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PubMed1990

Acute myocardial infarction associated with intravenous dipyridamole for rubidium-82 PET imaging.

This report describes the occurrence of chest pain and electrocardiographic features of acute myocardial infarction following intravenous dipyridamole-handgrip stress. Myocardial perfusion imaging (Rb-82 PET) demonstrated a stress-induced perfusion defect. Following failure to respond to medical therapy, urgent cardiac catheterization demonstrated total occlusion of the left anterior descending coronary artery. The vessel was revascularized, with limitation of myocardial damage evidenced by failure to develop anterior Q waves and only modest elevation of cardiac enzyme levels. Complications of intravenous dipyridamole stress are rare, this case constituting the first major problem in over 500 such procedures at this institution. However, this experience demonstrates the importance of vigilant observation during the performance of this technique.

Dipyridamole↗

PubMed1991

Impaired left ventricular filling during ST-segment depression provoked by dipyridamole infusion in patients with syndrome X.

The left ventricular filling and regional wall motion patterns were compared in 6 normal subjects, 20 patients with coronary artery disease, and 10 patients with syndrome X by means of Doppler and two-dimensional echocardiography during high-dose (0.9 mg/kg body weight in 10 min) dipyridamole infusion. During the procedure none of the normal subjects had chest pain or significant ST depression (greater than 0.1 mV) whereas 10 of 20 patients with coronary artery disease had ST depression, 3 with chest pain. Six patients with syndrome X had ST depression, 5 with chest pain. Regional wall motion abnormalities were identified in 6 patients with coronary artery disease who had ST depression but none were detected in normals or in patients with syndrome X. Compared with normals (-2.1 +/- 3.5%) there was a significant difference in percentage decrease in the peak early filling velocity in patients with coronary artery disease and ST depression (-10.3 +/- 6.2%; p less than 0.01) and in patients with syndrome X and ST depression (-9.4 +/- 6.9%; p less than 0.05). These findings indicate that, in the presence of dipyridamole-induced ST depression, patients with syndrome X have an abnormal left ventricular filling pattern similar to that observed in patients with coronary artery disease. This suggests that myocardial ischemia occurs in patients with syndrome X but the absence of regional wall motion abnormality suggests that it is diffuse.

Aged↗

PubMed1997

Detection of significant residual stenosis of the infarct-related artery after thrombolysis by high-dose dipyridamole echocardiography test: is it detected often enough?

BACKGROUND AND HYPOTHESIS: It has been reported that high-dose dipyridamole echocardiography test (DET) can be successfully used for the detection of critical residual stenosis of the infarct-related artery (IRA). However, we have recently noticed low sensitivity of DET for the detection of residual IRA stenosis in patients with single-vessel disease. This study sought to determine the value of DET for the detection of significant residual stenosis of the IRA after thrombolysis. METHODS: Dipyridamole echocardiography test was performed in 55 consecutive patients after a first acute myocardial infarction before hospital discharge. All patients underwent coronary angiography 23 +/- 6 days after infarction. RESULTS: Nine of 19 patients with positive DET revealed new adjacent asynergy and all of the patients had patient and significantly stenotic IRA. Sensitivity and specificity of DET in identifying significant residual stenosis of the IRA were 24 and 100%, respectively. Among 49 patients with significantly stenotic of occluded IRA, 40 patients without adjacent asynergy during DET had higher baseline wall motion score index (WMSI) compared with 9 patients who revealed adjacent asynergy during DET (1.45 +/- 0.30 vs. 1.24 +/- 0.18; p < 0.05). When all patients with positive DET (adjacent or remote asynergy) were compared with those with negative DET, no difference in baseline WMSI was found (1.37 +/- 0.24 vs. 1.44 +/- 0.24; p > 0.05). CONCLUSIONS: Our data indicate that sensitivity of DET in detecting significant residual stenosis of the IRA after thrombolysis is low. It seems that the extent of myocardial infarction affects the ability of DET to detect adjacent, but not remote asynergy.

