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PubMed1984

Modulation of cytarabine uptake and toxicity by dipyridamole.

The effect of dipyridamole, an inhibitor of membrane nucleoside transport, on the uptake and toxicity of cytarabine was examined in normal and malignant tissues. Preliminary pharmacokinetic data were obtained in mice and humans to determine appropriate dipyridamole dosage ranges for in vitro testing. At concentrations achievable in man, dipyridamole produced 75% and 94% reductions in cytarabine uptake in freshly harvested normal mouse and human bone marrow cells, respectively. Under the same conditions, greater than 90% reductions in cytarabine uptake were also seen in both L1210 murine leukemia and HL-60 human leukemia cells. In addition, treatment with dipyridamole also reduced the growth inhibitory effects of cytarabine on HL-60 cells in culture and protected mice from toxic doses of this antimetabolite. These results demonstrate the ability of dipyridamole to modulate the activity of cytarabine in both murine and human cells.

Animals↗
PubMed1984

Enhancement of the sensitivity of human colon cancer cells to growth inhibition by acivicin achieved through inhibition of nucleic acid precursor salvage by dipyridamole.

This study was undertaken to determine if salvage of nucleic acid precursors might constitute a mechanism of resistance to acivicin in human colon cancer cells and, if so, to establish whether dipyridamole, an inhibitor of nucleoside and nucleobase transport, can block the salvage process and restore sensitivity to acivicin. Acivicin inhibited the replication of human colon cancer cells (VACO 5) in vitro in a dose- and time-dependent fashion. In addition, marked cell lysis was evident after a 24-hr exposure to acivicin at concentrations greater than 1 microgram/ml. The primary metabolic effect of acivicin was depletion of the cytidine triphosphate and guanosine triphosphate pools. Adenosine triphosphate levels were also reduced, but apparently as a consequence of the guanosine triphosphate depletion. VACO 5 cells exposed to acivicin (3 micrograms/ml) efficiently salvaged low levels (1 micron) of cytidine, guanosine, and guanine and could, therefore, restore the depleted nucleotide pools. The combination of cytidine and guanosine, but not either nucleoside alone, provided significant protection against the growth-inhibitory properties of acivicin. Dipyridamole, at a noncytotoxic concentration (5 microM), blocked repletion of the cytidine triphosphate and guanosine triphosphate pools in cells exposed to acivicin and the nucleic acid precursors. As a result, the growth-inhibitory effects of acivicin were maintained. The salvage of cytidine was particularly sensitive to inhibition by dipyridamole, and no restoration of cytidine triphosphate pools was evident. The cellular uptake of a variety of nucleic acid precursors was differentially sensitive to inhibition by dipyridamole. The 50% inhibitory dose values ranged from 0.01 to 2.5 microM for cytidine and uridine, respectively. The results of this study indicate that, although the replication of VACO 5 cells was inhibited by acivicin, low levels of nucleosides and nucleobases can circumvent the cytotoxicity. Dipyridamole effectively blocked the salvage pathways and restored the sensitivity of the cancer cells to the antiproliferative actions of acivicin.

Antibiotics, Antineoplastic↗
PubMed1994

Safety of pharmacological (intravenous dipyridamole) stress for Thallium-201 perfusion imaging in patients with coronary artery disease unable to exercise.

Exercise Thallium-201 myocardial perfusion imaging is a sensitive technique for detection of CAD. However, in patients unable to perform exercise pharmacological stress with intravenous dipyridamole can be used to dilate coronaries. Out of 125 patients (21 men and 104 women; mean age 52.03 years) evaluated, 110 were considered to be unable to perform adequate stress by their physician while remaining 15 had LBBB. One hundred and seven patients had chest pain with or without a remote MI while 18 individuals were clinically asymptomatic but had ECG abnormalities. Intravenous dipyridamole was administered at a rate of 0.142 mg/kg/min for 4 min. After 3 min an i.v. bolus of T1-201 was given. Diffuse or occipital headache of mild to moderate intensity occurred in 50 (40%) cases; 39 patients experienced chest pain and had either a positive thallium scan (26 cases) suggestive of CAD or a normal thallium study (15 cases). Complete relief from dipyridamole induced symptoms was brought by i.v. aminophylline and sublingual nitrate in 51 of 54 cases (94%) and 11 of 18 (61%) respectively. We, therefore, conclude: 1) i.v. dipyridamole-thallium scintigraphy offers a safe, effective and reliable method for evaluating CAD in those who are unable to perform adequate exercise and 2) parenteral aminophylline is very effective antidote to dipyridamole.

