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PubMed1986

Inhibition of platelet aggregation in whole blood by dipyridamole and aspirin.

We have examined the effects of dipyridamole on platelet aggregation in whole blood both in vitro and after administration to man. The effects of dipyridamole ex vivo were compared with those of aspirin and a combination of dipyridamole and aspirin. In vitro dipyridamole was most effective as an inhibitor of platelet aggregation induced by platelet activating factor (PAF) and low concentrations of arachidonic acid (AA). Its inhibitory effect was always potentiated by adenosine suggesting that its effect on aggregation may be via inhibition of adenosine uptake into blood cells. Ex vivo, dipyridamole, aspirin and the combination of these drugs inhibited the platelet aggregation induced by PAF and AA. Again, adenosine increased the degree of inhibition. These results stress the importance of measuring platelet aggregation in the natural whole blood environment for detection of the inhibitory effects of dipyridamole and suggest a mode of action for the drug.

Aspirin↗

PubMed1982

Effect of dipyridamole on prostaglandin generation by human platelets and vessel walls.

These experiments were conducted to determine the effects of dipyridamole on human platelet aggregation, platelet thromboxane A2 (TXA2) and human vessel wall prostacyclin (PGI2) generation. Dipyridamole in varying concentrations (5 to 50 micrograms/ml) had no direct effect on ADP-induced platelet aggregation in vitro, but it potentiated PGI2-induced platelet aggregation inhibition at these concentrations. Dipyridamole also inhibited arachidonic acid-induced platelet TXA2 generation at these concentrations. In continuously perfused umbilical vein segments, dipyridamole treatment resulted in stimulation of PGI2 release determined by bioassay and by measurement of its stable metabolite 6-keto-PGF1 alpha. Minimum concentration of dipyridamole causing PGI2 release was 50 micrograms/ml. These in vitro studies suggest that anti-thrombotic effects of dipyridamole in man are mediated mainly by potentiation of PGI2 activity and to some extent by TXA2 suppression. Stimulation of PGI2 release by human vessels may not be seen in usual therapeutic concentrations.

Arachidonic Acid↗

PubMed1985

Prostacyclin production by rat aorta "in vitro" is increased by the combined action of dipyridamole plus pentoxifylline.

The present study evaluates the effect of dipyridamole and pentoxifylline, individually and in combination, on PGI2-like production and arachidonic acid metabolism of rat aorta "in vitro". Pentoxifylline 100 microM and dipyridamole 92 and 184 microM increased PGI2-like activity, as measured by the platelet aggregation inhibitory capacity of the aortic ring incubates, by 71%, 46% and 60% respectively; a greater increase in PGI2-like activity was observed with the combination of the drugs than when they were used separately. This effect was observed even at the lowest doses assayed. In fact, dipyridamole 9.2 microM plus pentoxifylline 1 microM increased the PGI2-like activity by 30% while the individual increase was 4.5% and 10.6% respectively. To obtain more information on the effect of the dipyridamole-pentoxifylline combination on arachidonic acid metabolism, arteries were incubated with (1-14C) arachidonic acid, and the 6-keto-PGF1 alpha and PGE2 quantified. Dipyridamole 92 microM plus pentoxifylline 1 and 10 microM increased 6-keto-PGF1 alpha and PGE2 production by about 30% and 48% respectively while the combination with pentoxifylline 100 microM increased the 6-keto-PGF1 alpha 76.5% and the PGE2 50%. The possible biological effect and therapeutic implications of increased PGI2 production by the arteries due to the dipyridamole-pentoxifylline combination remains to be ascertained.

Animals↗

PubMed1991

CD4+ TCR alpha beta+ T-cells developing after allogeneic bone marrow transplantation in patients with chronic myelogenous leukaemia. Dipyridamole inhibits functionally heterogeneous T-cell clones.