Aged↗

PubMed1998

Severe transmural myocardial ischemia after dipyridamole administration implicating coronary steal.

Myocardial perfusion imaging with coronary vasodilators is routinely used for patients with suspected coronary disease who are unable to exercise. Since these agents work by increasing blood flow without significantly changing myocardial oxygen demand, they generally do not produce ischemia. A minority of patients show evidence of ischemia which some investigators suggest is due to a coronary steal phenomenon, but this has been challenged by several investigators. We present the case of a patient who developed severe transmural myocardial ischemia manifested by ST-segment elevation and severe perfusion defects which occurred after dipyridamole administration and which were reversed with aminophylline and nitroglycerin. This case supports the notion that coronary vasodilation with dipyridamole can induce a coronary steal.

Coronary Angiography↗

PubMed1996

Hepatic sinusoidal fibrosis induced by cholesterol and stilbestrol in the rabbit: 1. Morphology and inhibition of fibrogenesis by dipyridamole.

This study documents the hepatic morphology and the ultrastructure of a model of hepatic fibrosis in rabbits. Rabbits were given a cholesterol-supplemented diet (1%), a stilbestrol diet (10 mg subcutaneously twice a week), or both treatments simultaneously for 7 weeks. Rabbits given the combined treatment developed sinusoidal and portal fibrosis with only a mild disturbance of acinar vascular relationships. Ultrastructurally, there was marked widening of the spaces of Disse by collagen fibers, basement membrane material adjacent to endothelial cells and hepatocytes, blunted hepatocellular microvilli, activated stellate cells, lipid droplets in endothelial cells and hepatocytes, and degranulated platelets in sinusoids. The hepatic hydroxyproline content was markedly increased (12.0 +/- 5.2 vs. 4.8 +/- 1.5 mmol/g of liver dry weight; P < .001). Plasma bile acids were markedly increased (222 +/- 180 vs. 12 +/- 5 in controls; P < .001). Dipyridamole (25 mg every 12 hours) that was given in addition to cholesterol and stilbestrol decreased the hepatic collagen content (-49% and -48%, in two experiments; P < .05 in both) and splenomegaly. This model provides a reliable method for the production of extensive sinusoidal fibrosis with capillarization of sinusoids. Hepatocellular degeneration is only mild to moderate, and fibrosis occurs slowly without the sudden pathological changes that occur with other models of hepatic fibrosis, such as with the administration of CCl4 or galactosamine. The mechanism of injury may involve the accumulation of bile salts or the generation of free radicals from cholesterol oxidation products. The possibility that the sinusoidal release of platelet-derived factors may have a role in the activation of stellate cells (lipocytes) is supported by the suppression of fibrogenesis by dipyridamole.

Animals↗

PubMed1989

Circumvention of adriamycin resistance by dipyridamole analogues: a structure-activity relationship study.

Dipyridamole restores sensitivity to Adriamycin (ADR) in drug-resistant cells. In an effort to elucidate the relationship between activity and chemical structure of dipyridamole, the ability to enhance the growth inhibitory effect of ADR, in multidrug-resistant (MDR) P388 murine leukemia cells, was determined for 43 derivatives and related compounds. Since both substituted pyrimidopyrimidines and pteridines enhanced the growth-inhibitory effect of ADR in drug resistant cells, the core skeleton may not be directly involved and rather serve as a carrier for the substituents connected with this activity. The exact positions of the active substituents on the core skeleton did not seem to be critical for exertion of the activity. Activity was dependent on the presence of 3 tertiary amine groups. However, not all tertiary amines showed the same potency which might be related to the degree of basicity and/or the spatial structure of these groups. The most active derivatives carried piperidine and pyrrolidine groups while derivatives with thiomorpholine, 3-hydroxypiperidine or dimethylamine groups had low activity. Activity was also dependent on the presence of a substituent with partial electronegative charges as found in a diethanolamine group. However, this function could be carried out, with even higher efficiency, by a substituent containing 6 pi electrons.

