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PubMed1985

Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine.

To determine the renal effects of inhibiting the uptake and subsequent metabolism of endogenous adenosine, dipyridamole, a nucleoside transport inhibitor, was infused intrarenally into anesthetized dogs. Dipyridamole (24 micrograms/kg per min) inhibited the cellular extraction of [14C]adenosine (72 +/- 3% vs. 9 +/- 3%) and elevated the excretion of endogenous adenosine (0.60 +/- 0.08 to 1.70 +/- 0.21 nmol/min, P less than 0.05). The action of exogenous adenosine to decrease glomerular filtration rate is known to be enhanced by sodium depletion, and is minimal or absent in sodium-loaded animals. To ascertain whether dietary sodium intake alters the renal effects of elevated endogenous adenosine, dipyridamole was infused into sodium-depleted and sodium-loaded dogs. In the sodium-depleted dogs (n = 9), dipyridamole infusion decreased the glomerular filtration rate by 59 +/- 7% (20 +/- 1 to 8 +/- 2 ml/min, P less than 0.05) which returned to control levels within 30 minutes after stopping infusion of dipyridamole. Renal vascular resistance was unchanged during dipyridamole infusion. In the sodium-loaded dogs (n = 5), dipyridamole had no effect on glomerular filtration rate (22 +/- 4 vs. 25 +/- 3 ml/min) or renal vascular resistance. In a separate series of sodium-depleted dogs (n = 8), the dipyridamole-induced decrease in glomerular filtration rate was completely reversed or inhibited by theophylline, an adenosine receptor antagonist. These experiments demonstrate that inhibition of cellular uptake of adenosine elevates adenosine levels, that dipyridamole decreases glomerular filtration rate in sodium-depleted but not sodium-loaded dogs, and that the decrease in glomerular filtration rate is inhibited by theophylline. We conclude that the decrease in glomerular filtration rate during dipyridamole administration is mediated by increased endogenous adenosine.

Adenosine↗

PubMed2003

Dipyridamole enhances NO/cGMP-mediated vasodilator-stimulated phosphoprotein phosphorylation and signaling in human platelets: in vitro and in vivo/ex vivo studies.

BACKGROUND AND PURPOSE: Dipyridamole and in particular dipyridamole in combination with low-dose aspirin are very effective in preventing recurrent stroke. However, the mechanism(s) underlying this dipyridamole effect have not been elucidated. Since dipyridamole inhibits the cGMP-specific phosphodiesterase type V in vitro, we hypothesized and tested whether therapeutically relevant dipyridamole concentrations enhance NO/cGMP-mediated effects in intact human platelets studied ex vivo. METHODS: Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), an established marker of NO/cGMP effects in human platelets, was quantified by phosphorylation-specific antibodies and Western blots. Serotonin secretion and thromboxane synthase activity were determined by fluorometric quantification of derivatized serotonin and synthase products, respectively. RESULTS: Endothelium-derived factors such as NO and prostaglandin I2 are known to elevate both cGMP and cAMP levels with concomitant platelet inhibition and VASP phosphorylation. In our in vitro experiments, therapeutically relevant concentrations (3.5 micromol/L) of dipyridamole amplified only cGMP-mediated VASP phosphorylation due to the NO donor sodium nitroprusside, but not cAMP-mediated effects. Furthermore, thromboxane synthase activity and serotonin secretion, events important for initial platelet activation, were inhibited by sodium nitroprusside, an effect also enhanced by dipyridamole, demonstrating the functional relevance of these observations. Finally, the ex vivo enhancement of NO/cGMP effects was also observed with platelets obtained from healthy volunteers treated with extended-release dipyridamole. CONCLUSIONS: Under therapeutically relevant conditions, dipyridamole enhances platelet inhibition by amplifying the signaling of the NO donor sodium nitroprusside. These data support the concept that enhancement of endothelium-dependent NO/cGMP-mediated signaling may be an important in vivo component of dipyridamole action.

Adult↗

PubMed1999

Effect of intravenous dipyridamole on cerebral blood flow in humans. A PET study.

