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PubMed1992

Dipyridamole decreases circulating renin-angiotensin system activity in hypertensive patients.

To study the effect of adenosine on renin release, n = 6 hypertensive patients, while on a constant 80 to 100 mEq/24 h Na+ diet, received oral 150 mg dipyridamole (an adenosine uptake inhibitor) three times daily for 3 days while upright plasma renin activity (PRA) and plasma aldosterone, urinary aldosterone, plasma and urinary Na+,K+, and creatinine clearance were monitored the day before (basal) the first and third day of the treatment and the day after the withdrawal (recovery). As compared to basal and to recovery, dipyridamole significantly decreased PRA, and plasma and urinary aldosterone without affecting plasma and urinary Na+ and K+, creatinine clearance, blood pressure, and heart rate. These data, showing that dipyridamole decreases PRA and aldosterone, confirm also in hypertensives that endogenous adenosine inhibits the circulating renin-angiotensin-aldosterone system.

Adenosine↗
PubMed1996

Stability of baclofen, captopril, diltiazem hydrochloride, dipyridamole, and flecainide acetate in extemporaneously compounded oral liquids.

The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Baclofen 10 mg/mL, captopril 0.75 mg/mL, diltiazem hydrochloride 12 mg/mL, dipyridamole 10 mg/mL, and flecainide acetate 20 mg/mL were prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in 120-mL amber, clear polyethylene terephthalate bottles. The source of all the drugs was tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle immediately after preparation and at various intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. A mean of at least 92% of the initial drug concentration was retained for up to 60 days in the baclofen, diltiazem hydrochloride, dipyridamole, and flecainide acetate liquids at both 5 and 25 degrees C. There were no substantial changes in the appearance or odor of any of the liquids or in the pH. Baclofen 10 mg/mL, diltiazem hydrochloride 12 mg/mL, dipyridamole 10 mg/mL, and flecainide acetate 20 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids.

Baclofen↗
PubMed1978

Proliferative activity of myocardial capillary wall cells in dipyridamole--treated rats.

The hearts of rats treated with dipyridamole were studied by light microscope autoradiography and measurement of tissue radioactivity after intravenous injection of 3H-thymidine. Total tissue radioactivity was significantly increased in the hearts of the dipyridamole-treated animals. Only capillary wall cells were labelled in the autoradiograms. The observations indicate a proliferation of capillary wall cells, suggesting a neoformation of myocardial capillaries during dipyridamole treatment.

Animals↗
PubMed1993

High-dose dipyridamole echocardiography test in coronary artery disease after heart transplantation.

In order to evaluate the usefulness of the high-dose dipyridamole echocardiography test (DET) for the detection of coronary artery disease (CAD) after heart transplant and for the assessment of prognosis, 80 heart transplant patients underwent this test within 48 h of the scheduled yearly coronary angiography. Coronary angiography showed normal coronary arteries in 55 patients and CAD in 25, eight of whom had > 50% luminal narrowing. Segmental hypokinesis on baseline echocardiography was present in 27 patients, 19 of whom had CAD (sensitivity = 76%; specificity = 85%). DET was negative in all the patients with normal coronary arteries (specificity = 100%). Out of 25 patients with CAD, eight had a positive DET and 17 a negative DET (sensitivity 32%), but DET was positive in seven of the eight patients with coronary artery stenosis > 50% (sensitivity 87%). During follow-up (9.8 +/- 4.5 months) seven cardiac events occurred in seven patients, all with CAD and wall motion hypokinesis (six on baseline echocardiogram and four after dipyridamole infusion). In our experience, DET does not seem adequate for the screening of post-transplant CAD, but useful in identifying patients with severe lesions (> 50%). Wall motion abnormalities on baseline echocardiogram or after dipyridamole infusion might identify patients who require closer surveillance. A longer experience is needed to confirm these results.

Adult↗
PubMed1993

Dipyridamole thallium-201 scintigraphy for improved detection of left anterior descending coronary artery stenosis in patients with left bundle branch block.

