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PubMed1997

Respiratory arrest during dipyridamole stress testing.

There is an increasing usage of radionuclide scanning to assess myocardial perfusion, with dipyridamole, the most commonly used stress agent. Although this is an effective, and usually very safe, means by which to assess myocardial blood supply, there have been several incidents of acute bronchospasm in asthmatic patients. There have, however, been no previous reports of respiratory arrest occurring in patients with emphysema. This case illustrates the dangers of administering intravenous dipyridamole, or even adenosine, to patients with chronic lung disease.

Cardiopulmonary Resuscitation↗

PubMedDate not supplied

Long-term inhaled nitric oxide plus dipyridamole for pulmonary arterial hypertension.

Inhaled nitric oxide (iNO) has been shown to be a potent and selective vasodilator in pulmonary arterial hypertension (PAH). However, the clinical experience in prolonged treatment is limited. We assess the safety and effectiveness of long-term administration of iNO in severe PAH. Two female patients were admitted to our hospital because of severe dyspnea (World Health Organization functional class IV) and hypoxemia. They were diagnosed with PAH (primary and secondary to congenital heart disease) and treated with iNO for 2 years. The delivery system consisted of an NO tank of 800 ppm, a modified gas-pulsing device, and nasal cannulas. On iNO treatment the patients showed remarkable improvement of symptoms, oxygenation and 6-min walk distance. After 16 months the patients began to experience a progressive rebound of symptoms. A phosphodiesterase type 5 inhibitor (dipyridamole) was added to iNO. This intervention proved useful in improving clinical deterioration and hemodynamics. This is the first study reporting 2-year iNO therapy in 2 patients with primary and secondary pulmonary hypertension. The combination of dipyridamole with iNO augments the pulmonary vasodilatation and may be useful in managing PAH.

Administration, Inhalation↗

PubMed2006

Dose titration to reduce dipyridamole-related headache.

BACKGROUND: Combination of low-dose aspirin and modified-release dipyridamole (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over aspirin alone. However, headaches were reported in more patients receiving dipyridamole-containing agents than in those receiving placebo. We undertook a randomized, double-blind, placebo-controlled trial to evaluate which dosing regimens of ASA+MR-DP have better tolerance. METHODS: This trial randomized 146 patients with a history of ischemic cerebrovascular disease into three groups: placebo (days 1-28), reduced dose (placebo on days 1-4, ASA+MR-DP once daily before bed during days 5-14, and b.i.d. on days 15-28), and regular dose (placebo on days 1-4, and ASA+MR-DP b.i.d. on days 5-28). Using Chinese diary card, headache was assessed as mean cumulated headache (Sigma frequency x intensity/occurrence days x study days) over the study period, and was graded 0-4 according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version 2.0. RESULTS: Intent-to-treat patients after randomization was 46 in placebo group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse effects, headache of any grade occurred significantly more in the regular dose group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated headache was higher (p < 0.05) in the regular dose group than in the reduced group during days 5-14. Of 27 patients who dropped out, 15 (55.6%) were due to headache, which was substantially more in regular dose (8, 53.3%), though the difference was statistically insignificant. CONCLUSIONS: Initial reduced dose treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems better tolerated by those susceptible to phosphodiesterase inhibitor-induced headache.

Aged↗

PubMed1983

Thallium-201 imaging after dipyridamole in patients with coronary multivessel disease.

In 60 patients with angiographically documented 2- or 3-vessel disease (at least 70%) thallium-201 images after dipyridamole (0.50 mg/kg bodyweight i.v.) and 4 h later were obtained. In 95% of the patients stress perfusion defects were found. In 48% of the cases scintigraphy correctly diagnosed the presence of multivessel disease, but in only 30% of the patients were all angiographically narrowed vessels detected. The reliability of the method was much higher in the detection of 'infarct stenoses' (96%) than of 'noninfarct stenoses' (46%). The regional sensitivity to assess stenoses of the left anterior descending artery (75%) and right coronary artery (73%) was greater than in stenoses of the left circumflex artery (37%). Thallium-201 scintigraphy after dipyridamole is a sensitive method for diagnosing the presence of coronary artery disease. The diagnostic value is severely limited however by the fact that coronary vasodilation may provoke perfusion abnormalities only in the most ischemic regions, whereas perfusion defects in other areas may not be detectable. Therefore this method does not allow the precise quantitation of all coronary stenoses in the majority of patients.

