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PubMed2001

Dipyridamole inhibits TGF-beta-induced collagen gene expression in human peritoneal mesothelial cells.

BACKGROUND: Peritoneal matrix accumulation is characteristic of peritoneal fibrosis (PF). Continuous ambulatory peritoneal dialysis (CAPD) patients who had persistent transforming growth factor-beta (TGF-beta) in their drained effluent had an increased risk of PF. We previously reported that TGF-beta stimulates the expression of types I and III collagen mRNA in cultured human peritoneal mesangial cells (HPMCs), which may predispose them to develop PF. Pharmacological interventions to attenuate TGF-beta-stimulated matrix accumulation in HPMC may have therapeutic potential for the treatment of PF. The SMAD family and the extracellular signal-regulated protein kinase (ERK1/2, p44/p42) pathways have been shown to participate in TGF-beta signaling. Our current study identified these signal pathways in HPMCs and investigated the molecular mechanisms involved in the inhibitory effects of dipyridamole on TGF-beta-induced collagen gene expression in HPMCs. METHODS: HPMCs were cultured from human omentum by an enzyme digestion METHOD: Expression of collagen alpha1(I) mRNA was determined by Northern blotting. The SMAD proteins and the ERK1/2 activity were determined by Western blotting. RESULTS: TGF-beta-stimulated collagen alpha1(I) mRNA expression of HPMC was inhibited by dipyridamole in a dose-dependent manner. Smad2 and ERK1/2 were activated in response to TGF-beta; however, TGF-beta had little effect on the protein expression of Smad4. The addition of PD98059, which blocked activation of ERK1/2, suppressed TGF-beta-induced collagen alpha1(I) mRNA expression in a dose-dependent manner. At a concentration that inhibited collagen gene expression (17 microg/mL), dipyridamole suppressed ERK1/2 activation by TGF-beta. In contrast, the same concentration of dipyridamole had no effect on TGF-beta-induced activation of Smad2. CONCLUSION: Dipyridamole inhibits TGF-beta-induced collagen gene expression in HPMC through modulation of the ERK pathway. Our study of dipyridamole may provide therapeutic basis for clinical applications in the prevention of PF.

Cells, Cultured↗

PubMed2002

A comparative randomized and placebo-controlled short-term trial of aspirin and dipyridamole for overt type-2 diabetic nephropathy.

OBJECTIVE: Our aim was to determine the effect of short-term therapy with anti-platelet drugs on type-2 diabetic nephropathy for which a generally accepted therapy is missing. MATERIAL AND METHODS: Seventy-six patients with type-2 diabetic nephropathy, who had normal renal function tests were randomized into the 4 groups; each group (n = 19) received one of the following treatments: aspirin (1000 mg), dipyridamole (750 mg), their combination or placebo daily for 2 months. Blood pressure, fasting blood sugar, serum electrolytes, creatinine clearance and 24 hours urine protein excretion rate was measured just before and at the end of the trial. RESULTS: Proteinuria and urinary protein: creatinine ratio decreased significantly in all 3 groups receiving aspirin and/or dipyridamole compared with the placebo group, also in each of those 3 groups comparing pre- and post-treatment values, while creatinine clearance rate, blood pressure, and blood sugar remained unchanged. At the end of the trial, the percentage proteinuria change was-15.9%,-14.8%,-37.3% and 1.9% in aspirin, dipyridamole, their combination and placebo groups respectively. The percentage proteinuria change had no positive correlation with demographic, clinical and laboratory findings but showed a strong positive correlation with mode of the therapy (r = 0.38, p = 0.0007). The percentage decline in proteinuria was significantly higher in the combination group than in the aspirin and dipyridamole groups. No side effects related to aspirin or dipyridamole was seen during the trial. CONCLUSIONS: Short-term trial of aspirin and/or dipyridamole significantly reduces proteinuria of type-2 diabetic nephropathy, with the most prominent effect seen with combination of the 2 drugs.