Aminophylline↗
PubMed1993

[Thallium 201 myocardial scintigraphy and left branch block. Comparative value of exercise test and dipyridamole test].

Stress Thallium 201 myocardial scintigraphy in patients with left bundle branch block often shows reversible septal perfusion defects even in the absence of coronary artery disease. This phenomenon seems more common when the patients have tachycardia. With the working hypothesis that dipyridamole stress testing, which does not greatly increase the heart rate, would be more appropriate than exercise stress testing to unmask coronary artery disease in this condition, the authors compared the results of two Thallium 201 scintigraphies performed after exercise and then after dipyridamole under the same conditions three weeks later, in 67 patients with complete left bundle branch block. Scintigraphy showed one or more reversible perfusion defects in 64/67 patients after exercise but only 32/67 patients after dipyridamole (p < 0.001). There was poor uptake in the septal region in 59 patients (88%) after exercise and in 25 patients (37%) after dipyridamole (p < 0.001). The specificity was evaluated in 23 patients estimated to have no coronary artery disease. If only unequi vocal perfusion defects were considered, the specificity after dipyridamole was higher than that after exercise, increasing from: 35% to 83% for septal defects (p < 0.01); 65% to 96% for anterior wall defects (p < 0.05); 61% to 87% for inferior wall defects (p < 0.05); 57% to 91% for apical defects (p < 0.01); 17% to 83% overall (p < 0.001). Lower values but with a comparable difference were observed when all forms of hypofixation (even minimal) were taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Prognostic implications of transient left ventricular cavitary dilation during exercise and dipyridamole-thallium imaging.

OBJECTIVE: To determine the prognostic implication of exercise and dipyridamole-induced transient left ventricular cavitary dilation (TLVD). DESIGN: TLVD was observed and a follow-up obtained in 61 patients after exercise and in 62 patients following dipyridamole infusion. PATIENTS: There was no statistical difference between groups in terms of sex, history of hypertension, diabetes, renal failure, previous myocardial infarction, severity of angina syndrome, congestive heart failure, resting electrocardiographic (ECG) abnormalities, clinical or ECG signs of ischemia during stress, number of reversible perfusion defects on thallium images or duration of follow-up (21 months). RESULTS: Dipyridamole patients were slightly older (64 versus 57 years) and displayed more thallium redistribution (P = 0.002). After a mean follow-up of 21 months, both fatal and nonfatal (myocardial infarction or cardiac death) cardiac events were more frequent in the dipyridamole group (50% versus 9%, P = 0.0001). CONCLUSIONS: Patients with dipyridamole-induced TLVD are at greater risk than those with exercise-induced TLVD at the authors' institution.

Aged↗
PubMed1994

Biokinetics of thallium-201 in normal subjects: comparison between adenosine, dipyridamole, dobutamine and exercise.

UNLABELLED: There are currently four common types of stress used with thallium-201 imaging in the diagnosis of coronary artery disease and risk assessment. The objective of this study was to examine the thallium biokinetics during exercise, adenosine, dipyridamole and dobutamine stress testing in 15 healthy volunteers. METHODS: Each subject underwent planar 201Tl imaging during maximal treadmill exercise testing, adenosine infusion (140 micrograms/kg/min for 6 min), dipyridamole infusion (142 micrograms/kg/min for 4 min) and dobutamine infusion (40 micrograms/kg/min). RESULTS: Absolute myocardial thallium activity was greater after pharmacologic testing than exercise, (p < 0.001 each). Thus, the activity was 505 counts/pixel with adenosine, 491 counts/pixel with dipyridamole, 517 counts/pixel with dobutamine and 409 counts/pixel with exercise. The myocardial thallium clearance was lower with pharmacologic testing than exercise; 9.7%/hr with adenosine, 9.9%/hr with dipyridamole, 11.3%/hr with dobutamine and 13%/hr with exercise (p < 0.01 each). The thallium uptake and clearance in the lung and liver were also greater with pharmacologic stress testing than exercise (p < 0.05). CONCLUSIONS: Thus, thallium biokinetics are different during pharmacologic stress testing with adenosine, dipyridamole and dobutamine than during exercise. Diagnostic criteria for quantitative analysis of myocardial perfusion imaging must therefore be specific for the type of stress used.