BACKGROUND AND PURPOSE: Dipyridamole increases the concentration of circulating adenosine, which is a potent vasodilator, by inhibition of uptake of adenosine into the erythrocytes, and hence produces coronary vasodilation. However, the effects of dipyridamole on cerebral circulation is not pronounced. This study investigates the effects of intravenous dipyridamole on cerebral blood flow (CBF) in humans with use of positron emission tomography (PET). METHODS: In each of 13 healthy subjects, CBF was measured using (15)O-labeled water and PET at rest and during hypercapnia, hypocapnia, and dipyridamole stress; corresponding CBF values were then compared. RESULTS: CBF values during dipyridamole stress were significantly lower than those measured at rest. The dipyridamole stress PaCO(2) was also significantly lower than the resting PaCO(2). The change in CBF during dipyridamole stress relative to PaCO(2) closely followed the relationship between CBF and PaCO(2) during hypocapnia. CONCLUSIONS: These results indicate that the observed decrease in CBF during dipyridamole stress was caused by a decrease in PaCO(2) rather than by any direct action of dipyridamole on CBF. The decrease in PaCO(2) during dipyridamole stress was most likely due to hyperventilation, which was a side effect of adenosine. These results support the hypothesis that circulating adenosine is largely prevented from binding to adenosine receptors of cerebral vessels by the blood-brain barrier.

Aged↗

PubMed1977

Binding of dipyridamole to human platelets and to alpha1 acid glycoprotein and its significance for the inhibition of adenosine uptake.

The interactions of dipyridamole with alpha(1) acid glycoprotein of plasma and with human platelets are related to inhibition of adenosine uptake by platelets. Binding studies by equilibrium gel filtration suggested that 1 mol of dipyridamole binds per mol of alpha(1) acid glycoprotein with a dissociation constant of 1.6 muM. Platelets contain two populations of binding sites, one with high and another with lower affinity for the drug. The binding of dipyridamole to the high-affinity sites follows a Michaelis-Menten binding pattern with a dissociation constant of 0.04 muM. Approximately 2 x 10(4) dipyridamole molecules are bound at the high-affinity sites of each platelet. The lower affinity sites bind the drug with a dissociation constant of 4 muM. In the presence of alpha(1) acid glycoprotein of plasma, the binding of dipyridamole to human platelets is inhibited. Correspondingly, the dipyridamole inhibition of adenosine uptake by platelets is reduced 1,000-fold by purified alpha(1) acid glycoprotein. The binding of dipyridamole to human platelets was found to be essential for its inhibition of adenosine uptake by platelets. Dipyridamole decreases the incorporation of [(14)C]adenosine radioactivity in platelet nucleotides and reduces the [(14)C]-ATP to [(14)C]ADP ratio. Purified alpha(1) acid glycoprotein reverses these effects of dipyridamole on adenosine metabolism of platelets in a concentration-dependent manner. An equilibrium of dipyridamole binding to alpha(1) acid glycoprotein and to platelets is proposed.

Adenine Nucleotides↗

PubMed1989

Relationship of thallium-201 defect and left ventricular function after dipyridamole infusion.

Tl-201 imaging and first-pass radionuclide ventriculography (RNV) by 4 min infusion of 0.56 mg/kg dipyridamole were performed on 22 patients with coronary artery disease in order to know the relationship of myocardial perfusion and left ventricular function after dipyridamole-infusion, and thereby to define whether Tl-201 defect with dipyridamole could imply myocardial ischemia. Initial and delayed Tl-201 images were divided into anterior, apical, and infero-posterior segments, and segmental perfusion defects were categorized as reversible, fixed and no defect. RNV on the 30-degree right anterior oblique view was also divided into anterior, apical, and infero-posterior wall to be evaluated for regional wall motion by a 5 point score before and after dipyridamole. Changes in left ventricular ejection fraction (LVEF) with dipyridamole were also calculated. Normal responses of regional wall motion and LVEF to dipyridamole were established from the data of 14 normal subjects. Reversible defects were closely associated (69%) with an abnormal response of regional wall motion (score decrease of 1 or more after dipyridamole). Both fixed defects and no defects showed little association with abnormal response of regional wall motion. Moreover, 77% of the patients having reversible-defect segment showed an abnormal response of LVEF (reduction of 3% or more following dipyridamole). However, patients without reversible defect did not show an abnormal response to dipyridamole. These results suggest that dipyridamole-induced Tl-201 defects represent a myocardial ischemia which causes a reduction of ventricular function.

