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PubMed1990

Dipyridamole radionuclide ventriculography in patients with coronary artery disease: comparison with ergometer exercise.

Intravenous administration of dipyridamole during radionuclide ventriculography (RNV) was performed in 26 consecutive patients with symptomatic coronary artery disease. The authors compared the results of dipyridamole-RNV with those of ergometer exercise-RNV in detecting myocardial ischemia. During exercise, ST depression, regional wall motion (RWM) abnormalities, and decreased left ventricular ejection fraction (LVEF) were observed in 21 (81%), 23 (88%), and 20 (77%) patients, respectively. However, after intravenous dipyridamole, ST depression, RWM abnormalities, and decreased LVEF were observed in 14 (54%), 15 (58%), and 2 (8%) patients, respectively. Although LVEF usually decreases during myocardial ischemia, LVEF did not decrease (57 +/- 11% to 58 +/- 10%), even in patients with ST depression, after intravenous dipyridamole. Maintained left ventricular ejection fraction is considered to be a hemodynamic effect of the potent arterial vasodilatation induced by dipyridamole. These results from dipyridamole-RNV in myocardial ischemia seem to conflict with the results from dipyridamole-thallium studies carried out to determine the capacity to detect coronary artery disease. Unknown mechanisms of dipyridamole other than the coronary steal phenomenon may be operative in the genesis of myocardial ischemia.

Coronary Disease↗

PubMed1997

Dipyridamole-induced angina pectoris during sestamibi stress test in patients with significant coronary artery disease: clinical, angiographic, and nuclear determinants.

Intravenous dipyridamole induces angina pectoris (AP) in some patients with significant coronary artery disease (CAD). The aim of this prospective study was to identify the angiographic, nuclear, and clinical determinants. The authors examined 50 patients consecutively with significant CAD on coronary angiography. All antiischemic medications were stopped twenty-four hours (nitrates only 6 hours) before injection of dipyridamole (0.84 mg/kg). ECGs were taken before, during, and after this injection. The regional myocardial activity of Tc-99m-Sestamibi at rest and after dipyridamole injection was measured with single-photon emission computed tomography (SPECT). During dipyridamole injection 20 patients had AP, of whom 15 had ST segment depression on ECG (P < 0.001). The only significant difference on coronary angiography between patients with dipyridamole-induced AP and those without AP was the presence of collaterals (P < 0.05). In patients with AP and collaterals, ECG and SPECT changes were always noted in the collateralized territory. Subgroup analysis showed that patients without previous myocardial infarction (MI, n = 17, P < 0.05) or nontransmural MI (n = 17, P < 0.05) had a good correlation between collaterals and AP, whereas patients with a history of transmural MI (n = 16) did not. No further significant variables could be found as a predictor of AP after dipyridamole injection. These findings suggest that AP during dipyridamole stress test is due to ischemia, which is not related to the severity of CAD. Ischemia is probably due to coronary steal to the collateralized territory in patients without transmural MI. Dipyridamole-induced angina pectoris is predictive for collaterals and may indicate viability in patients with MI.

Angina Pectoris↗

PubMed2001

Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells.

Sickling-induced cation fluxes contribute to cellular dehydration of sickle red blood cells (SS RBCs), which in turn potentiates sickling. This study examined the inhibition by dipyridamole of the sickling-induced fluxes of Na(+), K(+), and Ca(++) in vitro. At 2% hematocrit, 10 microM dipyridamole inhibited 65% of the increase in net fluxes of Na(+) and K(+) produced by deoxygenation of SS RBCs. Sickle-induced Ca(++) influx, assayed as (45)Ca(++) uptake in quin-2-loaded SS RBCs, was also partially blocked by dipyridamole, with a dose response similar to that of Na(+) and K(+) fluxes. In addition, dipyridamole inhibited the Ca(++)-activated K(+) flux (via the Gardos pathway) in SS RBCs, measured as net K(+) efflux in oxygenated cells exposed to ionophore A23187 in the presence of external Ca(++), but this effect resulted from reduced anion conductance, rather than from a direct effect on the K(+) channel. The degree of inhibition of sickling-induced fluxes was dependent on hematocrit, and up to 30% of dipyridamole was bound to RBC membranes at 2% hematocrit. RBC membrane content of dipyridamole was measured fluorometrically and correlated with sickling-induced flux inhibition at various concentrations of drug. Membrane drug content in patients taking dipyridamole for other clinical indications was similar to that producing inhibition of sickling-induced fluxes in vitro. These data suggest that dipyridamole might inhibit sickling-induced fluxes of Na(+), K(+), and Ca(++) in vivo and therefore have potential as a pharmacological agent to reduce SS RBC dehydration. (Blood. 2001;97:3976-3983)

