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PubMed2000

Hypocholesterolemic activity of dipyridamole: effects on chick plasma and lipoprotein composition and arachidonic acid levels.

We have studied the effects of dipyridamole treatment on chick plasma and lipoprotein composition in postprandial and fasting (12 h) conditions. Plasma cholesterol levels were higher in fasted than in fed chicks, whereas triglycerides declined during starvation. Dipyridamole treatment reduced plasma cholesterol content, mainly of the free cholesterol fraction. In postprandial conditions, total cholesterol content of high and low density lipoproteins decreased in a similar proportion to that observed in plasma. However, cholesterol and other chemical constituents of intermediate and very low density lipoproteins were more drastically reduced by dipyridamole than in plasma. Total amounts of these lipoprotein fractions were also reduced about 50%. The effects of dipyridamole in fasted animals were not significant. To our knowledge, this is one of the first reports about the response of lipoprotein cholesterol to dipyridamole treatment. A strong decrease was also found in the arachidonic acid content of plasma phospholipids and cholesterol esters fractions.

Journal Article↗
PubMed1996

Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries.

BACKGROUND: To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. METHODS AND RESULTS: Specimens were mounted on a myograph and relaxes through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A(2)-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. CONCLUSIONS: Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A(2) adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3' 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

Journal Article↗
PubMedDate not supplied

Aggrenox: an aspirin and extended-release dipyridamole combination.

Stroke is one of the leading causes of death in the United States. The risk of experiencing a recurrent stroke remains elevated for several years after an initial stroke or a transient ischemic attack (TIA), therefore secondary prevention is crucial in reducing the risk of stroke and the complications and costs associated with stroke. Aggrenox, a combination of low-dose aspirin and extended-release dipyridamole, is a new agent that is effective in the secondary prevention of stroke and transient ischemia of the brain. The clinical effect of its two antiplatelet agents are additive and significantly better than either aspirin or dipyridamole alone, although it has not been shown to be more effective than aspirin alone in preventing death. Aggrenox is much more expensive than aspirin alone but has been shown to be more cost-effective. At this point, much of the pharmacologic information concerning this combination agent is based on previous data about aspirin and immediate-release dipyridamole. This combination of aspirin and extended-release dipyridamole may play a significant role in secondary stroke and TIA prevention.

Aspirin↗
PubMed1964

AUGMENTATION OF INTERCORONARY ANASTOMOSIS BY LONG-TERM ADMINISTRATION OF A VASODILATOR DRUG, DIPYRIDAMOLE (PERSANTIN).

A study was carried out to assess the ability of dipyridamole to promote intercoronary anastomotic channels in the dog. Nineteen normal dogs received 150-300 mg. dipyridamole daily for 73 to 162 days and were compared with 18 control animals. Employing pentobarbital sodium (Nembutal) anesthesia and positive pressure ventilation, the chest was opened and the circumflex coronary artery was tied and cannulated distal to the tie. The average retrograde flow in the treated group was significantly higher than that in the control group (p < 0.02). Acute administration of dipyridamole intravenously produced comparable reduction of blood pressure and retrograde flow in both groups of animals. Thus the long-term administration of dipyridamole appears capable of promoting the growth of intercoronary anastomotic pathways in some animals even in the absence of any known ischemic stimulus. This would appear to be the result of sustained vasodilator action.

Animals↗
PubMed1991

Dipyridamole thallium scanning in the evaluation of coronary artery disease in elective abdominal aortic surgery.

Dipyridamole thallium scanning was routinely performed on 68 consecutive patients who presented for elective aortic surgery. All 68 patients were judged by clinical assessment to be at low risk for perioperative cardiac complications. In addition, 42 of 68 patients had a history of myocardial infarction, stable angina, or abnormal echocardiographic findings (group 1). Twenty-six of 68 patients did not have a history of myocardial infarction, angina, or abnormal echocardiographic findings (group 2). In group 1, 34 of 4 patients had positive results on dipyridamole thallium scanning, and 15 of these patients were found to have critical coronary artery disease on subsequent cardiac catheterization; nine underwent immediate coronary artery bypass grafting, and six had their coronary artery disease treated medically and their vascular operations cancelled. The remaining 27 patients in group 1 underwent elective operations, with six (22%) of 27 sustaining postoperative cardiac complications. None of the group 2 patients was found to have critical coronary artery disease. All patients in group 2 underwent aortic operation without cardiac complication. Routine dipyridamole thallium scanning detected a 22% (15 of 68) incidence of critical coronary artery disease overall. There was a 36% (15 of 42) incidence of critical coronary artery disease in group 1 patients vs 0% in group 2 patients (95% confidence interval, 21% to 50%). We conclude that the use of dipyridamole thallium scanning in low-risk patients for cardiac screening prior to elective aortic operations is beneficial in selected patients who have a history of myocardial infarction, angina, or abnormal echocardiographic findings, but is not necessary in patients with no history of coronary artery disease.