Adult↗

PubMed1992

Activation of sympathetic tone during dipyridamole test.

Cardiac imaging with dipyridamole infusion has been proposed as an exercise-independent tool for the diagnosis of coronary artery disease. Dipyridamole acts through the accumulation of adenosine, which reduces sympathetic tone in vasomotor nuclei of the brainstem and inhibits norepinephrine release in noradrenergic neurons but also activates arterial chemoreceptors. The aim of this study was to assess whether dipyridamole administration (up to 0.84 mg/kg over 10 minutes, a dosage commonly employed for diagnostic testing) may modulate sympathetic activity either directly or indirectly through blood pressure reduction or myocardial ischemia, which may be evoked by dipyridamole infusion and represent two recognized sympathetic stimuli. Twenty patients were studied with infusion combined with two-dimensional echocardiography and 12-lead ECG monitoring. Blood pressure was recorded each minute by a cuff sphygmomanometer. In all patients, we obtained venous blood samples for epinephrine (an index of adrenomedullary catecholamine release) and norepinephrine (an index of neuronal activity) both in resting conditions and at peak dipyridamole, ie, at the first minute after termination of dipyridamole infusion in negative cases or in the presence of obvious ischemia in positive cases (ie, as soon as a regional ventricular dyssynergy or an ST segment depression greater than 0.1 mV appeared). Epinephrine and norepinephrine determinations were made by a high performance liquid chromatography (HPLC) method. After dipyridamole, there was a significant rise in norepinephrine, while epinephrine did not change significantly. Dipyridamole-induced percentage variations of norepinephrine from baseline were not significantly correlated with mean blood pressure changes (r = .1, p = ns) and were of a similar extent in patients with (n = 10) and without (n = 10) dipyridamole-induced ischemia (+68 vs +73 percent, p = ns). Dipyridamole administration provokes an activation of sympathetic tone which can be detected even in the absence of myocardial ischemia and is not related to blood pressure changes. The increased catecholamine release appears to be of neuronal rather than adrenomedullary origin.

Adult↗

PubMed1999

Absence of heart rate increase during inferoposterior left ventricular hypoperfusion caused by dipyridamole infusion.

BACKGROUND: Stimuli such as inferoposterior myocardial infarction and right coronary injection with radiographic contrast media evoke a vasodepressor reflex characterized by bradycardia and hypotension (Bezold-Jarisch reflex). Dipyridamole acts by adenosine-mediated coronary vasodilation to disclose myocardial perfusion heterogeneity for thallium-201 scintigraphy. OBJECTIVE: To determine whether there is a relationship between the site of left ventricular hypoperfusion and the heart rate response to dipyridamole. DESIGN: One thousand eight hundred consecutive dipyridamole-thallium studies performed between 1985 and 1993 were reviewed to identify 48 subjects who met prespecified selection criteria. SETTING: Nuclear cardiology laboratory of a university teaching hospital. PATIENTS: Group 1 (n=26) had less than 5% pretest likelihood of coronary artery disease and normal thallium perfusion, group 2 (n=10) had isolated, completely reversible anterior perfusion abnormalities, and group 3 (n=12) had analogous inferoposterior perfusion abnormalities. INTERVENTIONS: Heart rate and blood pressure were recorded at baseline and each minute of supine dipyridamole infusion. MAIN RESULTS: After 4 mins of dipyridamole infusion, a significant increase in heart rate was observed in group 1 (+12 beats/min, P<0.05) and group 2 subjects (+12 beats/min, P<0.05) but not in group 3 subjects (+3 beats/min, not significant; P=0.016 compared with responses in the other two groups). Blood pressure was not affected by dipyridamole infusion in any group. CONCLUSIONS: Isolated, moderate or severe inferoposterior hypoperfusion in response to dipyridamole is not accompanied by an increase in heart rate, suggesting that the chronotropic response to dipyridamole is modulated by the presence and location of myocardial perfusion abnormalities. This observation is consistent with the concept that inhibition of adenosine reuptake by dipyridamole, leading to local increases of adenosine concentration, exerts direct and/or reflex effects on heart rate that are site specific. The absence of a rise in heart rate during dipyridamole infusion may be a marker of impaired coronary flow reserve in the inferoposterior left ventricular wall.