Animals↗

PubMed1990

Enhancement of an anti-tumor effect of interferon by dipyridamole in established human malignant melanoma cell lines.

Enhancement of the anti-proliferative effect of human interferon (HuIFN) preparations (alpha, beta and gamma) by dipyridamole was detected in a human malignant melanoma cell line, MM-ICB, which we originally established. Cell growth was inhibited by HuIFN alone, but a marked increase in inhibition was noted in vitro and in vivo when dipyrydamole was added. Cellular DNA synthesis, as determined by 3H-deoxythymidine incorporation into the acid-insoluble cellular fraction, was more inhibited by combined treatment than by any of the agents used alone. Two other melanoma cell lines that we established, MM-2CB and MM-3CB, also exhibited sensitivity to combined treatment both in vitro and in vivo. Furthermore, the HMV-I and SEKI melanoma cell lines were susceptible to the combination. Even non-cytotoxic concentrations of dipyridamole could enhance the effect of HuIFN on MM-ICB, MM-2CB, and SEKI cells.

Aged↗

PubMed1987

The use of intravenous dipyridamole in thallium 201 myocardial perfusion imaging.

Thallium 201 myocardial perfusion imaging is a standard method of evaluating regional myocardial blood flow. Myocardial perfusion is best evaluated at rest and during exercise, however, alternative methods have been sought to increase coronary blood flow in patients incapable of performing adequate exercise. A promising new method is the use of intravenous dipyridamole for pharmacologic stress imaging. It has distinct advantages over traditional treadmill exercise testing. The primary advantage of combining intravenous dipyridamole and thallium 201 is for testing patients in whom exercise is impractical or contraindicated. Examples include patients taking beta blockers and those who have had myocardial infarction or have severe peripheral vascular disease. To date, this agent has been available only to clinical investigators in approved protocols. With continued success, it should be approved for general use in the near future.

Coronary Circulation↗

PubMedDate not supplied

The course of pregnancy in patients with artificial heart valves treated with dipyridamole.

Continuing improvements in cardiac surgery and a wider selection of young patients for prosthetic valve replacement mean that an increasing number of women of childbearing age will undergo such procedures and will also subsequently become pregnant. At present, most patients with prosthetic heart valves are treated with anticoagulant drugs for life. The main problem with anticoagulant therapy during pregnancy is fetal and maternal hemorrhage. Congenital anomalies have been described in infants born to mothers treated with coumarin derivatives during the first trimester of pregnancy. Dipyridamole is known to decrease the adhesiveness of platelets or their ability to aggregate. We report the successful outcome of four pregnancies in patients with Starr-Edwards prostheses who were treated with dipyridamole during their pregnancies.

Adult↗

PubMed1991

Modulation of drug resistance in homoharringtonine-resistant C-1300 neuroblastoma cells with cyclosporine A and dipyridamole.

The development of resistance accounts for therapy failure in the majority of advanced cases of neuroblastoma in children. A new transplantable murine C-1300 neuroblastoma cell line was developed in vitro, by repeated exposure of a sensitive cell line to increasing, but sublethal, doses of Homoharringtonine (HHT). The ED50 of the highly resistant cells for HHT, using a standard agar colony assay, is 480 ng/ml, compared with 13 ng/ml for the sensitive parental line. The resistant cells have cross-resistance to a number of other agents, including adriamycin, vinca alkaloids, melphalan, and CCNU. Western blot analysis revealed progressive increases in P-glycoprotein, parallel to the graded development of resistance with a 29-fold elevation in the highest resistant cells. High-performance liquid chromatography (HPLC) indicated that resistant cells have a significantly lower uptake of HHT than parental sensitive cells. cyclosporine A (CsA) and dipyridamole (DPM) could modulate the acquired resistance and completely restore the cytotoxic effects of HHT and adriamycin as determined by the clonogenic assay. The reversal of resistance by CsA and DPM was dose dependent. With the relative low toxicity of dipyridamole and CsA in doses required for modulation of resistance, these agents may be candidates for clinical utilization in chemotherapy of resistant neuroblastoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1982

[Electron microscopic study of the in vitro effect of dipyridamol on the pseudorabies virus].