In patients with left bundle branch block (LBBB) undergoing thallium-201 exercise scintigraphy septal perfusion defects are frequently observed irrespective of the presence or absence of coronary artery disease. Consequently, in these patients the specificity for detecting stenoses in the left anterior descending coronary artery (LAD) by thallium-201 scintigraphy is relatively low. It has been hypothesized that pharmacological vasodilation would result in higher specificity than conventional exercise thallium-201 scintigraphy because of a more uniform exploitation of coronary flow reserve. Twenty-five consecutive patients with LBBB underwent dipyridamole thallium-201 imaging and coronary arteriography within 3 months. The prevalence of coronary artery disease was estimated at 48 +/- 19%. Sensitivity for detection of LAD lesions was 100% and specificity was 88%. The positive predictive accuracy and the negative predictive accuracy were 80% and 100% respectively. The 'false positive' septal defects were of the non-reversible type. The appearance of septal perfusion defects was not dependent on changes in heart rate during dipyridamole infusion. This study indicates the value of dipyridamole thallium-201 imaging for non-invasive detection of LAD stenosis in patients with LBBB.

Aged↗
PubMed1995

Dipyridamole and dobutamine: competitors or allies in pharmacological stress echocardiography?

Stress echocardiography has become an accepted and cost-effective method for diagnosing coronary artery disease. However, as exercise stress echocardiography is a demanding technique, difficult to reproduce, pharmacological stress echocardiography has become very popular in recent years. The two most popular tests from the pharmacological stress echocardiography arena are dipyridamole and dobutamine. They have enabled the technical limitations inherent in exercise echocardiography to be overcome, and have provided the opportunity to obtain, during stress, images of unchanged quality in comparison to baseline. However, the sensitivity of both pharmacological stresses applied separately is less than ideal in patients with milder forms of coronary artery disease and in patients under therapy. To overcome this, a new generation of pharmacological stress tests, the combined dipyridamole-dobutamine tests were introduced. A combined dipyridamole-dobutamine echocardiography stress test should suggest that the agents are natural allies rather than competitors but in some instances they are applicable only in selected patients, and each pharmacological agent may be clinically contraindicated for administration. This is the message from a large scale study of recent years.

Cardiotonic Agents↗
PubMed1994

Effect of aspirin and dipyridamole on proteinuria in idiopathic membranoproliferative glomerulonephritis: a multicentre prospective clinical trial. Collaborative Glomerulonephritis Therapy Study Group (CGTS)

Idiopathic membranoproliferative glomerulonephritis (MPGN) has a poor prognosis, with 90% of patients requiring dialysis treatment after 20 years regardless of therapy. Up to 34% of patients may die due to thrombotic complications or sepsis. This study investigates the influence of aspirin plus dipyridamole on proteinuria and renal function in nephrotic MPGN patients with moderately reduced glomerular filtration rate. Eighteen patients with biopsy-proven MPGN (15 type I, 3 type II) and nephrotic syndrome were randomly assigned to receive protein restriction, antihypertensive therapy (control group) or in addition aspirin and dipyridamole (treatment group). Patients were prospectively followed for a mean of 36 months. Serum creatinine remained unchanged after 36 months compared to baseline in both groups. In the treatment group proteinuria was reduced from 8.3 +/- 1.4 to 1.6 +/- 0.7 g/day (P < 0.05). In control patients proteinuria decreased from 7.1 +/- 1.6 to 4.3 +/- 1.1 g/day. After 36 months proteinuria was significantly lower in the treatment group compared to control (P < 0.02 Mann-Whitney rank sum test). In conclusion, aspirin plus dipyridamole may be of value in reversing nephrotic syndrome and associated risks in patients with MPGN and moderately reduced renal function.

Adult↗
PubMed1994

Biochemical modulation of 'classical' multidrug resistance by BIBW22BS, a potent derivative of dipyridamole.