Coronary Disease↗

PubMed2000

[The role of the echo-dipyridamole test in the diagnosis of coronary disease in patients with associated aortic stenosis].

BACKGROUND: Coronary vasodilator reserve is often significantly impaired in patients with aortic stenosis by several mechanisms: coronary artery disease, left ventricular hypertrophy, increase in cardiac chamber stiffness. The aim of this study was to evaluate the feasibility and the diagnostic accuracy of the dipyridamole echocardiography test in the diagnosis of coronary artery disease in patients with aortic stenosis. METHODS: Forty patients (26 males, 14 females, mean age 69 +/- 8.9 years) with aortic stenosis (mean valve area 0.7 +/- 0.3 cm2 calculated by the continuity equation) were studied by two-dimensional echocardiography during dipyridamole infusion up to 0.84 mg/kg over 10 min. Wall motion was graded for each segment as normal, hypokinetic, akinetic and dyskinetic. Dipyridamole echocardiography was considered positive for ischemia if wall motion in at least one segment worsened by at least one degree point level compared to wall motion at rest. All patients underwent coronary angiography (mean time after dipyridamole echocardiography 7 +/- 3 days). The chi 2 test and Student's t-test for paired data were used; a p value of < 0.05 was considered as statistically significant. RESULTS: Only one dipyridamole echocardiography was interrupted because of supraventricular tachycardia appearance. Nine patients showed new asynergy areas during dipyridamole echocardiography; 19 patients had ST segment downsloping of > or = 1 mm during dipyridamole infusion; 12 patients experienced angina during the test. Angiography showed a significant coronary stenosis in 10 patients. Dipyridamole echocardiography sensitivity was 80%, specificity was 96%; specificity of ST segment downsloping and angina were 63 and 76% respectively. CONCLUSIONS: Dipyridamole echocardiography in patients with aortic stenosis is safe and feasible with good sensitivity and better specificity. Our study suggests also that dipyridamole echocardiography test is able to rule out patients with aortic stenosis and coronary artery disease as opposed to those with angina without organic stenosis of the coronary vessels.

Aged↗

PubMed1991

Effect of exercise supplementation on dipyridamole thallium-201 image quality.

To determine the effect of different types of exercise supplementation on dipyridamole thallium image quality, 78 patients were prospectively randomized to one of three protocols: dipyridamole infusion alone, dipyridamole supplemented with isometric handgrip, and dipyridamole with low-level treadmill exercise. Heart-to-lung, heart-to-liver, and heart-to-adjacent infradiaphragmatic activity ratios were generated from anterior images acquired immediately following the test. Additionally, heart-to-total infradiaphragmatic activity was graded semiquantitatively. Results showed a significantly higher ratio of heart to subdiaphragmatic activity in the treadmill group as compared with dipyridamole alone (p less than 0.001) and dipyridamole supplemented with isometric handgrip exercise (p less than 0.001). No significant difference was observed between patients receiving the dipyridamole infusion, and dipyridamole supplemented with isometric handgrip exercise. We conclude that low-level treadmill exercise supplementation of dipyridamole infusion is an effective means of improving image quality. Supplementation with isometric handgrip does not improve image quality over dipyridamole alone.

Adult↗

PubMed1988

Pharmacokinetics of intraperitoneally administered dipyridamole in cancer patients.