Adult↗

PubMed1996

Protective effect of dipyridamole against lethality and lipid peroxidation in liver and spleen of the ddY mouse after whole-body irradiation.

The effects of dipyridamole on radiation damage in the mouse were investigated. Dipyridamole (i.p. 2 mg/mouse) administered 1 h before exposure, protected against gamma-irradiation. Pretreatment significantly decreased the death rate at 30 days from 89 to 33% (p<0.001) after 9 Gy whole-body irradiation. LD50 at 30 days was increased from 6.67 to 7.65 Gy in the dipyridamole pretreated group. The level of thiobarbituric acid reactive substances (TBARS) in the liver and spleen, a measure of free radical initiated liver peroxidation, increased 155, 193, 195, and 236% of control (without irradiation) in liver, and 132, 146, 168, and 276% of control (without irradiation) in spleen on days 2, 4, 7, and 10 after 9 Gy of whole-body irradiation respectively. The TBARS levels in both liver and spleen 2 days after irradiation were reduced to 73 +/- 7 and 60 +/- 19% respectively after dipyridamole treatment (2 mg/mouse, i.p. injection 1 h before exposure). In electron microscopic studies, mitochondria and endoplasmic reticulum in the irradiated mouse liver were swollen, but otherwise appeared normal after dipyridamole treatment. These results suggest that dipyridamole has a protective effect on animal survival 30 days after 60Co gamma-irradiation and inhibits lipid peroxidation - which is thought to play a part in the radiation injury in mouse liver and spleen.

Animals↗

PubMed1989

A comparison of myocardial thallium-201 image quality after either dipyridamole or exercise stress.

Exercise and dipyridamole provide two mechanistically different stress techniques for thallium-201 imaging. To date, comparisons of the two have relied solely on assessments of clinical results. However, because diagnostic accuracy ultimately depends on image quality, this study was undertaken to compare the image quality obtained by both techniques. The left anterior oblique images of 30 patients, who had thallium imaging after intravenous dipyridamole (0.56 mg kg-1 over 4 min) were compared with those of 30 patients who were imaged after symptom limited, Bruce protocol, treadmill exercise in the same time period. Myocardial and lung-background thallium uptake were compared after stress and on redistribution. The ratio of the best segmental myocardial thallium uptake (M) to that in a fixed lung-background region (B) was taken as an index (M/B) of image quality. Myocardial thallium uptake was significantly higher after dipyridamole than after exercise (P less than 0.001). Lung-background thallium uptake, however, was also higher (P less than 0.001) so that the resulting image quality indices (M/B) were similar (P = NS). The redistribution images gave the same results. In both techniques myocardial and lung-background thallium uptake counts dropped significantly from stress to redistribution images, but because they declined at similar rates, the resulting image quality index (M/B) remained unchanged. Adverse effects occurred less frequently in the dipyridamole stressed group. Thallium images performed after dipyridamole stress are at least equivalent in image quality to those after exercise stress. This technical study further strengthens the clinical case for the use of the dipyridamole stress technique in routine diagnostic imaging.

Dipyridamole↗

PubMed1993

A proischaemic action of nisoldipine: relationship to a decrease in perfusion pressure and comparison to dipyridamole.

