SEARCH · PubMed Health

Results for “DIPYRIDAMOLE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed2000

Antiarrhythmic efficacy of dipyridamole in treatment of reperfusion arrhythmias : evidence for cAMP-mediated triggered activity as a mechanism responsible for reperfusion arrhythmias.

BACKGROUND: Intracellular calcium overload is believed to play an important role in development of reperfusion arrhythmias. Dipyridamole, an inhibitor of cellular uptake of adenosine, may prevent or terminate reperfusion arrhythmias by reducing intracellular calcium overload. METHODS AND RESULTS: First, we tested for a preventive effect of dipyridamole. Sixty-one patients who underwent primary PTCA for treatment of acute anterior wall myocardial infarction were enrolled in this prospective study. Patients were divided into dipyridamole (DP) and nondipyridamole (non-DP) groups. The 2 groups had similar baseline characteristics. In the DP group, dipyridamole 0.5 mg/kg was infused intravenously for 3 minutes immediately before reperfusion during primary PTCA. Arrhythmias after reperfusion were analyzed from continuous ECG recordings. None of the patients in the DP group (n=23) had accelerated idioventricular rhythms (AIVR) or ventricular tachycardia (VT). In contrast, 7 (18.4%) had AIVR and 3 (7.9%) had VT in the non-DP group (n=38; P<0.01). Second, we tested for a termination effect of dipyridamole. Dipyridamole 0.5 mg/kg was infused intravenously while continuous ECG recordings were obtained in 9 patients who had either sustained AIVR (n=7) or sustained VT (n=2) after reperfusion of occluded coronary artery. Arrhythmias were terminated in all patients. CONCLUSIONS: These results indicate that administration of dipyridamole can prevent and terminate reperfusion arrhythmias such as AIVR and VT. cAMP-mediated triggered activity may, at least in part, be responsible for reperfusion-induced AIVR and VT.

Adenosine↗

PubMed1983

Dipyridamole dilates large coronary arteries in conscious dogs.

The effects of 0.25 mg/kg dipyridamole on left ventricular (LV) pressures, LV dP/dt, heart rate, aortic pressures, left circumflex coronary blood flow, and left circumflex coronary arterial diameters and on calculations of late diastolic coronary resistance and large coronary cross-sectional area were studied in 15 conscious dogs. Injection of dipyridamole, a drug that has a mechanism of action dependent on myocardial adenosine production, caused sustained increases in mean coronary blood flow (244 +/- 28%), large coronary arterial cross-sectional area (28 +/- 3.2%), heart rate (32 +/- 3.6%), and LV dP/dt (23 +/- 3.0%) and reductions in late diastolic coronary resistance (73 +/- 2.4%) and mean arterial pressure (14 +/- 1.9%). Neither beta-adrenergic-receptor blockade alone nor in conjunction with constant heart rate affected the dilation of large coronary arteries to dipyridamole significantly. Ganglionic blockade with hexamethonium also had little effect on the response of large and small coronary vessels to dipyridamole. Surprisingly neither beta-adrenergic-receptor nor ganglionic blockade abolished the rise in LV dP/dt observed after dipyridamole. Aminophylline, however, effectively eliminated the dilation of large coronary arteries and resistance coronary vessels in response to dipyridamole. In summary, as long as dipyridamole does not induce severe sustained hypotension it exerts potent effects on both coronary arterial resistance and large coronary arteries in the conscious dog. The coronary dilation is independent of reflex adrenergic activation, but appears dependent on myocardial adenosine production.

Adenosine↗

PubMed1983

Effects of dipyridamole-induced vasodilation on myocardial uptake and clearance kinetics of thallium-201.