Adult↗

PubMed1985

Plasmapheresis and dipyridamole for recurrent focal glomerular sclerosis.

A 38-year-old man had recurrence of nephrotic syndrome with focal glomerular sclerosis (FGS) in two consecutive cadaveric renal allografts. His first graft was lost to recurrent disease after 30 months. Because prior animal experiments performed when he had his first graft indicated a possible serum factor or factors capable of enhancing urine protein excretion, three plasmapheresis periods of 6-8 treatments each were performed 3, 23 and 34 months after recurrence of FGS in the second graft. Urine protein excretion was decreased transiently in the first treatment period when the allograft biopsy revealed only glomerular foot process effacement. The second and third plasmapheresis treatment periods were performed after typical lesions of FGS were present in the graft and moderate renal insufficiency occurred. Dipyridamole was also given at this time. There has been associated stabilization of renal function for over 31 months. Prior to this, renal function was significantly (p less than 0.001) decreasing with time. The reasons for stabilization of renal function in this man with recurrent FGS are not defined, but the results suggest the need to further evaluate plasmapheresis and the platelet inhibitor dipyridamole in native and recurrent FGS.

Adult↗

PubMed1986

Effect of dipyridamole treatment on proteinuria in pediatric renal disease.

The effect of dipyridamole on proteinuria was studied in 60 children with various renal diseases. A significant decrease in 24-hour urine protein excretion was observed within a few months after treatment in 32 (53%) of the patients with minimal or moderate mesangial proliferation. The effect was reproducible and parallelled by a reduction in plasma levels of beta-thromboglobulin. Renal function in patients significantly improved with the therapeutical effect. The appropriate dosage was 4-10 mg/kg daily and no serious toxicity was seen despite large dosage and even in long-term application. The data suggest that dipyridamole treatment appears safe and has a beneficial effect on proteinuria dependent on its effect on platelets in renal disease.

Adolescent↗

PubMed1988

Is the antiproteinuric effect of dipyridamole hemodynamically mediated?

We studied the acute antiproteinuric and renal hemodynamic effect of dipyridamole 30-60 mg intravenously in 13 salt-depleted patients with the nephrotic syndrome of different etiology. Whereas mean arterial pressure did not change, a small fall in glomerular filtration rate with a concomitant fall in filtration fraction and a decrease in urinary protein loss occurred. The fall in filtration fraction was positively correlated with the fall in proteinuria. This suggests that the antiproteinuric effect of dipyridamole is at least partly due to an efferent vasodilation with a fall in intraglomerular capillary pressure.

Dipyridamole↗

PubMed1991

Effects of dipyridamole on the short-term evolution of glomerulonephritis.

The aim of the present study is to evaluate the effect of dipyridamole (300 mg/day) versus placebo in a double-blind randomized trial on membranous glomerulonephritis (M-GMN), mesangial IgA glomerulonephritis (IgA-GMN), and segmentary and focal hyalinosis glomerulonephritis (SFH-GMN) during the first 3 months of treatment. In the case of M-GMN, proteinuria dropped by 60% of the basal value in patients treated with dipyridamole; in the case of IgA-GMN it dropped by 65-70%; and in the case of SFH-GMN it dropped by 40% of the basal value. Inhibition of proteinuria in M-GMN was correlated to platelet response, and above all, to the ADP-induced platelet aggregation in whole blood.

Dipyridamole↗

PubMed1992

Maternal hemorrhagic complications following prophylactic low-dose aspirin and dipyridamole therapy.

A case is reported of a severe postpartum maternal hemorrhagic complication, which was related to prophylactic antithrombotic therapy with daily low-dose aspirin (75 mg) combined with dipyridamole (225 mg) for the prevention of preeclampsia. The postpartum course was complicated by recurrent episiotomy site hematomas of nonclotted blood and prolonged bleeding time. Transfusion of platelet concentrates was necessary to control the bleeding. This case report draws attention to maternal hemorrhagic complications which may be associated with prophylactic low-dose aspirin and dipyridamole in pregnancy.

Adult↗

PubMed2003

Accumulation of radiolabelled platelets and fibrin on the carotid artery of rabbits after angioplasty: effects of heparin and dipyridamole.

