respectively. In the group of patients with most severe dyskinesia (regional ejection fraction < 35%, 42 segments) positive predictive value was 73% and 82%, while negative predictive value was 42% and 64% for low dose dobutamine and low dose dipyridamole respectively (p = ns). CONCLUSION: Although low dose dobutamine induced higher rate of positive responses during radionuclide ventriculography imaging, dipyridamole radionuclide ventriculography has shown superior, particularly negative, prognostic value for predicting functional recovery of infarcted regions.

Journal Article↗

PubMed2004

Economic assessment of the secondary prevention of ischaemic stroke with dipyridamole plus aspirin (Aggrenox/Asasantin) in France.

OBJECTIVE: To assess the cost effectiveness of aspirin 25 mg plus dipyridamole 200 mg twice daily in the secondary prevention of ischaemic stroke, according to the French social security perspective, using efficacy data from the second European Stroke Prevention Study (ESPS-2). The ESPS-2 was a double-blind, placebo-controlled clinical trial which assessed the efficacy of four secondary prevention strategies: (i) placebo; (ii) aspirin (acetylsalicylic acid) 25 mg twice daily; (iii) dipyridamole 200 mg twice daily; and (iv) aspirin 25 mg plus dipyridamole 200 mg twice daily. METHOD: We performed a cost-effectiveness analysis with Monte Carlo simulations to compute confidence intervals. We combined data from various sources including the Dijon Stroke Registry, Institut National de la Statistique et des Etudes Economiques, Etude du Coût de l'Infarctus Cérébral (Study of the Cost of Cerebral Infarction [ECIC]) study and the ESPS-2 trial. RESULTS: According to our findings, a preventive strategy with aspirin 25 mg plus dipyridamole 200 mg twice daily is associated with net benefits per avoided stroke recurrence amounting to USD 23,932 (95% CI -USD 32,609, USD 35,772) compared with aspirin 25 mg twice daily alone, and USD 31,555 (95% CI USD 4921, USD 74,515) compared with dipyridamole alone (1997 values). Sensitivity analysis demonstrated that dipyridamole plus aspirin was still cost effective when the average cost of adverse effects per episode (ignored in the original estimation of the cost-effectiveness ratios due to a lack of data) was assumed to be USD 8600 (50,000 French francs); this cost is unlikely as most of the adverse effects associated with aspirin plus dipyridamole are only slight to moderate in severity. CONCLUSIONS: In the secondary prevention of stroke in France, this study suggests, given its underlying assumptions and data, that aspirin 25 mg plus dipyridamole 200 mg twice daily is likely to be a cost-effective strategy from the social security perspective, when compared with other relevant strategies that were evaluated in the ESPS-2 trial.

Adolescent↗

PubMed1993

Prevention of human pancreatic cancer cell-induced hepatic metastasis in nude mice by dipyridamole and its analog RA-233.

BACKGROUND: Several studies have provided evidence suggesting that platelets play a key role in tumor metastasis. A number of antiplatelet agents have been used to prevent tumor metastasis in animal models and humans. Antiplatelet agents, dipyridamole (adenosine transport inhibitor), and RA-233 (inhibitor of cAMP PDE) were used to prevent tumor-cell-platelet interactions both in in vitro and in vivo systems; however, the data were not very conclusive. METHODS: Our studies used dipyridamole and RA-233 alone and in combination to investigate their effects on human pancreatic tumor cells (RWP-2)-induced platelet aggregation in human blood and on hepatic metastasis in nude mice. To examine effects of dipyridamole and RA-233 on liver metastasis, the tumor cells (RWP-2) were injected intrasplenically in nude mice grouped into control, dipyridamole (8 mg/kg), RA-233 (8 mg/kg), and dipyridamole plus RA-233 (8 mg/kg each). The agents were administered intraperitoneally 1 hour before and 24 hours after the tumor cell injection. RESULTS: When dipyridamole and RA-233 were used alone, only weak to moderate effects were seen on RWP-2 tumor cell-induced platelet aggregation. However, these agents, when combined, strongly inhibited the tumor cell-induced aggregation in human platelet-rich plasma. In tumor metastasis experiments, reductions of approximately 70% in hepatic nodules and 90% in surface area occupied by the tumor were seen with the combination treatment (dipyridamole plus RA-233) as compared with the control group of mice. CONCLUSIONS: This study suggests that the combination of dipyridamole and RA-233 provides an effective intervention for the antithrombotic approach to the treatment of cancer metastases.