OBJECTIVE: The calcium antagonist nisoldipine has recently been reported to induce rather than to attenuate ischaemia in some patients with stable angina. The aim of the study was to investigate the mechanisms underlying this proischaemic effect. METHODS: In 20 anaesthetised dogs systemic haemodynamic variables, regional myocardial blood flow (coloured microspheres), and systolic wall thickening (sonomicrometry) were measured during control conditions and following severe stenosis on the left circumflex coronary artery, before and after intravenous administration of equihypotensive doses of either nisoldipine (group I, n = 10) or dipyridamole (group II, n = 10). Finally, measurements were performed while the drug induced decreases in mean aortic pressure--18 (SD 6) mmHg in group I and 14(6) mm Hg in group II--were reversed by inflation of an intra-aortic balloon. RESULTS: The stenosis decreased posterior wall thickening to 50% of control, and posterior subendocardial blood flow from 1.48(0.27) to 0.61(0.19) ml.min-1.g-1 in group I and from 1.49(0.23) to 0.62(0.18) ml.min-1.g-1 in group II. Subendocardial blood flow was further decreased after administration of either nisoldipine [0.37(0.20) ml.min-1.g-1, p < 0.05 v stenosis] or dipyridamole [0.22(0.11) ml.min-1.g-1, p < 0.05 v stenosis]. Regional myocardial blood flow in the anterior region was increased. The drug induced reduction of subendocardial blood flow decreased posterior wall thickening further from 9.3(2.1) to 6.2(3.9)% (p < 0.05 v stenosis, group I) and from 9.1(1.7) to 4.3(2.4)% (p < 0.05 v stenosis, group II). When the drug induced decrease in aortic pressure was reversed, subendocardial blood flow again increased in group I [0.63(0.19) ml.min-1.g-1, p < 0.05 v stenosis and nisoldipine] whereas in group II it remained decreased [0.40(0.29) ml.min-1.g-1, NS v stenosis and dipyridamole]. There was restoration of posterior wall thickening in group I [10.4(3.8)%, p < 0.05 v stenosis and nisoldipine], but not in group II [5.2(3.5)%, NS v stenosis and dipyridamole]. CONCLUSIONS: Nisoldipine and dipyridamole decrease subendocardial blood flow and contractile function distal to a severe stenosis when aortic pressure is decreased. No aggravation of ischaemia by nisoldipine is seen when hypotension is prevented. In contrast, dipyridamole in the absence of hypotension still induces a redistribution of flow at the expense of the ischaemic region.

Animals↗

PubMed1991

Phase I and pharmacokinetic trial of intraperitoneal etoposide in combination with the multidrug-resistance-modulating agent dipyridamole.

Dipyridamole synergistically enhances the sensitivity of human ovarian carcinoma cells to etoposide in vitro. We conducted a phase I trial to investigate the feasibility of using dipyridamole to selectively increase the sensitivity to etoposide of tumors confined to the peritoneal cavity. Etoposide and dipyridamole were administered as a continuous 72-hour intraperitoneal infusion to 16 patients. The maximum tolerated dose of etoposide was 175 mg/m2 per day when administered with dipyridamole at a fixed dose of 24 mg/m2 per day. Dose-limiting toxic effects were leukopenia and thrombocytopenia. No other major toxic effects were observed. The free peritoneal etoposide and dipyridamole concentrations varied with the etoposide dose rate, reaching 218.9 and 25.3 microM, respectively, at an etoposide dose rate of 175 mg/m2 per day. The free etoposide and dipyridamole concentrations attained were well within the range needed for synergistic interaction.

Adult↗

PubMed1997

Assessment of coronary reserve by transoesophageal Doppler echocardiography. Direct comparison between different modalities of dipyridamole and adenosine administration.