Dipyridamole inhibited the proliferation of functionally heterogeneous CD4+ TCR alpha beta+ T-cell clones prepared from CML-patients 4-6 weeks after allogeneic bone marrow transplantation. The effect was seen when testing concentrations corresponding to the therapeutic serum level. Dipyridamole caused a dose-dependent inhibition of PHA-stimulated proliferation both for clones dependent on exogenous IL2 and clones undergoing autocrine proliferation. The inhibition was seen when using different accessory cells (PBM or BCL), and also when dipyridamole was present during IL2- or IL4-dependent proliferation of activated T-cells. The effect of dipyridamole was also investigated for 76 T-cell clones (76 CD4+ and 7 CD8+ clones) prepared by different cloning procedures from three patients. Although these clones were heterogeneous with regard to cytotoxic function, lymphokine production or lymphokine responsiveness, dipyridamole inhibited IL2-dependent proliferation of all clones. In addition dipyridamole inhibited proliferation of CML cells.

Adult↗

PubMed1995

Dipyridamole attenuates the development of iminodipropionitrile-induced dyskinetic abnormalities in rats.

The present investigation was undertaken to study the effect of dipyridamole on experimental dyskinesia in rats. The movement disorders were produced by intraperitoneal administration of iminodipropionitrile (IDPN) in the dose of 100 mg/kg per day for 12 days. Dipyridamole was administered orally, daily 30 min before IDPN in the doses of 0.5 g/kg, 1 g/kg, and 1.5 g/kg bodyweight in three different groups of rats. Twenty-four hours after the last dose of IDPN, animals were observed for neurobehavioral changes including vertical and horizontal head weaving, circling, backwalking, grip strength, and righting reflex. Immediately after behavioral studies brain specimens were collected for analysis of vitamin E, conjugated dienes, and lipid hydroperoxides as indices of oxygen-derived free radical (OFR) production. Our results showed that concurrent use of dipyridamole significantly protected rats against IDPN-induced neurobehavioral changes in a dose-dependent manner. Treatment of rats with dipyridamole inhibited IDPN-induced decrease of vitamin E and increase in conjugated dienes and lipid hydroperoxides in brain. These findings suggest the involvement of OFR in dipyridamole induced protection against the development of IDPN dyskinesia. Further studies are warranted to determine the role of dipyridamole as a prophylactic agent against the drug induced dyskinetic abnormalities.

Animals↗

PubMed1989

Assessment of regional myocardial perfusion by contrast echocardiography. II. Detection of changes in transmural and subendocardial perfusion during dipyridamole-induced hyperemia in a model of critical coronary stenosis.

Measurements of myocardial contrast (sonicated meglumine diatrizoate) intensity were compared with myocardial flow by radioactive microspheres before and after administration of dipyridamole (0.5 mg/kg body weight intravenously) in 10 open chest dogs with a critical stenosis in the left circumflex coronary artery. Computer measurements of contrast time-intensity curves corrected for background myocardial intensity were made along 12 transmural segments of the left ventricle at mid-papillary level and for the subendocardial and subepicardial half of each segment. After administration of dipyridamole, transmural flow in the control region increased significantly (p less than 0.001), resulting in a dipyridamole/baseline flow ratio (i.e., coronary reserve ratio) of 2.54 +/- 0.95. Similar changes (p less than 0.001) were seen by contrast echocardiography; the coronary reserve ratio was 2.10 +/- 0.60 with use of peak intensity and 3.48 +/- 1.58 with use of area under the time-intensity curve. In contrast, no significant changes were observed in myocardial flow, peak contrast intensity or area under the curve in the ischemic region after dipyridamole. In the control region the ratio of subendocardial to subepicardial flow was similar at baseline and after dipyridamole administration as assessed by microspheres (1.08 +/- 0.24 versus 1.17 +/- 0.25) or by area under the time-intensity curve (1.11 +/- 0.45 versus 1.11 +/- 0.56). In the ischemic region, the subendocardial/subepicardial flow ratio decreased significantly after dipyridamole administration as measured by microspheres (1.15 +/- 0.19 to 0.82 +/- 0.25; p less than 0.001) or by area under the curve (1.10 +/- 0.28 to 0.70 +/- 0.47; p less than 0.01). Thus, myocardial contrast echocardiography appears to be a sensitive technique with which to detect changes in myocardial flow induced by dipyridamole in the various myocardial layers of normal segments as well as of segments supplied by a critically stenotic coronary artery.

