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PubMed1989

A comparison of dipyridamole-thallium imaging and exercise testing in the prediction of postoperative cardiac complications in patients requiring arterial reconstruction.

The individual and combined predictive values of dipyridamole-thallium imaging and exercise testing were compared in a prospective study of 70 patients who had abdominal aortic aneurysms or aortoiliac occlusive disease that required surgical repair. All patients were evaluated clinically by the same cardiologist and had exercise stress testing and dipyridamole-thallium imaging before admission for surgery. Ten patients were excluded from the study because they had evidence of severe ischemia when tested (ST segment depression greater than 2 mm on exercise testing, severe multivessel disease on thallium imaging). The remaining 60 patients were operated on (abdominal aortic aneurysm repair, 40; aortobifemoral repair, 17; femorofemoral graft, 3). The test results were withheld from the surgeon, anesthetist, and cardiologist before surgery. A total of 22 patients experienced major cardiac complications postoperatively (acute pulmonary edema, 17; acute myocardial, infarction, 5; cardiac death, 2). Thallium imaging showed myocardial ischemia in 31/60 patients. Exercise testing was positive (greater than or equal to 1 mm ST segment depression) in 10/60 patients. Dipyridamole-thallium imaging with a high sensitivity and reasonable specificity is the initial test of choice. Exercise testing is a poor screening test because of its low sensitivity. The combination of the two tests gives the highest positive predictive value and the greatest likelihood ratio. Thus patients assessed initially and found to have positive thallium scan results may be further stratified by exercise testing.

Adult↗
PubMed1989

Caffeine reduces dipyridamole-induced myocardial ischemia.

The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-201Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed no, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

Caffeine↗
PubMed1989

[Maximal dilatation of the coronary bed using dipyridamole in the diagnosis of coronary insufficiency].

The authors give an account of the mechanism of action of dipyridamole. Via adenosine it produces selective and maximal vasodilatation of resisting coronary vessels in the non-ischaemic area. Thus redistribution of the blood flow from the ischaemic to the non-ischaemic portion of the heart muscle occurs along with clinical and electrocardiographic manifestations of cardiac angina which can be used for its diagnosis. The pharmacological dipyridamole test makes detection of myocardial ischaemia possible in a fundamentally different way as compared with other loading tests. The authors mention pharmacodynamic, metabolic, haemodynamic and associated phenomena of the action of dipyridamole and the mechanism of the opposite effect of aminophylline and nitroglycerin.

Coronary Circulation↗
PubMed1985

Dipyridamole-induced interferon production in mouse peritoneal leukocytes.

The in vitro explanted mouse peritoneal leukocytes were used for the optimization of the dipyridamole-induced interferon production. After 90-120 min incubation of cells with 30-100 microM dipyridamole, the production of interferon reached 6.4 X 10(4) IU/ml. It was demonstrated that the interferon production phase is preceded by the dipyridamole-dependent increase in cAMP concentration. The possibility of cAMP involvement in the mechanism of interferon production is being discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Quantitative relationship between global left ventricular thallium uptake and blood flow: effects of propranolol, ouabain, dipyridamole, and coronary artery occlusion.