The pharmacokinetics of i.p. administered dipyridamole was studied in six patients to explore the feasibility of using this drug as a modulator of antimetabolite activity in extravascular spaces. Infusions of dipyridamole (50 mg/m2 in 2 liters of normal saline) into the peritoneal cavity resulted in peak drug concentrations 5 to 20 times higher in that cavity than in the plasma. The peritoneal decay data for dipyridamole fitted very well to a single compartment open pharmacokinetic model with one exponential term, while the plasma data are adequately described by a single compartment model with two exponentials (a short absorption phase). The mean peritoneal half-life for total extractable dipyridamole was 3.3 +/- 1.9 (SD) h, and the mean peritoneal clearance was 0.4 +/- 0.3 liters/h/m2. The mean plasma half-life of total dipyridamole in our patients was 2.2 +/- 1.2 h, and the mean clearance value was 5.7 +/- 4.7 liters/h/m2. The area under the concentration versus time curve was calculated to be 626 +/- 312 microM-h for the peritoneal cavity and 45 +/- 20 microM-h for the plasma. Using membrane ultrafiltration, we have measured the concentration of free (non-protein bound) dipyridamole in each patient. While the peritoneal clearance values of free and total drug are comparable, the plasma clearance of free dipyridamole was 47 +/- 39 liters/h/m2. This increased plasma clearance resulted in a plasma area under the concentration versus time curve of 8.3 +/- 5.1 microM-h, which suggests minimal systemic exposure. Our data show that instillation of dipyridamole into the peritoneal cavity resulted in much higher local drug exposure than systemic exposure, confirming the feasibility of using this drug to augment antimetabolite activity within the peritoneal cavity. Since dipyridamole is highly protein bound in the plasma but less so in the peritoneal cavity, these data imply that peritoneal exposure to active (free) dipyridamole is far greater than systemic exposure in our patients.

Aged↗

PubMed1988

Dipyridamole preserved platelets and reduced blood loss after cardiopulmonary bypass.

Cardiopulmonary bypass activates and depletes platelets, which may contribute to postoperative bleeding. In addition, activated platelets may be deposited in the coronary vasculature after ischemia and cardioplegia, which may delay recovery of cardiac function and metabolism and may contribute to early bypass graft occlusion. The antiplatelet agent dipyridamole reduces platelet activation and depletion and may decrease postoperative bleeding and transfusion requirements. A prospective randomized trial was conducted in 58 patients undergoing elective coronary bypass operations to compare the effects of oral (19 patients) and intravenous (21 patients) dipyridamole to the results obtained in a control group (18 patients) who received no dipyridamole. Preoperative oral administration of dipyridamole resulted in lower plasma drug concentrations in the early postoperative period than perioperative intravenous administration (p = 0.0001 by analysis of variance). Postoperative arterial platelet counts were highest in the patients receiving intravenous dipyridamole, intermediate in those receiving oral dipyridamole, and lowest in the control group (p = 0.03 by analysis of variance). Postoperative blood loss and blood product transfusions were significantly reduced with both oral and intravenous dipyridamole (p = 0.04 by analysis of variance). Dipyridamole preserved platelets and reduced postoperative bleeding. Intravenous dipyridamole resulted in higher platelet counts than oral dipyridamole and may be required to reduce postoperative bleeding in high-risk patients.

Administration, Oral↗

PubMed1995

[Use of high doses of atropine during dipyridamole echocardiography: safety and efficacy of the combined test].

BACKGROUND: Recent reports demonstrated an increased accuracy of dipyridamole echocardiography test with the intravenous infusion of 0.25 to 1 mg of atropine in 1-4 consecutive administrations at the end of the test. The effect of higher doses of atropine during dipyridamole echocardiography, potentially able to further increase heart rate and myocardial oxygen consumption, has not been evaluated. The aim of the study was to evaluate the effect of high doses of atropine during dipyridamole echocardiography and to investigate the possible pharmacological interference between dipyridamole and atropine. METHODS: One-hundred consecutive patients (M = 81, F = 19; mean age 58 yrs) without inducible wall motion abnormalities at 14th minute of a high-dose (0.84 mg/Kg in 10') dipyridamole echocardiography test were studied. Seventy-five patients referred to the test in pharmacological wash-out were randomly divided in three groups: 25 patients (Group 1) received 10 mcg/Kg of atropine in 60"; 25 patients (Group 2) received 15 mcg/Kg of atropine in 120"; 25 patients (Group 3) received 20 mcg/Kg of atropine in 120"; moreover, 25 patients with a full-dose oral beta-blocker therapy (Group 4) received 20 mcg/Kg of atropine in 120". Atropine was infused during the 15th and 16th minute of the test. Heart rate (HR) changes and new wall motion abnormalities induced by atropine were considered and compared for each Group. In 60 patients (15 randomly selected from each Group) the effect on mean HR and R-R interval (msec) of the same dose of atropine infused during dipyridamole echocardiography was evaluated in resting conditions 24 hours apart. RESULTS: The dipyridamole-atropine test was well tolerated and accomplished in all patients. HR increased significantly in all Groups of patients in comparison with pre-atropine HR values (Group 1: +14 +/- 8 b/m', p < 0.0001; Group 2: +19 +/- 8 b/m', p < 0.0001; Group 3: +22 +/- 9 b/m', p < 0.0001; Group 4: +19 +/- 8 b/m', p < 0.0001; Groups 2, 4 vs Group 1: p = 0.03, Group 3 vs Group 1: p = 0.002). No patients in Group 1 (0%), 3 patients in Groups 2 and 3 (12%), and 5 patients in Group 4 (20%) showed new wall motion abnormalities after atropine infusion (Group 4 vs Group 1: p = 0.06). Effects of atropine on HR and mean R-R interval were significantly more pronounced in resting conditions than during dipyridamole test (HR: +25 +/- 11 vs +18 +/- 9 b/m', p < 0.001; R-R: -256 +/- 122 vs -127 +/- 68 msec, p < 0.0001). CONCLUSIONS: High doses of atropine during dipyridamole echocardiography test are safe and more effective for induction of new wall motion abnormalities than usual doses, particularly in patients tacking beta-blockers. The likelihood of an antagonistic mechanism between atropine and endogenous, dipyridamole-induced adenosine on sinus node is supported from our results.

