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PubMed2001

Dipyridamole-atropine stress echocardiography versus exercise SPECT scintigraphy for detection of coronary artery disease in hypertensives with positive exercise test.

OBJECTIVES: Many different stress echocardiographic and radionuclide perfusion imaging tests have been proposed for detecting epicardial coronary artery disease (CAD) in hypertensive patients. Their relative diagnostic and prognostic value has not been exactly established. BACKGROUND: A positive exercise electrocardiography test has a low diagnostic specificity in hypertensive patients and warrants for a complementary imaging test to confirm the diagnosis of coronary artery disease. METHODS: Hypertensive patients (n = 53), (29 males, aged 58 +/- 10 years) with normal left ventricular function detected by echocardiography and previous positive exercise test ( > or = 0.15 mV of ST segment depression on 12 lead electrocardiogram) underwent dipyridamole-atropine stress echocardiography (DASE) and thallium-201 stress/ rest myocardial single-photon emission computed tomography (SPECT). All patients had coronary angiography within 15 days and independently of imaging test results. RESULTS: Coronary angiogram showed significant ( > or = 50% qualitatively assessed diameter reduction) epicardial coronary artery disease in 23 (43%) patients. Sensitivity for detection of coronary artery disease was significantly higher for scintigraphy (DASE = 78% versus SPECT = 100%, P < 0.05) while specificity was higher for echo (DASE = 100% versus SPECT = 47%, P < 0.00001). Diagnostic accuracy was also higher for echo (DASE = 91% versus SPECT = 70%, P < 0.01). CONCLUSION: In patients with exercise-nduced ST segment depression, dipyridamole stress echo and SPECT perfusion scintigraphy are both good diagnostic options, with DASE characterized by higher specificity, lower sensitivity, and at least comparable diagnostic accuracy than SPECT.

Adult↗
PubMed1993

A comparison of the redistribution and reinjection techniques in dipyridamole thallium tomography.

The effect of the injection of additional thallium after a redistribution study and prior to a further resting study was evaluated in 21 patients with angiographically proven coronary artery disease. Using dipyridamole as the stress mechanism, the studies were carried out tomographically and the results analysed quantitatively with the Bull's-eye technique. Two patients had normal scans. Of the remaining 19, 11 patients had a perfusion defect which appeared irreversible on redistribution imaging. However, six of these patients demonstrated improved or normal uptake after the second injection of thallium. Of the eight patients with a reversible defect, two revealed considerably greater reversibility after reinjection. These results indicate that the reinjection of thallium prior to the resting study significantly (P < 0.02) improves the detection rate of ischaemia during dipyridamole thallium tomography.

Coronary Disease↗
PubMed1995

Gastric activity on dipyridamole 201Tl myocardial perfusion imaging: a clinically useful finding.

To determine the potential association of increased 201Tl uptake by the stomach with symptoms referable to gastritis, 39 consecutive patients experiencing chest pain syndromes underwent a routine dipyridamole 201Tl pharmacological stress test. With the patient in a fasting state, dipyridamole was infused intravenously (0.56 mg kg-1), shortly followed by 201Tl infusion and subsequent image acquisition for single photon emission tomography (SPET). The original 32 SPET images over 180 degrees of arc were interpreted without knowledge of clinical data, using a 4-point scoring system. Patients with active symptoms of gastro-oesophageal discomfort (n = 17) were found to have significantly greater 201Tl stomach uptake scores, compared to the little or no uptake in the 22 patients without such active symptoms (P = 0.0001). A stepwise logistic regression analysis was used to determine which factor(s) showed independent predictive value of 201Tl gastric uptake. The only two independent variables identified were the presence of active gastritis symptoms and the use of anti-gastritis medications. Elevated gastric 201Tl uptake may be a clinically useful finding indicative of gastric inflammation that may be of value in the differential diagnosis of chest and epigastric discomfort.

Aged↗
PubMed1995

Comparison of myocardial ischaemia in post-infarction patients with and without angina: assessment by dipyridamole 201T1 imaging.