Animals↗

PubMed1992

Comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous dipyridamole in normal men.

OBJECTIVE: This study compared quantitatively the efficacy of intravenous adenosine and dipyridamole for pharmacologic induction of myocardial hyperemia. BACKGROUND: Pharmacologic vasodilation is used increasingly for induction of myocardial hyperemia in conjunction with radionuclide imaging of myocardial blood flow. Although both intravenous dipyridamole and adenosine have been used, the magnitude of hyperemia induced by these agents and the hyperemia to baseline blood flow ratios have not been quantified and compared. METHODS: Twenty normal volunteers were studied with dynamic positron emission tomography (PET) and intravenous nitrogen-13 ammonia. Myocardial blood flow was quantified with a two-compartment tracer kinetic model. RESULTS: Myocardial blood flow at rest averaged 1.1 +/- 0.2 ml/min per g and increased significantly to 4.4 +/- 0.9 ml/min per g during adenosine and 4.3 +/- 1.3 ml/min per g after dipyridamole administration. Hyperemia to baseline flow ratios averaged 4.3 +/- 1.6 for adenosine and 4.0 +/- 1.3 for dipyridamole. The average flow ratios and the maximal flows achieved were similar for both agents, but there was considerable variation in the individual response to these agents, as indicated by the range of hyperemia to baseline flow ratios (from 2.0 to 8.4 for adenosine and from 1.5 to 5.8 for dipyridamole). In addition, the hyperemic responses to dipyridamole and to adenosine differed by greater than 1 ml/min per g in nine subjects. CONCLUSIONS: Despite these inter- and intraindividual differences, we conclude that both agents are equally effective in producing myocardial hyperemia.

Adenosine↗

PubMed1992

Silent versus symptomatic dipyridamole-induced ischemia after myocardial infarction: clinical and prognostic significance.

The prevalence and prognostic significance of silent myocardial ischemia were prospectively assessed in 217 patients (mean age 57 +/- 9 years, 83% male) recovering from a first uncomplicated acute myocardial infarction and undergoing a dipyridamole echocardiography test before hospital discharge. Clinical, angiographic, exercise electrocardiographic (ECG) and dipyridamole echocardiographic variables were also examined. Of the 217 patients, 89 had no echocardiographically proved dyssynergy after dipyridamole, whereas 128 had dipyridamole-induced wall motion abnormalities that were silent in 94 (Group I) and symptomatic in 34 (Group II). There was no intergroup difference with respect to dipyridamole time (i.e., the time from onset of the test to frank dyssynergy: 7 +/- 3 vs. 8 +/- 3 min; p = NS); prevalence of inferior myocardial infarction (69% vs. 71%; p = NS); ischemic ECG changes during the test (83% vs. 71%; p = NS); diabetes (8.5% vs. 6%; p = NS); ongoing medical therapy; multivessel disease (57% vs. 56%; p = NS); and baseline left ventricular ejection fraction (57 +/- 13% vs. 57 +/- 10%; p = NS). There was also no significant difference between Group I and Group II with respect to wall motion score index at peak dipyridamole effect (1.77 +/- 0.39 vs. 1.78 +/- 0.36; p = NS). Patients were followed up for 24 +/- 4 and 25 +/- 5 months, respectively (p = NS). Life table analysis revealed no difference in unstable angina, reinfarction and death between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Stress echocardiography: comparison of exercise, dipyridamole and dobutamine in detecting and predicting the extent of coronary artery disease.