Administration, Oral↗

PubMed1998

[Prognostic value of dipyridamole echocardiography in 1st acute uncomplicated myocardial infarction].

BACKGROUND: To assess the prognostic value of dipyridamole stress echocardiography in survivors of a first uncomplicated acute myocardial infarction. PATIENTS AND METHODS: A total of 75 patients (68 men, 7 women) aged 58 years (range, 37-77) were studied 3-5 days after a first acute myocardial infarction and followed up for a mean of 10 months. Dipyridamole infusion was administered at high doses: 0.56 mg/kg, adding 0.28 mg/kg if the test was still negative. Two-dimensional echocardiography was continuously recorded during infusion and the test was considered positive if a decrease in regional contractile function appeared and negative if no assynergy was observed up to 15 min after the beginning of dipyridamole administration. A wall motion score index of regional function was derived by summation of individual segment scores divided by the number of interpreted segments. This was calculated for rest and peak dipyridamole echocardiograms. Fifty of 75 patients underwent coronary angiography based on clinical criteria. RESULTS: There were 31 coronary events: 4 deaths, one reinfarction, 13 angina. Thirteen patients underwent coronary revascularization (9 bypass and 4 angioplasty). Dipyridamole echocardiography was positive in 29 patients (39%) and negative in 46 patients (61%). Twenty patients (69%) presented coronary events in the group of positive test versus only 11 (24%) of negatives (p = 0.0001). Four patients died in the positive group while none in the negative group. Sensitivity, specificity and accuracy for all cardiac events were 65, 80 and 73%, respectively. Significant variables from univariate analysis were dipyridamole stress echocardiography response, wall motion score index at peak dipyridamole, ischemic changes in ECG and treatment with two or more antianginal drugs. Multivariate analysis showed positive dipyridamole echocardiography as the only independent prognostic factor to predict cardiac events in postmyocardial infarction patients (RR = 2.56; 95% CI = 1.12-5.84). Four of 19 patients with one vessel disease and 17 of 22 patients with 2-3 vessel disease presented a positive dipyridamole test; whereas the test was negative in the remaining nine patients with normal coronary angiography. CONCLUSION: Dipyridamole stress echocardiography is a safe and feasible pharmacologic stress imaging method to stratify postmyocardial infarction patients at risk of cardiovascular events.

Adult↗

PubMed2000

Aggrenox: a fixed-dose combination of aspirin and dipyridamole.