BACKGROUND: This study was undertaken to compare the coronary vasodilator response to different application modalities of intravenous vasodilators, in order to identify the optimal pharmacological protocol for the evaluation of coronary reserve by means of transoesophageal Doppler echocardiography. METHODS: Blood flow velocity in the left anterior descending artery, coronary vascular resistance and left main coronary artery cross-sectional area were assessed by transoesophageal echo-Doppler during an i.v. adenosine bolus (5 mg), a 5-min adenosine infusion (infusion rate 140 micrograms. kg-1 min-1), and low (0.56 mg.kg-1. 4 min-1), and high-dose (0.84 mg.kg-1.9 min-1) dipyridamole infusions in 10 healthy normals (Group 1) and in 20 patients (Group 2) with either coronary microvascular disease (11 patients) or coronary artery disease (nine patients). RESULTS: In both groups, the highest flow velocity and the lowest coronary vascular resistance were observed during the adenosine infusion. Flow velocity values and indices of coronary vasodilator capacity observed after the adenosine bolus and the high-dose dipyridamole infusion were very close to those obtained during the adenosine infusion, especially in Group 1. Coronary flow velocity was lower and coronary vascular resistance higher after low-dose dipyridamole, significantly in Group 2. The maximal flow response to the adenosine bolus was observed within a few seconds after the injection, and was very short. The peak response to the adenosine infusion was observed 57 +/- 27 s after its start. The coronary flow velocity response to dipyridamole was dose dependent and differed between Groups 1 and 2. CONCLUSION: In combination with transoesophageal Doppler echocardiography, a short-lasting adenosine infusion at a rate of 140 micrograms.kg-1.min-1 seems to be preferable to an adenosine bolus and dipyridamole infusion. The effect of the bolus is too short for an accurate measurement of coronary flow velocity, while the dipyridamole infusion, especially at a low dose, induces a submaximal vasodilator response.

Adenosine↗

PubMed1992

Pharmacological stress echocardiography in the diagnosis of coronary artery disease and myocardial ischaemia: a comparison between dobutamine and dipyridamole.

The objective of this study was to relate regional wall motion abnormalities assessed by dobutamine and dipyridamole stress echocardiography to quantitative measurements of coronary artery stenoses in consecutive patients referred for coronary angiography, and to compare haemodynamic effects of and complications related to the two agents. Patients underwent stress echoes on separate days in random sequence and had coronary angiography within 3 days of stress echocardiography. Echocardiograms were assessed by two investigators unaware of the patients' coronary anatomy. Coronary angiograms were also assessed quantitatively using the computer-assisted Cardiovascular Angiography Analysis System. There were 46 consecutive patients referred for coronary angiography; 28 were using beta-antagonists. Main outcome measures were sensitivity and specificity for dobutamine and dipyridamole stress echocardiography for detection of coronary artery disease (wall motion abnormalities at rest or stress) and myocardial ischaemia (stress induced new wall motion abnormalities). Sensitivity for the detection of myocardial ischaemia was found to be 57% for dobutamine and 64% for dipyridamole. Specificities were 78% and 89% respectively. Sensitivities for detection of coronary artery disease (lesion > or = 50% diameter stenosis) was 79% for dobutamine and 82% for dipyridamole; specificities were 78% and 89% respectively. These differences between the two agents are not significant. There were no severe side effects with either agent. Mean heart rate rose significantly with both tests but was higher with dobutamine; mean systolic blood pressure rose with dobutamine and fell with dipyridamole. It was concluded that dobutamine and dipyridamole stress echocardiography have similar sensitivities and specificities for detection of myocardial ischaemia and coronary artery disease although the haemodynamic effects of the two agents are different. Both are free from serious complications.

Adult↗

PubMed1995

Dipyridamole slows the rate of isovolumic pressure fall in patients with normal coronary arteries.

Dipyridamole is currently used for thallium imaging and stress echocardiography. The coronary and haemodynamic effects of dipyridamole are well documented while its effects on left ventricular relaxation remain to be determined. The aim of the present study was to evaluate the effects of dipyridamole on left ventricular relaxation rate in healthy subjects. High fidelity pressure recordings were obtained at fixed atrial pacing (89 +/- 2 beats.min-1) in 10 subjects with normal left ventricular angiography and coronary arteriograms. Left ventricular pressure was recorded at rest and 5 min after a 4 min infusion of dipyridamole (0.14 mg.kg-1.min-1). Dipyridamole infusion decreased left ventricular systolic pressure (P < 0.01) and time to left ventricular systolic pressure (P < 0.01), with no changes in end-diastolic pressure or peak rate of pressure rise. The peak rate of isovolumic pressure fall decreased (from 1957 +/- 105 to 1488 +/- 100 mmHg.s-1, P < 0.01) and the time constant of isovolumic relaxation increased (from 37 +/- 2 to 44 +/- 3 ms, P < 0.02). In conclusion, our study indicates that acute administration of clinically relevant doses of dipyridamole displays deleterious effects on heart relaxation in healthy humans.