BACKGROUND: Modulators of the 'classical' multidrug resistance (mdr) phenotype have low efficacy in patients with solid tumors. We analyzed BIBW22BS, 4-[N-(2-hydroxy-2-met- hyl-propyl)-ethanolamino]-2,7-bis(cis-2,6-dimethyl-morpho- lino)-6-phenylpteridine, a derivative of dipyridamole, for its higher potential to modulate mdr. MATERIALS AND METHODS: Four human malignant cell lines: BRO, A2780, GLC4, SW1573, the Pgp-positive sublines: BRO/mdr1.1, 2780AD and the non-Pgp sublines: GLC4/ADR, SW1573/2R120 were used in vitro to investigate BIBW22BS as a modulator of the antiproliferative effects of vincristine and doxorubicin and to compare the potency of BIBW22BS with that of dipyridamole, verapamil, bepridil and flunarizine. BRO/mdr1.1 s.c. well-established xenografts in nude mice were used to study the modulating properties of BIBW22BS 50 mg/kg i.v. followed after one h by vincristine 1 mg/kg i.p. or doxorubicin 8 mg/kg i.p. weekly x 2. RESULTS: BIBW22BS was 20- to 100-fold more potent than dipyridamole in the reversal of resistance in the Pgp-positive sublines. Reversal of resistance was obtained in a dose-dependent manner and was complete at concentrations of 0.5-2.5 microM. At non-toxic, equimolar concentrations of 1.0 microM BIBW22BS showed higher modulating potency than the calcium-channel blockers. BIBW22BS did not affect resistance in the non-Pgp sublines. BRO/mdr1.1 s.c. xenografts have stable multidrug-resistance characteristics upon serial transplantation. BIBW22BS, vincristine, or doxorubicin as single agents were not effective in vivo, while the addition of BIBW22BS could significantly reduce the tumor growth expressed as the T/C% of vincristine from 109% to 48% and that of doxorubicin from 55% to 32%. However, reversal of vincristine resistance in BRO/mdr1.1 xenografts was not complete when compared to the efficacy of vincristine in BRO xenografts. CONCLUSION: The results encourage the further preclinical development of BIBW22BS as a modulator of 'classical' multidrug resistance in cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Dipyridamole thallium-201 imaging very early after uncomplicated acute myocardial infarction in patients treated with thrombolytic therapy.

The aim of this study was to assess the safety and prognostic value of dipyridamole 201T1 imaging very early after acute myocardial infarction in patients treated with thrombolytic therapy. Fifty-two consecutive patients with an uncomplicated clinical course underwent quantitative planar dipyridamole 201T1 imaging 2 5 days after acute myocardial infarction. The patients were followed for 14 +/- 7 months after discharge. No major complications occurred during the test. Of the 30 patients with redistribution, five (16.6%) developed in-hospital unstable angina as against none of the 22 patients without redistribution. During follow-up, a total of live late cardiac events were observed: two deaths and two cases of unstable angina in the group with reversible defects and one reinfarction in the group with fixed defects. The 1-year actuarial probability of being free of cardiac events was, respectively, 66 +/- 10% and 94 +/- 5% in the patients with and without redistribution (P < 0.01). In conclusion, in patients treated with thrombolysis, dipyridamole-201T1 imaging very early after uncomplicated acute myocardial infarction is a feasible and safe test. Patients with fixed defects appear to be at low risk and may be candidates for early discharge; the presence of redistribution identifies a subgroup of patients who may benefit from further careful clinical evaluation.

Adult↗
PubMed1989

Dipyridamole-echocardiography test: historical background and physiologic basis.

Dipyridamole was first introduced as an antianginal, coronary vasodilator agent. It was soon found that this drug could not prevent effort ischaemia; on the contrary, given intravenously, it could frequently induce ischaemia in the presence of coronary artery stenosis. This property was exploited for the diagnosis of coronary artery disease. The dipyridamole-induced ischaemia was detected by different techniques: ST-segment depression, thallium 201 scintigraphy and echocardiography. This review article describes the mechanisms underlying dipyridamole-induced ischaemia and discusses the value of this pharmacologic stress test for the detection of coronary artery disease.