Ninety patients with old myocardial infarction were studied to evaluate the efficacy of intravenous dipyridamole 201Tl imaging for the detection of myocardial ischaemia in post-infarction patients, and to compare the prevalence of ischaemia in 63 patients with post-infarction angina (group I) and 27 patients without angina (group II). Thirty-four of the patients in group I and 15 of the patients in group II received coronary arteriography (CAG) for comparison; these were labelled groups IA and IIA, respectively. On 201Tl imaging, the incidence of scar with ischaemia in the infarct zone and scar with ischaemia at a distance were 72% and 42% in all patients, 89% and 52% in group I vs 33% and 19% in group II (P < 0.001 and P < 0.01, respectively). On CAG testing, the rates of infarct-related recanalization vessel and multi-vessel disease were 76% and 68% in group IA vs 40% and 40% in group IIA (P < 0.05 and P > 0.05, respectively). Thus, dipyridamole 201Tl imaging is a useful modality and post-infarction angina a proper indicator in the detection of myocardial ischaemia in post-infarction patients

Adult↗
PubMed1998

The safety of dipyridamole-thallium imaging in patients with critical aortic valve stenosis and angina.

Angina pectoris occurs in many patients with critical aortic valve stenosis, but in less than 50% of cases is it due to atherosclerotic coronary disease. Pre-operative coronary angiography is used to determine whether coronary revascularization is required in addition to aortic valve replacement. The aim of this study was to determine the safety and image quality of dipyridamole-thallium imaging (DPT) in excluding coronary artery disease requiring a coronary artery bypass graft in patients with aortic valve stenosis requiring aortic valve replacement. Dipyridamole-thallium imaging and coronary angiography were performed less than one month apart in patients with clinical and echo-Doppler evidence of aortic valve stenosis requiring aortic valve replacement. Coronary angiography and DPT were each interpreted by experienced observers blind to the other result. The safety of DPT was judged by symptoms, ECG changes, haemodynamic effects and the need for stress reversal. Image quality was determined from the myocardial-to-background thallium uptake ratio in a normal segment. Twelve patients with aortic valve stenosis (gradient 95 +/- 24 mmHg) were studied, all of whom had left ventricular hypertrophy. The dominant symptom was angina pectoris in eight patients, syncope in three and dyspnoea in one. None had previous myocardial infarction, but two were smokers, six were hyperlipidaemic and one was hypertensive. The patients tolerated DPT well and only one required stress reversal. The quality of the DPT images was good. The DPT image was entirely normal in eight (66%) patients, none of whom had coronary artery disease. Reversible defects were seen in four patients, all of whom had significant coronary artery disease. We conclude that DPT is safe in patients with aortic valve stenosis and angina pectoris. The image quality is good despite left ventricular hypertrophy. In patients with angina pectoris and aortic valve stenosis, coronary angiography can safely be restricted to those with abnormal myocardial perfusion results.

Aged↗
PubMed2001

Non-invasive prediction of angiographic progression of coronary artery disease by dipyridamole-stress echocardiography.

BACKGROUND: Coronary angiography is the currently accepted standard means for assessing progression of coronary artery disease. A dipyridamole-echocardiography test (DET) might provide an alternative non-invasive functional imaging method for this purpose. OBJECTIVE: To assess whether variations in results of serial DET match variations in angiographic assessments of coronary artery disease. METHODS: From the Pisa Institute of Clinical Physiology stress-echocardiography data bank (1983-1998), we selected 60 patients satisfying the inclusion criteria of coronary angiography and DET having each been performed and interpreted twice independently and within 1 week. The second angiographic and stress-echocardiographic assessment was performed 45+/-31 months after the initial one. Angiographic progressors were defined a priori as patients with any progression of stenosis to occlusion and those with any stenosis > 30% with > 20% progression of stenosis measured by visual and quantitative coronary angiography. Stress-echocardiography progressors were defined as those patients who had previously had a negative test of a test having a positive result and those patients who had positive results of tests both in initial testing and in a second session of testing with the latter having a peak wall-motion-score index > 0.12 (on a scale of 1, normal to 4, dyskinetic in a 16-segment model) larger than the former. RESULTS: Of the 60 patients, 44 were angiographic 'progressors' and 16 were 'non progressors'. Stress-echocardiographic responses were concordant with angiographic identification for 39 of 44 progressors and 15 of 16 non-progressors, with an overall concordance of 90%. CONCLUSIONS: Measurement of dipyridamole-stress-echocardiographic response allows one to separate angiographic progressors and non-progressors efficiently, simply by taking into account the presence, extent and severity of stress-induced abnormalities of wall motion.

