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[Dipyridamole preconditioning protects against ischemia/reperfusion injury of rat liver].

OBJECTIVE: To investigate the protective mechanism of dipyridamole preconditioning against hepatic ischemia/reperfusion injury. METHODS: Thirty SD rats were randomly divided into normal control group, ischemia/reperfusion group, and dipyridamole group, with 10 rats in each group. Using 45-minute ischemia/reperfusion rat model at normal temperature, 10 mg/kg of dipyridamole normal saline were injected into portal vein before ischemia. Only normal saline was injected in the ischemia/reperfusion group. An hour later, blood was obtained from the portal vein to determine the enzyme levels, including alanine aminotransferase (ALT) , lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha), and endothelin-1 (ET-1). The alteration in pathological morphology of the ischemia lobe was observed. The content of adenosine phosphates in the liver was determined. RESULTS: The ALT and LDH activity, TNF-alpha, ET-1 levels were significantly higher in the ischemia/reperfusion group than those in the control group (all P<0.01). The levels of these variables were much lower in the dipyridamole group than those of the ischemia/reperfusion group (P<0.01), but little higher than those of the control group (P>0.05). The adenosine phosphates levels of ischemia/reperfusion group were significantly lower than those of the control group (P<0.01). They were much higher in the dipyridamole group than those of the ischemia/reperfusion group (P<0.01), but little higher than those of the control group (P>0.05). The control group had obvious alteration in pathological morphology, but only slight alteration was found in dipyridamole group, compared with control group. CONCLUSION: Dipyridamole preconditioning protects against ischemia/reperfusion injury of the liver.

Animals↗

Dipyridamole-echocardiography in coronary artery disease.

Regional wall motion impairment incurred by means of dipyridamole-induced ischemia, is regarded with higher sensitivity and specificity than the conventional findings in the ECG. Based on the latter considerations, a new test, the dipyridamole echocardiogram has been introduced in which the development of regional wall motion impairment is designated as the positive diagnostic criterion. Dipyridamole is a vasodilator of coronary arterioles. During the course of the examination, three consecutively occurring mechanisms are considered responsible for the appearance of dipyridamole-induced ischemia in the presence of coronary stenosis. The ischemia is initially attributed to a steal-effect, then to reflex-induced rise in rate-pressure product and, lastly, to a vasospastic component. In 680 patients with thoracic pain, on use of 0.84 mg/kg over ten minutes, there was a sensitivity of 74% in detection of angiographically-documented coronary artery disease, defined as greater than 70% stenosis in at least one major coronary artery, and a specificity of 95%. The onset of regional wall motion impairment after dipyridamole infusion was correlated with the severity of the disease, the localization of the wall motion impairment enabled delineation of the localization of the stenosis in the coronary vascular system. By means of the dipyridamole echocardiogram, the effectiveness of therapeutic measures such as PTCA, ACVB, medical antianginal treatment and thrombolysis can be assessed. Lastly, the dipyridamole echocardiogram provides important information with regard to prognosis.

Coronary Disease↗

False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion.

The vasodilator effect of intravenously administered dipyridamole may be caused by an increase in endogenous plasma adenosine levels. We evaluated the effect of caffeine, an adenosine receptor antagonist, on the diagnostic results of dipyridamole-201Tl myocardial imaging in eight patients with coronary artery disease. Caffeine infusion significantly attenuated the dipyridamole-induced fall in blood pressure and the accompanied increase in heart rate. The infusion of dipyridamole alone resulted in chest pain and ST-segment depressions on the electrocardiogram in four patients, whereas none of these problems occurred when the tests were repeated after caffeine. In six of eight patients, caffeine was responsible for false-negative dipyridamole-201Tl tests. Semiquantitive scores of the dipyridamole-induced 201Tl perfusion defects were decreased by caffeine from 9.0 +/- 0.9 to 2.0 +/- 1.1 points (p less than 0.05). Computerized analysis revealed a caffeine-mediated reduction in the percent reversibility of the images from 46% +/- 16% to 6% +/- 10% (p less than 0.05). We conclude that the use of caffeinated products prior to dipyridamole-201Tl testing may be responsible for false-negative findings.