Myocardial thallium-201 (201Tl) uptake and clearance after intravenous administration of dipyridamole (150 micrograms/kg) were determined in 12 open-chest anesthetized dogs with a partial coronary artery stenosis. 201Tl (1.5 mCi) was injected intravenously and myocardial biopsy specimens were obtained 10 min, 60 min, and 2 hr after injection. Serial changes in 201Tl activity in the normal zone and in the zone of partial stenosis were correlated with microsphere-determined regional blood flow and distal coronary pressure. Another nine dogs with equivalent stenosis not given dipyridamole before 201Tl served as controls. In the 12 dogs given dipyridamole, 201Tl activity at 10 min in the zone of stenosis was reduced to 42 +/- 5% of initial normal zone activity (p less than .001) and remained at 44 +/- 3% of initial normal zone activity at 2 hr. There was a good correlation (.81) between the percent reduction in myocardial 201Tl activity and the percent reduction of peak hyperemic flow as determined by measuring the percentage difference in peak coronary flow after a transient 10 sec occlusion under control and stenotic conditions. In contrast, 201Tl clearance was rapid in the normal zone, with 201Tl activity decreasing to 55 +/- 3% of initial normal zone activity by 2 hr. A redistribution pattern was produced because of the disparate clearance rates from hyperperfused and relatively hypoperfused myocardial regions. The relative 201Tl defect decreased from 58% to 11% from 10 min to 2 hr. In the normal zone dipyridamole increased epicardial flow from 1.03 +/- 0.09 (SEM) to 3.52 +/- 0.36 ml/min/g (p less than .0001) and endocardial flow from 1.19 +/- 0.09 to 2.96 +/- 0.20 ml/min/g (p = .0001). In the zone of partial stenosis the increase in epicardial flow after dipyridamole was less marked (1.01 +/- 0.10 to 1.55 +/- 0.15 ml/min/g; p = .009) and endocardial flow decreased (0.84 +/- 0.11 to 0.64 +/- 0.15 ml/min/g; p = .04). Coronary perfusion pressure distal to the stenotic zone fell from 65 +/- 3 to 50 +/- 3 mm Hg after dipyridamole. In the nine control dogs with equivalent stenosis, 201Tl uptake and washout were not significantly different in the stenotic zone compared with the normal zone. These data indicate that dipyridamole-induced vasodilation in the presence of a partial stenosis results in diminished uptake and delayed clearance compared with increased uptake and more rapid clearance in normally perfused myocardium producing an initial 201Tl defect with delayed redistribution.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1997

Dipyridamole-induced ischemia as a prognostic marker of future adverse cardiac events in adult patients with hypertrophic cardiomyopathy. Echo Persantine Italian Cooperative (EPIC) Study Group, Subproject Hypertrophic Cardiomyopathy.

BACKGROUND: Myocardial ischemia may play a role in the natural history of hypertrophic cardiomyopathy (HCM). To assess the relative prevalence and the prognostic value of dipyridamole-induced ischemia, 79 patients with HCM and without concomitant coronary artery disease (53 men; mean age, 46+/-15 years) underwent a high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole test with 12-lead ECG and two-dimensional echo monitoring and were followed up for a mean of 6 years. METHODS AND RESULTS: Twenty-nine patients (37%) showed ECG (ie, ST depression > or = 2 mV) signs of myocardial ischemia during dipyridamole test (group 1), whereas 50 (63%) had a negative test (group 2). No patient had transient wall motion abnormalities during the dipyridamole test. During the follow-up, 16 events (ie, left ventricular or atrial enlargement, unstable angina, syncope, atrial fibrillation, and bundle-branch block) occurred in 29 patients in group 1 and 5 in 50 patients in group 2 (55% versus 10%, P<.001). Patients with a positive dipyridamole test showed worse 72-month event-free survival rates compared with patients with a negative test (36.2% versus 84.2%, P<.001). A forward stepwise event-free survival analysis identified dipyridamole test positivity by ECG criteria (chi2=19.7, P=.0001), rest gradient (chi2=11.3, P=.0008), and age (chi2=4.1; P=.0413) as independent and additive predictors of subsequent events. CONCLUSIONS: ECG signs of myocardial ischemia elicited by dipyridamole are frequent in patients with HCM and identify patients at higher risk of cardiac events, suggesting a potentially important pathogenetic role of inducible myocardial ischemia in determining adverse cardiac events in these patients.

Adult↗

PubMed1990

ST segment depression elicited by dipyridamole infusion in asymptomatic hypertensive patients.