Arteries↗

PubMed1995

Protective effect of beta-blockade on dipyridamole-induced myocardial ischaemia. Role of heart rate.

This study was designed to investigate the effect of heart rate changes on dipyridamole echocardiographic tests in patients with coronary artery disease treated with propranolol. We prospectively studied 12 patients (8 men and 4 women; mean age 56.5 +/- 8.7 years) selected by: (a) angiographic evidence of significant coronary artery disease; (b) adequate echocardiographic window; (c) positive dipyridamole echocardiography test results in baseline conditions (step I); (d) test reproducibility in the absence of treatment; (e) negative dipyridamole echocardiography test results after 7 days of treatment with propranolol (120 mg.day-1) in twice divided doses daily (step II). In all patients treated with propranolol, dipyridamole echocardiographic testing was repeated 24 h after the last negative test. In these patients, transoesophageal atrial pacing was performed at peak dipyridamole infusion to increase heart rate to values similar to those observed at baseline (step III). At baseline, heart rate and rate-pressure product were significantly lower in patients treated with propranolol (-20.3% and -22.5% in group II, P < 0.001 vs step I; -24.3% and -26.4% in group III, P < 0.05 vs step I), but the different treatments did not produce significant differences in systolic and diastolic blood pressure. At peak dipyridamole infusion, heart rate and rate-pressure product increased with either placebo or propranolol treatments with respect to baseline, while remaining significantly lower with propranolol as compared to placebo (-29.6% and -29.5% in step II, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1991

Increased prevalence of ventricular arrhythmias in essential hypertensives with dipyridamole-induced ischemic-like S-T segment changes.

Essential hypertensives are at greater risk for ventricular arrhythmias than normotensive controls. A reduction in coronary flow reserve may be one of the mechanisms underlying this increased prevalence of ventricular dysrhythmias in hypertensives. It has previously been shown that dipyridamole infusion may provoke ischemic-like S-T segment depression in essential hypertensives with angiographically normal coronary arteries and reduced flow reserve. The aim of the present study was to assess whether electrocardiographic positivity (S-T segment depression greater than 0.1 mV from baseline) during dipyridamole testing (12-lead electrocardiogram and two-dimensional echomonitoring, with the infusion of 0.84 mg/kg dipyridamole over 10 min) might identify hypertensives at greater risk for ventricular dysrhythmias. We therefore studied 51 mild-to-moderate essential hypertensives by dipyridamole testing and 48-h Holter monitoring. All patients were off therapy for at least 2 weeks before testing and Holter evaluation. Left ventricular mass (by Penn convention) and ejection fraction (by Teichholtz rule) were evaluated by two-dimensional echocardiography. Lown classes 0-1 were found in 31 patients (Group 1) and Lown classes II-IV in 20 (Group 2). The two groups overlapped for mean blood pressure (121 +/- 9 versus 124 +/- 8 mmHg), left ventricular mass index (120 +/- 27 versus 141 +/- 42 g/m2) and left ventricular ejection fraction (54 +/- 6 versus 52 +/- 6). An electrocardiographically-positive dipyridamole test was found in seven of Group I and 16 of Group II patients (23 versus 80%, P less than 0.01). No patient showed a transient, either regional or global, systolic dysfunction during dipyridamole testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

PubMed1999

Verapamil reduces dipyridamole-induced myocardial ischemia in patients with coronary artery disease.