Adenosine↗

PubMed1999

Wavelet transform analysis of heart rate variability during dipyridamole-induced myocardial ischemia: relation to angiographic severity and echocardiographic dyssynergy.

BACKGROUND: Analysis of heart rate variability (HRV) is a valuable noninvasive method for quantifying autonomic cardiac control in humans and has been utilized during dipyridamole echocardiographic test to differentiate positive from negative test results. HYPOTHESIS: We aimed to evaluate, by means of HRV analysis, the influence of the angiographic severity of coronary artery disease on cardiac autonomic control during dipyridamole-induced myocardial ischemia. METHODS: We analyzed RR interval variability changes during dipyridamole-induced myocardial ischemia in 31 selected patients (mean age 54 +/- 9 years) with available coronary angiography and positive dipyridamole echocardiographic test. Spectral components of HRV were assessed by means of wavelet transform analysis for the last 5 min before the beginning of the test (baseline) and for 5 min after the onset of ischemia-related events (peak dipyridamole effect). RESULTS: Patients were divided into three groups according to the number of coronary diseased vessels (Group A, single-vessel disease; Group B, double-vessel disease; Group C, triple-vessel disease). No difference was detectable at baseline among the three groups. After dipyridamole, low-frequency power, a measure of sympathetic modulation of heart rate, increased and echocardiographic wall motion score index worsened in all groups (p < 0.001). The increase in low-frequency power was more evident in Group C patients than in the other two groups (p < 0.005). Furthermore, after dipyridamole, a direct correlation was found between low-frequency power and wall motion score index (r = 0.59; p < 0.001). CONCLUSIONS: These data suggest that HRV analysis performed during dipyridamole echocardiographic test provides useful information to assess the severity of coronary artery disease.

Autonomic Nervous System↗

PubMed1987

Quantitative [3H]dipyridamole autoradiography: evidence for adenosine transporter heterogeneity in guinea pig brain.

[3H] Dipyridamole binding in guinea pig brain slices has been characterized. Binding of [3H] dipyridamole to guinea pig forebrain slices was found to be rapid, reversible and saturable. Saturation experiments revealed a class of high affinity binding sites with a Bmax value of 592 +/- 118 fmol/mg protein and Kd value of 10.8 nM +/- 2.1 nM in the analysed concentration range. In competition experiments, the adenosine transport inhibitors hexobendine and dipyridamole itself were the most potent displacers (inhibition constants of 4.6 nM +/- 1 nM and 11.5 nM +/- 3 nM) with "pseudo-Hill" coefficients close to 1. Competition curves with nitrobenzylthioinosine, another adenosine transport inhibitor, however, showed a biphasic profile with a "pseudo-Hill" coefficient of 0.33 +/- 0.04. Just 42% +/- 4% of [3H] dipyridamole binding were inhibited by nanomolar concentrations of nitrobenzylthionosine and only micromolar concentrations displaced the remainder. Subsequent quantitative autoradiography demonstrated regional differences in the inhibition of [3H] dipyridamole binding by submicromolar concentrations of nitrobenzylthioinosine. While in cortical areas of cerebrum and cerebellum 500 nM nitrobenzylthioinosine displaced binding of [3H] dipyridamole to only about one-third of its sites (in the Purkinje cell layer less than 10%), it showed similar potency as dipyridamole in various areas of the brainstem and hypothalamus. This biphasic and regionally heterogenous interaction of nitrobenzylthioinosine with [3H] dipyridamole binding sites in guinea pig brain slices strongly suggests heterogeneity of adenosine transporters.

Adenosine↗

PubMed1992

Efficiency of labelling of red blood cells with technetium-99m after dipyridamole infusion for thallium-201 stress testing.

Experimental studies have suggested that dipyridamole may inhibit red blood cell labelling with technetium-99m. To evaluate whether this effect is clinically relevant to the performance of radionuclide ventriculography after dipyridamole-thallium stress testing, in vitro red blood cell labelling was compared immediately before and after thallium-201 stress scintigraphy combined with either dipyridamole infusion (30 patients) or exercise stress (20 patients). Modified in vivo red blood cell labelling efficiency was assessed in a further 36 patients following dipyridamole infusion and was compared with that in 15 patients following exercise stress. The importance of a reversal of the dipyridamole effects by aminophylline was evaluated for in vitro and modified in vivo techniques. The red blood cell labelling efficiency was not significantly different in patients following dipyridamole compared with that obtained following exercise stress for both in vitro (93% +/- 4% versus 91% +/- 4%) and modified in vivo (87% +/- 19% versus 90% +/- 6%) techniques. Also, in vitro red blood cell labelling efficiency after dipyridamole was not different to that before stress testing (93% +/- 4% versus 92% +/- 4%). Reversal with aminophylline had no significant effect on the in vitro labelling efficiency with either the in vitro technique (94% +/- 3% with reversal versus 92% +/- 5% without) or the modified in vivo technique (91% +/- 4% with reversal versus 82% +/- 26% without). These results suggest that the red blood cell labelling efficiency is not compromised by the preceding dipyridamole-thallium stress testing but can be optimised by using in vitro labelling.