Anemia, Sickle Cell↗

PubMed2002

Intravenous dipyridamole enhances the effects of inhaled nitric oxide and prevents rebound pulmonary hypertension in piglets.

Inhaled nitric oxide (NO) is increasingly used in the treatment of pulmonary hypertension, despite its potential toxicity and the risk of life-threatening rebound pulmonary hypertension upon its discontinuation. We investigated whether i.v. dipyridamole, a cGMP phosphodiesterase inhibitor, increased the effects of inhaled NO and prevented rebound pulmonary hypertension. In 14 anesthetized and mechanically ventilated piglets, pulmonary hypertension was induced with U-46619, a thromboxane A(2) analogue. Response to NO and rebound pulmonary hypertension were evaluated without and with i.v. dipyridamole. Low-dose dipyridamole (10 micro g/kg/min) increased cardiac output and augmented the effects of inhaled NO on pulmonary vascular resistance, with marginal additive effect on mean pulmonary artery pressure. Pulmonary vascular resistance decreased from 904 to 511 (20 parts per million NO) (p < 0.0005) and 358 dyne s cm(-5) (20 parts per million NO + dipyridamole) (p < 0.001 versus NO alone), and mean pulmonary artery pressure decreased from 29.0 to 20.5 (p < 0.0001) and 19.3 mm Hg (NS versus NO), respectively. Mean arterial pressure decreased from 85 to 74 mm Hg (dipyridamole + NO) (p < 0.01). High-dose dipyridamole (100 micro g/kg/min) with inhaled NO reduced pulmonary vascular resistance to 334 dyne s cm(-5) but also decreased mean arterial pressure to 57 mm Hg. Eight piglets developed rebound pulmonary hypertension. Two died of acute right ventricular failure and, in five, rebound pulmonary hypertension was prevented by low-dose dipyridamole. In conclusion, low-dose i.v. dipyridamole augments the effects of inhaled NO on right ventricular afterload with moderate changes in systemic hemodynamics, and can prevent rebound pulmonary hypertension.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2001

Near-field amplification of antithrombotic effects of dipyridamole through vessel wall cells.

Many studies have demonstrated that dipyridamole is not purely an antiplatelet agent but also exerts its antithrombotic properties through the vessel wall. Using a laboratory model in which bovine endothelial cells are seeded to form a subendothelial matrix (SEM), investigators have shown that dipyridamole enhances the antithrombotic action of the endothelium, probably by increasing intracellular levels of cAMP and cGMP through phosphodiesterase inhibition. If so, the antithrombotic action of dipyridamole should also be observable away from the endothelium itself, i.e., a near-field effect. To test this hypothesis, we reseeded the SEM with a monolayer of human umbilical vein endothelial cells (hUVECs), occluding a portion of the SEM with teflon stops. We then treated the SEM with and without hUVECs with various doses of dipyridamole and exposed them to whole blood under flow conditions. Human endothelial cells cultured on the SEM increased its ability to reduce thrombus formation in the adjacent SEM. Dipyridamole enhanced this antithrombotic effect of hUVECs in a dose-dependent manner. No increment in antithrombotic effect was seen in dipyridamole-treated SEM without hUVECs. We therefore conclude that endothelial cells have near-field antithrombotic properties that are enhanced by dipyridamole. Possible explanations for the near-field enhancement effect of dipyridamole are discussed in light of the published literature.