Aged↗
PubMed1986

Intravenous adenosine in the treatment of supraventricular tachycardia: a dose-ranging study and interaction with dipyridamole.

Increasing doses of adenosine were given by rapid intravenous bolus to seven patients with spontaneous supraventricular tachycardia. Adenosine restored sinus rhythm in 10 of 14 episodes of narrow complex tachycardia. In those patients in whom adenosine produced only transient ventricular slowing the underlying rhythm was atrial flutter. Transient dyspnoea occurred in all patients. In two patients taking dipyridamole the mean dose of adenosine which produced an electrophysiologic effect (restoration of sinus rhythm or ventricular slowing to under 100 beats min-1) was 1.0 +/- 0.52 mg, whereas in other patients the mean dose was 8.8 +/- 2.6 mg, suggesting potentiation of the action of adenosine by dipyridamole.

Adenosine↗
PubMed1988

Effect of dipyridamole on blood glucose and liver cyclic AMP levels and platelet count during endotoxaemia in mice.

1. Blood glucose, liver cyclic AMP (cAMP) levels, and platelet count were studied at different times during a 12 h interval after intravenous (i.v.) endotoxin injection (40 mg/kg) in mice. 2. Blood glucose and liver cAMP levels showed a progressive decrease in endotoxic mice and the decrease was significant after 8 and 12 h. 3. Dipyridamole (50 mg/kg) administered intraperitoneally (i.p.) 7 h post-endotoxin improved blood glucose and liver cAMP levels. 4. Platelet counts were decreased after 1 h in endotoxic mice and remained decreased up to 8 h. Dipyridamole administered soon after endotoxin improved platelet counts in endotoxic mice and increased survival rate to 100%.

Animals↗
PubMed2004

The actions of sodium nitroprusside and the phosphodiesterase inhibitor dipyridamole on phasic activity in the isolated guinea-pig bladder.

OBJECTIVE: To investigate the actions of the nitric oxide (NO) donor sodium nitroprusside (SNP) and phosphodiesterase (PDE) inhibitors, which purport to affect intracellular cGMP levels, on the phasic activity generated by agonist stimulation of the isolated whole bladder of the guinea pig. MATERIALS AND METHODS: Isolated whole bladders from female guinea pigs (270-300 g) were used in all experiments. Each bladder was cannulated via the urethra and suspended in a chamber containing oxygenated solution at 33-35 degrees C. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder. RESULTS: In the unstimulated bladder, SNP at up to 300 micromol/L caused only small (<2 cmH(2)O) rises in intravesical pressure. In the presence of phasic activity induced by either muscarinic or nicotinic stimulation, SNP at > 30 micromol/L, produced a dose-dependent increase in the frequency of the transients. The cells responding to SNP with an increase in intracellular cGMP were identified by immunofluorescence, and were in the suburothelial layer and within the muscle bundles. Smooth muscle cells of the detrusor body did not show a rise in cGMP. Exposure to the cGMP/PDE inhibitor zaprinast had no effect on phasic activity, but exposure to dipyridamole produced a transient rise in frequency, followed by an inhibition. Dipyridamole also significantly increased the amplitude of the phasic activity. CONCLUSION: These data show an excitatory role for NO/cGMP in the integrated regulation of phasic bladder activity. One population of cells which may be involved may be in the suburothelial layer and within the muscles. The differential sensitivity to PDE inhibitors affecting cGMP suggests that the cells responsible express specific isoforms of these regulatory enzymes. The importance of these observations, their possible role in the integrated physiology of the bladder and origins of bladder pathology, are discussed.

Animals↗
PubMed1994

Noninvasive study of left ventricular function and systemic haemodynamics during dipyridamole echocardiography stress test.