In asymptomatic patients with essential hypertension, electrocardiographic changes suggestive of myocardial ischemia can be elicited by rapid pressure lowering or by pronounced coronary arteriolar dilation. The aim of this study was to assess whether dipyridamole infusion might induce ischemic-like electrocardiographic changes in asymptomatic essential hypertensive patients and to describe the clinical and echocardiographic correlates possibly associated with this response. We therefore studied a control group of 20 normotensive individuals and a group of 28 asymptomatic patients with mild-to-moderate essential hypertension. All underwent dipyridamole-echocardiography testing (12-lead electrocardiogram and two-dimensional echocardiographic monitoring with dipyridamole infusion, 0.84 mg/kg over 10'). No patient showed transient regional dyssynergy during dipyridamole infusion. None of the normotensive and 10 of 28 of the hypertensive participants had horizontal or downsloping ST segment depression more than 0.1 mV during dipyridamole (0% versus 36%, p less than 0.01). Hypertensive patients with ("responders") (n = 10) and without ("nonresponders") (n = 18) ST segment depression showed similar values of percent fractional shortening in baseline conditions (32 +/- 5 versus 33 +/- 6, p = NS) and at peak dipyridamole infusion (45 +/- 8 versus 43 +/- 5, p = NS). The peak early to peak late velocity ratio values (evaluated from transmitral flow tracings by Doppler technique) were also similar in baseline conditions (0.86 +/- 0.14 versus 0.94 +/- 0.30, p = NS) and at peak dipyridamole (0.72 +/- 0.15 versus 0.78 +/- 0.32, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2001

Urodilatin, a natriuretic peptide stimulating particulate guanylate cyclase, and the phosphodiesterase 5 inhibitor dipyridamole attenuate experimental pulmonary hypertension: synergism upon coapplication.

In a model of acute pulmonary hypertension in intact rabbits, we investigated the vasodilatory potency of intravascularly administered urodilatin, a renal natriuretic peptide type A known to stimulate particulate guanylate cyclase. Urodilatin infusion was performed in the absence and presence of the phosphodiesterase (PDE) type 5 inhibitor dipyridamole. Stable pulmonary hypertension was evoked by continuous infusion of the thromboxane mimetic U46619, resulting in approximate doubling of the pulmonary artery pressure (PAP). When infused as sole agents, both urodilatin and dipyridamole dose-dependently attenuated the pulmonary hypertension, with doses for a 20% decrease in PAP being 30 ng/kg min for urodilatin and 10 microg/kg min for dipyridamole. A corresponding decrease in systemic arterial pressure (SAP) was noted to occur in response to both agents. Sequential intravenous administration of a subthreshold dose of dipyridamole (1 microg/kg min), which per se did not affect pulmonary and systemic hemodynamics, and a standard dose of urodilatin (30 ng/kg min) resulted in a significant amplification of both the PAP and the SAP decrease in response to the natriuretic peptide. At the same time, manifold enhanced plasmatic cyclic guanosine monophosphate (cGMP) levels were detected. Aerosolized dipyridamole also dose-dependently attenuated pulmonary hypertension, with only 1 microg/kg min being sufficient for a 20% decrease in PAP, with no SAP decline. Preceding administration of subthreshold aerosolized dipyridamole (50 ng/kg min) did, however, cause only a minor amplification of the pulmonary vasodilatory response to a subsequently infused standard dose of urodilatin. In conclusion, this is the first study to show that urodilatin does possess vasodilatory potency in the pulmonary circulation, and enhanced plasma levels of cGMP and synergy with the PDE5 inhibitor dipyridamole both strongly suggest that this effect proceeds via guanylate cyclase activation. The effect of infused urodilatin is, however, not selective for the pulmonary vasculature, as the systemic vascular resistance declines in a corresponding fashion.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

Acute electrophysiological effects of dipyridamole on sinus node function in patients with sick sinus syndrome.

One of the most widely used tests for evaluation of sinus node function is sinus node recovery time (SNRT), which requires right heart catheterization. On the other hand SNRT has high specificity but only moderate sensitivity in the diagnosis of sick sinus syndrome (SSS). The authors studied acute electrophysiologic effects of dipyridamole (0.40 mg/kg IV) in 16 patients with clinical SSS. All of them had normal SNRT and had undergone permanent DDD pacemaker implantation. By the aid of temporary pacing inhibition, the authors noninvasively measured the corrected sinus node recovery time (SNRTc) and sinus cycle length (SCL) before and after dipyridamole administration. SCL was slightly decreased from a mean basal value of 1025 +/-323 to 913+/-213 msec after dipyridamole administration (mean -10%), but this was not statistically significant. SNRTc was increased from a mean basal value of 344+/-91 to 606+/-156 msec after dipyridamole administration (+76% P< or =0.004). These results suggest that dipyridamole must be used cautiously in patients with SSS. Intravenous dipyridamole may be a useful test to assess sinus node function. SNRT measurement after intravenous dipyridamole may increase sensitivity of this test in patients with suspected SSS and normal SNRT.