Caffeine↗

Inadequate exercise leads to suboptimal imaging. Thallium-201 myocardial perfusion imaging after dipyridamole combined with low-level exercise unmasks ischemia in symptomatic patients with non-diagnostic thallium-201 scans who exercise submaximally.

This study was undertaken to establish the additional value of 201TI imaging after dipyridamole in combination with low-level exercise in 15 symptomatic patients with non-diagnostic 201TI scans, who exercised submaximally. Most patients had angina, ST-segment depression and even exertional hypotension and were referred for stress 201TI testing for determining the functional significance of known coronary artery disease. Six patients with a normal exercise 201TI test and one patient with an apical defect only were found to have 37 segments (of 105 segments) with reversible perfusion defects after dipyridamole infusion. One patient showing two reversible defects after exercise had five reversible segments after dipyridamole. Seven patients with fixed defects in 28 segments after exercise and two with small areas of border zone ischemia in seven additional (sub)segments, demonstrated fixed in defects in only nine segments but reversible defects in 40 segments after dipyridamole. Quantitative analysis resulted in 24.8 +/- 28.5 (mean value) sample points below -2 s.d. of the mean normal uptake after exercise, which increased to 72 +/- 26.5 after dipyridamole infusion (p less than 0.005). The washout analysis resulted in a mean value of 5.5 +/- 8.1 sample points below -2 s.d. after exercise, increasing to 33.3 +/- 22.1 after dipyridamole (p less than 0.005). Thallium-201 myocardial perfusion imaging after dipyridamole combined with low-level upright bicycle exercise may unmask scintigraphic evidence for ischemia in symptomatic patients who would otherwise have non-diagnostic imaging studies during submaximal exercise.

Coronary Disease↗

Dobutamine versus dipyridamole echocardiography in coronary artery disease.

Dobutamine and dipyridamole echocardiography are gaining popularity as exercise-independent stress tests for the diagnosis of coronary artery disease. To compare the feasibility, sensitivity, and specificity of dobutamine echocardiography to dipyridamole echocardiography, we conducted both tests, on different days and in random order, on 35 patients with chest pain and suspected coronary artery disease. Dobutamine was administered in scalar doses up to 40 micrograms/kg per minute and dipyridamole up to 0.84 mg/kg for 10 minutes. Dobutamine echocardiography testing was positive in eight of 16 (50%) patients with single-vessel disease and in 11 of 12 (92%) patients with multivessel disease, resulting in an overall sensitivity of 68% for the presence of coronary artery disease. Dipyridamole echocardiography testing showed the same sensitivity as dobutamine in patients with multivessel disease but a lower sensitivity (31%) in single-vessel disease, resulting in an overall sensitivity of 57%. The specificity of both tests was 100%. An ST segment shift of more than 1 mm compared with baseline was documented in 74% of the positive dobutamine echocardiography tests and in 81% of the positive dipyridamole echocardiography tests. No major complications occurred during both tests. Ventricular arrhythmias occurred in 11 patients with dobutamine and in none with dipyridamole (31% versus 0%, p less than 0.001). Thus, in our selected population dobutamine echocardiography testing demonstrated a similar overall sensitivity and specificity for the diagnosis of coronary artery disease compared with dipyridamole, with a slightly better sensitivity for single-vessel disease but a greater arrhythmogenic potential.

Angiography↗

Dipyridamole binding to proteins in human plasma and tissue culture media.

Dipyridamole (Persantin), a commonly used coronary vasodilator and antithrombotic drug, has been intensively studied for its potential use in combination chemotherapy for cancer, and, recently, for acquired immunodeficiency syndrome. However, the strong binding of dipyridamole to proteins in human plasma complicates quantitative extrapolations from in vitro data to the clinic. To aid in such extrapolations, we incubated dipyridamole in human plasma and in tissue culture media containing 10% fetal calf serum (FCS), and determined the equilibrium levels of free drug. In human plasma, after addition of 2 to 10 mumol/L dipyridamole (i.e., in the therapeutically relevant concentration range), the fraction of free drug averaged between 1.9% and 3.5%. In 10% FCS, after addition of 0.08 to 5 mumol/L dipyridamole (i.e., the experimentally relevant concentration range), mean free fractions were in the 75% to 100% range. Relating various total dipyridamole levels in the therapeutically relevant range in human plasma to those in 10% FCS that provided identical fractions of free drug gave ratios in the 24 to 55 range. Thus, a multiplication factor in the above range is suggested for the interconversion of in vitro and in vivo dipyridamole concentrations that provide equivalent levels of free drug.