Left ventricular function and systemic haemodynamics were noninvasively assessed during cardiac stress testing with dipyridamole (0.84 mg kg-1 i.v.) in 10 subjects (44-61 years) with normal coronary arteries (group 1), and in 14 patients (46-77 years) with coronary artery disease either without (group 2, n = 6) or with (group 3, n = 8) echocardiographic evidence for myocardial ischaemia during test. Left ventricular wall motion and dimensions, and aortic root pressure and flow were obtained by Doppler echocardiography combined with an externally traced subclavian artery pulse calibrated with brachial artery pressures. Peripheral arterial resistance, total arterial compliance, and aortic characteristic impedance were estimated from aortic root pressure and flow, by use of a three-element windkessel model of the systemic circulation. Left ventricular ejection fraction improved from baseline to peak stress in group 1 (mean +/- SD: 62 +/- 6% vs. 65 +/- 6%, P = 0.05), whereas it was not significantly changed in group 2 (58 +/- 10% vs. 56 +/- 6%) and decreased in group 3 (53 +/- 10% vs. 43 +/- 10%, P < 0.05). Otherwise, the haemodynamic response was similar in the three groups: heart rate and cardiac index increased by at least 30% and 37%, respectively, whereas stroke index and arterial pressures were maintained at or slightly above baseline. Peripheral resistance decreased by at least 22%, and total arterial compliance and aortic characteristic impedance were not significantly altered during test. The worsening of wall motion abnormality at peak stress in group 3 was not significantly related to the change in systemic haemodynamics. Thus, dipyridamole acted predominantly on the arterioles without significantly influencing the large systemic arteries. Myocardial ischaemia during test impaired regional and global left ventricular function, but did not influence the systemic haemodynamic response.

Adult↗
PubMed1974

Effects of dipyridamole on neurogenic and non-neurogenic dilator responses of arterial smooth muscle.

1 In the isolated, perfused parametrial artery of the guinea-pig dipyridamole (10-100 ng/ml) potentiated dilator responses to adenosine 5'-triphosphate (ATP), glyceryl trinitrate and non-cholinergic, non-adrenergic inhibitory nerve stimulation to similar extents. In contrast dilator responses to acetylcholine were generally unaffected or reduced.2 These results support previous electro-physiological evidence that in this preparation cholinergic vasodilatation is mediated by a cellular mechanism different from that involved in the response to non-cholinergic dilator nervous activation.3 The results also suggest that potentiation of a neurally-mediated inhibitory response of smooth muscle by dipyridamole does not necessarily implicate ATP as the transmitter involved in this response.

Acetylcholine↗
PubMed1982

Effect of dipyridamole on the formation of 6-oxo-prostaglandin F1 alpha by the rat isolated aorta and ram seminal vesicle microsomes.

1 Dipyridamole (1 and 10 muM) enhanced the production of 6-oxo-prostaglandin F1 alpha by rat aortic tissue. 2 Dipyridamole (5 to 40 muM) did not influence the PGI2-synthetase activity in ram seminal vesicle microsomes whereas, in concentrations ranging from 100 to 200 muM, it reduced the metabolism of exogenously added arachidonic acid. The latter effect may be due to an inhibition of the cyclooxygenase.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Arachidonate metabolism is changed by dipyridamole in guinea pig isolated lungs.

Fifty nmol of 14C-arachidonic acid was injected into the pulmonary circulation of guinea pig isolated lungs and the metabolites were analysed from the non-recirculating perfusion effluent. The main metabolites in the effluent were thromboxane B2 (TxB2), 6-keto-PGF1 alpha, a metabolite group migrating on TLC plate near to 15-keto-PGE2 and a group of two metabolites (probably 12L-hydroperoxy- and 12L-hydroxy-5,8,10,14-eicosatetraenoic acids). Pulmonary infusion of dipyridamole (20 microM) increased the amount of TxB2 in the perfusion effluent. The amounts of other metabolites were unchanged, 2, 20 or 100 microM of dipyridamole had no effect in vitro on the activity of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase in the 100,000 X g supernatant fraction of guinea pig lungs.

Animals↗
PubMed1982

The prophylactic effect of dipyridamole on the size of myocardial infarction following coronary artery occlusion.

Experimental myocardial infarction was induced in adult female Sprague-Dawley rats by ligation of the left coronary artery. During four weeks preceding the operation the animals were given dipyridamole (3 mg/kg initial body weight) i.p. twice a day 5 days per week. Control animals were given saline. Ten days after the operation the rats were killed and the hearts serially sectioned and stained. The volumes of necrotic and non-necrotic myocardial tissue were determined by morphometry on the histological sections. In the dipyridamole-treated animals the volume of non-necrotic myocardium was larger and the necrotic tissue volume smaller than in the control animals.

Animals↗
PubMed1984

Theophylline antagonizes cardiovascular responses to dipyridamole in man without affecting increases in plasma adenosine.