Cells, Cultured↗

PubMed2001

Inhibition of thrombus formation by low-dose acetylsalicylic acid, dipyridamole, and their combination in a model of platelet-vessel wall interaction.

Effects of low-dose acetylsalicylic acid (ASA, 50 mg/day), dipyridamole (sustained-release preparation 400 mg/day), and their combination were investigated in a model of human platelet-vessel wall interaction. In a randomized, double-blind clinical pharmacology trial in 96 healthy subjects, the inhibition of mural platelet thrombus was measured ex vivo using blood samples collected both before and 2 hours after a 3.5-day treatment with ASA, dipyridamole, ASA combined with dipyridamole, or placebo. Both the size and the number of platelet thrombi adherent to a thrombogenic matrix after a 15-minute flow experiment were identified by automated fluorescence microscopy. ASA treatment alone reduced the mean size of all thrombi by about 45%, and dipyridamole alone achieved an approximate 17% reduction in the mean size of all thrombi. The combination of both agents had an additive effect. Formation of the subpopulation of very large thrombi was reduced by ASA and dipyridamole to a similar extent, with their combination producing an effect at least twice as strong as that witnessed in a single treatment. These results suggest that ASA and dipyridamole affect platelet thrombus growth by different mechanisms of action. These findings provide the pharmacologic rationale for the combination of ASA (suppressing the synthesis of prothrombotic thromboxane A2) and dipyridamole (by feedback inhibition of platelet activation via local accumulation of adenosine) as a highly effective and safe combination for secondary prevention of stroke. They are consistent with the clinical findings of the Second European Stroke Prevention Study (ESPS-2). In this large trial, the addition of dipyridamole (400 mg/day in a sustained-release preparation) to aspirin (50 mg/day) doubled the efficacy of aspirin in the secondary prevention of stroke without increasing the risk for bleeding.

Aspirin↗

PubMed2003

Intermittent nitric oxide combined with intravenous dipyridamole in a piglet model of acute pulmonary hypertension.

UNLABELLED: Continuous administration of inhaled nitric oxide is now widely used as a potent and selective pulmonary vasodilator. We have evaluated the effects of IV dipyridamole, a cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor, on the magnitude and duration of action of inhaled nitric oxide (NO)-mediated pulmonary vasodilation. We hypothesized that inhibition of cGMP degradation could augment and prolong the pulmonary vasodilating effects of NO and allow for intermittent NO inhalation. In eight anesthetized and mechanically ventilated piglets, IV U-46619, a thromboxane A(2) analog, was used to induce pulmonary hypertension. The effects of 2, 5, and 10 ppm of NO, delivered during 4 min for each concentration and followed by a 10-min NO-free interval after each NO concentration, were evaluated without and with dipyridamole. Pulmonary vascular resistance decreased from 825 +/- 49 dynes. s. cm(-5) (U-46619) to 533 +/- 48 dynes. s. cm(-5) (10 ppm NO) (P < 0.05 versus U-46619) and 396 +/- 42 dynes. s. cm(-5) (dipyridamole 10 microg kg-1x min-1 and 10 ppm NO) (P <0.05 versus NO), and cardiac output increased from 1.93 +/- 0.09 L/min to 2.03 +/- 0.13 L/min and 2.60 +/- 0.30 L/min (P < 0.05 versus NO). Mean arterial blood pressure decreased from 90 +/- 5 mm Hg (10 ppm NO) to 75 +/- 3 mm Hg (dipyridamole plus 10 ppm NO) (P < 0.01). The pulmonary vasodilation obtained with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by 72%. We conclude that dipyridamole augments the effects of NO on right ventricular afterload, allows for intermittent NO inhalation, and can significantly reduce exposure to NO. IMPLICATIONS: IV dipyridamole prolongs the action of inhaled nitric oxide (NO) in a piglet model of acute pulmonary hypertension. Intermittent NO inhalation combined with IV dipyridamole decreases pulmonary artery pressure for a prolonged period of time and reduces exposure to NO.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1995

A longitudinal evaluation of dipyridamole drug use in an ambulatory elderly population.