Coronary Disease↗
PubMed1990

Thallium-201 scintigraphy after dipyridamole infusion with low level exercise. II. Quantitative analysis vs visual analysis.

To determine the value and limitations of quantitative analysis of thallium-201 imaging after intravenous dipyridamole in combination with low level exercise, 81 patients with suspected coronary artery disease (CAD) were evaluated prospectively. The results of quantitative analysis were compared with the results of visual analysis. All patients underwent coronary arteriography and left ventricular angiography. Significant CAD was present in 59 patients (73%); multivessel CAD was observed in 33 patients (42%). Mild side-effects such as headache, vertigo and nausea were experienced by 12 patients (15%). To establish 'test-specific' normal limits in quantitative analysis of uptake and washout of thallium-201 after dipyridamole infusion with low level exercise we studied 20 healthy volunteers with a likelihood of CAD less than or equal to 1%. Sensitivity and specificity of quantitative analysis for overall detection of significant CAD were 76% and 73%, respectively vs 78% and 86%, respectively with visual analysis (P = NS). Sensitivity for the detection of multivessel CAD was slightly higher with quantitative analysis (73%) than with visual analysis (70%), but the specificity was lower (75% vs 92%) (P = NS). Sensitivity of quantitative analysis in relation to vessels involved was slightly lower than with visual analysis (RCA and LAD: P = NS; LCX: P less than 0.05). Of 14 patients with false-negative results, four had multivessel CAD. Thus, quantitative analysis after the combination of dipyridamole infusion with low level exercise did not improve the diagnostic value as assessed by semi-quantitative visual analysis.

Adult↗
PubMed1990

Thallium-201 scintigraphy after dipyridamole infusion with low-level exercise. III. Clinical significance and additional diagnostic value of ST segment depression and angina pectoris during the test.

Intravenous dipyridamole thallium testing is a useful alternative procedure for assessing coronary artery disease (CAD) in patients who are unable to perform maximal exercise tests. Ischaemic ST segment depression and angina pectoris are frequently observed during the test, in particular when exercise is added to dipyridamole infusion. To establish the clinical significance and additional diagnostic value of these markers of ischaemia during dipyridamole low-level exercise testing (DXT) 57 patients with CAD (group A), 21 patients with normal or near-normal coronary arteries at coronary arteriography (group B), and 20 healthy subjects with low likelihood of CAD (group C) were studied. During DXT ischaemic ST segment depression was observed in 28 patients (47%) of group A and in two patients (10%) of group B. Angina pectoris was experienced by 35 patients (61%) of group A and by five patients (24%) of group B. The positive predictive value of both ST depression and angina pectoris was high (88 and 93%, respectively), but the negative predictive values were low (42 and 40%, respectively). Combining ST segment analysis with the findings of thallium imaging significantly increased the diagnostic accuracy of the test. ST segment depression, angina pectoris, and thallium abnormalities were highly specific findings if the study population consisted of asymptomatic subjects with a low likelihood of CAD (group C). Sensitivity for the detection of the presence of CAD increased with the extent of CAD for all parameters studied. Thus, ST depression and angina pectoris, alone or in combination, during DXT have little diagnostic significance, although sensitivity is increased in patients with triple-vessel CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Postoperative myocardial infarction and cardiac death. Predictive value of dipyridamole-thallium imaging and five clinical scoring systems based on multifactorial analysis.

Sixty-six patients unable to complete a standard preoperative exercise test because of physical limitations were studied to determine the predictive value of individual clinical parameters, of clinical scoring systems based on multifactorial analysis, and of dipyridamole-thallium imaging before major general and vascular surgery. Study endpoints were limited to postoperative myocardial infarction or cardiac death before hospital discharge. There were nine postoperative cardiac events (seven deaths and two nonfatal infarctions). There was no statistical correlation between cardiac events and preoperative clinical descriptors, including individual clinical parameters, the Dripps-American Surgical Association score, the Goldman Cardiac Risk Index score, the Detsky Modified Cardiac Risk Index score, Eagle's clinical markers of low surgical risk, and the probability of postoperative events as determined by Cooperman's equation. There were no cardiac events in 30 patients with normal dipyridamole-thallium scans or in nine patients with fixed myocardial perfusion defects. Of 21 patients with reversible perfusion defects who underwent surgery, nine had a postoperative cardiac event (sensitivity, 100%; specificity, 43%). In the six other patients with reversible defects, preoperative angiography showed severe coronary disease or cardiomyopathy. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically before major general and vascular surgery, whereas dipyridamole-thallium imaging successfully identified all patients who sustained a postoperative cardiac event.