Effects of the vasodilator dipyridamole (Dip) on plasma adenosine levels, heart rate, blood pressure and skin microcirculation were studied in 13 healthy male volunteers. Venous plasma concentrations of adenosine, catecholamines, dipyridamole and theophylline were determined by HPLC. Skin capillary blood cell velocity (CBV) was measured by videophotometric capillaroscopy in the finger nailfold. The adenosine uptake inhibitor Dip (approximately 1-3 microM in plasma) increased plasma adenosine from 0.15 +/- 0.03 to 0.29 +/- 0.03 microM (p less than 0.01) and heart rate (HR) by 13 +/- 2 beats/min (p less than 0.01) and reduced diastolic blood pressure by 6 +/- 2 mmHg (p less than 0.05). Dip did not significantly affect the skin circulation since basal CBV, digital pulse amplitude (DAPA), skin temperature and post-occlusive reactive hyperemia were unchanged. Plasma catecholamine levels were also unaffected. The adenosine receptor antagonist theophylline (45-55 microM in plasma) did not influence basal plasma catecholamine or adenosine levels, HR, blood pressure or skin microcirculation. Following theophylline Dip caused similar elevations of plasma adenosine but no changes in HR or blood pressures. Our results support the hypotheses that Dip dilates blood vessels in man by elevating endogenous adenosine and that theophylline acts as an adenosine antagonist. Under basal conditions, the skin microcirculation appears to be regulated mainly by factors other than adenosine.

Adenosine↗
PubMed1988

Enhancement of adenosine-induced relaxant responses of the guinea-pig isolated taenia coli and aortae by a novel nootropic agent BY-1949: comparison with dipyridamole.

In muscle strips of guinea-pig taenia coli and aortae, the effects of 3-methoxy-11-methyldibenz[b,f][1,4]oxazepine-8-carboxylate (BY-1949) on the relaxant response to adenosine have been compared with those of dipyridamole. BY-1949 (3 x 10(-5)-10(-4) M) as well as dipyridamole (3 x 10(-7)-10(-5) M) resulted in a significant potentiation of relaxant responses to a cumulative administration of adenosine (10(-6)-10(-3) M), but the drugs did not affect the response to noradrenaline and acetylcholine. The results indicate that BY-1949 exerts a selective potentiating effect on reactivity to exogenous adenosine.

Adenosine↗
PubMed2004

Residues Met89 and Ser160 in the human equilibrative nucleoside transporter 1 affect its affinity for adenosine, guanosine, S6-(4-nitrobenzyl)-mercaptopurine riboside, and dipyridamole.

The human equilibrative nucleoside transporter 1 (hENT1) is an important modulator of the physiological action of adenosine. We identified amino acid residues involved in adenosine transport using a yeast-based assay to rapidly screen and identify randomly generated hENT1 mutants that exhibited decreased sensitivity to inhibition of adenosine transport by various hENT1 competitive inhibitors. We identified Met89 and Ser160 as important in the affinity of hENT1 for various substrates and inhibitors. Mutation to Met89Cys or Ser160Cys significantly (p < 0.05) increased the S6-(4-nitrobenzyl)-mercaptopurine riboside (NBMPR) IC50 values by approximately 4- and 6-fold, respectively (42 +/- 13 and 65 +/- 1.6 nM) compared with the wild-type transporter (11 +/- 0.7 nM). The double mutant Met89Cys/Ser160Cys synergistically increased the NBMPR IC50 value to approximately 19-fold of that of the wild-type transporter. In contrast, compared with wild-type hENT1, the sensitivity to dipyridamole inhibition was significantly (p < 0.05) increased by only the Ser160Cys (approximately 2.6-fold) or the double mutant Met89Cys/Ser160Cys (approximately 4.7-fold) but not by the Met89Cys mutant. Mutation to Met89Cys or Ser160Cys increased the Km of adenosine (approximately 8- and 3-fold) and the Ki of guanosine (approximately 6- and 2-fold). The double mutant increased both the Km value of adenosine and the Ki value of guanosine by approximately 8-fold and seemed to confer no additional reduction in adenosine or guanosine affinity than that by mutation of Met89 alone. Together, these data indicate that transmembrane domains (TMDs) 2 (Met89) and 4 (Ser160) of hENT1 interact and are important in conferring sensitivity to NBMPR. In contrast, Ser160 and Met89 of hENT1, respectively, play a dominant role in conferring sensitivity to dipyridamole and adenosine/guanosine affinity.

Adenosine↗