The quantitative relationship between fractional myocardial thallium uptake and radioactive microsphere-determined flow was studied in 33 open chest dogs under baseline conditions during increased coronary flow (dipyridamole), decreased coronary flow (propranolol and coronary artery stenosis), inhibition of Na-K ATPase (ouabain), and regional infarction. Myocardial contents of thallium and microspheres were compared in left ventricular (LV) biopsies taken 5, 10, 15, 30, and 60 min after thallium injection, expressed as fractions of injected dose. Maximal LV thallium uptake occurred 10 min after injection and the 10-min values were therefore used for subsequent comparisons. Combining all dogs, fractional LV thallium content (% injected dose) correlated well with fractional LV blood flow (% cardiac output) (r = 0.95). However, for fractional LV flows in the low, normal, or moderately elevated range (LV flow/cardiac output less than 9%), thallium content consistently exceeded flow by about 15%. This relationship was not altered by ouabain or regional ischemia or infarction. For greatly elevated fractional LV flows (greater than 9%), thallium content was not significantly different from flow. To explain these differences, myocardial and systemic extraction fractions for thallium were determined in eight dogs with a dual tracer method. At baseline, myocardial extraction fraction was significantly greater than systemic (88 +/- 0.4% compared with 75 +/- 1%, p less than 0.001). During dipyridamole, myocardial extraction fraction decreased and myocardial and systemic values were no longer significantly different (82 +/- 1% compared with 79 +/- 1%). These results show that the fraction of injected thallium dose taken up by the LV myocardium exceeds the delivered fraction of cardiac output over a wide range of LV flows, and is not altered by ouabain-induced inhibition of sodium-potassium ATPase or regional myocardial infarction. This difference is explained by a greater myocardial than systemic extraction fraction for thallium. During high LV flows produced by dipyridamole, fractional LV thallium uptake and flow become similar as myocardial and systemic extraction fractions equalize.

Animals↗
PubMed1988

Variability of serum drug level following a single oral dose of dipyridamole.

Serum dipyridamole levels were measured in 27 patients undergoing planar thallium-201 myocardial perfusion scintigraphy after receiving a 300 mg oral dose. Mean serum dipyridamole level was 2.9 +/- 1.6 mcg/ml (range 0.2-5.7). No correlation was found between serum level and symptoms, heart rate or blood pressure response, peak heart to lung thallium activity ratio, peak heart to liver thallium activity ratio, or peak myocardial thallium washout. Serum level following a single oral dose of dipyridamole is unpredictable and patients with low drug levels cannot be easily identified at the time of study.

Administration, Oral↗
PubMed1987

Effects of dipyridamole on prostaglandin synthesis in human fibroblasts.

The effect of varied doses of dipyridamole (Persantin) on the arachidonic acid metabolites prostaglandin (PG)I2, PGE2 and thromboxane (TX)A2 has been studied in human skin fibroblasts cultured in vitro. A 24-h exposure to the drug induced a dose-dependent increase of all the examined prostaglandins (PG's). Bradykinin stimulation of cells that had been preexposed to the drug induced a continuous increase in PG-production as compared to controls, despite the absence of the drug. In addition, an acute 5-min exposure to dipyridamole produced an increased thromboxane production, but no consistent changes of PGI2 or PGE2, and it inhibited significantly and dose-dependently the comcomitant bradykinin stimulated production of all the examined PG's. The implications of a combined dipyridamole-acetylsalicylic acid therapy is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Plasma collection using nafamostat mesilate and dipyridamole as an anticoagulant.

Nafamostat mesilate (FUT-175) is a strong protease inhibitor and is used as an anticoagulant in extracorporeal circulation. In the present study, we administered FUT and dipyridamole as anticoagulants during donor plasmapheresis, and the additional effect of dipyridamole was examined. In dogs weighing about 15 Kg, donor plasmapheresis was performed using a cellulose triacetate membrane plasmaseparator (PEX-15, Nipro), and 300 ml of filtrated plasma was obtained within 30 minutes. These dogs were divided into two groups, 50 mg/h of FUT alone was infused (group A, n = 10), and the same dose of FUT and 25 mg/h of dipyridamole were infused (group B, n = 5) during plasmapheresis. Changes of the coagulation system, blood cell counts and complement system were investigated. In clinical cases, an artificial liver support therapy using FUT as an anticoagulant was performed on 8 patients with acute liver failure, and blood compatibility was examined. In dogs, RBC counts and hematocrits were almost stable, but WBC counts were decreased to about 70% of the previous value. Platelets counts were about 60% and 80% of the previous value, in group A and group B, respectively, at the end of the plasmapheresis (P less than 0.01). Clotting factor VII was diminished to about 20% and 35% of the previous value in group A and B, respectively. In clinical cases, all patients received the plasma exchange combined with hemodialysis using FUT as an anticoagulant, and no distinct side effect was observed during plasma exchange.

Adult↗
PubMed1988

[The significance of systolic time intervals in the dipyridamole test for the diagnosis of coronary disease].