Aged↗
PubMed1987

Dipyridamole-induced myocardial ischemia.

Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary "steal" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.

Adult↗
PubMed1995

Reduced red blood cell deformability in patients with rheumatoid vasculitis. Improvement after in vitro treatment with dipyridamole.

OBJECTIVE: To assess red blood cell deformability (RCD) in patients with rheumatoid arthritis (RA) without extraarticular manifestations and in RA with vasculitic complications (RV), and to assess whether in vitro dipyridamole improves RCD. METHODS: An improved filtration technique was used to measure RCD in 15 patients with RA, 18 patients with RV, and 20 age- and sex-matched normal control subjects. Washed erythrocytes suspended in buffer, at 5% hematocrit, were filtered through 4.7 mu Nuclepore Hemafil PC membranes. The initial steady-state relative filtration pressure (iRFP) was used as an index to assess RCD. A lower iRFP value reflects increased deformability, a higher value reflects a decrease. For each sample, 2 cell suspensions were prepared, one blank (control) and one containing 5 microM dipyridamole. RESULTS: The mean iRFP values of cells obtained from patients with RV were significantly higher than those of cells obtained from normal controls. There were no appreciable differences in iRFP between RA patients and normal controls. When the erythrocytes were pretreated in vitro with 5 microM dipyridamole before filtration, their deformability improved markedly (iRFP values were reduced) in all study subjects, compared with untreated cells. CONCLUSION: RCD is reduced in patients with RV, and treatment with dipyridamole may be beneficial if reduced RCD contributes to impaired microvascular perfusion.

Adult↗
PubMed1990

Aspirin and dipyridamole and their limitations in the therapy of coronary artery disease.

We have reviewed some of the voluminous literature on the effects of aspirin combined with dipyridamole on coronary thrombosis. There is clear evidence that aspirin is partially effective in preventing platelet aggregation and subsequent thrombosis in experimental constricted and damaged coronary arteries of dogs. Clinical studies show a clear reduction in myocardial infarction in male human subjects who are given aspirin as therapy for unstable angina, or as prophylaxis in asymptomatic individuals. In many studies aspirin and dipyridamole have been combined and are effective. We have not found dipyridamole to be effective in the dog with coronary artery constriction and find no substantial evidence that it is effective in preventing myocardial infarction in man. Until definitive studies show that combining dipyridamole with aspirin is more effective than aspirin alone, we do not recommend its use for prevention of coronary thrombosis.

Animals↗
PubMed1991

In vitro protein binding behavior of dipyridamole.

The in vitro protein binding behavior of dipyridamole in plasma and buffered protein solutions was investigated by equilibrium dialysis. The drug was highly protein bound (approximately 98%) in heparinized human plasma, and the extent of protein binding remained constant for drug concentrations over the range of therapeutic interest of 0.1-10 micrograms/mL. Comparable binding results were obtained with a mixture of 80 mg % of alpha 1-acid glycoprotein and 40 g/L of human serum albumin in pH 7.4 phosphate buffer solution. Pure alpha 1-acid glycoprotein (80-400 mg %) or pure human serum albumin (40 g/L) in phosphate buffer gave significantly (p less than 0.05) lower binding results, indicating that both proteins are responsible for the high binding of dipyridamole in plasma. Addition of alpha 1-acid glycoprotein to heparinized human plasma, to simulate an acute phase increase in the protein, had no effect on the fraction of free drug in plasma. Binding of dipyridamole to heparinized human plasma or human serum albumin in buffer was concentration independent through 40 micrograms/mL. The free fraction of dipyridamole increases with concentrations exceeding 40 micrograms/mL.

Dialysis↗
PubMed1997

Direct determination of dipyridamole in serum.