We investigated the dynamic accumulation of platelets and fibrin after balloon injury of the carotid arteries in rabbits in vivo. In addition, effects of heparin and dipyridamole treatment were also tested. Autologous (99m)Tc-labelled platelet and (123)I-labelled fibrin accumulation was measured at one minute intervals for 4 hours following balloon injury of the carotid artery. Platelet accumulation occurred rapidly, with an approximately 125% increase occurring within 30 min after injury. There was no further activity for up to 4 hours. This accumulation could be inhibited with an intravenous infusion of PGI2 (500 ng/kg/hr). Fibrin accumulation occurred slowly and continuously over the 4 hour measurement period. Injection of an anti-fibrin antibody inhibited fibrin accumulation. Heparin (25 U/kg/hr for 4 hrs) administration resulted in a significant 82 +/- 19% and 68 +/- 13% reduction in platelet and fibrin accumulation, respectively. This dose of heparin was associated with a 2-fold prolongation of the aPTT. Dipyridamole (0.45 mg/kg/hr for 4 hrs) resulted in a 46 +/- 12% and 70 +/- 25% reduction of platelet and fibrin accumulation, respectively. Thus, we demonstrated that the dynamics of platelet and fibrin accumulation following balloon injury in rabbits are very different. The vessel wall continues to be thrombogenic for fibrin up to 4 hours after injury even though platelet accumulation has ceased after one hour. We conclude that the local thrombotic events following balloon injury are complex and that not only platelets but also fibrin is important in regulating responses to injury.

Angioplasty, Balloon↗

PubMed2005

Effects of aspirin, clopidogrel and dipyridamole administered singly and in combination on platelet and leucocyte function in normal volunteers and patients with prior ischaemic stroke.

The aim of this study was to assess whether triple antiplatelet therapy is superior to dual and mono therapy in attenuating platelet and leucocyte function. Aspirin (A), clopidogrel (C), and dipyridamole (D) were administered singly and in various combinations (A, C, D, AC, AD, CD, ACD), each for two weeks (without washout) to 11 healthy subjects and to 11 patients with previous ischaemic stroke in two randomised multiway crossover trials. At the end of each two-week period platelet aggregation, platelet-leucocyte conjugate formation and leucocyte activation were measured ex vivo blinded to treatment. Platelets were stimulated with collagen; additional measurements were made with adenosine diphosphate (ADP), platelet activating factor (PAF), adrenaline and the combination of, ADP, PAF and adrenaline. Results show that in the presence of collagen, ACD was superior to all antagonists or combinations, except AC, in reducing aggregation, platelet-leucocyte conjugate formation, and monocyte activation (all p<0.05). ACD was also more potent than other treatments, except AC, in inhibiting the aggregation and platelet-monocyte conjugate formation induced by the combination of ADP, PAF and adrenaline. The effects were similar in both volunteers and stroke patients. No serious adverse events or major bleeding events occurred. Triple antiplatelet therapy did not appear to be more effective than combined aspirin and clopidogrel in moderating platelet and leucocyte function. Any additional clinical benefit provided by dipyridamole may be through other mechanisms of action.

Adult↗

PubMed1990

Myocardial kinetics of Tc-MIBI in canine myocardium after dipyridamole.

Technetium 99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) is a promising new myocardial perfusion imaging agent producing excellent rest images. Imaging, however, will need to be performed with exercise or dipyridamole to detect ischemia and to differentiate salvaged but still ischemic myocardium from scar. Accordingly, 12 dogs were given mild-to-moderate left circumflex coronary stenoses (group 2), and 10 dogs were given severe stenoses (group 3). In five control dogs (group 1), there was no stenosis. After an intravenous infusion of dipyridamole (0.08 mg/kg/min for 4 minutes), Tc-MIBI was injected into the right atrium. Over the next 4-hour study period, myocardial Tc-MIBI activities were continuously monitored in both the left anterior descending (LAD) (normal) and left circumflex (LCx) (ischemic) coronary artery (ischemic) zones using miniature cadmium telluride radiation detectors and serial gamma camera images were acquired when necessary. Tc-MIBI was rapidly taken up by nonischemic, mild-to-moderate, and severe ischemic myocardium. The initial myocardial uptake of Tc-MIBI was linearly related (r = 0.97) to regional myocardial blood flow at rates up to 2.0 ml/min/g. After the initial uptake, the mean 4-hour fractional myocardial clearance was similar between the control (0.09 +/- 0.03 [+/- SEM]) and group 2 (0.07 +/- 0.03) and group 3 (0.09 +/- 0.03) ischemic zones. Tc-MIBI blood clearance was rapid and biexponential with an initial fast clearance phase followed by a slow clearance phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1998

Prognostic value of dipyridamole-thallium myocardial scintigraphy in patients with Kawasaki disease.

