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PubMed1990

Intravenous dipyridamole thallium-201 SPECT imaging methodology, applications, and interpretations.

Dipyridamole TI-201 imaging is an ideal alternative to exercise TI-201 scintigraphy in patients who are unwilling or unable to perform maximum exercise stress. The use of intravenous dipyridamole, alone or in combination with exercise, has not been approved for clinical practice by the Food and Drug Administration. Once approval is granted, the test will become a widely used and important component of the cardiac work-up. The indications, methodology, side effects, and utility of dipyridamole cardiac imaging in the clinical setting are discussed and a variety of examples presented.

Coronary Disease↗
PubMed1990

[Systemic effects of intravenous dipyridamole in patients of various age groups].

Aim of this study was to assess the role of age-related vascular response in the onset of i.v. dipyridamole effects. The results of 129 patients who underwent a dipyridamole infusion were reviewed. The patients were divided into three according to age: 47 patients of less than 50 years (group I), 54 patients aged between 50 and 60 years (group II) and 28 patients of more than 60 years (group III). For each group heart frequency (HF) and systolic blood pressure (SBP) were considered in basal conditions, at the end of infusion and at the minimum value of SBP (SBP min); moreover the time in reaching SBP min was considered (time to SBP min). At the end of the infusion no significant changes in SBP were observed in all groups while the SBP min value reached from group III were significantly lower than basal (142.6 +/- 20.4 mmHg, p less than 0.02). The HF, without significant differences among the three groups in basal conditions, increased significantly at the end of infusion only in group I and II, with a more significant increase in group I at the time of SBP min with respect to groups II and III. The group 3 showed moreover, a significant longer time to SBP min (286 +/- 208 sec) respect to the group I and II (145 +/- 130 and 160 +/- 177 sec respectively) (p less than 0.02). From these data it can resume that age could be a factor to determine hemodynamic response to intravenous dipyridamole.

Adult↗
PubMed1990

[How important is dipyridamole in patients with ischemic heart disease?].

Dipyridamol does not have a proven, clinically significant antithrombotic effect. Treatment is relatively expensive. Dipyridamol can cause ischaemia of the heart muscle in patients with ischaemic heart disease. Dipyridamol administration as part of antithrombotic treatment should therefore be selective. Large does can be used as a supplementary loading test for detection of the ischaemic focus.

Coronary Disease↗
PubMed1990

[Angina pectoris induced by oral administration of dipyridamole].

Five cases scheduled for myocardial elective coronary artery bypass (CAB), who developed angina and ischemic electrocardiographic changes, after oral administration of dipyridamole (100 mg) are reported. Dipyridamole induced myocardial ischemia has been demonstrated in subjects with coronary artery disease, if this drug is administered intravenously. To our knowledge, only one study reported this side effect, after oral route, in four patients awaiting urgent CAB, for unstable angina. Based on our and other Authors experience, preoperative dipyridamole should be used with caution, especially in patients with unstable angina.

Administration, Oral↗
PubMed1990

[Effect of aminophylline on thallium-201 washout rate during myocardial perfusion imaging with dipyridamole].

Thallium-201 myocardial perfusion imaging with dipyridamole was performed on 78 patients (pts) with suspected coronary artery disease (CAD). Twenty eight pts had normal coronary arteries (control group), and 50 pts had 50% or greater stenosis in one or more major coronary arteries (CAD group). In control group, aminophylline (Am) was infused intravenously on 12 pts during dipyridamole testing. Mean washout rate (WR) of these 12 pts was greater than that of 16 pts without Am (42% vs 35%, p less than 0.01). Then normal limit of WR was defined separately from the pts of control group with and without Am. The sensitivity for detecting the pts with CAD by WR analysis which normal limit was calculated separately with and without Am was 92% (46/50). When normal limit of WR was determined from all pts in control group, the sensitivity decreased to 84% (42/50). Am significantly affected thallium-201 washout during dipyridamole testing. WR of CAD pts should be estimated by specific set of normal limit with and without Am.

Aminophylline↗
PubMedDate not supplied

Diagnostic accuracy of single photon emission computed tomography with thallium-201 for the identification of diseased coronary arteries. Comparison between dipyridamole infusion and exercise stress test.