OBJECTIVE: To describe the pharmacology, pharmacokinetics, efficacy, and safety of a fixed-dose combination of aspirin and extended-release (ER) dipyridamole indicated for the secondary prevention of stroke. DATA SOURCES: Published articles and abstracts were identified from a MEDLINE search (1966-December 1999) using the search terms dipyridamole, aspirin, antiplatelet, antiaggregation, and stroke prevention. Pertinent articles written in English were considered for review. Additional articles were identified from the references of retrieved literature. STUDY SELECTION AND DATA EXTRACTION: Studies including a combination of aspirin/dipyridamole in human subjects were evaluated. Emphasis was placed on randomized, controlled trials. DATA SYNTHESIS: Aspirin is a platelet inhibitor that works by inhibiting platelet cyclooxygenase, which reduces the production of thromboxane A2. Dipyridamole is a platelet inhibitor that is thought to work in part by inhibiting platelet cyclic-3',5'-adenosine monophosphate and cyclic-3',5'-guanosine monophosphate phosphodiesterase. The active metabolite of aspirin, salicylic acid, is highly bound to plasma protein and has a plasma half-life of two to three hours. Dipyridamole is also highly bound to plasma proteins, and the ER formulation has a plasma half-life of 13 hours. The first European Stroke Prevention Study (ESPS-1) found the combination of aspirin/dipyridamole to be superior to placebo in the prevention of stroke and transient ischemic attack (TIA). The ESPS-1, however, did not include an aspirin-only treatment arm. Therefore, it was unclear whether the combination of aspirin/dipyridamole was superior to aspirin alone. As a result, a second trial was conducted that included treatment arms of aspirin alone, ER dipyridamole alone, combination therapy, and placebo. The combination of aspirin 25 mg plus ER dipyridamole 200 mg twice daily was shown in the ESPS-2 to be significantly better than either agent given individually in preventing stroke and TIAs (p < 0.001). CONCLUSIONS: The American College of Chest Physicians (ACCP) recommends aspirin 50-325 mg/d to be the initial antiplatelet of choice for the prevention of atherothrombotic cerebral ischemic events. However, with the favorable results of the ESPS-2, it may be appropriate to substitute aspirin/ER dipyridamole for aspirin alone as the drug of choice. This combination appears to have a favorable adverse effect profile. The relative effectiveness of aspirin/ER dipyridamole compared with clopidogrel and ticlopidine has yet to be determined. If alternative antiplatelet therapy is needed, the ACCP recommends clopidogrel rather than ticlopidine because of its lower incidence of adverse effects. The ACCP further states that the combination of aspirin plus dipyridamole may be more effective than clopidogrel; these agents have a similarly favorable adverse effect profile.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Dipyridamole and exercise SPET provide different estimates of myocardial ischaemic areas: role of the severity of coronary stenoses and of the increase in heart rate during exercise.

In patients unable to perform a maximal exercise test, dipyridamole single-photon emission tomography (SPET) has a higher capacity than exercise SPET to detect coronary artery disease (CAD). However, in patients with myocardial ischaemia who are able to perform a maximal exercise test, it is not known whether these two tests may be equally used to assess the areas of myocardial ischaemia. This study was aimed at comparing the results provided by dipyridamole and exercise SPET in CAD patients with documented exercise myocardial ischaemia. Forty CAD patients who had undergone exercise thallium-201 SPET and who had myocardial ischaemia documented by an unequivocally positive exercise test underwent an additional 201Tl SPET study after dipyridamole infusion and low-level (40 W) exercise. The extent of defects was compared between the two tests and predictors of discrepant results were sought among data from exercise testing and coronary angiography. The extent of SPET defects was equivalent between the two tests in only 11 patients (28%), larger defects being observed with exercise in 18 [average difference: 12%+/-5% of left ventricle (LV)] and with dipyridamole in 11 (average difference: 15%+/-11% of LV). The best independent predictors of discrepancies between the two tests were: (1) increase in heart rate at exercise SPET, with defects being smaller at exercise than after dipyridamole in none of the patients with an increase >60 bpm (0/14), but in 42% of the others (11/26; P=0.004); and (2) an ischaemic territory related to a <70% coronary stenosis, for which SPET defects were always induced at exercise (10/10) but in only 30% (3/10) with dipyridamole (P=0.0004). Exercise and dipyridamole SPET provide different estimates of myocardial ischaemic areas. Dipyridamole allows the unmasking of perfusion abnormalities in patients who have low increases in heart rate at exercise SPET. However, dipyridamole is also much less efficient at inducing perfusion abnormalities in the ischaemic areas supplied by coronary stenoses of intermediate severity at rest angiography.