BACKGROUND: Although coronary artery lesions are critical complications of Kawasaki disease, their long-term outcome is still unclear. It is sometimes difficult to monitor progressive changes from aneurysms to stenotic lesions because coronary angiography (CAG) cannot be repeated very often, especially in infants. Our prospective study was designed to evaluate the prognostic value of dipyridamole-thallium single-photon-emission CT (SPECT) in the long-term follow-up of patients with Kawasaki disease. METHODS AND RESULTS: Of 459 consecutive patients with Kawasaki disease, coronary aneurysms were detected in 90 cases by echocardiography during the acute stage. After paired studies of selective CAG and SPECT were conducted, all patients were followed up and monitored for the occurrence of any cardiac events for > or =8 years. During the follow-up interval, there were 15 cardiac events (1 death, 5 infarctions, 2 coronary artery bypass graft operations, and 7 occurrences of unstable angina). Of patients who had some event, thallium redistribution was found on SPECT in 14 (93%, P<0.001). Of the various clinical and scintigraphic image variables, the presence of thallium redistribution was the best multivariate independent predictor of a late cardiac event (chi2=57.8, P<0.0001). The number of aneurysms detected on CAG added minimal statistical improvement to the model (chi2=1.9, P=0.0009). CONCLUSIONS: Dipyridamole-thallium SPECT is safely performed and is useful and important for risk stratification in the long-term follow-up of patients with Kawasaki disease.

Age of Onset↗

PubMed1991

Influence of molecular structure on the synergistic action of theophylline or dipyridamole derivatives in the prostaglandin-type inhibition of platelet aggregation.

Approximately 30 new derivatives of theophylline and dipyridamole have been prepared and examined as potentiators of the inhibition of platelet aggregation induced by the prostaglandin analogue BW 245C. Potentiating activity has been found to be sensitive to molecular size and also to the presence of specific groups. Polymeric adducts based on dextran, poly(ethylene glycol) or poly(N-vinyl pyrrolidone), and aliphatic esters with alkyl chain-lengths greater than 7 are inactive in potentiation. Derivatives containing carboxyl groups are also inactive. Potentiation is discussed in terms of platelet membrane penetration and extra- and intra-cellular processes. The latter are invoked to account for the enhanced potentiation shown by dipyridamole and derivatives when aggregation is induced by PAF-acether rather than ADP. One derivative of particular interest is the adduct of theophylline with 1,2,5,6-diisopropylidene-D-glucose, containing a furanose ring. This is a more active potentiator than theophylline itself, possibly owing to its molecular resemblance to cAMP. On conversion to the pyranose form all activity is removed.

Animals↗

PubMed1980

Effects of aspirin and dipyridamole on the degradation of adenosine diphosphate by cultured cells derived from bovine pulmonary artery.

To improve understanding of the mechanisms by which ADP is degraded during passage through the pulmonary vascular bed, we examined cultured endothelial and smooth muscle cells of bovine pulmonmary artery for their abilities to metabolize [8-14C]ADP. ADP is rapidly converted to AMP and then to adenosine, hypoxanthine, and inosine. Inosine is the major metabolite produced by endothelial cells. Radioactivity (5-10%) is accumulated intracellularly primarily as ATP. Medium containing 50 micro M ADP incubated with endothelial cells rapidly loses its ability to aggregate platelets and becomes antiaggregatory under conditions in which prostacyclin is absent. The antiaggregatory activity is probably the result of accumulated adenosine. 10 micro M dipyridamole inhibits cellular uptake of radioactivity by greater than 90%, and inosine in the medium is largely replaced by adenosine. This is accompanied by increased anti-aggregatory activity of conditioned medium, which can be matched by authentic adenosine at the same concentration. 1 mM aspirin had no effect on the metabolism of ADP by endothelial cells. Our results suggest: (a) Metabolism of ADP during passage through the lung is mainly the result of endothelial ADPase. (b) ADP released from aggregating platelets can be converted to the antiaggregatory substance, adenosine. Dipyridamole may exert some of its antithrombotic actions by preventing the intracellular uptake of adenosine, thereby increasing its concentration near the site of thrombus formation. (c) The ability of the vessel wall to degrade ADP should not be compromised by the use of aspirin as an antithrombotic drug. (d) Endothelium may retain some of its antithrombogenicity when prostacyclin generation is impaired.