Myocardial perfusion imaging with 201Tl and single-photon emission computed tomography (SPECT) was carried out in two groups of patients, subsequently submitted to diagnostic coronary angiography. SPECT was performed in group 1 (41 patients) after slow i.v. infusion of dipyridamole and in group 2 (162 patients) after tracer injection at maximal ergometric exercise. To evaluate the diagnostic capability of SPECT in the detection of diseased coronary vessels, the left ventricular myocardium was subdivided into 6 segments related to the three major coronary arteries. Sensitivity for the left anterior descending artery was 77% in group 1 and 79% in group 2; specificity was 80% and 96%, respectively. Sensitivity for the right coronary artery was 91% in group 1 and 85% in group 2; specificity was 81% and 73%. For the left circumflex artery sensitivity was 65% for group 1 and 67% for group 2, while specificity was 89% and 88%, respectively. Myocardial SPECT results after ergometric exercise and dipyridamole infusion turned out to be almost superimposable. Dipyridamole stress might be considered appropriate as a provocative test when physical exercise cannot be carried out.

Adult↗
PubMed1987

Dipyridamole-induced neoformation of capillaries in the rat heart. Quantitative stereological study on papillary muscles.

Eighteen young male Wistar rats were randomly divided into two groups of equal size. Each experimental animal was treated with the powerful vasodilating drug dipyridamole (4 mg kg-1 intraperitoneally twice daily) for a period of 6 weeks. The control animals received sham injections with saline. The rats were fixed by retrograde vascular perfusion. Seven transverse and two longitudinal sections per animal were randomly selected from the left ventricular papillary muscles for stereological investigation. Length density of capillaries (length of capillaries per unit of tissue volume), surface density of capillaries (surface area of capillaries per unit of tissue volume) and the "true" three-dimensional capillary-fiber ratio (length of capillaries per unit length of myocardial fibers) were estimated by means of the Dimroth-Watson distribution, a mathematical model of directional statistics which assumes that the capillary directions scatter around the longitudinal axis of the muscle. This model was recently introduced into the stereology of myocardial capillaries and leads to a more accurate quantitation of the capillary network than parameters used hitherto, such as the "capillary density" (number of capillary profiles per mm2 of cross sectional area) and the "capillary-fiber ratio" (number of capillary profiles per number of myofiber profiles in cross sections). After chronic dipyridamole treatment, the length density of myocardial capillaries (+5%; p less than 0.02), the surface density of capillaries (+8%, p less than 0.01) and the three-dimensional capillary-fiber ratio (+6%, p less than 0.05) were increased. It is therefore concluded that the vasodilating drug dipyridamole evokes capillary growth in the heart which may be induced by mechanical factors via the enhanced myocardial blood flow. Investigation of the frequency distribution of capillary directions in space in both groups provided evidence that the capillary growth resulted from neoformation of capillaries.

Animals↗
PubMedDate not supplied

Modulation of 5-fluorouracil toxicity by uridine, deoxyuridine, orotate and dipyridamole in normal tissues of rats with liver adenocarcinoma.

The cytotoxicity of 5-FU, given by the hepatic artery, was measured by its incorporation into the acid soluble fraction, RNA and DNA in normal tissues and an adenocarcinoma transplanted into the liver in rats. Other substances were simultaneously administered by the portal vein to modulate the cytotoxicity. None of them had any significant influence on the incorporation of 5-FU into tumor. Dipyridamole decreased the incorporation of 5-FU into liver RNA and increased the nucleotide/DNA and RNA/DNA ratios so that the incorporation into mg RNA per liver cell was unchanged. Dipyridamole decreased the incorporation into the acid soluble fraction, RNA and DNA of the small intestine and also into RNA per mg DNA. It increased the nucleotide/RNA and RNA/DNA ratios in the bone marrow. Orotate decreased the incorporation into liver and intestinal RNA. Uridine increased the incorporation into liver RNA. The results obtained with dipyridamole were the most pronounced. Studies are continuing with this and other membrane transport inhibitors.

Adenocarcinoma↗
PubMed1989

Administration of aspirin-dipyridamole reduces proteinuria in diabetic nephropathy.