The investigations concerning the significance of the systolic time intervals in the dipyridamole test for the diagnosis of the coronary heart disease were carried out in 15 healthy test persons and 40 patients with coronary heart disease. Apart from the systolic time intervals calculated according to Weissler and co-workers also the behaviour of the ST segment, the R wave in lead V5 (RV5) and the sum of the amplitudes of the R waves (sigma R) were estimated concerning sensitivity, specifity and predictive value. At a sensitivity of 65% for the behaviour of the ST segment under influence of the dipyridamole test this was smaller for RV 5, sigma R, ICT and LVET/S1S2, on the other hand greater for PEPI and OS2I (p less than 0.05). The other time intervals did not differ in their sensitivity to the ST segment. The specifity and the predictive confirming value were 100% for the changes of the ST segment. In the analysis of the other parameters no differences were stated (p greater than 0.05). The predictive value, excluding a coronary heart disease, was 51.7% for the ST segment and still higher for PEPI and OS2I (p less than 0.05). By the analysis of the systolic time intervals the diagnosis value of the dipyridamole test continues to increase.

Adult↗
PubMed1987

[Dipyridamole thallium-201 myocardial scintigraphy in coronary diagnosis; a comparison of methods with thallium-201 myocardial scintigraphy after ergometer stress].

Two scintigraphic methods, resting dipyridamole and exercise thallium-201 myocardial perfusion imaging, to detect and localize coronary artery stenosis were compared in 32 patients suffering from coronary artery disease. The sensitivity of detecting a greater than 50% coronary stenosis was 94% for exercise thallium-201 perfusion imaging and 88% for dipyridamole thallium-201 perfusion imaging. The overall sensitivity and specificity of localizing a greater than 50% coronary stenosis by the two methods were also not significantly different. The results of the two scintigraphic methods were independent of the severity of coronary artery disease. Dipyridamole thallium-201 myocardial perfusion imaging provides a useful and safe alternative test for detecting and localizing coronary artery stenosis in patients unable to perform maximal exercise.

Coronary Disease↗
PubMed1986

[Reverse redistribution in dipyridamole-loading thallium-201 images using single photon emission computed tomography].

This study demonstrated the clinical significance of reverse redistribution, i.e., a decrease in the relative Tl activity in the redistribution image compared to that of the stress image after administration of dipyridamole. Dipyridamole was infused intravenously at a rate of 0.142 mg/kg per min for four min, and a stress image was obtained 10 min after the injection of two mCi 201Tl. Each patient returned for redistribution scanning in the identical position three hours after the isotope injection. The myocardial image of Tl was analyzed by single photon emission computed tomography and its washout rate was calculated by the segmental ROI method. Myocardial function and the motion of left ventricular wall were analyzed by 99mTc-RBC-gated cardiac pool imaging. The results were as follows: Reverse redistribution was noted in 27 (21.6%) of 125 consecutive Tl dipyridamole and redistribution myocardial imaging studies. The stress image demonstrated normal perfusion (group 1) and reduced perfusion (group 2) of Tl. Group 1 consisted of 17 patients with diabetes mellitus, supraventricular arrhythmias, hypertension, and others. Group 2 consisted of 10 patients with subendocardial infarction, diabetes mellitus, and hypertension, and others. The percentage prevalence of reverse redistribution among patients with supraventricular arrhythmia was 62.5% (five of eight patients), with subendocardial infarction 60.0% (three of five), with hypertension 42.8% (six of 14), and with diabetes mellitus 40.0% (eight of 20), while in those with transmyocardial infarction and angina pectoris no reverse redistribution percentage was found. The washout rate of Tl in normal perfusion areas was 44.0 +/- 12.8%, the reverse redistribution of group 1 was 47.4 +/- 12.8%, and of group 2 was 51.2 +/- 8.2%. The washout rate of the reverse redistribution of group 2 was significantly greater than that of the normal areas. In gated cardiac pool imaging, patients in group 2 had significantly larger areas showing abnormal contraction of the left ventricular wall and significantly lower ejection fraction than did group 1. In the electrocardiogram ST segment depression was noted more frequently in group 2 than group 1. No Q wave was present in the corresponding reverse redistribution area. These results suggest that reverse redistribution might occur in a region with a combination of scarred and normal myocardium, the metabolically affected myocardium, and an area with relatively increased myocardial blood flow. The patients in group 2 seem to have the more pathological myocardium than do those in group 1.