Dipyridamole at a concentration of 50 microM/ml displays no activity on adsorption and penetration of pseudorabies virus in chicken embryonal cells. Furthermore, first stages of virus replication take place within the nucleus, whereas incomplete virus cores defective in DNA content are found within the nucleoplasm at times when the regular viral replication has been finished in controls. Defective pseudorabies virus particles lacking in DNA-content of the core, can be observed at the end of normal replication time. Consequently, the antiviral activity of dipyridamole may be due to blocking of the synthesis or of the incorporation of infectious viral DNA into the virus core.

Animals↗

PubMed1996

Myocardial signal response to dipyridamole and dobutamine: demonstration of the BOLD effect using a double-echo gradient-echo sequence.

The purpose of this study was to examine the differential myocardial signal responses due to the blood oxygen level dependent (BOLD) effect in magnetic resonance imaging (MRI) under differing conditions of myocardial oxygen supply and demand. The signal response was measured when myocardial blood flow was increased in excess of oxygen demand or when flow was increased in response to increased myocardial oxygen demand. Normal volunteers were studied using a segmented, interleaved, double-echo, gradient-echo sequence at baseline conditions and during pharmacological stress with either dipyridamole (n = 5) or dobutamine (n = 6). Changes in T2* in the myocardium during stress were calculated. Peak coronary flow velocity was measured at rest and during stress using a breath-hold phase contrast technique. Administration of dipyridamole induced a 124 +/- 27% increase in coronary blood flow which resulted in a 46 +/- 22% increase in T2*, consistent with a decrease in myocardial venous deoxyhemoglobin concentration as myocardial oxygen supply exceeds demand. In contrast, the administration of dobutamine resulted in a 41 +/- 25% increase in coronary blood flow but no significant change in T2* (-5 +/- 19%), consistent with a lack of change in myocardial venous deoxyhemoglobin concentration and balanced oxygen supply and demand. Thus, alterations in the relationship between myocardial oxygen supply and demand appear to be detectable using BOLD MRI.

Adrenergic beta-Agonists↗

PubMed1983

Myocardial biosynthesis of prostaglandins with special consideration of prostacyclin and the influence of dipyridamole and propranolol.

Experiments with isolated perfused hearts of guinea pigs and rats showed that cardiac action is linked to formation of prostaglandinlike substances (PLS) and prostacyclin (PGI2). Perfusion of the hearts with arachidonic acid or pretreatment with a linoleic-acid-supplemented diet significantly increased the content of PLS and PGI2 and exerted an economic effect on the heart performance. Dipyridamole induced a marked increase in the coronary flow and PGI2 formation of the hearts but decreased the enhanced myocardial PGI2 biosynthesis after perfusion with arachidonic acid. Propranolol also caused a rise in PGI2 efflux but did not show any influence on PGI2 formation after arachidonic acid. Dipyridamole and propranolol prevent decreased PGI2 formation after acetylsalicylic acid, supporting the view that a combination of these drugs exerts a preventive effect in patients with angina pectoris and heart infarction.

Animals↗

PubMed1992

Atrial fibrillation after intravenous dipyridamole for thallium imaging.

Dipyridamole 0.56 mg/kg was administered intravenously for thallium tomography after myocardial infarction. Fast atrial fibrillation developed which failed to resolve with aminophylline. Sinus rhythm returned within 3 days. Myocardial tomography revealed apical infarction without reversible ischaemia. Atrial fibrillation after dipyridamole is rare and may be caused by direct electrophysiological effects on the atrial myocardium.