A new method for the determination of dipyridamole in serum for concentrations between 10 and 100 ng ml-1 by means of matrix isopotential synchronous fluorescence spectrometry and derivative techniques is proposed. This new method is useful for the determination of compounds in samples with unknown background fluorescence, such as dipyridamole in serum, without the need for tedious preseparation. The determination was performed in an ethanol/water medium (15% v/v) at a pH value of 10.0, provided by adding an ammonium chloride/ammonia buffer solution. Since dipyridamole is a stimulant which is very much used like a doping substance in sport, the method was successfully applied to the determination of dipyridamole in serum. Better sensitivity and repeatability are achieved for these matrices than with the fluorometric ones described in the literature. An exhaustive statistical analysis has been developed for all calibration graphs. This treatment includes robust regression such as least median of squares which also detects outliers and leverage points. The overall least-squares regression has been applied to find the more exact straight line which fits the experimental data. The error propagation has been considered to calculate the detection limit, determination limit, and the repeatability of the method.

Dipyridamole↗
PubMed1989

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers.

To establish test specific normal limits for quantitative analysis of uptake and washout of 201Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as less than or equal to 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the 201Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37% +/- 2.11%. The regional washout in the 70 degrees LAO view (46.65% +/- 1.10%) was significantly higher than in the anterior and 30 degrees LAO views (43.44% +/- 1.50% and 43.02% +/- 1.45%, respectively). Profiles of uptake and washout of 201Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of 201Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of 201Tl derived from healthy volunteers who underwent the same combined protocol.

Adult↗
PubMed1985

Cardiac sarcoidosis: reversion of myocardial perfusion abnormalities by dipyridamole.

A Tl 201 scan was performed on one young patient who met all of the criteria for the diagnosis sarcoidosis. A resting scan before treatment showed marked defects which were not resolved on the redistribution scan, thus leading to the diagnosis of cardiac sarcoidosis, which was also suspected from clinical signs. After dipyridamole infusion (0.142 mg/kg per minute over 4 min), his 201Tl scan was quite normal. Haemodynamic investigation showed a low coronary sinus blood flow with a low lactate extraction: these abnormalities were fully reversed by i.v. dipyridamole infusion. Afterwards, the patient was given oral dipyridamole (450 mg/day) over 4 weeks; at the end of this treatment, his resting 201Tl scan was quite normal. These results suggest that myocardial perfusion abnormalities in sarcoidosis may be reversible after pharmacological vasodilation. Thus, in order to assess cardiac sarcoidosis, a resting myocardial scan should be performed before a scan after dipyridamole infusion. These results may have clinical, pathophysiological and therapeutic implications with regard to cardiac sarcoidosis.

Adult↗
PubMed1991

A phase II trial of PALA + dipyridamole in patients with advanced soft-tissue sarcoma.

A total of 21 patients with advanced soft tissue sarcoma enrolled in a phase II trial of 3.5 g/m2 N-phosphonacetyl-L-aspartate (PALA) given intravenously every 3 weeks plus 50 mg/m2 dipyridamole (Persantine) given orally every 6 h. Dipyridamole administration was initiated 1 week before the first dose of PALA. Peak and trough plasma concentrations of dipyridamole were measured before and after the first dose of PALA in 14 patients. In all, 19 patients were evaluable for therapeutic response. One subject experienced partial regression of a pulmonary metastasis; no other major response was observed. Diarrhea was the most prominent toxicity; in one patient it was life-threatening and was associated with a severe rash. On the day preceding PALA administration, the median peak plasma concentration of dipyridamole was 2,208 ng/ml and the median trough value was 904 ng/ml. Similar values were obtained on the day of PALA administration. Although the levels achieved were similar to those required to modulate the activity of PALA in preclinical systems, the therapeutic results obtained in the present study were not superior to those reported for PALA alone in previously treated patients with soft-tissue sarcoma.

Adult↗
PubMed1995

Digital high frame rate stress echocardiography for detection of coronary artery stenosis by high dose dipyridamole stress testing.