Adult↗
PubMed1987

Effects of low doses of aspirin and dipyridamole on platelet aggregation in the dog coronary artery.

The circumflex coronary artery of pentobarbital-anesthetized dogs was partially obstructed with an externally applied rigid plastic band. Platelet aggregation at the site of stenosis caused a gradual decline in blood flow in the artery, which was monitored with an electromagnetic flow probe placed proximally to the obstructor. The effects of drugs on platelet aggregation were evaluated by monitoring changes in both the rate and the degree of decline in blood flow. In most dogs, aspirin inhibited intravascular platelet aggregation (ED50 = 1 mg/kg). Dipyridamole, even at doses that severely depressed blood pressure (1 mg/kg), had no effect on platelet aggregation. However, in dogs that had been pretreated with a low dose of dipyridamole (0.2 mg/kg), the antiaggregatory activity of aspirin was enhanced. This potentiation was evident only at low doses of aspirin (0.03 and 0.1 mg/kg), where the drug was 10 times more active; at high aspirin doses, which depressed vascular cyclooxygenase, no potentiation was seen. Further evidence that the mechanism of this synergism may depend on endogenous prostacyclin production at the site of the partial obstruction was seen when cyclooxygenase inhibitors applied topically on the exposed artery eliminated the antiaggregatory effect of low doses of aspirin. It is important to note that the protective effect of dipyridamole and low-dose aspirin was less than that seen at the high doses of aspirin alone, suggesting that the theoretical benefits of platelet-specific doses of aspirin may be overstated.

Animals↗
PubMed1987

Dipyridamole-thallium scanning in patients undergoing vascular surgery. Optimizing preoperative evaluation of cardiac risk.

Dipyridamole-thallium imaging has been suggested as a method of preoperatively assessing cardiac risk in patients undergoing major surgery. To define more clearly its proper role in preoperative assessment, we prospectively evaluated 111 patients undergoing vascular surgery. In the first set of 61 patients, our data confirmed the value of preoperative dipyridamole-thallium scanning in identifying the patients who suffered postoperative ischemic events. Events occurred in eight of 18 patients with reversible defects on preoperative imaging, compared with no events in 43 patients with no thallium redistribution (confidence interval for the risk difference: 0.624, 0.256). The results also suggested that clinical factors might allow identification of a low-risk subset of patients. To test the hypothesis that patients with no evidence of congestive heart failure, angina, prior myocardial infarction, or diabetes do not require further preoperative testing, we evaluated an additional 50 patients having vascular procedures. None of the 23 without the clinical markers had untoward outcomes, while ten of 27 patients with one or more of these clinical markers suffered postoperative ischemic events (confidence interval for the risk difference: 0.592, 0.148). In the clinical high-risk subset, further risk stratification is achieved with dipyridamole-thallium scanning.

Aged↗
PubMed1987

[Dipyridamole test and myocardial scintigraphy with Tl-201 in the diagnosis of myocardial ischemic pathology].

We studied 19 consecutive subjects affected by effort angina using following tests: ecg stress test, stress 201-Tl scan, coronary arteriography; 201-Tl scan, coronary arteriography, hemodynamic, echo 2 D, ecgraphic monitoring during Dipyridamole test (D). Basing on coronary arteriography results we divided patients; in the group A (10 patients with significant stenoses greater than or equal to 50%) stress ecg and scintigraphy were positive in 9 patients; Dipyridamole test induced angor and ecgraphic changes in 5 patients and in 4 left ventricle wall motion disorders, 201-Tl scan was positive in all 9 patients tested. In the group B (9 subjects with no significant stenosis) ecgraphic changes were observed in 2 subjects and 201-Tl scan was positive in 6 subjects; D induced in 2 cases angor, in 1 case ecgraphic changes, in 1 case left ventricle wall motion disorders and the same 201-Tl defects in 6 previously individualized patients. In both groups we observed at coronary arteriography during D identical findings in comparison with the immediately before performed. In our experience D infusion is confirmed as provocative test of ischemia. The same ischemic pattern observed at stress and Dipyridamole scintigraphy in patients with no significant coronary stenosis suggests as pathogenetic mechanism the regional lack of dilatory reserve.