Adenosine↗
PubMed1994

Dipyridamole myocardial perfusion imaging.

Dipyridamole is a pharmacologic stressor used in place of exercise for myocardial perfusion imaging in patients who cannot exercise due to various physical limitations. Perfusion studies with dipyridamole can identify coronary artery disease (CAD) as accurately as maximal exercise stress testing. In addition, dipyridamole myocardial perfusion studies are useful to stratify patients according to risk of subsequent cardiac events. As dipyridamole is infused, it blocks the reabsorption and metabolism of adenosine normally produced in the body, producing the desired effect on the heart, coronary hyperemia. Dipyridamole can be used with 201Tl and 99mTc myocardial perfusion tracers, for either planar or SPECT imaging, in patients who cannot exercise or who can only exercise at submaximal levels.

Adenosine↗
PubMed1993

[What coronary findings predispose to premature termination of a strong positive dipyridamole test?].

Besides the exercise-ECG the dipyridamole-test is used in the noninvasive diagnosis of coronary artery disease (CAD). In many cases the test must be terminated due to angina or ST-segment depression before reaching the regular end point of the investigation. The test then is graded as highly positive. It was the aim of this study to answer the question what changes in the coronary angiogram one has to expect in patients with a highly positive dipyridamole-test. In 45 females and 173 males the dipyridamole-test was carried out giving 0.75 mg dipyridamole/kg bodyweight intravenously over a period of 10 min. In case of angina pectoris and/or ST-segment depression > 0.2 mV occurring within 12 min after beginning of injection the test was graded positive. The test was defined highly positive in the case of early termination during the injection period because of angina or ST-segment depression. All patients had undergone a coronary angiography. 70 out of 218 dipyridamole-tests had to be terminated before the regular end of the test. There was no correlation between the time of termination of the dipyridamole-test and the grade of CAD. The group of patients in which the test had to be terminated early because of angina and ST-segment depression more often had coronary stenoses > 75% in at least one major coronary artery (94.5%) compared with those patients in which only angina led to the termination of the test (69.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Left ventricular function assessed with echocardiography and myocardial perfusion assessed with scintigraphy under dipyridamole stress in pediatric patients after repair for anomalous origin of the left coronary artery from the pulmonary artery.

Twenty-three patients who underwent operation for anomalous origin of the left coronary artery from the pulmonary artery were reexamined with two-dimensional echocardiography and thallium 201 perfusion imaging. Follow-up studies were performed 0.6 to 16.2 years (median 2.9 years) after operation. In 22 of 23 patients, a two coronary artery system had been established by implantation of the left coronary artery into the aorta (n = 8) or by anastomosis of the left subclavian artery with the left coronary artery (n = 14). The left coronary artery had been ligated in only one patient. For stress testing, 0.8 mg dipyridamole per kilogram body weight was infused in a 10-minute period in 20 of the 23 patients. High-dose dipyridamole infusion increased mean heart rate (98.1 +/- 27.1 to 122.3 +/- 19.2 beats/min, p < 0.001) and mean left ventricular ejection fraction (54.8% +/- 11.8% to 61.3% +/- 12.5%, p < 0.05) and decreased left ventricular end-diastolic volume index (38.8 +/- 26.7 to 29.9 +/- 8.3 ml/m2, p < 0.005). At rest, left ventricular dimensions were abnormal in only one patient, in whom the anastomosis with the left coronary artery proved to be occluded, as seen with subsequent angiography. Left ventricular function seen with two-dimensional echocardiography was normal in 19 patients and was compromised in 3 (all of whom had major structural anomalies of the left ventricle, such as left ventricular aneurysm, occlusion of the anastomosis, or mitral valve prosthesis). Patients with R-wave loss as seen with preoperative electrocardiography tended to have larger left ventricular volumes at follow-up (69.2 +/- 56.5 ml/m2 versus 32.4 +/- 9.6 ml/m2, p < 0.07). Ten of 20 patients had normal thallium 201-perfusion scans. In 9 of 20 patients defects revealed by permanent thallium 201-perfusion were observed and determined to be myocardial scars. Transient perfusion defects under dipyridamole stress with redistribution at rest occurred in three children, two of whom also had permanent thallium 201 defects. None of the three patients had angina-like symptoms or S-T segment changes during dipyridamole stress. Left ventricular ejection fraction, however, decreased severely during dipyridamole infusion in the single patient with ligature of the left coronary artery. The two remaining patients had normal echocardiographic left ventricular function under stress, and the diagnosis of myocardial ischemia as seen with scintigraphy must be questioned.(ABSTRACT TRUNCATED AT 400 WORDS)