Blood Proteins↗

Dipyridamole reduces urinary albumin excretion in diabetic patients with normo- or microalbuminuria.

The effect of 150 mg/day dipyridamole p.o. on urinary albumin excretion (UAE) was studied in 48 patients with diabetes mellitus without clinically discernible nephropathy. In 42 patients who were followed at an outpatient clinic, albumin/creatinine ratio (Ualb/Ucreat: mg/mmol) of untimed urine obtained from the same subjects repetitively was employed as an index of UAE. In 6 hospitalized patients, albumin excretion rate (AER) (micrograms/min) of 24-h-collected urine was determined. When followed without dipyridamole for 10.8 (the mean) months (N = 27, outpatients), the mean Ualb/Ucreat increased from 8.1 to 20.5. Of these, 11 patients with Ualb/Ucreat greater than 1.0 at the end of the observation period subsequently received dipyridamole for 4.2 months, and the ratio decreased from 49.0 to 7.3. When treated with dipyridamole for 9.0 months without a pre-treatment observation period (N = 15, outpatients), the ratio decreased from 9.8 to 5.6. AER of hospitalized patients who received dipyridamole for 10.0 days reduced from 68.0 to 21.9. All of these changes were statistically significant. Urinary beta 2 MG, blood pressure, serum creatinine and glycemic control were unaffected by the dipyridamole treatment. We conclude that dipyridamole reduces UAE in diabetic patients with subclinical level of albuminuria.

Adult↗

Dipyridamole testing compared to exercise stress for thallium-201 imaging in patients with left bundle branch block.

Because of numerous reports of false positive results with thallium-201 (Tl-201) stress testing in patients with left bundle branch block, the authors decided to evaluate another mode of coronary vasodilatation, dipyridamole, for the diagnosis of coronary atheromatosis. Nine patients were prospectively studied with stress and dipyridamole Tl-201 scintigraphy; both tests were performed within three to 79 days of one another. Five of the patients also had coronary angiograms (four within one year, one five years earlier). Four of the patients had normal results with both tests (two normal angiograms, two not performed); two had reversible septal defects with stress-induced coronary vasodilatation but normal dipyridamole studies (only one had an angiogram, which was normal); one patient had a fully reversible septal defect with stress and a fixed defect with dipyridamole (normal angiogram); one had a partially reversible septal stress defect which was fixed with dipyridamole; and one had a normal stress study but a reversible septal defect with dipyridamole (an angiogram performed five years earlier showed 30 to 40% stenosis of the anterior descending artery). Because it seems that dipyridamole produces fewer false positive results, it should be used instead of stress testing to induce coronary vasodilatation in patients with left bundle branch block.

Angiography↗

Investigation on the effect of dipyridamole and papaverine on regional blood flow and cardiac hemodynamics in anesthetized dogs.

Vasodilating effects of dipyridamole were compared with those of papaverine in anesthetized open-chest dogs. Dipyridamole i.v. produced a significant fall in aortic blood pressure and significant increases in aortic and coronary blood flows. Vertebral blood flow did not alter, but renal blood flow was transiently decreased. Left ventricular dP/dt, heart rate and left ventricular enddiastolic pressure were hardly affected by dipyridamole. Papaverine i.v. significantly increased aortic, vertebral and coronary blood flows, left ventricular dP/dt and heart rate and significantly decreased aortic blood pressure and left ventricular enddiastolic pressure. Renal blood flow was instantly decreased by papaverine. Percent change in each vascular resistance showed decreases in total peripheral, vertebral and coronary vascular resistances in response to both drugs, and the decrease in coronary vascular resistance was the most remarkable. Renal vascular resistance was increased by dipyridamole, while it was decreased by papaverine. Percent change in double product (heart rate x systolic arterial blood pressure) showed a monophasic decrease pattern with dipyridamole and a biphasic pattern with an initial, transient decrease followed by an increase with papaverine. The present results indicate that dipyridamole and papaverine produce marked coronary vasodilatation, and that papaverine is different from dipyridamole in cardiotonic properties.