The aim of this study was to evaluate the effects of verapamil administration on dipyridamole-induced transient wall-motion abnormalities as detected by two-dimensional echocardiographic monitoring in patients with coronary artery disease. Twenty-eight patients (16 men and 12 women; mean age, 60+/-7 years) with angiographic evidence of significant coronary artery disease, positive dipyridamole echocardiography test results at basal condition on two consecutive days, were prospectively studied. Patients were randomized to verapamil (360 mg/day) or placebo treatments, given in three divided doses daily for 7 days; at the end of this time, each patient crossed over to the alternate regimen. Dipyridamole echocardiographic testing was repeated at the end of each treatment period. Our data demonstrate that verapamil significantly reduces the dipyridamole-induced wall-motion score index, a quantitative marker of acute myocardial ischemia (1.7+/-0.4 vs. 1.3+/-0.2; p<0.001). Hemodynamic data show that the drug reduces heart rate and rate-pressure product at basal condition (heart rate from 75+/-8 to 67+/-9 beats/min; p<0.001; rate-pressure product from 99+/-13 to 86+/-13 U x 10(-2); p<0.001) and at peak dipyridamole infusion (heart rate from 96+/-8 to 89+/-6 beats/min; p<0.001; rate pressure product from 127+/-21 to 118+/-13 U x 10(-2); p<0.05) with respect to placebo treatment. We conclude that verapamil is able to reduce dipyridamole-induced ischemia, as detected by two-dimensional echocardiographic monitoring, in patients with coronary artery disease by reducing, at least partially, myocardial oxygen consumption. Moreover, its beneficial action could be related to the effects of the drug on coronary collateral circulation and on sympathetic modulation.

Aged↗

PubMed2000

Echo-dipyridamole stress test evaluation of isosorbide-5-mononitrate efficacy and tolerance in patients with coronary heart disease: interplay with sympathetic activity.

In 22 patients with stable myocardial ischemia, we prospectively studied the short- and long-term effects of isosorbide-5-mononitrate (5-ISMN) on dipyridamole-induced myocardial ischemia, the ability of dipyridamole-stress echocardiography to evaluate nitrate tolerance, and the role of activation of the neurohumoral system in nitrate tolerance development, assessed by modifications of catecholamines plasma levels and heart rate variability. After brief treatment with 5-ISMN, dipyridamole-stress echocardiography was negative in 19 of 22 patients (p < 0.001 vs. placebo). During the sustained phase, dipyridamole-stress echocardiography was positive after both placebo and active drug (p = NS vs. placebo). Heart rate variability showed significantly higher values in power of the low frequency (LF) band and low- to high-frequency ratio (L/H), as well as significantly lower values of the power of the high-frequency (HF) band (all p < 0.001) during brief but not during sustained administration of 5-ISMN. Norepinephrine plasma levels were significantly higher (p < 0.001) during short-term 5-ISMN administration but not during the sustained phase. Our results indicate that short-term administration of 5-ISMN antagonizes dipyridamole-induced myocardial ischemia and show the loss of antiischemic efficacy in 95% of patients during sustained treatment, demonstrating that dipyridamole-stress echocardiography is a useful tool to assess the presence of nitrate tolerance. Spectral analysis of heart rate variability and norepinephrine values confirm that brief nitrate administration increases sympathetic activity, a possible crucial trigger event in the development of nitrate tolerance, whereas prolonged nitrate treatment is not associated with prolonged neurohumoral activation.

Aged↗

PubMed1999

The effects of dipyridamole stress test on plasma levels of soluble adhesion molecules intracellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and L-selectin in patients with ischemic heart disease and patients with syndrome X.