STUDY OBJECTIVE: To determine the pattern of dipyridamole use over the past 14 years. DESIGN: A longitudinal health screening program of ambulatory elderly participants was used to study changes in dipyridamole drug use. Participants included all subjects screened in the Florida Geriatric Research Program since 1978. The main outcome measure in this study was self-reported dipyridamole use at every visit to the program since August 1, 1978. RESULTS: A total of 3.6% of men (mean age, 82.6 years) and 3.4% of women (mean age, 80.8 years) reported the use of dipyridamole in the 1991-1992 period. The prevalence of dipyridamole use ranged from a low of 1.6% in 1978-1979 to a high of 7.3% in 1986-1987. There was a significant increase in the use of this drug from 1978-1979 to 1991-1992 (p < 0.038). Over the 14-year period of study, the percent of subjects using dipyridamole concurrently with coumarin anticoagulants ranged from a low of 5.8% to a high of 17.9%. CONCLUSIONS: The level of dipyridamole use in this elderly population has increased since 1978-1979. The only FDA indication for this drug is in combination with coumarin anticoagulants to prevent postoperative thromboembolic complications of cardiac valve replacement. Less than 20% of patients in this study used the drug in combination with coumarin anticoagulants. Educational programs are needed to improve the prescribing of dipyridamole.

Aged↗

PubMed1996

Effect of dipyridamole on vascular responses of porcine ciliary arteries.

This study investigated the effects of dipyridamole in isolated porcine ciliary arteries (diameter 200-250 microns). Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. Dipyridamole induced concentration-dependent relaxations of porcine ciliary arteries with endothelium precontracted with thromboxane analogue U-46619 (10(-6)M), KCl (50 mM), or endothelin-1 (10(-8)M). Removal of the endothelium of the ciliary vessels and preincubation of the arteries with L-NAME (10(-5)M), or indomethacin (10(-5)M), or the combination of the two drugs significantly reduced the relaxation to dipyridamole (p = 0.002-0.03). Similar vascular responses could be observed in a time-dependent analysis of the effect of a single concentration dipyridamole (10(-4)M). The stimulator of cAMP forskolin also caused relaxations. Endothelin-1 (10(-12)-10(-7)M) and U-46619 (10(-10)-10(-6)M) induced potent contractions of porcine ciliary arteries. Preincubation with dipyridamole (10(-5)M) reduced contractions to endothelin-1 as compared to control (p < 0.004), while contractions to U-46619 were only slightly affected under these conditions (n.s.). These findings demonstrate that dipyridamole is a vasodilator in porcine ciliary arteries. Endothelial nitric oxide and prostacyclin contribute importantly to the effects of dipyridamole. Further studies are required to show whether these properties of dipyridamole may also occur in vivo and offer clinical use in patients with ocular vasospasms and other ophthalmic vascular dysfunctions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2005

Dipyridamole for renal phosphate leak in successfully renal transplanted hypophosphatemic patients.

AIM AND BACKGROUND: Hyphosphatemia can be seen in renal transplant recipients. Hyperparathyroidism, glucocorticoid treatment, renal denervation and impairment of renal tubular phosphate reabsorption are the most common causes of hyphosphatemia in these patients. It is well-known that dipyridamole enhances renal tubular phosphate reabsorption in some clinical conditions. We did not find any information about the effect of dipyridamole in renal transplant recipients (RTRs) with hypophosphatemia. For this reason, we decided to give dipyridamole 11 RTRs with hypophosphatemia. PATIENTS AND METHODS: Eleven RTRs whose serum phosphate and creatinine levels were below 2.5 mg/dl and 2 mg/dl, respectively, were included in this study. None of the patients received drugs altering phosphate metabolism and they did not change their routine diets. Urinary phosphate excretion and tubular phosphate reabsorption (TPR) were calculated before and 3 weeks after dipyridamole treatment. RESULTS: The mean levels of serum-urine (daily) phosphate and TPR before dipyridamole treatment were 1.94 +/- 0.46 mg/dl, 7,187.5 +/- 1,833.49 mg/day and -2.78 +/- 0.62, respectively. After treatment, the mean levels of serum-urine phosphate and TPR were 2.73 +/- 0.46 mg/dl, 4,845.27 +/- 1,138.99 mg/day and -1.48 +/- 0.80, respectively. Serum and urine phosphate levels and TPR were found to be significantly different before and after dipyridamole therapy (p < 0.05). CONCLUSION: Short-term dipyridamole therapy increased TPR and serum phosphate levels and decreased urinary phosphate excretion. We did not observe negative effect on renal functions in these cases. Although the number of the cases included in this study is small, dipyridamole is an effective choice in management of hypophosphatemic RTRs.