Aged↗

PubMed1987

Effects of dipyridamole on adenosine concentration, insulin sensitivity and glucose utilisation in soleus muscle of the rat.

Adenosine has been shown to modulate the sensitivity of skeletal muscle to insulin (Budohoski et al. 1984). In an attempt to further characterize the modulatory action of adenosine on insulin sensitivity in skeletal muscle we have investigated the effect of the nucleoside transport inhibitor dipyridamole in isolated incubated soleus muscle strips. At a concentration of 50 microM, dipyridamole increased the concentration of adenosine in the soleus muscle by 36% and in the incubation medium by 32%. At this concentration of dipyridamole, the basal rates (in the presence of 1 microunit of insulin/ml) of lactate formation, 2-deoxy [2,6-3H]glucose phosphorylation and glucose oxidation were decreased by 48%, 43% and 47% respectively, whilst the rate of glycogen synthesis was unaffected. Insulin-stimulated rates (in the presence of 10,000 microunits of insulin/ml) of lactate formation, 2-deoxy [2,6-3H] glucose phosphorylation, glycogen synthesis and glucose oxidation were decreased by 70%, 30%, 26% and 20% respectively in the presence of 50 microM dipyridamole. Although 50 microM dipyridamole was required to exert a significant effect on medium and soleus muscle adenosine concentrations, statistically significant effects on glycolytic rate were observed at concentrations as low as 2 microM dipyridamole. It is concluded that the results are not consistent with dipyridamole exerting an effect on skeletal muscle carbohydrate metabolism solely through elevation of the intracellular or interstitial adenosine concentration, but strongly suggest that dipyridamole inhibits glucose transport and/or phosphorylation in skeletal muscle.

Adenosine↗

PubMed1997

Technetium-99m sestamibi myocardial tomography based on dipyridamole echocardiography testing in hypertensive patients with chest pain.

The non-invasive diagnosis of coronary artery disease in hypertensives with chest pain is an important clinical concern because all exercise-dependent tests display limited feasibility and diagnostic accuracy; by contrast, dipyridamole echocardiography testing has been shown to have a similar feasibility and accuracy in hypertensive and normotensive subjects. The aim of this study was to evaluate the diagnostic capability of technetium-99m sestamibi tomography based on dipyridamole echocardiography testing in hypertensives with chest pain, and to compare the scintigraphic results with those of coronary angiography, exercise electrocardiography and dipyridamole echocardiography. Forty subjects with mild to moderate hypertension, chest pain and no previous myocardial infarction were submitted to 99mTc-sestamibi tomography (at rest and after high-dose dipyridamole echocardiography) and to exercise electrocardiography testing. At coronary angiography 22 patients (group A) had significant epicardial coronary artery disease (>/=70% stenosis of at least one major vessel) and 18 normal main coronary vessels (group B). Dipyridamole 99mTc-sestamibi imaging was positive in 21/22 patients of group A and in 5/18 of group B. Dipyridamole echocardiography was positive in 18/22 patients of group A and in 5/18 of group B. Exercise electrocardiography was positive in 15/22 patients of group A and in 11/18 of group B. Four out of five subjects in group B with positive results in all the tests showed a slow run-off of angiographic contrast medium, probably due to small-vessel disease. Significant epicardial coronary artery disease in hypertensives with chest pain is unlikely when dipyridamole 99mTc-sestamibi tomography is negative. When scintigraphy is positive, either epicardial coronary artery disease or a small-vessel disease condition is possible. The association of scintigraphy with dipyridamole echocardiography testing allows the assessment of contractile function and myocardial perfusion by a single pharmacological stress.

Chest Pain↗

PubMed1988

Augmentation of coronary bypass graft flow induced by dipyridamole and its relation to bypass graft patency.