Child, Preschool↗
PubMed1993

Cerebrovascular accident associated with dipyridamole thallium-201 myocardial imaging: case report.

A patient with known aortoiliac occlusive disease and hypertension suffered a cerebrovascular accident 6.5 min after the administration of intravenous dipyridamole during a 201Tl myocardial study. Despite aminophylline administration, the patient developed a completed stroke. The mechanism most likely responsible for precipitating this patient's stroke is dipyridamole-induced vascular steal. Although dipyridamole-201Tl myocardial imaging is relatively free of major complications, the morbidity and mortality associated with a cerebrovascular accident is significant. The possibility of precipitating a cerebrovascular accident during dipyridamole-201Tl imaging should be considered in all patients with significant risk factors for stroke before performing a dipyridamole cardiac study.

Cerebrovascular Disorders↗
PubMed1996

[The 3-year prognosis of patients with suspected coronary disease and a normal myocardial scintigraphy with thallium-dipyridamole].

OBJECTIVES: To assess the 3-year prognosis of patients with suspected coronary artery disease and a normal dipyridamole-thallium scintigram. POPULATION: 43 patients, 16 male and 27 female, mean age 55.8 +/- 9.2 years with suspected coronary artery disease. Forty-two patients had anginal complaints. There was a previous positive treadmill exercise test in 14 patients. All the patients had a normal dipyridamole-thallium SPECT. METHODS: Dipyridamole was infused at a rate of 0.56 mg/kg in 4 minutes followed by 3 minutes of low-level cycloergometer exercise. Two mCi of thallium-201 were injected 3 minutes after the end of dipyridamole infusion. Stress and redistribution SPECT acquisitions were performed respectively 5-10 minutes and 4 hours after thallium-201 injection. The cardiac events during a 3-year follow-up were analysed. RESULTS: No patient had unstable angina, PTCA, CABG or death. One patient suffered an inferior myocardial infarction 28 months after the scintigraphy. The event rate was 0.78% per patient per year. CONCLUSION: Three-year prognosis in patients with suspected coronary artery disease after a normal dipyridamole thallium SPECT is excellent approaching that of the general population.

Adult↗
PubMedDate not supplied

[Usefulness of the measurement of the left-ventricular isometric relaxation time by echo-Doppler during the administration of dipyridamole or dobutamine as a method of inducing myocardial ischemia].

Myocardial isquemia prolongs ventricular relaxation. The purpose of this study was to assess the isovolumetric relaxation time of the left ventricle (IVRT) as a parameter of global ventricular relaxation, during the administration of Dipyridamol or Dobutamine intravenously. We studied 58 patients with ischemic heart disease uncovered by the administration of pharmacological agents. They were divided in two groups: 22 patients in the group of Dipyridamole, which was administered intravenously at a dose of 0.84 mg/kg during 10 minutes and 36 patients in the group of Dobutamine administered at a dose of 5, 10, 20, 30 and 40 mcg/kg/min in stepping fashion every three minutes. Coronariography was performed in all patients. The measurements of the maximal velocities of the E and A waves, as well as the deceleration time of the E wave and the pressure half time of the mitral flow did not show significant changes in both groups. If the study was positive by criterion of alteration of the wall motion, the IVRT corrected from the heart rate (IVRT/C) had an increase in 54% (p < 0.01) with respect to baseline values in the same patient in the Dipyridamole group and in the Dobutamine group the increment of the IVRT/C was 26% (p < 0.20). The sensibility (Sen), specificity (Sp) and positive predictive value (PPV) of the IVRT/C increments in detecting proximal significant obstruction of the left anterior descending coronary artery of trivascular disease in the Dipyridamole group was of 50%, 100% and 100% respectively. In the Dobutamine group the Sen was of 74%, the Sp of 60% and the PPV of 89%. Nor Dipyridamol neither Dobutamine produced a significant prolongation of IVRT/C when alterations of wall motion were absent or when the existing alterations were not exacerbated. On the basis of these results we concluded that the measurement of the IVRT/C in studies of myocardial ischemia with pharmacological provocative maneuvers is an additional useful parameter together with segmental alterations of wall motion to differentiate positive from negative studies.