Adult↗
PubMedDate not supplied

Characterization of conditions in which dipyridamole enhances methotrexate toxicity in L1210 cells.

In vitro studies in exponentially growing L1210 cells utilizing DNA flow cytometry and cell proliferation measurements indicate enhancement of methotrexate effects by Dipyridamole provided: Methotrexate concentrations exceed those required to shut off maximally de novo pathways of purine and pyrimidine synthesis (i.e. 30 nM for 48 h), and Dipyridamole concentrations exceed 3 microM. In 10% fetal calf serum, this concentration inhibits tritiated thymidine uptake by about 80%. These data should prove helpful in the planning of clinical studies with dipyridamole or other inhibitors of nucleoside transport used to potentiate inhibitors of de novo pathways.

Animals↗
PubMed1986

[Changes in segmental and general left ventricular myocardial contractility and intracardiac hemodynamics in the dipyridamole test of patients with ischemic heart disease (data of roentgenocontrast ventriculography)].

The dipyridamole test was performed during diagnostic coronaro-ventriculography in 7 patients showing no angiographic signs of coronary atherosclerosis (group 1) and 15 patients with a 75% stenosis in one or more coronary arteries (group 2). The test provoked an anginal attack in 11 (73%) second-group patients that was accompanied with the emergence or aggravation of asynergy in 10 (67%) or ischemic electrocardiographic changes in 7 (47%). In all cases, the anginal attack was associated with a rise in end diastolic pressure. All first-group patients showed no response to the dipyridamole test as evidenced clinically and electrocardiographically. No asynergic zones were identified on any of the ventriculograms recorded after dipyridamole administration.

Adult↗
PubMed1985

[Epidemiological trial of the prophylactic effectiveness of the interferon inducer dipyridamole with respect to influenza and acute respiratory diseases].

The epidemiological effectiveness of dipyridamol, an interferon-inducing agent used for the prevention of influenza and viral acute respiratory diseases, was tested in 4 epidemiological trials, 3 of them carried out as double blind trials. Observations were made in groups of adults (a research institute, a factory) and children (a kindergarten, a school), comprising 1040 subjects in the test groups and 771 subjects in the control groups. The drug was used during the whole epidemic period (January--March 1983) according to the following schedule: 1 oral administration in 8 days, in doses of 8 mg for adults, 50 mg for schoolchildren and 24 mg for children in the kindergarten. The epidemiological effectiveness of the drug was evaluated by comparing the total morbidity rates in influenza and acute respiratory diseases in the test and control groups. The results of 4 trials showed a pronounced epidemiological effectiveness of dipyridamol. The values of the epidemiological effectiveness index of the drug were 2.38 in the kindergarten, 1.55 at the school, 7.42 at the factory and 2.16 at the research institute. The results of the study of dipyridamol suggest that further investigations should be made with a view to use it for the mass prevention of influenza and acute respiratory diseases.

Acute Disease↗
PubMedDate not supplied

[Effect of dipyridamole and papaverine on adenosine absorption by the lymphocytes].

It was shown that dipyridamole and papaverine induce concentration-dependent inhibition of the absorption of [14C] adenosine by thymocytes. This action is different in lymphocytes from different lymphoid organs and blood. Dipyridamole enhances the effect of various papaverine concentrations on the absorption of adenosine by thymocytes, but it does not exceed the maximal effect, achieved by the latter in high doses. It is supposed, that dipyridamole inhibits the cell transport of adenosine and papaverine influences the adenine-nucleotide metabolism.

Absorption↗