Adult↗

PubMed1984

Dipyridamole: a critical evaluation.

Dipyridamol is a vasodilator that is used primarily in clinical practice as an antiplatelet agent. It increases coronary blood flow and was originally introduced as an antianginal agent. An ability to prolong a shortened platelet survival has been used to justify its value in preventing thromboembolic complications. Conditions characterized by a reduction in platelet survival and where dipyridamole has been used include heart valve replacement, arterial grafting, cerebrovascular disorders, and disorders of peripheral circulation. The in vivo effect of dipyridamole on platelet aggregation has not been well defined and may depend on additional factors. Prostaglandins appear to have important roles in platelet homeostasis; their relationships to the action of dipyridamole are discussed. Dipyridamole usually is combined with aspirin for synergistic anti-aggregatory purposes. However, the nature of the interaction has not been elucidated and benefit from the addition of dipyridamole has not been demonstrated in clinical studies. A review of clinical studies using dipyridamole indicates that it currently has limited value.

Angina Pectoris↗

PubMed1995

Xanthine interference with dipyridamole-thallium-201 myocardial imaging.

Both theophylline and caffeine have been shown to antagonize adenosine and are associated with false-negative test results with dipyridamole-T1-201 imaging. This has led to recommendations for theophylline and caffeine abstinence for at least 24 hours prior to dipyridamole-T1-201 imaging. Because pentoxifylline and its metabolites are structurally similar to theophylline and caffeine, and pentoxifylline has adenosine antagonistic properties, one might presume that pentoxifylline may also attenuate the diagnostic yield of dipyridamole-T1-201 imaging. To the best of our knowledge, the pharmacodynamic interaction between pentoxifylline and dipyridamole and its effects on dipyridamole-T1-201 imaging in patients have never been studied adequately. However, a single study in 7 dogs does suggest that there may be no significant interaction. In addition, we must also consider the nonacute nature of the clinical use of pentoxifylline in peripheral vascular disease and the critical need for accurate dipyridamole-T1-201 imaging results and the cost associated with this procedure. Until such information is available in humans, it would be prudent to discontinue pentoxifylline, in addition to caffeinated foods, caffeine-containing drug products, and theophylline, at least 24 hours prior to dipyridamole-T1-201 imaging.

Adenosine↗

PubMed1992

Dipyridamole electrocardiography test for the assessment of the severity of coronary artery disease.

The purpose of this study was to investigate the relationship of dipyridamole-induced ST changes to the severity of coronary artery disease. The subjects were 100 patients without myocardial infarction who underwent coronary arteriography for the diagnosis of coronary artery disease. The dipyridamole injection test (D) (0.568 mg/kg/4 min), and symptom-limited treadmill exercise test (T) were performed separately. Body surface electrocardiographic mapping of 87 leads was performed in both tests. The incidences of significant ST depression greater than or equal to 0.10 mV, number of leads showing significant ST depression (nST) and the maximal voltage of ST depression (maxST) in D and T were compared to the number of diseased coronary arteries. In patients without significant coronary stenosis (0VD group), the incidence of ST depression in the dipyridamole test was significantly lower than that in the treadmill test (D 9% vs T 47%, p less than 0.01). While, in one vessel disease (1VD), two vessel disease (2VD), and three vessel disease (3VD) groups, there was no significant difference in the incidence of ST depression between the dipyridamole test and the treadmill test (in 1VD, D 44% vs. T 65%; in 2VD, D 67% vs. T 93%; and in 3VD, D 93% vs. T 96%). In the dipyridamole test, nST was 0.6 +/- 2.4 in 0VD, 4.5 +/- 6.9 in 1VD, 4.1 +/- 4.5 in 2VD, and 10.6 +/- 8.1 in 3VD. Significant differences were found between 0VD and 1VD (P less than 0.05), 0VD and 3VD (P less than 0.01), 1VD and 3VD (P less than 0.01), and 2VD and 3VD (p less than 0.01). The maxST in the dipyridamole test was 0.02 +/- 0.04 mV in 0VD, 0.10 +/- 0.12 mV in 1VD, 0.13 +/- 0.11 mV in 2VD, and 0.22 +/- 0.11 mV in 3VD. Significant differences were found between 0VD and 1VD (p less than 0.01), 0VD and 2VD (p less than 0.01), 0VD and 3VD (p less than 0.01), 1VD and 3VD (p less than 0.01), and 2VD and 3VD (P less than 0.01). For the diagnosis of 3VD, the dipyridamole ECG test had as high a sensitivity (93% vs 96%), higher specificity (68% vs 38%, p less than 0.01), and higher predictive accuracy (75% vs 54%, p less than 0.01) than the treadmill test.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