Anesthesia↗

Methotrexate and dipyridamole combination chemotherapy based upon inhibition of nucleoside salvage in humans.

We have carried out a clinical trial in 23 patients to determine whether dipyridamole modulates the clinical effect of methotrexate. This trial was based upon in vitro studies which indicate that dipyridamole potentiates the cytotoxic action of methotrexate through inhibition of thymidine salvage. Methotrexate was given as a bolus injection 24 h after initiation of a high dose dipyridamole infusion. The trial was designed so that methotrexate was escalated in individuals until toxicity occurred and then the methotrexate dose resulting in toxicity was repeated without dipyridamole. During the course of this study the methotrexate dose was escalated from 10 to 130 mg/m2. While individual patient tolerance varied, moderate to severe myelosuppression and/or mucositis occurred frequently in patients receiving the combination with methotrexate doses greater than or equal to 60 mg/m2. Ten of 10 patients who experienced moderate or severe toxicity with the combination had significantly less toxicity when treated with methotrexate alone. Dipyridamole did not increase toxicity by an alteration in methotrexate elimination. The potentiation of methotrexate by dipyridamole in these patients suggests that physiological thymidine levels are sufficient to perturb the clinical effects of methotrexate and that thymidine salvage may represent a mechanism for clinical resistance to methotrexate. These results also suggest that a high dose dipyridamole regimen can be used as a pharmacological approach to test the role of nucleoside membrane flux on the clinical action of other standard chemotherapeutic drugs. Phase II studies testing the clinical efficacy of this combination should use a methotrexate dose of 60 mg/m2 with a provision for methotrexate dose escalation based upon individual patient tolerance.

Antineoplastic Combined Chemotherapy Protocols↗

Nitrobenzylthioinosine-sensitive nucleoside transport system: mechanism of inhibition by dipyridamole.

Dipyridamole-mediated inhibition of nucleoside transport by the nitrobenzylthioinosine (NBMPR)-sensitive facilitated diffusion system in mammalian erythrocytes was investigated. [3H]Dipyridamole was a competitive inhibitor of uridine equilibrium exchange influx into guinea pig erythrocytes (apparent Ki 1 nM). Analysis of the results using total inhibitor levels instead of cell-free inhibitor concentrations increased the apparent Ki value to 7 nM. Similarly, [3H]dipyridamole inhibition of zero-trans-[14C] uridine influx was consistent with simple competitive inhibition (apparent Ki 1.4 +/- 0.7 nM). In contrast, [3H]dipyridamole behaved as a noncompetitive inhibitor of zero-trans-[14C]uridine efflux (apparent Ki 0.7 +/- 0.2 nM). In a second series of experiments, [3H]dipyridamole was found to bind to a single class of high affinity sites on plasma membranes from human erythrocytes (apparent Kd 0.65 +/- 0.07 nM) with a maximum number of binding sites similar to that determined with the nucleoside transport inhibitor NBMPR. Binding of dipyridamole to these sites was blocked by the nucleoside transport inhibitors NBMPR, nitrobenzylthioguanosine, and dilazep and in a competitive manner by adenosine and uridine (apparent inhibition constants 0.1 and 0.9 mM, respectively). These inhibition constants are similar to the apparent Km for adenosine and uridine equilibrium exchange in human erythrocytes. These results are consistent with the notion that, in mammalian erythrocytes, dipyridamole interacts with the NBMPR-sensitive transporter at the same site as NBMPR, which is preferentially located on the outer surface of the cell membrane totally or partially within the permeation site.

Animals↗

[The effect of dipyridamole on pulmonary venous flow in patients with ischemic heart disease].