We assessed in a pilot study the effect on some aspects of renal function of 6 weeks' administration of a combination of aspirin-dipyridamole (990 mg/225 mg daily) administered on a double-blind crossover schedule in 16 insulin-dependent diabetic patients with nephropathy. Total 24-h urinary protein excretion (16 patients) was significantly reduced during aspirin-dipyridamole administration from a geometric mean (range) of 1.9 (0.4-7.7) g/24 h to 1.4 (0.5-9.9) g/24 h (2P less than 0.05). Indium-labelled platelet survival (eight patients), glomerular filtration rate and renal blood flow (eight patients) showed no significant change following aspirin-dipyridamole therapy, even though plasma creatinine concentration increased from 118 (65-371) to 130 (76-438) mumol/l (2P less than 0.05). Diabetic control and blood pressure remained unchanged throughout the study. Although the results showed that this treatment significantly reduced proteinuria in patients with diabetic nephropathy, the mechanism of action was not entirely clear.

Adult↗
PubMed1989

Spontaneous atherosclerotic lesions and prostacyclin formation in rabbits: effects of combined dipyridamole and aspirin.

The influence of dipyridamole and lysine acetylsalicylate on the incidence of atherosclerotic lesions and on arterial prostacyclin formation was studied in rabbits. Male New Zealand rabbits received i.m. for 16 months dipyridamole (12.5 mg/kg/day) and lysine acetylsalicylate (0.5 mg/kg/day). The incidence of spontaneous atherosclerotic lesions in the aorta was reduced by 16.4% with respect to untreated animals. Administration of the drugs significantly increased prostacyclin formation with respect to the untreated rabbits both in animals developing (1124 +/- 197 pg/mg/3 min vs 316 +/- 49 pg/mg/3 min) or not developing lesions (499 +/- 40 pg/mg/3 min vs 246 +/- 19 pg/mg/3 min). The observed increase in prostacyclin formation could account for the lowered incidence of atherosclerotic lesions in rabbits receiving the combination of dipyridamole and lysine acetylsalicylate.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

[The dipyridamole-echo-ECG test in hypertensives with microvascular angina].

Microvascular angina - chest pain syndrome in the presence of angiographically normal epicardial coronary arteries and reduced flow reserve - has been also described in patients with essential hypertension and it has been linked to the development of left ventricular hypertrophy. Dipyridamole-Echocardiography Test (DET: 2D-echo and 12 lead ECG monitoring with dipyridamole infusion, up to 0.84 mg/kg over 10') was performed in 28 essential hypertensives meeting the following inclusion criteria; 1) history of chest pain; 2) angiographically normal coronary arteries; 3) normal resting regional and global left ventricular function. A group of 12 (age and sex matched) normotensives with the same inclusion criteria, as well as with negative exercise stress test, was also evaluated. During DET, none, either in essential hypertensives or in control group, developed a regional dyssynergy of contraction; 15 in essential hypertensives, and 2 in control group had a diagnostic (greater than 0.1 mVolt from baseline) ST segment depression on ECG tracing (54 vs 17% p less than 0.01); 16 in essential hypertensives and 2 in control group had chest pain (57 vs 17%, p less than 0.01). None of the control group and 9 of the essential hypertensives had echocardiographically assessed left ventricular hypertrophy. In the essential hypertensives group, ventricular hypertrophy was present in 7/20 patients with and in 2/8 patients without dipyridamole induced chest pain and/or ST segment depression (35 vs 25%, p = ns). In conclusion, essential hypertensives patients with chest pain and angiographically normal coronary arteries frequently show "echocardiographically silent" angina and/or ST segment depression during DET. The presence of ventricular hypertrophy does not appear to be a prerequisite for the induction of angina in these patients.

Angina Pectoris↗
PubMed1989

Inhibition and stimulation of photoreceptor phosphodiesterases by dipyridamole and M&B 22,948.