BACKGROUND: Adhesion of activated leukocytes to the endothelium as a result of myocardial ischemia/reperfusion has been shown to be involved in the development of tissue injury. Leukocyte adhesion to the endothelium occurs via adhesion molecules expressed on the surface of both cell types. Upon cell activation these proteins may be released into the circulation and measured in a soluble form. AIM: To verify whether the dipyridamole stress test, performed in patients with ischemic heart disease (IHD) and in patients with syndrome X, modifies plasma levels of the soluble adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin and L-selectin. METHODS: Plasma levels of the soluble endothelial adhesion molecules ICAM-1, VCAM-1 and E-selectin, as well as of the soluble leukocyte adhesion molecule L-selectin, were measured in venous blood samples taken before and 7 min after administration of dipyridamole in patients with IHD, patients with syndrome X and healthy individuals. Myocardial perfusion was evaluated using single photon emission tomography. The plasma levels of soluble VCAM-1, ICAM-1, E-selectin and L-selectin were all measured using enzyme-linked immunosorbent assays. RESULTS: After infusion of dipyridamole, plasma levels of ICAM-1 increased significantly in patients with IHD, whereas they remained unchanged in patients with syndrome X and in the control group. In patients with IHD, the initial plasma levels of VCAM-1, E-selectin and L-selectin, before administration of dipyridamole, were higher than those observed in patients with syndrome X and than those in the control group. Plasma levels of soluble VCAM-1, E-selectin and L-selectin decreased significantly in patients with IHD following the dipyridamole stress test, whereas they remained unchanged in patients with syndrome X, and in the control group. CONCLUSION: In patients with IHD, administration of dipyridamole induces myocardial ischemia resulting in modification of plasma levels of the soluble adhesion molecules.

Adult↗

PubMed2002

Dipyridamole myocardial perfusion single photon emission computed tomography in patients with slow coronary flow.

OBJECTIVE: Several studies have indicated that the velocity of contrast dye increases after intravenous dipyridamole infusion in patients with a slow-flow pattern (SFP). In this study we compared the results of coronary arteriography and exercise myocardial perfusion single photon emission computed tomography (SPECT) in patients with SFP. We also investigated the changes in myocardial perfusion in patients with abnormal exercise myocardial perfusion SPECT by using a pharmacological stress test with dipyridamole. DESIGN AND PATIENTS: This study included 60 patients who revealed SFP in their coronary arteriograms. Slow coronary flow diagnoses were made using the frame count method. A single day rest-exercise technetium-99m hexakis-2-methoxy-isobutyl isonitrile (Tc-99m MIBI; Du Pont Pharma SA, Belgium) SPECT was performed in all patients. Patients who had reversible perfusion defect (RPD) on the exercise SPECT were evaluated with dipyridamole myocardial perfusion scintigraphy. RESULTS Patients with SFP revealed both higher frame counts in native coronary arteries and higher mean frame counts. The coronary frame count was 26.4 +/- 3.5 in control patients and 64.40 +/- 16.64 in patients with SFP, respectively (P < 0.001). Exercise perfusion SPECT showed RPD in 17 patients (group 1), but was normal in 43 others (group 2). There were no statistically significant differences between groups 1 and 2 in frame counts. Myocardial perfusion was normalized in all 17 patients of group 1 after dipyridamole infusion. CONCLUSIONS: In patients with SFP perfusion, changes may improve with dipyridamole infusion. This study indicates that this improvement can be shown by dipyridamole SPECT. Furthermore, no correlation was observed between the time needed to fill a native coronary artery and RPD of the myocardium.

Coronary Angiography↗

PubMed2006

Effects of long-term oral dipyridamole treatment on coronary microcirculatory function in patients with chronic stable angina: A substudy of the persantine in stable angina (PISA) study.