Assessment of left ventricular function using radionuclide angiography after dipyridamole infusion.

Thirty-six patients with significant coronary artery stenosis and no previous myocardial infarction and 25 subjects with normal coronary arteries underwent 99mTc RNV before and after coronary vasodilatation induced by dipyridamole, 0.75 mg/kg, given IV over 10 min. In subjects with normal coronary arteries, dipyridamole induced an increase in LVEF (from 66 +/- 8 to 76 +/- 8 percent; mean +/- SD; p less than 0.001); in patients with significant coronary artery stenosis (greater than or equal to 75 percent narrowing of at least one major vessel), dipyridamole injection did not affect LVEF (from 63 +/- 12 to 62 +/- 12 percent). In ten patients a complete, successful PTCA was performed and the RNV with the dipyridamole test repeated. The EF did not change with the dipyridamole test before PTCA (63 +/- 7 to 65 +/- 9 percent), but increased significantly after PTCA (62 +/- 11 to 70 +/- 9 percent; p less than 0.01). Sensitivity and specificity of EF changes after dipyridamole infusion were 75 and 76 percent, respectively. The test produced no major side effects or complications. Radionuclide angiography with dipyridamole helps to detect coronary artery stenosis and might be used to assess the effects of angioplasty on coronary flow reserve.

Adult↗

PubMedDate not supplied

Effects of dipyridamole on peritoneal clearances.

To see if oral dipyridamole increases peritoneal clearances in humans undergoing peritoneal dialysis, two types of double-blind clinical studies were undertaken. In a single-dose study, 7 patients were randomized to take dipyridamole or placebo early in a peritoneal dialysis with 2 L, hourly cycles; later in the same dialysis a crossover administration was studied. In a multidose study, 17 patients were randomized to take dipyridamole or placebo three times daily and clearance studies were performed on days 1, 4, and 8 during 2 L, hourly peritoneal dialysis cycles. Neither the single dose of dipyridamole or placebo significantly altered drainage volumes, clearances, or dialysate protein from control periods. In the multidose study, mean values on dipyridamole or placebo were not significantly changed from respective baseline predrug values. Mean values with dipyridamole and placebo usually were not significantly different. Dipyridamole did not appear to improve peritoneal clearances even with repeated ingestion.

Adult↗

PubMed2000

The dipyridamole effect on the photoactive bacteriochlorophyll interaction with quinone acceptors in reaction centers of purple bacteria.

The effect of Dipyridamole (10(-6)-10(-3) M) on the photomobilized electron transport in the system of quinone acceptors Q(A)-Q(B) of isolated photosynthetic reaction centers of Rhodobacter sphaeroides and on its temporary stabilization on Q(B) was studied. Depending on the type of the detergent present in the reaction center (lauryl dimethylamine oxide, Triton X-100, sodium dodecyl sulfate, and sodium cholate), dipyridamole could increase the time of the electron transfer to Q(B). The dipyridamole effect on the efficiency of the electron stabilization on Q(B) for reaction centers with different detergents was revealed in slowing down the process of dark reduction of photoactive bacteriochlorophyll from Q(B) at initial concentrations of added dipyridamole (10(-6)-10(-5) M) with following acceleration of the process at the dipyridamole concentrations of 10(-4)-10(-3) M. The pH lowering from 6.8-7.0 to 5.9-6.0 increased the dipyridamole effect. The possibility of the dipyridamole effect on the structural-dynamic state of the reaction center complex, including its hydrogen bond system, which influences the studied parameters of functional activity, is suggested.