Atrial Fibrillation↗

PubMed1994

Serum caffeine levels after 24 hours of caffeine abstention: observations on clinical patients undergoing myocardial perfusion imaging with dipyridamole or adenosine.

Although caffeine attenuates the vasodilatation produced by dipyridamole and adenosine, and is therefore contraindicated when these agents are used for myocardial perfusion scintigraphy, caffeine levels in clinical patients undergoing standard imaging protocols have not been studied. Eight-six patients undergoing clinically indicated intravenous dipyridamole (n = 75) or adenosine (n = 11) thallium-201 myocardial perfusion scintigraphy, all of whom reported abstention from products containing caffeine for 24 h, were studied prospectively. Blood samples were drawn prior to initiation of the pharmacologic infusion, and serum caffeine levels were determined using an enzyme immunoassay technique. Results of these determinations were correlated with maximum pulse and blood pressure changes measured during and immediately after the stressor infusion, and thallium imaging findings. Detectable caffeine levels were found in 34 patients (40%), ranging from 0.1 to 5.0 mg/l. There was no significant difference in mean systolic blood pressure decrease or mean pulse increase between patients with caffeine levels > 1.0 mg/l (20.4 +/- 18.2 mmHg, 11.0 +/- 8.9 BPM; n = 5) and those with lower (0.1 to 0.9 mg/l) (15.4 +/- 9.5 mmHg, 14.4 +/- 8.2 BPM; n = 29) or no detectable caffeine levels (18.0 +/- 11.5 mmHg, 16.6 +/- 10.1 BPM; n = 52). Redistribution on thallium imaging was also identified with a similar frequency in these three groups (2/5, 40%; 8/29, 28%; 22/52, 42% respectively).

Adenosine↗

PubMed1992

Effects of aspirin, dipyridamole, nifedipine and cavinton which act on platelet aggregation induced by different aggregating agents alone and in combination.

The effects of aspirin, nifedipine, dipyridamole and cavinton on platelet aggregability in patients with atherosclerosis has been studied using various agents to induce aggregation. The drugs reduced platelet aggregability when aggregation was induced by ADP, adrenaline, or collagen alone. However, if platelet aggregation were induced by combinations of the agonists (including combinations of ADP with either adrenaline or platelet-activating factor (PAF), adrenaline with PAF, and collagen with ADP), the anti-aggregant effects of aspirin, dipyridamole, and cavinton were significantly reduced. The effect of nifedipine was less markedly reduced, especially by combinations which included adrenaline. The data suggest that positive agonist interactions may lead to a reduction in the therapeutic activity of antiplatelet drugs.

Adenosine Diphosphate↗

PubMed1976

[Experiments on the medicamental treatment of the noise-induced cochlear damage. Part I. The effect of dipyridamol and allopurinol on the RMP of the cochlea (guinea pig) after noise (author's transl)].

Dipyridamol has in addition to a coronardilatating effect an ati-thrombotic one too. Moreover it facilitates the release of O2 from haemoglobin by increase of the concentration of 2,3-diphosphoglycerate in the erythrocytes. Allopurinol causes a potential resynthesis of ATP in the cells by inhibition of the metabolism of uric acid. Both substances therefore seemed to be suitable for a medicamental therapy of the noise-induced cochlear damage. The expected favourable effect of Dipyridamol and Allopurinol on the organ of Corti after sound exposure (RMP-measurement before and after exposure to pure tone 120 dB SPL) however had not been confirmed by experiment on animals (guinea pig).

Allopurinol↗

PubMed1990

Persistent chest pain following oral dipyridamole for thallium 201 myocardial imaging.

A patient was admitted to the hospital with acute chest pain. After acute myocardial infarction was ruled out, he underwent a stress thallium 201 scintigraphy using oral dipyridamole and developed persistent angina with ST-segment elevation. This complication has not been reported previously. It is recommended that appropriate intervention be available if severe ischemia develops following administration of dipyridamole for diagnostic imaging.

Angina Pectoris↗