Coronary Angiography↗

PubMed1999

Practicability and safety of dipyridamole cardiac imaging in patients with severe chronic obstructive pulmonary disease.

We tested the practicability of dipyridamole myocardial nitrogen-13 ammonia positron emission tomography (dipyridamole (13)NH(3 )PET) for the perioperative risk assessment of coronary artery disease (CAD) in a cohort of patients with severe chronic obstructive pulmonary disease (COPD) undergoing lung volume reduction surgery (LVRS). Twenty consecutive LVRS candidates, 13 men and 7 women (mean age 57+/-2 years), without symptoms of CAD were prospectively studied by dipyridamole (13)NH(3 )PET. Side-effects and overall tolerance were assessed by a questionnaire and visual analogue scale. Repeated pulmonary function tests were performed before and 4, 12, 16 and 30 minutes after dipyridamole injection. All dipyridamole (13)NH(3 )PET studies were negative for CAD. Seventeen patients underwent LVRS without cardiac complications; three patients did not undergo LVRS for other reasons. Nine patients suffered intolerable dyspnoea requiring i.v. aminophylline. Mean FEV(1) decreased significantly after dipyridamole infusion: in nine patients the reduction in FEV(1)exceeded 15% from baseline. We found that dipyridamole is not well tolerated and causes significant bronchoconstriction in patients with severe COPD. Although all dipyridamole-induced side effects can be promptly reversed by aminophylline, dipyridamole cannot be recommended as a pharmacological stress in this setting.

Ammonia↗

PubMed2002

Effects of dipyridamole on Plasmodium falciparum-infected erythrocytes.

This study assessed the antimalarial activity of dipyridamole, a well-known vasodilator and inhibitor of platelet aggregation. Dipyridamole was effective against all of the erythrocytic stages such as rings, trophozoites and schizonts, and induced ultrastructural changes during the transition from trophozoite to schizont in vitro. Merozoites were also inhibited from invading dipyridamole-treated erythrocytes. It seems that dipyridamole binds to the erythrocyte membrane blocking the receptors for the merozoite. The 50% inhibitory concentration (IC(50)) of dipyridamole against Plasmodium falciparum infection was 30 nM. The IC(50) of chloroquine decreased from 97.0 nM to 13.7 nM when combined with dipyridamole (0.1 nM). Therefore, we suggest that dipyridamole has antiplasmodial activity due to its ability to arrest parasite development and by inhibiting merozoite invasion of the erythrocytes. Chloroquine activity against P. falciparum is also enhanced by the addition of dipyridamole. Treatment with a combination of chloroquine and dipyridamole may lead to a more effective treatment for chloroquine-resistant strains of P. falciparum.

Anemia, Hypochromic↗

PubMed1991

Early assessment of coronary artery bypass graft patency by high-dose dipyridamole echocardiography.

To assess the role of high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiographic testing in the evaluation of coronary artery bypass graft patency early after surgery, 18 consecutive patients with angina underwent dipyridamole echocardiography and coronary angiography before and 7 to 10 days after bypass surgery. Coronary angiography showed 2- or 3-vessel disease in 7 and 11 patients, respectively. A total of 53 bypass grafts were performed. Before bypass surgery 14 patients had a positive and 4 a negative test result. No complication occurred during the test performed early after surgery. Of the 14 patients with positive dipyridamole echocardiographic results before surgery, 10 had negative and 4 had positive results after surgery. All 4 patients had negative results before and after surgery. In the 4 patients with positive results after dipyridamole echocardiographic testing before and after bypass surgery, dipyridamole time increased from 5.8 +/- 5 to 9.3 +/- 0.9 minutes (p = 0.3) after the procedure and wall motion score index at peak dipyridamole changed from 1.55 +/- 0.2 to 1.28 +/- 0.3 (p = 0.05). Forty-nine of 53 grafts were patent as seen on angiography. Dipyridamole echocardiographic results were positive in 4 of 5 patients who had at least 1 obstructed graft or native vessel obstructed distal to bypass graft insertion. The remaining patient had diagnostic electrocardiographic changes during dipyridamole infusion without wall motion abnormalities. Dipyridamole echocardiographic results were negative in all 13 patients who had complete revascularization. In the 4 patients with positive test results, the procedure correctly identified the localization of the diseased bypass graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