OBJECTIVES: This study was designed to compare exercise, dipyridamole and dobutamine echocardiography in the same patients and to evaluate, by measuring physiologic and echocardiographic variables, the mechanisms by which exercise and dobutamine induce ischemia. BACKGROUND: The diagnostic value of stress echocardiography has been widely reported, but the specific effects of exercise, dipyridamole and dobutamine have not been directly compared. Furthermore, no echocardiography study has evaluated left ventricular volume changes at ischemic threshold during exercise and dobutamine administration. METHODS: One hundred patients with suspected (Group A, n = 60) or known (Group B, n = 40) coronary artery disease underwent all three tests in random order. RESULTS: In Group A, the sensitivities of exercise (mean 76%, 95% confidence interval [CI] 58% to 94%) and of dobutamine echocardiography (72%, 95% CI 53% to 91%) were higher than that of dipyridamole (52%, 95% CI 31% to 73%; p = 0.01 and p = 0.02, respectively). Specificity did not differ significantly among tests (94% for exercise [95% CI 86% to 100%] and 97% for dipyridamole and dobutamine [95% CI 91% to 100%]). Accuracy was identical for exercise and dobutamine (87%) and higher than that for dipyridamole (78%, p = 0.06). In Group B, the accuracy in predicting coronary disease extent was 71% for exercise, 33% for dipyridamole and 75% for dobutamine. At ischemic threshold, end-systolic volume index and the ratio of systolic blood pressure to end-systolic volume, a variable related to myocardial contractility, were significantly lower and higher, respectively, with dobutamine than during exercise (p < 0.05). CONCLUSIONS: In a clinical setting, exercise echocardiography should represent the first diagnostic approach because it has high diagnostic efficacy and provides additional information on exercise capacity; pharmacologic stress, particularly that of dobutamine, provides a pivotal diagnostic tool when exercise is not feasible or its results are nondiagnostic. Our preliminary data on echocardiographic evaluation at ischemic threshold support the view that myocardial contractility is a major factor in inducing ischemia during dobutamine infusion.

Coronary Disease↗

PubMed1995

A potent chain-breaking antioxidant activity of the cardiovascular drug dipyridamole.

The antioxidant properties of the antithrombotic drug dipyridamole have been studied using lipid oxidation assays based on the generation of peroxy radicals by azo compounds. Dipyridamole was observed to prevent both peroxidation of arachidonic acid micelles in aqueous solution and peroxidation of methyl linoleate in organic solvents; in contrast to vitamin E, dipyridamole was found to scavenge both hydrophilic and hydrophobic radicals. The rate constant for the reaction of dipyridamole with methyl linoleate peroxyl radicals at 37 degrees C was calculated as 2 x 10(6) M-1s-1, in comparison to 1 x 10(6) M-1s-1 of vitamin E under the same conditions. The antioxidant efficiency of the drug was confirmed in experiments with radiolysis-induced oxidation and through measurements of malondialdehyde production and diene formation. As a result of radical scavenging, a relatively stable dipyridamole radical was formed that could be detected by electron spin resonance spectroscopy. The particular antioxidant properties of dipyridamole may explain the vasodilating and antiplatelet effects of this cardiovascular drug.

Antioxidants↗

PubMed2004

Fluorescence spectroscopic determination of dipyridamole binding on pancreas-1 tumor cell membrane.

BACKGROUND: The traditional method to determine the binding sites of inhibitors bound to nucleoside transporters on cell membrane is the radioactive assay. This method suffers from radiolabel instability and the need to dispose of reactive materials. Fluorescence spectroscopy has been increasingly applied to biochemical analysis due to its high sensitivity and selectivity. We describe fluorescence spectroscopy for the determination of the binding sites of dipyridamole bound to nucleoside transporters on pancreas-1 tumor cell membrane. METHODS: Pancreas-1 tumor cell was cultured in Dulbecco's modified Eagle medium under appropriate conditions. The cell plasma membrane was separated from the ultrasonically dissolved cell mixture by gradient centrifugation. After dipyridamole was bound to the cell membrane, the test sample was obtained by ultrasonically dissolving the labeled membrane in 10 mmol/l tris-HCl membrane lysis solution. Under selected experimental conditions, the fluorescence intensity of dipyridamole was determined. RESULTS: At lambda em of 295 nm and lambda em of 485 nm, dipyridamole was proportional to its concentration ranging from 1.0 x 10(-12) to 5.0 x 10(-11) mol/l with a detection limit of 2.8 x 10(-13) mol/l (0.14 pg/ml) at 3sigma. The value of affinity constant of the cell membrane to dipyridamole was 4.7(+/-0.5) x 10(10) l/mol and the average total number of binding sites of a pancreas-1 tumor cell was 1.9(+/-0.2) x 10(6). CONCLUSIONS: The proposed method can be used in the study of binding characters of dipyridamole on the cell membrane.