Cardiotonic Agents↗
PubMed1996

Severe hypotension induced by combination of dobutamine and dipyridamole.

Pharmacologic testing with dobutamine or dipyridamole in conjunction with echocardiography has become an accepted method for diagnosis of coronary artery disease (CAD). The sensitivity of dobutamine echo ranges from 68 to 86%, and of dipyridamole from 53 to 69% for diagnosis of CAD. Our purpose was to investigate whether the addition of dipyridamole to dobutamine, which may improve the test sensitivity, is safe. Ten patients with low probability of CAD underwent dobutamine echo; 5 were control patients and 5 patients had low dose dipyridamole added at the maximal dose of dobutamine. Four of the latter patients had severe hypotension, while no hypotension was observed in control patients. Our findings suggest that this combination of dobutamine and dipyridamole can be hazardous and should not be used in patients with suspected CAD.

Adult↗
PubMed1996

[Importance of dipyridamole transesophageal echocardiography in the diagnosis of ischemic heart disease].

The importance of dipyridamol echocardiography in the diagnosis of ischaemic heart disease (IHD) was described repeatedly. Nevertheless in roughly 20% patients the transthoracic echocardiographic examination at rest is inaccurate or cannot be carried out because the ultrasonic visibility is poor. In these patients transoesophageal dipyridamol echocardiography (TEE Dip) can provide a suitable alternative. This is why the authors evaluated 36 patients examined on account of IHD before and after administration of 0.80 mg/kg dipyridamol. The left ventricle was visualized in the transgastric short axis and from the apical view. Angiography revealed significant stenosis of the coronary arteries in 23 patients. In 18 patients after administration of dipyridamol new motility disorders developed, in 5 patients with motility of the left ventricular wall, impaired at rest, no new disorder of kinetics developed, i.e. the test was falsely negative. Thirteen patients had no signs of stenosis of the coronary arteries and three developed disorders of the motility of the left ventricular wall. The sensitivity of TEE Dip for the diagnosis of left ventricular ischaemia was 78% and the specificity 79%. Dipyridamol load transoesophageal echocardiography is a method suitable for clinical application with a still satisfactory sensitivity and very good specificity and it can be implemented without involving the risk of serious side-effects.

Adult↗
PubMed1997

[Whole body distribution of Tc-99m-sestamibi after pharmacological stress with arbutamine and dipyridamole compared with resting conditions].

AIM: Arbutamine is a new catecholamine that has been developed as a pharmacologic stress agent for the diagnosis of coronary artery disease. Optionally, it can be used in myocardial scintigraphy. The pharmacologic effect compared to dipyridamole was assessed looking at the whole body distribution of Tc-99m-Sestamibi. METHODS: 9 patients were investigated after injection of Tc-99m-Sestamibi during rest, after infusion of arbutamine, and after vasodilatation with dipyridamole. RESULTS: Infusion of arbutamine results in a measurable diminished radiotracer deposition in the lower limb as compared to dipyridamole. The amount of myocardial activity of Tc-99m-sestamibi, however, is also reduced as shown by the percentage of myocardial activity compared to the whole body distribution (2.5% +/- 0.4% for arbutamine vs. 2.8% = 0.5% for dipyridamole) in addition, the heart/lung ratio is lower after application of arbutamine (12.1% +/- 0.5% vs. 2.4% +/- 0.4%). CONCLUSION: After infusion of arbutamine the percentage of myocardial activity as well as the contrast of the myocardium to the surrounding lungs is decreased as compared to dipyridamole. Further studies should reveal whether this difference is relevant in diagnosing coronary artery disease.