Aged↗
PubMed1992

Preoperative and long-term cardiac risk assessment. Predictive value of 23 clinical descriptors, 7 multivariate scoring systems, and quantitative dipyridamole imaging in 360 patients.

A total of 360 patients underwent preoperative cardiac risk assessment using 23 clinical parameters, seven multivariate clinical scoring systems, and quantitative dipyridamole-thallium imaging to predict postoperative and long-term myocardial infarction and cardiac death after noncardiac surgery. There were 30 postoperative and an additional 13 cumulative long-term cardiac events after an average follow-up of 15 months. Clinical descriptors were not useful in predicting the outcome of individual patients. The postoperative and long-term cardiac event rates were 1% and 3.5%, respectively, in patients with normal scans or fixed perfusion defects, and 17.5% and 22% in patients with reversible defects. Using quantitative indices reflecting the amount of jeopardized myocardium, patients could be stratified by dipyridamole imaging into multiple scintigraphic subsets, with corresponding postoperative and 1-year coronary morbidity and mortality rates ranging from 0.5% to 100% (p = 0.0001). Thus, postoperative and long-term cardiac events cannot be predicted clinically, whereas quantitative dipyridamole imaging accurately identifies high-risk patients who require preoperative coronary angiography.

Aged↗
PubMed2002

Nucleoside transport inhibitors, dipyridamole and p-nitrobenzylthioinosine, selectively potentiate the antitumor activity of NB1011.

NB1011, a novel anticancer agent, targets tumor cells expressing high levels of thymidylate synthase (TS). NB1011 is converted intracellularly to bromovinyldeoxyuridine monophosphate (BVdUMP) which competes with the natural substrate, deoxyuridine monophosphate, for binding to TS. Unlike inhibitors, NB1011 becomes a reversible substrate for TS catalysis. Thus, TS retains activity and converts BVdUMP into cytotoxic product(s). In vitro cytotoxicity studies demonstrate NB1011's preferential activity against tumor cells expressing elevated TS protein levels. Additionally, NB1011 has antitumor activity in vivo. To identify drugs which interact synergistically with NB1011, we screened 13 combinations of chemotherapeutic agents with NB1011 in human tumor and normal cells. Dipyridamole and p-nitrobenzylthioinosine (NBMPR), potent inhibitors of equilibrative nucleoside transport, synergized with NB1011 selectively against 5-fluorouracil (5-FU)-resistant H630R10 colon carcinoma cells [combination index (CI)=0.75 and 0.35] and Tomudex-resistant MCF7TDX breast carcinoma cells (CI=0.51 and 0.57), both TS overexpressing cell lines. These agents produced no synergy with NB1011 in Det551 and CCD18co normal cells (CI > 1.1) lacking TS overexpression. Dipyridamole potentiated NB1011's cytotoxicity in medium lacking nucleosides and bases, suggesting a non-salvage-dependent mechanism. We demonstrate that nucleoside transport inhibitors, dipyridamole and NBMPR, show promise for clinically efficacious combination with NB1011.

Antimetabolites, Antineoplastic↗
PubMed1980

Effect of dipyridamole on ischemia-induced changes in cardiac performance and metabolism.