Administration, Oral↗

PubMed1992

Disposition of oral dipyridamole in patients undergoing thallium 201 myocardial imaging.

Oral dipyridamole has been used in conjunction with thallium 201 imaging to diagnose coronary artery disease in patients unable to exercise. However, the pharmacokinetic disposition of high-dose dipyridamole, particularly the time to maximum drug concentration, has not been described in patients undergoing oral dipyridamole-thallium 201 scanning. Therefore, we measured serial concentrations in 20 outpatients undergoing thallium 201 testing after a single 400-mg oral dose of dipyridamole. In patients with positive thallium scans (group A), concentrations were slightly higher than in those with negative scans (group B). The variability in concentrations for both groups ranged from 3-118%. The area under the dipyridamole concentration-time curve from 0-4 hours ranged from 2.9-2.3 microgram.hr/ml. The time to peak plasma level for dipyridamole ranged from 0.5-2.5 hours, with two patients having undetectable levels at the time of thallium 201 injection. Dipyridamole concentrations did not correlate with changes in diastolic or systolic blood pressure, or heart rate. Although it is unknown what concentration is required to produce changes in coronary flow velocity, use of oral dipyridamole in this setting resulted in highly variable concentrations. In addition, these data suggest that a small percentage of patients will not have detectable concentrations at the time of the first thallium 201 scan, possibly limiting the usefulness of this agent in conjunction with thallium scintigraphy in some patients.

Administration, Oral↗

PubMed1992

[Echocardiography with intravenous dipyridamole infusion in the assessment of ischemic cardiopathy. A comparison with the stress test].

BACKGROUND: Diagnosis of ischemic cardiomyopathy by noninvasive methods is a challenge for the clinician. Echocardiography with intravenous administration of dipyridamole has been proposed as an alternative to exercise stress test in this setting. METHODS: Intravenous administration of dipyridamole (0.84 mg/kg in 6 minutes) with two-dimensional echocardiography and 12-lead electrocardiographic monitoring was performed in 50 patients. The test was considered positive when contractility of any of the left ventricular segments decreased, at least, one grade. In that moment, dipyridamole administration was stopped and aminophylline (40-240 mg over 1 to 3 minutes) was given. All patients underwent exercise stress test and coronary angiography. RESULTS: Significant coronary artery disease (70% stenosis in, at least, one of the major vessels) was demonstrated in 32 patients. Twenty of these had a positive dipyridamole echocardiography test (62%) and 23 had a positive exercise stress test (71%). None of the patients without significant coronary artery disease had a positive dipyridamole echocardiography test and 5 patients (23%) has a positive exercise stress test. Dipyridamole echocardiography test had and overall sensitivity of 60% and a specificity of 100%. Exercise stress test had an overall sensitivity of 75% (NS) and a specificity of 67% (p less than 0.01). Dipyridamole echocardiography test was well tolerated: there were no complications during the test. One patient had a transitory type I second-degree AV block. CONCLUSIONS: Dipyridamole echocardiography is a high specificity test for coronary artery disease and has a similar sensitivity than exercise stress test. It is well tolerated and in the authors' experience there were no complications.

Adult↗

PubMed1990

The incidence of serious hemodynamic changes in physically-limited patients following oral dipyridamole challenge before thallium-201 scintigraphy.