Adrenergic beta-Agonists↗
PubMed1997

Plasticity of cardiovascular nucleoside transporters following chronic dipyridamole treatment.

Dipyridamole (37.5 mg/kg, s.c., b.i.d.), a potent inhibitor of nucleoside transport, was administered to guinea pigs for 14 days in order to investigate the effects of: 1) chronic dipyridamole treatment on [3H]nitrobenzylthioinosine ([3H]NBMPR) binding: 2) chronically released endogenous adenosine on adenosine A1 and A2 receptors. Comparisons of the binding capacities (Bmax) and equilibrium dissociation constants (Kd) in vehicle-treated (VTA) and dipyridamole-treated animals (DTA), revealed a 100 percent increase in Kd of [3H]NBMPR binding in the kidney of DTA but not in heart or brain. There were no changes in adenosine A1 or A2 receptor activities in kidney and brain as measured by [3H]R-phenylisopropyladenosine and [3H]5'-N-ethyl-carboxamidoadenosine binding, respectively. The data suggest that cardiac and central nucleoside transporters may be either less susceptible to chronic dipyridamole administration or have a different adaptive mechanism. Also, endogenous adenosine, which may be chronically released upon dipyridamole treatment, has no effect on adenosine receptors.

Adenosine↗
PubMed1998

Pulmonary uptake of technetium-99m-sestamibi induced by dipyridamole-based stress or exercise.

UNLABELLED: On poststress images with 99mTc-sestamibi (MIBI), increased lung uptake of the radiotracer may reflect severe or multivessel coronary artery disease. METHODS: We measured pulmonary/myocardial ratios of MIBI at standardized times on immediate poststress acquisitions and on delayed tomographic acquisitions. In 1500 sequential patients referred for rest and stress myocardial tomography, ancillary planar images were obtained 4 min postinjection at peak stress with exercise, either alone (exercise, n = 674), or after intravenous dipyridamole (dipyridamole, n = 826). RESULTS: Based on 95% confidence limits in the angiographic normals, high values for immediate acquisitions were found in 17% of dipyridamole studies and 15% of exercise studies. High values for delayed acquisitions were found in 10% of dipyridamole studies and 9% of exercise studies. For both stress modes, increased values were related (p < 0.001) to ischemic perfusion defects for immediate images, to fixed defects for delayed images, and to ventricular dilation in both cases. By logistic regression analysis, body weight and history of infarction were also minor independent determinants (p < 0.01) of delayed acquisitions. In a subset of 250 cases with angiographic correlation (163 with dipyridamole; 87 with exercise), immediate lung uptake was highly correlated with ventricular dysfunction and with coronary stenoses (p < 0.0001). Relationships were similar to those in a historic control series imaged with 201TI. Values for delayed poststress images, and for corresponding rest images, showed strong relationships to ventricular dysfunction but not to stenosis severity. CONCLUSION: The relationships of immediate lung uptake to scintigraphic and angiographic disease patterns suggest its possible diagnostic use as an indicator of stress-induced ventricular decompensation.

Cardiac Catheterization↗
PubMed1976

Effects of dipyridamole on the smooth muscle cells of the guinea-pig's taenia coli.

Effects of dipyridamole on the smooth muscle of the guinea-pig's taenia coli were studied using the single and double sucrose gap method. Dipyridamole (10(-5) M) affected neither the non-adrenergic inhibitory junction potential, elicited by field stimulation, nor the membrane hyperpolarization induced with ATP applied exogenously, but did potentiate the accompanying relaxations. The muscle spike activity was reduced by dipyridamole without affecting the membrane potential or the membrane resistance. Carbachol induced a depolarization of the muscle cell membrane and thus a contraction of the muscle. Dipyridamole did not modify the membrane potential change produced by carbachol but decreased the size and time course of the contraction. From these results it is concluded that dipyridamole does not potentiate non-adrenergic relaxations by interfering with the neuromuscular transmission, which has been assumed to be purinergic.

Adenosine Triphosphate↗