Bacteriochlorophylls↗

PubMed2002

Dipyridamole may be used safely in patients with ischaemic heart disease.

It is thought that up to 50% of patients with cerebrovascular disease will have concurrent ischaemic heart disease. Dipyridamole co-formulated with aspirin has been shown to increase the relative reduction in risk of second stroke in patients with prior stroke/transient ischaemic attack beyond that obtaining with aspirin alone. We have sought to resolve the question of whether dipyridamole treatment increases the risk of cardiac adverse events in patients with co-existing ischaemic heart disease. The published literature, periodic safety update reports, the randomised controlled trials of antiplatelet agents in stroke prevention and those including dipyridamole in cardiovascular indications, have been reviewed and analysed. The early reports of serious adverse cardiac effect attributable to dipyridamole occurred in patients with severe coronary artery disease using dipyridamole as a stress test adjunct to cardiac imaging. The randomised controlled trials databases show no evidence of mortality and only isolated cases of significant cardiac morbidity attributable to dipyridamole at recommended oral doses in patients with ischaemic heart disease. We conclude that patients with cerebrovascular and mild to moderate concomitant ischaemic heart disease may be treated safely with dipyridamole for the secondary prevention of stroke.

Dipyridamole↗

PubMed1992

Plasma adenosine and cardiovascular responses to dipyridamole in fetal sheep.

The effects of dipyridamole infusion on fetal arterial plasma adenosine level, [ADO], and the systemic cardiovascular system were studied in 10 fetal sheep at 130-135 days gestational age. Dipyridamole (0.25 mg/kg) was infused into the fetuses intravenously during normoxia and hypoxia. Plasma [ADO] was measured using high-performance liquid chromatography, (HPLC), and fetal heart rate and arterial blood pressure were monitored throughout the study. These studies were performed in the absence and presence of theophylline, an adenosine receptor antagonist. During normoxia (PO2, 23.8 +/- 2.0 Torr), dipyridamole infusion increased fetal plasma [ADO] from 0.82 +/- 0.10 microM to 1.41 +/- 0.16 microM within 1 min (P < 0.01) and fetal heart rate from 157 +/- 6 bpm to 174 +/- 7 bpm (P < 0.01), but did not change mean blood pressure. Fetal plasma [ADO] and fetal heart rate returned to basal levels quickly. Treatment with theophylline did not alter the elevation of plasma [ADO] after dipyridamole infusion, but abolished responses of fetal heart rate to dipyridamole infusion. After 15 min of hypoxia with an average arterial PO2 of 15.4 +/- 1.1 Torr, fetal plasma [ADO] increased to 1.15 +/- 0.14 microM (P < 0.01). Dipyridamole infusion then further raised fetal plasma [ADO] to 1.67 +/- 0.27 microM (P < 0.01). The duration of the increase of fetal plasma [ADO] after dipyridamole infusion was no longer in hypoxia than in normoxia, however there was no significant change in the pattern of transient fetal bradycardia and persistent hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed2004

Dipyridamole inhibits hydroxylamine augmented nitric oxide (NO) production by activated polymorphonuclear neutrophils through an adenosine-independent mechanism.