Adenosine Diphosphate↗

PubMedDate not supplied

High-dose dipyridamole and gated sestamibi SPECT imaging provide diagnostic resting and stress ejection fractions useful for predicting extent of coronary artery disease.

A decline in ejection fraction at stress compared with rest images has been associated with increased severity of coronary artery disease (CAD) and suggests a poorer prognosis. Myocardial perfusion imaging (MPI) using high-dose dipyridamole (HDD) has been shown to more accurately detect CAD than either standard dose dipyridamole (SDD) or exercise-induced stress (EST), but has not been looked at to determine its usefulness in detecting changes in stress and rest ejection fractions. To determine the relationship between changes in left ventricular ejection fraction (LVEF) and the severity of CAD, 36 Individuals underwent gated single photon emission computed tomography (SPECT) MPI using HDD. In each case resting and stress LVEFs were determined along with MPI results. Subjects with single-vessel CAD demonstrated an increase in LVEF from 77.8% (sd +/-8.8%) to 85.6% (sd +/-8.4%) resulting in a statistically significant increase in LVEF of 7.8% (p = 0.009). Patients with two-vessel disease showed a smaller increase from 73.2% (sd + 8.3%) to 79.8% (sd + 9.8%) following HDD stress. This increase was statistically (p = 0.008) significant. Patients with triple-vessel CAD showed a reduction in LVEF from 67.4% (sd +/-14.07) to 65.1% (sd +/-16.5%) which represented a decrease in LVEF of 2.7% and approached (p = 0.25) but did not reach statistical significance. Both the resting and stress LVEFs were statistically lower (p<0.05) in patients with triple-vessel CAD. Changes in resting LVEF (REF) and HDD pharmacologically induced stress LVEF (SEF) provide a valuable diagnostic marker as to the number of significantly diseased coronary arteries and can be acquired from gated SPECT sestamibi images.

Adult↗

PubMed1984

Atherosclerosis and cerebral ischemic attacks: intakes of cerebrography with xenon133 inhaled and platelet tests in the diagnosis, clinical and therapeutic monitoring; the preventive role of dipyridamole.

A study of patients to develop the significance of the role of the blood platelets in the recurrence of transient cerebral ischemic attacks in patients with cerebral atheromatous, develop the effectiveness of dipyridamole in the prophylactic therapeutic regimen. In the group treated with dipyridamole, a 76.3% clinical improvement was recorded (mean increases of 11.2 ml/min. and 11.4 ml/min. of the cerebral hemispheric flows), 15.8% of cases stabilized (mean increases of 1.7 ml/min. and 1.2 ml/min.) and 7.9% failures (mean decreases of 10.4 ml/min. and 14.3 ml/min.) of these same flows. The cerebrography with xenon133 inhaled as well as the platelet tests used, constitute unfailing means of diagnosing and monitoring the clinical development.

Adult↗

PubMed1987

Glucose and erythrocyte ATP: distinctive effects of dipyridamole and of ticlopidine.

This experiment suggests the following points: 1. Erythrocytes in control patients and in atherosclerosis patients seem to have a variable grade of affinity for adenosine and for plasma glucose. This variable grade seems to fix the level of the adenosine triphosphate (ATP) reserves and induces the erythrocytes' deformability. 2. The drop in the level of ATP reserves that induces the poor deformability of the erythrocytes in atherosclerosis patients would appear to be caused by two consecutive shortages: first a shortage that seems to be related to a deficiency of erythrocyte adenosine as the ATP shortage disappears with dipyridamole treatment and then a shortage induced by the lack of erythrocyte glucose and suppressed by the addition of ticlopidine to the dipyridamole treatment.

Adenosine↗