The effect of the coronary vasocilator agents dipyridamole and nifedapine on ischemia-induced changes in cardiac performance and coronary flow was studied in extra-corporeal-circulation supported, open-chest dogs during cardio-pulmonary bypass. Coronary flow and isovolumic cardiac performance were measured prior to clamping the aorta to induce global ischemic for 60 min and again after 30 min of reperfusion. Both agents given prior to ischemia significantly enhanced the coronary flow measured 30 min after reperfusion. Almost complete complete return of pre-ischemic left ventricular dp/dt and diastolic compliance was seen if dipyridamole was administered prior to the onset of ischemia. Dipridamole administered at the end of the ischemic period and prior to reperfusion also prevented the ischemia-induced fall in dp/dt but not the decrease in compliance. Myocardial high energy phosphate compounds decreased markedly during global ischemia and dipyridamole administration had no effect on the rate or extent of their depletion. Nifedapine administration led to even greater post-ischemic coronary vasodilation; however, the ischemia-induced decline in myocardial performance was not prevented.

Animals↗
PubMedDate not supplied

Comparative effects of a new calcium antagonist, FR 7534, nitroglycerin, and dipyridamole on regional myocardial blood flow and cardiac contractility during partial coronary artery occlusion in the dog.

The present study was designed to determine the effects of three different types of coronary vasodilators--FR 7534 (a new calcium antagonist), nitroglycerin, and dipyridamole--on the transmural blood flow and contractile function in the normal and ischemic myocardium of anesthetized dogs. Radioactive microspheres (15 muc) and Walton-Brodie strain gauge arches were used to measure tissue blood flow and contractile force, respectively. During 5 min intravenous infusions of nitroglycerin (5 microgram/kg/min) or dipyridamole (50 microgram/kg/min), which produced approximately 20% reductions in mean aortic pressure, blood flow and contractile force in ischemic myocardium decreased significantly. Under similar conditions, FR 7534 (10 microgram/kg/min) produced a significant decrease in ischemic contractile force, but tissue blood flow to the ischemic area did not change. In contrast, when mean aortic pressure was controlled by administration of methoxamine, nitroglycerin produced significant increases in ischemic blood flow (42%) and contractile force (47%), whereas dipyridamole produced significant decreases (41 and 32%, respectively). On the other hand, FR 7534 plus methoxamine produced a significant increase in ischemic blood flow (70%); however, ischemic contractile force did not change. These results demonstrate FR 7534 to affect the oxygen supply-demand balance in ischemic myocardium favorably by maintaining blood flow and depressing contractility during hypotension or by increasing flow during controlled systemic pressure.

Animals↗
PubMed2000

Antioxidant effect of oral dipyridamole during cerebral hypoperfusion with human carotid endarterectomy.

We sought to test the hypothesis of an antioxidant effect of dipyridamole in vivo in a model of cerebral hypoperfusion. Twenty-one patients (65+/-10 years, 11 men) undergoing carotid endarterectomy were allocated in two groups (group 1, 10 with dipyridamole, 200 mg p.o., 3-4 h before surgery; group II, 11 with placebo) in a double-blind placebo-controlled randomized design. Blood was sampled from ipsilateral jugular bulb, and plasma vitamin E content was assayed before, after 15 and 30 min of clamp, and 2 and 10 min after declamping. In 12 of them, lipoperoxides were assayed. Vitamin E plasma content decreased significantly in group II (rest, 3.71+/-0.22 mmol/mol of cholesterol, 100%) after clamp (91.5% of rest, p < 0.01) and remained unchanged during declamping (90.9% of rest, p < 0.01), but did not change in group I (rest, 3.5+/-0.44 mmol/mol of cholesterol, 100%) during clamping (99.9% of rest; p = NS) and after declamping (97.6% of rest; p = NS). Lipoperoxide concentration did not change in group I (rest, 302+/-8 a.u.; clamp, 296+/-13 a.u.; p = NS vs. rest; declamp, 304+/-8 a.u.; p = NS vs. rest), and increased significantly in group II (rest, 313+/-5 a.u.; clamp, 352+/-9 a.u.; p < 0.01 vs. rest; declamp, 343+/-6 a.u.; p < 0.05 vs. rest). Cerebral oxidative stress associated with human carotid endarterectomy can be attenuated by pretreatment with oral dipyridamole.

Aged↗