Few high affinity inhibitors of the photoreceptor phosphodiesterases have been identified. We show here that dipyridamole and M&B 22,948 (Zaprinast), potent inhibitors of the cGMP-binding, cGMP-specific phosphodiesterase (PDE), also inhibit trypsin- or transducin-activated bovine rod and cone photoreceptor phosphodiesterases at submicromolar concentrations. Dixon plots demonstrated that the inhibition of trypsin-activated rod PDE was competitive, with Ki values of 140 nM for M&B 22,948 and 380 nM for dipyridamole. Both of these drugs were much more potent than other PDE inhibitors, including isobutylmethylxanthine (IBMX). These results reinforce the suggestion that the photoreceptor and the cGMP-binding, cGMP-specific PDE are closely related. In addition, the high affinity and selectivity of these agents should make them useful for probing the regulation and function of PDE in the photoreceptor. At low substrate concentrations, the effects of these drugs on basal unactivated PDE activity were similar to those seen with trypsin- or transducin-activated PDE. At millimolar substrate concentrations, however, the effects of the drugs were biphasic; PDE activity was stimulated at drug concentrations from 1 to 10 microM and inhibited at higher concentrations. Stimulation was not observed with IBMX. This stimulation of activity apparently was not an allosteric effect caused by direct binding of the dipyridamole and M&B 22,948 to the high affinity noncatalytic cGMP binding sites on the PDEs; whereas no cooperativity of cGMP binding to this site has been demonstrated, the drugs actually stimulated the binding of low concentrations of cGMP to this site. In addition, whereas preincubation with cGMP and cGMP analogs blocked the stimulation exerted by the drugs, they did so only at much higher concentrations than those necessary for saturation of the high affinity noncatalytic cGMP site. Because the stimulation can only be seen at higher substrate levels than are thought to exist in the photoreceptor, only the inhibitory effects of the drugs are likely to be pharmacologically relevant. However, the stimulation exerted by these drugs may point to a hitherto unknown allosteric interaction between the catalytic and regulatory sites on the PDE or to a previously unrecognized regulatory site.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1989

[Evaluation of the effects of macerated oral dipyridamole on the ergometric test].

Eighteen male patients with ages varying from 42 to 72 years (average 60.6), with coronary heart disease confirmed by angiography, on regular rehabilitation program and on regular use of dipyridamole were submitted to three exercise stress tests: a control test (TE1) and forty minutes after oral administration of macerated dipyridamole in doses of 150 mg (TE2) and 300 mg (TE3), respectively. The comparison between the data of TE2 and TE1 demonstrated that in TE2 the ST depression was more accentuated in the smallest maximal load attained and in the effort peak as well. The comparison between the data of TE3 and TE1 showed that in TE3: 1) the ST depression was more evident in the effort peak and in the smallest attained load; 2) the heart rate and the product heart rate x blood pressure were smaller in the effort peak; 3) the total time of angina and the time for its relief after effort, were longer. The other exercise stress test parameters did not show any significant changes. These data, suggest that the physical effort overload, after dipyridamole administration, produced a more marked myocardial ischemia, whose degree was proportional to the dose.

Administration, Oral↗
PubMed1989

[The effect of the administration of slow releasing type of dipyridamole on teflon graft patency for experimental superior vena cava replacement in mongrel dogs].

Teflon graft tubes (10 mm in diameter, 20-25 mm in length) were implanted in 40 mongrel dogs for replacement of the superior vena cava and were followed 12 days to 6 months after the operation. In these, 22 dogs in Group I were given a slow releasing type of dipyridamole (10 mg/kg, daily) and 18 dogs in the other group were not given for the control study. The results were compared in each group. The medicated group showed much less rate of graft thrombosis 2/22 (9.1%) vs. 9/18 (50%), less rate of intimal hyperplasia 2/22 (9.1%) vs. 18/18 (100%) and also less rate of graft obstruction 1/22 (4.5%) vs. 9/18 (50%). These findings demonstrated that the medicated group can expect highly significant (p less than 0.01) superior patency of the graft with dipyridamole in macroscopic findings. Also, microscopic and electron microscopic findings showed much more smooth healing of the surface of the graft. We concluded that postoperative administration of a slow releasing type of dipyridamole may be effective for smooth endothelialization of Teflon graft used as the experimental superior vena cava replacement.

Animals↗
PubMed1989

[Prolonged myocardial ischemia after the high-dose dipyridamole test].

The intravenous dipyridamole test is considered a safe procedure with a very low incidence of severe cardiac effects and is routinely used in the diagnosis and prognosis of coronary artery disease. We report the case of a 63-year-old female with negative exercise stress test who developed prolonged and extensive myocardial ischemia after the high-dose intravenous dipyridamole echocardiography test. Aminophylline and nitroglycerin were employed but were ineffective and the patient was successfully treated with systemic thrombolysis. At coronary angiography, 48 hours later, a 50% stenosis in the proximal LAD was documented. We stress that high-dose intravenous dipyridamole can induce a severe ischemic response whose occurrence is unpredictable according to the pre-test clinical features.