In 56 patients with ischaemic heart disease the authors evaluated the blood flow in the pulmonary veins, using transoesophageal echocardiography by the pulsed Doppler technique in the left upper pulmonary vein. They assessed the peak systolic velocity (pVS), the systolic integral time-velocity (S-VTI), the peak diastolic velocity (pVD) and the integral time velocity in the diastolic part of the flow (D-VTI). They found a statistically significant correlation between the ratio pVS/pVD and the LVEDP assessed by the invasive method (r = 0.812). In 36 patients the authors evaluated the flow rate and time-velocity integral at rest and after administration of 0.78 mg/kg dipyridamol by the i.v. route. In 17 patients with affections of 2 or 3 coronary arteries (group A) after the administration of dipyridamol an increase of the maximal flow rate occurred in the diastolic portion of the flow (at rest 54.7 +/- 12.5, after dipyridamol 64.9 +/- 14.8 cm/s). The systolic flow velocities did not change in this group of patients (at rest 52.2 +/- 3.0, after dipyridamol 54.3 +/- 14.0 cm/s). In 19 patients with a negative coronarographic finding (group B) or with stenosis of one coronary artery after dipyridamol administration the systolic peak velocity increased (from 58.0 +/- 10 to 70.2 +/- 14.8 cm/s). The pVD values increased slightly after dipyridamol (at rest 42.5 +/- 14.3, after dipyridamol 52.1 +/- 15.6 cm/s).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗

[Pharmacologic myocardial protection during percutaneous transluminal coronary angioplasty (PTCA) by intracoronary dipyridamole: hemodynamic, contractile and dynamic ventricular consequences].

Percutaneous transluminal coronary angioplasty (PTCA) represents a suitable model to establish myocardial ischemia in man. Balloon inflation usually is accompanied by a significant deterioration in left ventricular systolic and diastolic properties. A brief episode of ischemia followed by reperfusion termed preconditioning has been identified as a mechanism rendering the myocardium more resistant to ischemia. Adenosine is considered as important mediator of preconditioning. Dipyridamole represents an important drug interfering with myocardial adenosine metabolism by inhibiting its cellular reuptake. The aim of this study was to investigate if an intracoronary infusion of dipyridamole represents a suitable tool in preventing the deterioration of left ventricular performance and hemodynamics during PTCA. In 20 patients undergoing elective coronary angioplasty of a major vessel assessment of angiographic left ventricular performance and left ventricular hemodynamics was performed before, during and after coronary angioplasty. Patients were randomly allocated to study group 1 receiving an intracoronary infusion of dipyridamole prior to PTCA and study group 2 where conventional pretreatment was performed. In study group 3 intracoronary dipyridamole infusion was performed in 10 patients with coronary artery disease during coronary angiography in order to evaluate its effect on baseline hemodynamics and left ventricular performance. Dipyridamole-pretreatment resulted in a significant preservation of systolic and diastolic left ventricular performance during PTCA, as documented by an uneffected global ejection fraction (in comparison to a deterioration of 29.2% in study group 2) and an increment in diastolic stiffness of only 12.7% (in comparison to an increment of 57.3% in study group 2). Furthermore, a significant prolongation of achievable balloon-inflation times of 48.4% could be obtained in study group 1. In addition, incidence of arrhythmias seemed to be reduced in study group 1. Apart from two cases of coronary steal phenomenon no significant side effects of dipyridamole infusion could be detected. Finally, in study group 3 dipyridamole-pretreatment per se induced a significant amelioration of angiographically assessed left ventricular systolic performance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

[Optimal protocol for 99mTc-tetrofosmin myocardial SPECT imaging with exercise or dipyridamole stress test and the characteristics of bullseye normal file].

To determine optimal protocol for 99mTc-tetrofosmin SPECT imaging, 30 normal volunteers underwent treadmill or dipyridamole stress test with 770 MBq of tetrofosmin injection. Anterior planar images were acquired every 10-15 minutes for calculating heart/liver ratio. SPECT images were also obtained every 30 minutes for generating Bullseye normal files. In analysis of spatial tracer distribution among normal files, myocardium in Bullseye plot was divided in 9 areas, where mean values of % tracer uptake were calculated and compared by analysis of variance (ANOVA). In those 9 areas, mean values of SD (SD mean) were also compared for predicting artificial blackout in the Bullseye plot among 3 standard normal files: dipyridamole-201Tl, dipyridamole-tetrofosmin (60 min post-injection), and treadmill-tetrofosmin (30 min post-injection). In planar image analysis, high initial uptake in the liver and its acceptable clearance were noted in dipyridamole stress test. Adequate heart/liver ratio was accomplished immediately after treadmill, but 40 minutes later after dipyridamole stress test. ANOVA analysis showed no statistical difference in the spatial % tracer uptake among normal files, irrespective of time after acquisition, data collection time, or difference of tracer. However, SD means in inferior and lateral area of treadmill-tetrofosmin file were significantly small compared to that of dipyridamole-201Tl normal file (p < 0.02 by ANOVA). Thus, we conclude that optimal timing for tetrofosmin SPECT imaging is immediately after treadmill, but at least 40 minutes after dipyridamole stress test. In addition, we should also keep in mind that unexpected blackout may appear in inferior and lateral area, when applying our normal files for reference.