Polymorphonuclear neutrophils (PMN) are thought to play a role in reperfusion injury and ischemia. These effects are partly mediated by toxic oxygen species (superoxide anion, hydrogen peroxide and hydroxyl radical) acting at the level of the endothelium. It was demonstrated recently that the superoxide anion reacts with nitric oxide (NO) and that interaction leads to the generation of highly toxic peroxynitrite. Several drugs were tested so far in order to affect PMN function. It was demonstrated that dipyridamole (2,6-bis-diethanolamino-4,8-dipiperidinopyrimido-(5,4-d)-pyrimidine) can influence neutrophil function by inhibiting adenosine uptake. However, this action can not fully explain all of the observed effects of dipyridamole action on PMN metabolism. The aim of our study was to evaluate the influence of dipyridamole on nitric oxide production by activated polymorphonuclear neutrophils. Incubation of PMNs with hydroxylamine (HA) and phorbol myristate acetate (PMA) generated nitrite (36.4+/-4.2 nmol/h 2x10(6) PMN), dipyridamole at 100 micromol/l, 50 micromol/l and 10 micromol/l caused a considerable drop in nitrite production (11.8+/-1.8, 19.7+/-2.7 and 27.4+/-3.2 nmol/h, respectively). Neither adenosine nor the adenosine analogue could mimic the dipyridamole effect. Moreover theophylline, an adenosine inhibitor could not reverse the dipirydamole action on PMN metabolism. We also found that dipyridamole inhibited hydrogen peroxide release from neutrophils. Catalase that scavenges hydrogen peroxide also largely abolished nitric oxide release from PMN. It is evident that dipyridamole inhibits hydroxylamine-augmented nitric oxide production by activated polymorphonuclear neutrophils through an adenosine-independent mechanism.

Adenosine↗

PubMed1992

[Comparative study of anticoagulant management after coronary artery bypass surgery--warfarin versus dipyridamole].

A prospective randomized study was performed in 137 coronary artery bypass surgery cases to determine if the administration of antiplatelet drugs would improve the patency of coronary artery bypass grafts. The warfarin group received warfarin and thrombotest was controlled to 20% or so. The dipyridamole group received both 300 mg of dipyridamole and 250 mg of aspirin orally each day. These two groups were compared for study in grafts patency. Results were analyzed by chi-square. In the warfarin group, 66 patients had three ITA-LAD grafts and 115 saphenous vein grafts (including 4 sequential grafts). In the dipyridamole group, 71 patients underwent 38 ITA grafts and 167 saphenous vein grafts (including 56 sequential grafts). Eighty-eight of the 107 grafts (82%) were patent in the warfarin group, and 190 of 205 grafts (95%) were patent in the dipyridamole group (p less than 0.01). Of the two ITA grafts in the warfarin group, no graft was occluded, a patency of 100%. In the dipyridamole group, 35 of 38 ITA grafts (92%) were patent. In the warfarin group, 86 of 105 saphenous vein grafts (82%) were patent. In the dipyridamole group, 155 of 167 saphenous vein grafts (95%) were patent (p less than 0.01). In the study of grafted coronary vessel, the patency of left anterior descending coronary artery, diagonal branch and right coronary artery was not significant between two groups. In the dipyridamole group, the patency of left circumflex coronary artery was 93%, and that of the warfarin group was 50% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Multiple effects of dipyridamole on neutrophils and mononuclear leukocytes: adenosine-dependent and adenosine-independent mechanisms.

Dipyridamole is an antithrombotic drug that has been shown to influence not only platelet function but also some aspects of leukocyte activation. In this study we demonstrate that dipyridamole effectively inhibits superoxide anion generation by neutrophils, mononuclear leukocytes, and whole blood stimulated with N-formyl-methionyl-leucyl phenylalanine and calcium ionophore A23187. In addition, the drug, at concentrations as low as 1 mumol/L, inhibits the expression of procoagulant activity--basal and stimulated--by mononuclear leukocytes. It is shown that, similar to its effect on platelets, dipyridamole influences these leukocyte functions indirectly, that is, through an increase of extracellular adenosine that in turn inhibits both superoxide anion generation by leukocytes and the expression of procoagulant activity by mononuclear leukocytes. In fact, adenosine deaminase, which metabolizes adenosine to inactive product, prevents the effects of dipyridamole on superoxide anion generation and on the expression of procoagulant activity by leukocytes. Experiments carried out with 8-phenyl-theophylline indicate that the adenosine-dependent effects of dipyridamole may involve multiple pathways, only some of which are dependent on the interaction of adenosine with its receptors. Dipyridamole also dose-dependently inhibits the synthesis of leukotrienes B4 and C4 by stimulated neutrophils and mononuclear leukocytes through a mechanism that is not mediated by the presence of adenosine in the extracellular medium. The reported effects of dipyridamole on separate and distinct pathways involved in leukocyte activation are of relevance in the overall evaluation of the antithrombotic activity of this drug.

Adenosine↗