Coronary Disease↗
PubMed1989

[Effect of dipyridamole on the functional state of the atrioventricular node].

Effect of dipyridamole on sinoatrial node function was evaluated in 24 patients during invasive cardiac electrophysiological examination. 3 multipolar USCI electrodes were inserted into the heart through femoral veins using Seldinger's method. Intracardiac potentials (A, H, V) and ecg tracings (I, II, III, aVR leads) were recorded during sinus rhythm and right atrial stimulation - continous, with gradually increasing pacing frequency and during extrastimulation, with gradually shortening of coupling interval. 0.5 mg/kg b.w. of dipyridamole (Curantyl, Germed, GDR) was intravenously administrated. During the initial examination and 5 minutes after the end of a drug injection following parameters were estimated: sinus cycle length (SCL), sinoatrial conduction time using Narula's and Strauss's methods (respectively SACTN, SACTS), maximal, corrected and standardized sinus node recovery time (respectively SNRTmax, SNRTcor, SNRTnorm) and maximal second postimulation pause (II pause max). Statistically significant (p less than 0.01) shortening of SCL by 26%, SACTN by 17%, SACTS by 13% SNRT max by 21%, II pause max by 26% was observed after dipyridamole administration. Only in the patient with sinoatrial node dysfunction dangerous bradycardia occurred.

Action Potentials↗
PubMed1989

[Detection and classification of coronary artery disease by dipyridamole perfusion scintigraphy: its prognostic significance].

To detect coronary artery disease (CAD) noninvasively and to predict the occurrence of future cardiac events, 671 patients were evaluated using dipyridamole perfusion scintigraphy. 1. Although chest pain and ST depression were induced by the administration of dipyridamole in 34% and 22% of the patients, respectively, and additional intravenous aminophylline was needed in 19% of the patients, dipyridamole perfusion scintigraphy could be completed in nearly all patients. In contrast, treadmill exercise test was not accomplished in 24% of the patients. 2. The patients were classified in three groups by scintigraphic perfusion defects; i.e., group I (322 patients) with fixed defects, group II (107 patients) with reversible defects, and group III (242 patients) without perfusion defects. The patients in Group I were subclassified three groups according to three high risk parameters (extensive fixed defect, partial redistribution and diffuse slow washout)--group Ia (69 patients) with two or more high risk parameters, group Ib (144 patients) with one high risk parameter and group Ic (109 patients) without high risk parameters. 3. Coronary angiography performed in 377 patients revealed significant CAD (luminal narrowing greater than or equal to 50%) in 96%, 89%, 56%, 90% and 8% of the patients in groups Ia, Ib, Ic, II and III, respectively. Multi-vessel CAD was present in 87%, 32%, 11%, 51% and 2% of the patients in each group, respectively.

Adolescent↗
PubMed1989

Effect of aspirin alone and aspirin plus dipyridamole in early diabetic retinopathy. A multicenter randomized controlled clinical trial. The DAMAD Study Group.

In a double-blind randomized controlled clinical trial conducted in two French and two United Kingdom centers, the effect of antiplatelet agents, i.e., aspirin alone (330 mg 3 times daily) or in combination with dipyridamole (75 mg 3 times daily), was tested versus placebo in 475 patients with early diabetic retinopathy. The assessment of retinopathy was based on change in the number of microaneurysms (MAs) present in the macular field, as seen on fluorescein angiograms, over 3 yr. Forty-one patients did not complete the study. At least three readable initial and yearly angiograms were available on 420 patients (266 treated with insulin and 154 not treated); the results reported are based on these patients. The mean yearly increase in definite MAs was similar in insulin-treated and non-insulin-treated diabetic patients. There was no significant difference between the aspirin-alone group (0.69 +/- 5.1 mean +/- SD, n = 145) and the aspirin-plus-dipyridamole group (0.34 +/- 3.0, n = 142). In the placebo group the mean yearly increase (1.44 +/- 4.5, n = 133) was significantly higher than in the treated group (P = .02, 1-tailed t test). There was a clear relationship between the deterioration in ophthalmological signs and the increase in mean yearly MAs (clinically stable, 0.38 +/- 3.96, n = 293; deteriorating, 1.79 +/- 4.89, n = 127; P = .002, 2-tailed t test). We conclude that aspirin alone and in conjunction with dipyridamole significantly slows the progression of MA evolution in early diabetic retinopathy.

Adult↗