Binding Sites↗

PubMed2005

Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans.

BACKGROUND: Adenosine receptor stimulation induces several effects that could limit ischemia-reperfusion injury. We hypothesize that treatment with the nucleoside uptake inhibitor dipyridamole increases endogenous adenosine and limits ischemia-reperfusion injury in humans. METHODS: Ischemia-reperfusion injury was studied in forearm skeletal muscle by technetium Tc 99m-labeled annexin A5 scintigraphy. Ischemia-reperfusion injury was induced by unilateral forearm ischemic exercise. Immediately on reperfusion, annexin A5 labeled with technetium Tc 99m was administered intravenously, and ischemia-reperfusion injury was expressed as the percentage difference in radioactivity between the experimental arm and the control arm 1 and 4 hours after reperfusion. Targeting was quantified in the region of the thenar muscle and forearm flexor muscles. This approach was used in 9 healthy male volunteers after a 1-week treatment with dipyridamole (200 mg, slow release, twice daily) and in 23 control subjects. RESULTS: Dipyridamole treatment significantly reduced annexin A5 targeting in skeletal muscle compared with the control group (thenar region, 13% +/- 7% versus 22% +/- 15% at 1 hour after reperfusion and 9% +/- 6% versus 27% +/- 13% at 4 hours for dipyridamole and control groups, respectively [P = .01]; flexor region, 4% +/- 8% versus 7% +/- 6% at 1 hour after reperfusion and 1% +/- 4% versus 10% +/- 9% at 4 hours for dipyridamole and control groups, respectively [P = .01]). CONCLUSIONS: One week of oral treatment with the nucleoside uptake inhibitor dipyridamole (200 mg, slow release, twice daily) significantly limits ischemia-reperfusion injury in humans in vivo, as assessed by technetium Tc 99m-labeled annexin A5 scintigraphy of forearm skeletal muscle.

Administration, Oral↗

PubMed2005

Combined administration of intravenous dipyridamole and inhaled nitric oxide to assess reversibility of pulmonary arterial hypertension in potential cardiac transplant recipients.

BACKGROUND: Irreversible, severe pulmonary hypertension (PH) can produce right heart failure and early mortality after cardiac transplantation. We hypothesized that dipyridamole, an inhibitor of Type 5 phosphodiesterase, would augment the ability of inhaled nitric oxide (NO) to identify reversibility of PH. METHODS: In 9 patients with congestive heart failure (CHF) and severe PH who were breathing 100% oxygen during right heart catheterization, we administered inhaled NO (80 ppm) alone and in combination with intravenous dipyridamole (0.2-mg/kg bolus, with an infusion of 0.0375 mg/kg/min). RESULTS: Compared with breathing oxygen alone, NO inhalation decreased pulmonary artery pressure and pulmonary vascular resistance (PVR) (by 10 +/- 4% and 26 +/- 12% [mean +/- SEM], respectively; both p < 0.05). The combination of NO and dipyridamole reduced PVR (43 +/- 7%; p < 0.05) to a greater extent than did administration of NO alone, and increased the duration of pulmonary vasodilation produced by NO inhalation. Combined administration of inhaled NO and intravenous dipyridamole increased cardiac index (by 23 +/- 10%) and reduced SVR (by 19 +/- 6%, both p < 0.05) without changing systemic arterial pressure. NO inhalation reduced PVR to <200 dyne x s/cm5 in 3 of 7 patients who had a PVR of >200 dyne x s/cm5 when breathing oxygen alone, whereas the combination of NO and dipyridamole decreased PVR to <200 dyne.s/cm(5) in 2 additional patients. CONCLUSIONS: Intravenous dipyridamole augments and prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with severe PH and, when administered in combination with NO inhalation, can identify PH reversibility in potential cardiac transplant recipients in whom a pulmonary vasodilator response to inhalation of NO alone is not observed.

Administration, Inhalation↗

PubMed2004

Dipyridamole and headache--a pilot study of initial dose titration.