To evaluate the effect of dipyridamole on coronary bypass graft flow, 10 mg of dipyridamole was injected intravenously, during the measurement of graft flow, at the time of surgery. Its concentration in serum was measured and compared with that after oral administration. In 50 individual vein grafts performed on 35 patients, graft flow increased from 65 +/- 37 to 96 +/- 55 ml/min (p less than 0.001) after the dipyridamole injection and the arterial pressure decreased slightly. In 40 grafts whose graft flow was increased by more than 10 ml/min by dipyridamole, the patency rate (at 5 weeks) was 98 per cent, whereas that of the 10 other grafts, which responded poorly, was only 50 per cent (p less than 0.01). The serum concentration of dipyridamole, 3 minutes after intravenous injection, was 1.46 +/- 0.68 micrograms/ml, while the level of orally administered dipyridamole, in 3 groups of patients who were given 50 mg, 75 mg and 100 mg, three times a day, respectively, was steady, being 0.68 +/- 0.20 micrograms/ml, 1.43 +/- 0.41 micrograms/ml and 1.73 +/- 0.50 micrograms/ml, 2 hours following ingestion. We concluded that intravenous dipyridamole increases the graft flow and that a better patency is obtained in those grafts in which the graft flow is increased by more than 10 ml/min. It is also expected that routine doses of oral dipyridamole possibly increase the graft flow after coronary bypass surgery.

Administration, Oral↗

PubMed2005

BCRP transports dipyridamole and is inhibited by calcium channel blockers.

PURPOSE: We investigated whether dipyridamole and various calcium channel blockers are inhibitors and/or substrates of breast cancer resistance protein (BCRP). METHODS: The effect of dipyridamole and the calcium channel blockers on mitoxantrone efflux by BCRP-overexpressing human embryonic kidney (HEK) cells was determined by flow cytometry. The ability of some of these compounds to reverse BCRP-mediated mitoxantrone resistance was measured by cytotoxicity assays. Transport studies were performed using radiolabeled compounds. RESULTS: Dipyridamole, nicardipine, nitrendipine, and nimodipine effectively inhibited BCRP-mediated mitoxantrone efflux; however, bepridil, diltiazem, and verapamil had no significant effect. Nifedipine is a much weaker BCRP inhibitor compared with other dihydropyridines tested. Nicardipine and dipyridamole were the most potent BCRP inhibitors among the compounds tested with IC50 values of 4.8 +/- 1.3 and 6.4 +/- 0.9 microM, respectively. Nicardipine and dipyridamole also effectively reversed BCRP-mediated mitoxantrone resistance in HEK cells. [3H]Nitrendipine was found not to be transported by BCRP. However, the transport of [3H]dipyridamole by BCRP was observed in both HEK and Madin-Darby canine kidney cells stably expressing the transporter, and this transport was completely abolished by fumitremorgin C, a known BCRP inhibitor. CONCLUSIONS: Dipyridamole and several dihydropyridines are effective BCRP inhibitors, but bepridil, diltiazem, and verapamil are not. We also identified a new BCRP substrate, dipyridamole.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed1986

Dipyridamole-echocardiography test in patients with exercise-induced ST-segment elevation.

Fourteen consecutive patients with exercise-induced ST-segment elevation in the absence of previous infarction and basal left ventricular asynergy at rest performed a dipyridamole test (infusion of dipyridamole, 0.14 mg/kg/min intravenously for 4 minutes) during 12-lead electrocardiographic (ECG) and 2-dimensional echocardiographic monitoring. In 7 of the 14 patients, dipyridamole infusion consistently induced ST-segment elevation in the leads that showed ST elevation on effort; reversible asynergy (occurring in the region corresponding to the ECG leads with diagnostic changes) could always be documented by echocardiography. In 2 patients dipyridamole induced reversible asynergy in presence of ST-segment depression. In these 9 patients angiography invariably revealed a severe organic stenosis in the coronary artery feeding the region that became transiently asynergic after dipyridamole. In the other 5 patients (all of whom had either spontaneous or ergonovine-induced ST-segment elevation), the dipyridamole test yielded no significant echocardiographic or ECG change; coronary angiography showed absent (2 patients) or significant (3 patients) coronary artery disease. In conclusion, dipyridamole may induce transmural ischemia in humans, as detected by the electrical hallmark of ST elevation; this ECG pattern, in contrast to ST depression, reliably predicts the presence and site of transient regional asynergy. When dipyridamole induces ST-segment elevation, severe basal stenosis is invariably present in the coronary artery supplying the transiently asynergic myocardial region.

Adult↗

PubMed1988

Usefulness of the dipyridamole-exercise echocardiography test for diagnosis of coronary artery disease.