Diagnostic accuracy of high dose dipyridamole stress echocardiography (0.84 mg i.v./kg) for detecting coronary artery stenosis was assessed in 94 patients undergoing coronary angiography, and adverse effects were registered in the total study population of 120 patients. Echocardiographic analysis was performed with digital systolic cineloops with high frame-rate (47 frames/sec) for optimal left ventricular wall motion display. Results showed sensitivity of 73% for detection of arterial luminal stenosis > or = 75% or retrograde collateral flow to an occluded coronary artery. Sensitivity for detection of 1-vessel stenosis was 43% (6 of 14 patients), and for 2- and 3-vessel disease 79% (19 of 24) and 88% (16 of 18), respectively. Specificity was 92% (35 of 38), diagnostic accuracy 81%. The stenosed coronary artery was correctly localized in 85% of positive tests. Dipyridamole-induced increase in wall motion score index differed significantly between patients with 1-, 2-, and 3-vessel disease (0.02 +/- 0.17, 0.15 +/- 0.17, and 0.27 +/- 0.24, respectively), and early positive tests (dipyridamole dose of 0.56 mg/kg) were almost exclusively seen in patients with multivessel disease. Six patients (5%) developed symptomatic bradycardia and hypotension during the test. In conclusion, dipyridamole stress echocardiography is useful for detection and localization of coronary artery stenosis, particularly in patients with multivessel disease.

Collateral Circulation↗
PubMedDate not supplied

Effects of dipyridamole on collateral flow and regional myocardial function in conscious dogs with newly developed collaterals.

Studies were conducted on six conscious dogs instrumented for measurement of subendocardial segment lengths in the area perfused by the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCCA), LCCA flow, and left ventricular pressure. Externally inflatable occluders were placed around the proximal LAD and LCCA. Collateral channels sufficient for the resting metabolic demands in the occluded LCCA perfusion territory were induced by repeated, brief LCCA occlusions. Dogs were then subjected to two consecutive brief periods of LAD occlusion. Dipyridamole (0.25 mg/kg) was injected intravenously 3 min prior to the second LAD occlusion. The collateral blood flow from the LCCA to the occluded LAD area was measured as the stepwise decrease in LCCA flow upon release of the LAD occlusion. During LAD occlusion after dipyridamole treatment collateral blood flow velocity decreased to 3.8 +/- 1.1 cm/s (+/- standard error) compared with a value of 4.9 +/- 0.9 cm/s measured during LAD occlusion without dipyridamole treatment. Percentage systolic segment shortening in the collateral dependent zone significantly deteriorated from 14.3 +/- 5.2 to 9.7 +/- 5.0% (p less than 0.05). Electrocardiograms taken simultaneously from endocardial ultrasonic transducers in the ischemic segment revealed significant increases in ST-segment level from 4.2 +/- 0.6 to 5.4 +/- 0.6 mV. These findings indicate that dipyridamole adversely affects the extent of myocardial ischemia in the collateral-dependent zone.

Animals↗
PubMed1981

Dipyridamole suppresses uptake of thymidine in human and bovine cells in vitro.

Dipyridamole has been shown to induce proliferative activity in heart muscle capillary wall cells in the rat. To test whether this effect is due to direct cellular stimulation we tested the substance in various in vitro systems (human lymphocytes, glial cells and endothelial cells; and bovine endothelial cells). During these conditions dipyridamole did not influence cellular proliferation. In all cell systems tested, uptake of labelled thymidine showed an inhibition by dipyridamole. This confirms the earlier finding that dipyridamole inhibits nucleoside uptake, and extends the finding to human cells.

Animals↗
PubMed1996

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease.

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.

Adult↗
PubMed2005

Dipyridamole, an underestimated vascular protective drug.

Dipyridamole, developed almost half a century ago, acts by inhibiting nucleoside transport, which increases adenosine levels leading to inhibition of platelet aggregation and vasodilatation mainly in the coronary tree. It is a vaso-protective drug with proven efficacy in the prevention of strokes. Adenosine receptor 2 inhibitory purines, ubiquitously available in food and drink, inhibit the vasomotor effects of dipyridamole but not its action on platelet aggregation. This and the slow build-up of blood levels of dipyridamole after oral application may explain why incidents of drug-induced angina ("coronary steal") were never reported in the prevention trials. The prevention of arterial thrombosis and the positive remodeling of the arterial system (arteriogenesis) by elevated blood flows suggest that dipyridamole may be able to halt the progression of organ manifestations of atherosclerosis. Clinical trials for the secondary prevention of vascular occlusions in other vascular beds should be encouraged.

Adenosine↗