Headache is reported by about one third of patients using dipyridamole (DP) after stroke or TIA. No study has systematically examined if initial dipyridamole titration may affect this headache. We therefore randomised patients to (1) standard aspirin and dipyridamole treatment b.i.d. for 2 weeks or (2) titration with aspirin only in the morning and aspirin and dipyridamole in the evening for 5 days, followed by 9 days of standard aspirin and dipyridamole treatment. Among 57 patients included for analysis, moderate to severe headache was reported by 28% in the standard treatment group and 25% in the titration group (n.s.). Headache for more than two consecutive days occurred in 24% and 11%, respectively. Rescue medication because of headache for more than 2 days was used by 14% and 0% in the respective groups. The cumulative number of days with headache was more than twice as high in the standard treatment group. The total numbers of other side effects were 25 and 11 in the two groups. The observed differences in this pilot study were not statistically significant, but nevertheless suggest that titration with an initially lower dose of dipyridamole may be considered to reduce headache and thereby increase compliance. A larger study is needed to clarify this with sufficient statistical power.

Aged↗

PubMedDate not supplied

Relationship of transient ischemic dilation in dipyridamole myocardial perfusion imaging and stress-induced changes of functional parameters evaluated by Tl-201 gated SPECT.

BACKGROUND: This study assessed whether transient ischemic dilation (TID) of the left ventricle is related to ischemic stunning, manifested by stress-induced decrease of left ventricular ejection fraction (LVEF) and worsening of wall motion, by use of dipyridamole-stress and redistribution thallium 201 gated single photon emission computed tomography (SPECT). METHODS AND RESULTS: Ninety-two consecutive patients undergoing dipyridamole Tl-201 gated SPECT were included. Patients with a TID ratio in the highest quartile were defined as having TID. In patients with TID, end-diastolic volume (EDV) and end-systolic volume (ESV) were both significantly greater on dipyridamole-stress images than on redistribution images (P < .001). The degree of enlargement was much greater for ESV than EDV. In patients without TID, EDV and ESV were both decreased after stress (P < .001). Patients with TID had a lower mean LVEF on dipyridamole-stress images than on redistribution images (P < .001). Patients without TID had a higher mean LVEF on dipyridamole-stress images than on redistribution images (P < .001). Patients with TID had a significant worsening of global wall motion on dipyridamole-stress images than on redistribution images (P < .001), but patients without TID did not. CONCLUSION: TID was significantly correlated with ischemic stunning, and the enlargement of ESV was an important factor resulting in TID.

Aged↗

PubMed1997

Pharmacologic stress-induced regional myocardial blood flow heterogeneity and left ventricular wall thickening abnormality: comparison of intravenous adenosine with dipyridamole in a model of critical coronary stenosis.

Variations in reported sensitivity of myocardial perfusion scans or wall motion abnormalities during pharmacologic stress with intravenous adenosine and dipyridamole may be caused by differences in myocardial oxygen demand or myocardial blood flow redistribution induced by each agent. To investigate the physiologic correlates of functional abnormalities during pharmacologic stress testing, regional myocardial blood flow (radiolabeled microsphere technique) and left ventricular segmental wall thickening (quantitative two-dimensional echocardiography) were measured in 9 dogs with an open chest model of critical stenosis of the left circumflex coronary artery. Data were obtained at baseline and peak drug infusion for intravenous adenosine (0.42 mg/kg over a 3-minute period) and for intravenous dipyridamole (0.56 mg/kg over a 4-minute period). Adenosine and dipyridamole induced regional flow abnormality in 7 (77%) of 9 dogs. Myocardial segments with decreased endocardial/epicardial flow ratio were similar for both agents (2.9 +/- 1.8 vs 2.7 +/- 1.3, p = [NS]). Segments with myocardial flow heterogeneity (ratio of endocardial flow to control left anterior descending/left circumflex endocardial flow) were similar for both agents (2.7 +/- 0.9 vs 2.3 +/- 1.0, p = NS). Adenosine-induced wall thickening abnormality (77% vs 55% with dipyridamole) correlated with regional flow abnormality. Significantly lower mean arterial pressure (53 +/- 1.7 mm Hg vs 64 +/- 1.9 mm Hg, p < 0.01) and more prolonged drug effect (18 +/- 6.4 min vs 3 +/- 1.4 min, p < 0.001) were seen for dipyridamole compared with adenosine. Adenosine induces regional flow abnormality similar to dipyridamole but with less hemodynamic perturbation, and adenosine-induced wall thickening abnormality more closely parallels regional flow abnormality.