To test the hypothesis that a dipyridamole infusion might sensitize the myocardium to exercise-induced ischemia, 33 patients with effort chest pain syndrome--including 24 with and 9 without angiographically documented coronary artery disease (CAD)--and 10 control subjects were studied. As inclusion criterion, all enrolled subjects had a negative resting high-dose dipyridamole-echocardiography test result for both mechanical (development of a transient asynergy) and electrocardiographic (greater than 0.1 mV ST-segment shift) changes. All performed 2 supine exercises during 2-dimensional echocardiography and 12-lead electrocardiography monitoring, immediately after high-dose (0.84 mg/kg over 10 minutes) dipyridamole (dipyridamole-exercise stress test) or placebo (exercise stress test) infusion. The overall sensitivity (by electrocardiographic, echocardiographic or combined criteria) for CAD detection was 10 of 24 for exercise stress test and 21 of 24 for dipyridamole-exercise stress test (42 vs 88%, p less than 0.01). The specificity was 19 of 19 for exercise stress test and 18 of 19 for dipyridamole-exercise stress test (100 vs 95%, difference not significant). Both exercise stress test and dipyridamole-exercise stress test yielded negative results in the 10 control subjects, with a similar peak rate-pressure product (X 1/100) reached in the 2 tests (287 +/- 55 vs 274 +/- 42, difference not significant). Eight patients (all with significant CAD) had positive results of their exercise stress test and all 8 had also positive dipyridamole-exercise stress test results, at a significantly lower rate-pressure product with respect to the exercise stress test (253 +/- 49 vs 204 +/- 35, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Intravenous dipyridamole-induced myocardial ischemia during percutaneous transluminal coronary angioplasty in humans.

Percutaneous transluminal coronary angioplasty was used as a model of controlled myocardial ischemia to study the effect of intravenous dipyridamole on myocardial ischemia and coronary hemodynamics in 10 patients. All patients had 1-vessel coronary artery disease with visualized collaterals. Intravenous dipyridamole increased myocardial ischemia during inflations. ST elevation, as measured by intracoronary electrogram, increased significantly from the control inflation to the second inflation after dipyridamole injection (0.05 +/- 0.23 vs 0.44 +/- 0.43 mV, p less than 0.03). Of the 10 patients, 8 developed new or more severe angina with subsequent inflations after dipyridamole. The pulmonary artery wedge pressure increased significantly from the control inflation to the fourth inflation (15 +/- 8 vs 20 +/- 9 mm Hg, p less than 0.05). The coronary wedge pressure showed a decreasing trend with subsequent inflations after dipyridamole but did not reach statistical significance. The double product (heart rate X blood pressure) was not significantly altered by dipyridamole. The findings indicate that intravenous dipyridamole increases myocardial ischemia during balloon occlusion. The constancy of the double product and the trend toward a decrease in coronary wedge pressure suggest that dipyridamole may induce ischemia by reducing the amount of collateral flow through a coronary steal phenomenon.

Adult↗

PubMed1990

Functional significance of myocardial perfusion defects induced by dipyridamole using thallium-201 single-photon emission computed tomography and two-dimensional echocardiography.

The mechanisms responsible for inhomogeneous myocardial blood flow after oral administration of a large dose (300 mg) of dipyridamole were assessed in 27 patients with serial thallium-201 single-photon emission computed tomography (SPECT) and simultaneous 2-dimensional echocardiograms. Myocardial tomographic images were obtained 50 minutes and 3 to 4 hours after administration of dipyridamole. Two-dimensional echocardiograms were recorded at baseline and then every 15 minutes for 60 minutes. Dipyridamole caused only a mild reduction in blood pressure (from 129 +/- 18 to 126 +/- 16 mm Hg) and a mild increase in heart rate (from 69 +/- 15 to 73 +/- 4 beats/min). Sixteen patients had perfusion defects after dipyridamole by SPECT, which underwent partial or total filling-in. Fourteen of these patients (87.5%) had either a new abnormality or further deterioration of a preexisting wall motion abnormality by 2-dimensional echocardiography, and thus were considered to have developed transient ischemia during dipyridamole administration. Ten of 11 patients (91%) with normal perfusion or fixed defects by SPECT had no further deterioration in wall motion after oral dipyridamole, and were thus considered to have no evidence of myocardial ischemia. In conclusion, most patients with transient thallium-201 defects after dipyridamole develop transient worsening of resting wall motion by 2-dimensional echocardiography, suggestive of true myocardial ischemia. Because myocardial oxygen demand, as indicated by the heart rate-blood pressure product, did not change significantly, the mechanism of myocardial ischemia in these patients is likely to be diminished regional blood flow related to a "subendocardial steal" induced by dipyridamole.

Angina Pectoris↗