Dipyridamole has liberalized referrals for stress TI-201 chloride (thallium) studies at the Iowa City Veterans Administration Medical Center. Seventy-five percent of referrals now receive dipyridamole and, unlike patients who tolerate conventional exercise testing, these patients are often quite debilitated. Therefore, the hemodynamic consequences of dipyridamole were reviewed in 120 consecutive, physically-limited patients referred for thallium scintigraphy following an average oral dose of 5.4 mg/kg. Each patient's blood pressure was measured every 5 minutes for 1 hour after dipyridamole and compared with several clinical factors to determine if blood pressure change was predictable. In all patients, blood pressure changed from 136 +/- 21/83 +/- 15 (mean +/- 1 SD) to 117 +/- 25/72 +/- 15 following dipyridamole administration. One hundred nine of the 120 patients had a blood pressure decline from 137 +/- 21/82 +/- 12 to 113 +/- 21/70 +/- 13. Of the 109, 43% (N = 47) had a systolic blood pressure decline greater than 20 mmHg, 16% (n = 18) greater than 40 mmHg, and 13% (n = 14) greater than 50 mmHg. Thirteen percent (n = 14) required emergent reversal of the dipyridamole with aminophylline. Significant hypotension is relatively common but generally unpredictable after oral dipyridamole. Therefore, patient eligibility criteria should be carefully considered; strict hemodynamic monitoring must be routine in the usual patient undergoing thallium scintigraphy after oral dipyridamole challenge.

Administration, Oral↗

PubMed1990

Gastric antiulcer and cytoprotective effects of dipyridamole in rats.

Dipyridamole has been studied for its ability to inhibit gastric secretion and to protect gastric mucosa against the injuries caused by hypothermic restraint stress, indomethacin and various necrotizing agents including 80% ethanol, 0.6 M HCl, 0.2 M NaOH and 25% NaCl in rats. The results of this study demonstrate that dipyridamole has both prophylactic and curative effects on various experimentally induced gastric ulcers. It produced inhibition of normal and histamine-stimulated gastric secretion in rats. The intensity of gastric lesions induced by indomethacin and hypothermic restraint stress was reduced significantly by dipyridamole. Our findings also showed that dipyridamole protect gastric wall against hypothermic restraint stress-induced mucus depletion. It produced marked cytoprotective effect against all the necrotizing agents used in this study. The cytoprotective effect of dipyridamole against 80% ethanol was reversed significantly by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that dipyridamole inhibits the formation of gastric lesions by mucosal generation of prostaglandins. The concentration of nonprotein sulfhydryls were decreased significantly in gastric mucosa after administration of 80% ethanol. Treatment with dipyridamole replenish the reduced level of gastric mucosal nonprotein sulfhydryls, thus suggesting the mediation of its protective effect through sulfhydryls. Our findings show that dipyridamole possesses both antisecretory and antiulcer effects. Further studies are required to determine its role in the prophylaxis and or the treatment of gastric ulcer disease.

Animals↗

PubMed1989

Left ventricular oxygen tensions in dogs during coronary vasodilation by enflurane, isoflurane and dipyridamole.

The purpose of this study was to investigate the effects of the anesthetics enflurane and isoflurane and of the coronary vasodilator dipyridamole on myocardial oxygen balance and myocardial tissue oxygen tensions. The studies were performed in 24 open-chest dogs during basal anesthesia with a narcotic. Myocardial blood flow (MBF) was measured using radioactive microspheres, myocardial surface tissue PO2 by means of a platinum multiwire surface electrode. One control group and three experimental groups were studied: enflurane (1.1 vol%), isoflurane (0.7 vol%, both end-tidal concentrations), and dipyridamole (0.4 mg/kg). Mean arterial pressure significantly decreased to an average of 70 mm Hg in all three experimental groups. Although MBF was unchanged during enflurane (-18%) and isoflurane (+20%), it increased during dipyridamole (+304% p less than 0.05 vs baseline and control, enflurane, and isoflurane groups). Myocardial oxygen consumption decreased significantly during enflurane and isoflurane but remained unchanged during dipyridamole. Thus, the ratio between myocardial oxygen delivery and consumption increased 6% with enflurane (p less than 0.05 vs baseline), 47% with isoflurane (p less than 0.05 vs baseline and control group) and 280% with dipyridamole (p less than 0.05 vs baseline and control, enflurane, and isoflurane groups). Coronary venous PO2 remained unchanged during enflurane but increased significantly during isoflurane and dipyridamole. Left ventricular surface tissue PO2 was unchanged in enflurane and isoflurane animals and decreased slightly, yet significantly, during dipyridamole. All variables remained unchanged in the control group. Thus, isoflurane and dipyridamole interfered with MBF autoregulation and increased myocardial oxygen delivery out of proportion to myocardial demands.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Mechanism of the antiplatelet action of dipyridamole in whole blood: modulation of adenosine concentration and activity.

Dipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5'-deoxy-5'-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness. Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.

Adenosine↗

PubMed1986

Hyperemic myocardial perfusion imaging for noninvasive detection of coronary disease in man: comparison of treadmill exercise and intravenous dipyridamole infusion.

To further understand hyperemic myocardial perfusion imaging, the effects of exercise and intravenous dipyridamole on coronary flow, coronary stenosis luminal area, stenosis flow resistance, and regional myocardial perfusion were evaluated in patients with arteriographically documented coronary artery disease. Coronary hemodynamics were assessed in 24 patients undergoing routine diagnostic catheterization. Coronary flow was measured by coronary sinus thermodilution. Computer assisted stenosis measurements were made. During isometric handgrip coronary sinus flow increased to 1.7 X baseline value, and epicardial coronary arteries constricted to increase predicted stenosis flow resistance by 40%. A 4-minute intravenous dipyridamole infusion (0.56 mg/kg) increased coronary sinus flow to 2.4 X baseline with, on average, no change in the stenotic coronary lumen diameter. During simultaneous isometric handgrip and dipyridamole infusion coronary sinus flow increased to 3.3 X baseline value and stenosis flow resistance increased an average of 36%. Regional myocardial perfusion was assessed in 33 patients by thallium201 myocardial perfusion imaging following maximal treadmill exercise and again following intravenous dipyridamole infusion. Regional thallium201 imaging effects were correlated with measurements of angiographic coronary disease. Sensitivity and specificity for detecting a greater than or equal to 50% stenosis were 85% and 64% (p less than .005), respectively, for dipyridamole and 84% and 68% (p less than .005) for exercise thallium201. In summary, coronary blood flow increases with isometric exercise and is near maximal following intravenous dipyridamole. Quantitative arteriographic techniques demonstrate isometric exercise-induced constriction of coronary stenoses and increased stenosis flow resistance. Stenosis flow resistance increases following intravenous dipyridamole only for severe (greater than or equal to 65%) lesions. Treadmill exercise and intravenous dipyridamole are comparably effective hyperemic stimuli for creating regional perfusion differences for the noninvasive detection of coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation↗

PubMed1986

Thallium-201 myocardial imaging during coronary vasodilation induced by oral dipyridamole.

Myocardial perfusion imaging of 201TI injected during maximum exercise has been an important diagnostic tool for coronary artery disease. Pharmacologic coronary vasodilation by i.v. infusion of dipyridamole may be used in lieu of exercise stress for purposes of diagnostic perfusion imaging. However, i.v. dipyridamole is not currently available from commercial sources for widespread routine use. Accordingly, this study was carried out in order to determine whether high dose, oral dipyridamole would be useful as a coronary vasodilator for purposes of diagnostic perfusion imaging. Fifty-eight patients undergoing diagnostic coronary arteriography also had myocardial perfusion imaging with 201TI under conditions of rest, maximum exercise stress, and high dose oral dipyridamole. Of those patients who had a defect on exercise thallium images, 75% also had a perfusion defect on thallium images after high dose oral dipyridamole. These results indicate that oral dipyridamole causes sufficient coronary arteriolar vasodilation and increase of coronary flow in nonstenotic arteries to identify perfusion defects comparable to those seen on maximum exercise stress in at least 75% of cases. In 25% of patients with exercise defects, no perfusion defect was seen after oral dipyridamole. Thus, oral dipyridamole is a potent coronary vasodilator, comparable to exercise stress in most cases, but in a minority of patients may not be comparable to exercise stress.

Administration, Oral↗