Adenosine↗

PubMed1983

Comparison of the antithrombotic action of calcium antagonist drugs with dipyridamole in dogs.

Because platelet activation is associated with fluxes of intracellular calcium, calcium antagonist drugs such as verapamil and nifedipine may have useful platelet inhibitor effects. Accordingly, the effect of these drugs was compared with that of dipyridamole, an established platelet inhibitor, in preventing the deposition of indium-111-labeled autologous platelets and thrombus development in polytetrafluoroethylene (Gore-Tex) grafts interposed in both femoral arteries in mongrel dogs. Eight dogs received verapamil 7.5 micrograms/kg/min perioperatively, 8 dogs received nifedipine 4 micrograms/kg/h perioperatively, 8 dogs received dipyridamole 50 mg orally given twice during the 24 hours before operation, and 16 control dogs received isotonic saline solution perioperatively. After 3 hours of perfusion, the median weight of the grafts and luminal thrombus was less in dogs treated with dipyridamole (465.1 mg), verapamil (453.7 mg), or nifedipine (389.7 mg) than in control dogs (680.2 mg) (p less than 0.001). In addition, the estimated total platelet deposition along the graft was reduced in dogs treated with dipyridamole was reduced in dogs treated with dipyridamole (2,073.2 X 10(6)) (p less than 0.01), verapamil (1,898.9 X 10(6)) (p less than 0.001), and nifedipine (1,474.8 X 10(6)) (p less than 0.001) as compared with controls (3,056.2 X 10(6)). When the mural thrombus was removed from 14 grafts, a median 73% of the platelets were located in the interface between thrombus and graft. We conclude that all 3 drugs prevent thrombus formation by inhibiting platelet activity in this model, and that the calcium antagonist drugs are as effective as dipyridamole.

Animals↗

PubMed1995

Dipyridamole echocardiography for diagnosis of coexistent coronary artery disease in hypertrophic cardiomyopathy. Echo-Persantine International Cooperative (EPIC) Study Group--Subproject Hypertrophic Cardiomyopathy.

The recognition of coexistent coronary artery disease (CAD) in patients with hypertrophic cardiomyopathy may be difficult by noninvasive testing based upon electrocardiographic changes or perfusion defects. Dipyridamole-stress echocardiography has proved a sensitive and highly specific test for noninvasive diagnosis of CAD in various patient subsets. To establish the feasibility, safety, and diagnostic accuracy of dipyridamole-stress echocardiography in patients with hypertrophic cardiomyopathy, we performed high-dose dipyridamole testing (up to 0.84 mg/kg over 10 minutes) in 88 patients with hypertrophic cardiomyopathy (63 men; mean age +/- SD, 46 +/- 17 years). A subset of 60 patients was referred for coronary angiography independently of test results; CAD was defined as > or = 50% diameter narrowing in at least 1 major coronary vessel. Dipyridamole echocardiography/electrocardiography testing was completed in all patients, with no limiting side effects or adverse reactions. In the subgroup of 60 patients with coronary angiography (14 with and 46 without CAD), chest pain occurred in 18 patients (8 with and 10 without CAD, p = NS); ST-segment depression > or = 2 mm from baseline in 28 (7 with and 21 without CAD, p = NS); and transient dyssynergy in 10 patients (10 with and none without CAD, p < 0.0001). Assuming the transient regional dyssynergy to be the only criterion of positivity, the dipyridamole echocardiography test showed 71% sensitivity, 100% specificity, 100% positive predictive value, and 93% diagnostic accuracy for diagnosis of angiographically assessed CAD. We conclude that high-dose dipyridamole echocardiography testing may be considered a feasible and accurate tool for the noninvasive diagnosis of CAD in patients with hypertrophic cardiomyopathy.

Adult↗