AIMS: A meta-analysis of 13 randomized placebo-controlled trials demonstrated a benefit for dipyridamole therapy, particularly with longer duration of treatment. Although the mechanism of this effect is not well understood, dipyridamole increases endogenous tissue adenosine, which may have a beneficial effect on myocardial perfusion. Therefore, we measured the effects of dipyridamole on myocardial blood flow (MBF) and coronary flow reserve (CFR) by using positron emission tomography and H2O in patients with coronary artery disease. METHODS: Forty-four patients with angiographically documented coronary artery disease were double-blind randomized to either oral dipyridamole [200 milligrams (mg) twice daily (bd)] or placebo as add-on to conventional antianginal treatment for 24 weeks. MBF was measured at rest and during dobutamine stress at baseline and study completion for the region subtended by the most severe coronary artery stenosis (Isc) and remote myocardium subtended by arteries with minimal or no disease (Rem). CFR was calculated as MBF-peak/MBF-rest. RESULTS: Thirty-five patients completed the study. Isc MBF-rest decreased in patients receiving dipyridamole (0.10 mL/minute/g; P = 0.03) and increased in the placebo group (0.16 mL/minute/g; P = 0.01) during the 24-week study. No significant change in MBF-peak was demonstrated in either group. Consequently, Isc-CFR increased significantly in patients receiving dipyridamole (1.65 +/- 0.47 vs 1.83 +/- 0.67; P < 0.05). By contrast, Isc-CFR decreased significantly in those receiving placebo (1.74 +/- 0.44 versus 1.38 +/- 0.46; P < 0.03). No change was seen in Rem-CFR territories. CONCLUSIONS: At the end of treatment, a reduction in baseline MBF but no significant changes in hyperemic MBF were observed in ischemic myocardial territories, and therefore the significance of the observed improvement in CFR remains unclear.

Administration, Oral↗

PubMed1995

Dipyridamole combined with tumor necrosis factor-alpha enhances inhibition of proliferation in human tumor cell lines.

In the search for cytokines whose antiproliferative action could be enhanced by combination with dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrim idine, the combination of tumor necrosis factor-alpha (TNF-alpha) with this agent was evaluated in various human tumor cell lines. Inhibition of the proliferation of human melanoma cell lines MM-1CB and HMV-1 by TNF-alpha (1-10(2) U/ml) was enhanced in culture dishes by combination treatment with dipyridamole (0.1-10 microM). The enhancement effect was also detected in other tumor cell lines: T98 (glioma), SCC-1CB (squamous cell carcinoma), HAC-2 (ovarian clear-cell carcinoma), HLE (hepatoma), HEC-1 (endometrial adenocarcinoma) and HOC-21 (ovarian serous cystadenocarcinoma). The incorporation of [14C]amino acids and [3H]uridine into acid-insoluble cell materials in the combination-treated cells was not significantly different from that in cells treated with TNF-alpha or dipyridamole. However, the incorporation of [3H]thymidine was specifically inhibited in all cell lines examined after more than 12 h of the TNF-alpha and dipyridamole combination treatment, although neither agent alone inhibited this incorporation. On the other hand, the growth of tumors induced by the injection of MM-1CB and HMV-1 cells into nude mice was more markedly inhibited by the subcutaneous administration of TNF-alpha in combination with orally administered dipyridamole than by either agent alone. The results presented suggested that dipyridamole is beneficial in assuring the effectiveness of anti-cancer cytokine therapy.

Amino Acids↗

PubMed1983

Dipyridamole increases red cell deformability.

The effects of dipyridamole on red cell filterability both in vitro and ex vivo were measured. In a balanced, randomised and double-blind trial, six healthy male and female volunteers (22-37 years) were given dipyridamole 400 mg/day or matching placebo in four divided doses for 3 days, and heparinised venous blood samples were taken 1 h after the ingestion of the last dose. Filterability of red cells was increased significantly (P less than 0.05 paired t-test) when the subjects were on dipyridamole compared with placebo. In separate experiments, 15 min incubation with 2 or 20 micrograms/ml dipyridamole in vitro was found to have no effect on the filterability of freshly prepared red cell suspensions. After 24 h storage at 4 degrees C, the filterability of red cells was significantly decreased (P less than 0.01) and this could be partially prevented by adding dipyridamole to the stored cells (P less than 0.05). These results suggest that dipyridamole has an effect on the behaviour of the red cell membrane to increase the deformability of the cells. This may contribute to its therapeutic effect.

Adult↗