Analysis of Variance↗

Interaction of dipyridamole, a nucleoside transport inhibitor, with the renal transport of organic cations by LLCPK1 cells.

Dipyridamole is a well-known inhibitor of nucleoside transport by various cell membranes and is frequently used in in vitro studies that characterize nucleoside transport properties. Because interactions between the renal transport of organic cations and nucleosides have previously been suggested, we studied the effect of dipyridamole on the renal transport of the typical organic cations cimetidine and N1-methylnicotinamide by LLCPK1 monolayer cells grown on a permeable support. [14C]Mannitol was used to correct for extracellular flux. Basolateral to apical transcellular flux (transepithelial flux-extracellular flux) of [3H]cimetidine was significantly reduced by the monolayer cells (90%) in the presence of 50 microM dipyridamole. In addition, the effect of dipyridamole on cimetidine renal transport was dose dependent (IC50 = 7.7 microM). The dipyridamole inhibitory effect was nearly comparable with the effect of 1 mM quinine (a typical organic cation transport inhibitor), which led to 95% inhibition of cimetidine renal transport over time. The dipyridamole effect on N1-methylnicotinamide renal transport was less potent. The effect of 1 mM of typical probes of the nucleoside transporters (i.e., thymidine, adenosine, uridine) and the effect of 100 nM of another nucleoside transport inhibitor, dilazep, were also studied on cimetidine transport by LLCPK1 monolayer cells. These compounds did not exert any significant effect. These results suggest that dipyridamole, a widely used nucleoside transport inhibitor, is also an inhibitor of organic cation renal transport and they alert us to possible interactions between the renal transport of nucleosides and organic cations. This finding also has relevance to the interpretation of in vitro studies using this agent as a nucleoside membrane transport inhibitor.

Animals↗

[Echocardiographic analysis of segmental and global myocardial contractility after administration of dipyridamole in patients with ischemic heart disease].

Aims of the study were to assess the usefulness of global and segmental myocardial contractility parameters detected during dipyridamole echocardiography test in diagnosis of ischaemic heart disease. Dipyridamole time (the time from the onset of dipyridamole infusion to development of asynergy) was also evaluated. The study included 97 patients with suspected or known ischaemic heart disease (32 patients after acute myocardial infarction), mean age 48.5 years. All patients underwent dipyridamole stress echocardiography and afterwards coronary angiography. Significant stenosis (< or = 70% lumen reduction in at least one major coronary vessel) was present in 52 (54%) patients-group I. Normal coronary arteries or no significant stenosis were found in 45 (46%) patients-group II. Significant increase of wall motion score index was observed in group I. No significant change with two and there vessels disease have shorter dipyridamole time than patients with one vessel disease. Significant decrease in ejection fraction during dipyridamole echocardiography test was found in group I, whereas not significant increase in ejection fraction was observed in group II. Dipyridamole echocardiography test is a sensitive, specific and well tolerated test in the diagnosis of ischaemic heart disease.

Adult↗

[Echocardiography or stress scintigraphy with dipyridamole for the stratification of risk after acute myocardial infarction?].

UNLABELLED: Increased risk of subsequent cardiac events after an acute infarction can be identified through dipyridamole infusion. It remains to be determined whether echocardiographic or scintigraphic imaging modes are equivalent. The aim of our study was to compare the prognostic information obtained early after an acute uncomplicated myocardial infarction through high-dose dipyridamole coupled with echocardiography or scintigraphy via Tc 99m sestamibi SPECT imaging. METHODS AND RESULTS: Fifty-one patients underwent simultaneous dipyridamole stress echocardiography and scintigraphy at a mean +/- SD of 12 +/- 3 days after admission for acute uncomplicated myocardial infarction. A subgroup of 44 patients performed exercise testing according to maximal symptom limited protocol. All patients were followed prospectively for 346 +/- 273 days (range 11-959). Cardiac events occurred in 20 patients (39%), and 1 death, 2 myocardial reinfarctions and 17 cases of unstable angina were recorded. Univariate predictors of cardiac events were: positive dipyridamole echo (p < 0.001), ischemia in the infarct zone or in remote zones by echo (p < 0.001), ejection fraction < 40% (p = 0.042) and positive exercise testing (p = 0.003). Risk was best predicted by multivariate Cox analysis on the basis of 1) ischemia in remote zones by dipyridamole echo (p < 0.001) and 2) ischemia in the infarct zone by dipyridamole echo (p = 0.003), blood pressure at peak exercise < 150 mmHg (p = 0.010) and non-Q wave infarction (p = 0.003). CONCLUSIONS: Echocardiographic imaging during dipyridamole infusion is superior to sestamibi scintigraphy for predicting events after uncomplicated myocardial infarction.

Aged↗

[Dipyridamole-echocardiography and thallium exercise myocardial scintigraphy in the diagnosis of obstructive coronary or microvascular disease in hypertensive patients with left ventricular hypertrophy and angina].

BACKGROUND: Hypertensive patients with left ventricular hypertrophy can be affected with angina pectoris for significant epicardial coronary stenosis or microvascular disease with normal coronarography. Exercise-electrocardiography test is positive in both conditions. The aim of the present study was to assess the accuracy of dipyridamole-echocardiography test and thallium exercise myocardial scintigraphy in the diagnosis of epicardial coronary stenosis or microvascular disease in hypertensive patients with left ventricular hypertrophy and angina pectoris. METHODS: Forty-two hypertensive patients (22 males, age 40-76 years, mean 58.6 +/- 10.1), with left ventricular hypertrophy, typical angina pectoris, ischemia that can be induced by exercise-electrocardiography test, without previous myocardial infarction, myocardial revascularization or diabetes mellitus, underwent dipyridamole-echocardiography test, thallium exercise myocardial scintigraphy and coronarography. Dipyridamole-echocardiography test was performed with dipyridamole (0.56 mg/kg over 4 minutes, followed by 0.28 mg/kg from the 8th to the 10th minute) + atropine (1 mg from the 12th to 15th min.) and was positive for a transient dyssynergy of contraction of at least 2 myocardial segments; the left ventricle was divided into 16 segments. SPECT thallium myocardial scintigraphy was performed after bicycle exercise and then three hours later, and it was positive for reversible uptake defects of at least 2 segments with a 22-segment model. Coronarography was performed with Judkin's technique and was positive if at least one large epicardial vessel was narrowed by more than 50%. RESULTS: Coronarography: normal in 25 cases (59.5%, 8 males), pathologic in 17 (40.5%, 14 males): left main coronary artery in 1 (5.9%), three vessels in 5 (29.4%), two vessels in 3 (17.7%), 1 vessel in 8 (47%). Dipyridamole-echocardiography-test: positive in 15 cases (35.7%), negative in 27 (64.3%); sensitivity 88.2%, specificity 100%, diagnostic accuracy 95.2%, positive predictive value 100%, negative predictive value 92.6%. Thallium exercise myocardial scintigraphy: positive in 30 cases (71.4%), negative in 12 (28.6%); sensitivity 100%, specificity 48%, diagnostic accuracy 69%, positive predictive value 56.7%, negative predictive value 100%. CONCLUSIONS: Dipyridamole-echocardiography test has higher diagnostic accuracy and when positive, it predicts significant epicardial coronary stenosis. It can be less sensitive in one-vessel patients (2 false negatives were stenosis 75% of left anterior descending and 60% of 1st diagonal). Thallium exercise myocardial scintigraphy is complementary because when negative, it excludes epicardial coronary stenosis and confirms microvascular disease. In hypertensive patients with left ventricular hypertrophy and suspected angina pectoris, the following flow-chart may be proposed: the first test is exercise-electrocardiography test. Only those who are positive at low-to-intermediate workload then undergo dipyridamole-echocardiography test. Those who are positive in this then undergo coronarography, while the negative ones undergo thallium exercise myocardial scintigraphy. Those who are positive at thallium exercise myocardial scintigraphy perform the coronarography, while cases with negative results do not undergo further diagnostic tests since they are affected with microvascular disease.

Adult↗