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Diagnostic value of exercise electrocardiography and dipyridamole stress echocardiography in hypertensive and normotensive chest pain patients with right bundle branch block.

OBJECTIVES: Studies on the diagnostic value of exercise electrocardiography in right bundle branch block produced controversial results, and data on the accuracy of stress echo are still lacking. The aim of the study was to compare the diagnostic value of exercise electrocardiography and dipyridamole stress echo in chest pain patients with right bundle branch block, and to verify whether stress testing accuracy is affected by history of hypertension. METHODS: The study group was made up of 71 patients (56 men, aged 63 +/- 8 years) with chest pain of unknown origin and complete right bundle branch block. Of them, 35 were hypertensives and 36 normotensives. Patients performed, on different days and in random order, exercise electrocardiography and dipyridamole stress echo and underwent coronary angiography. RESULTS: Significant (> or = 70% diameter stenosis) coronary artery disease was found in 34 patients (17 hypertensives and 17 normotensives). Positive exercise electrocardiography (ST-segment shift > 1 mm at 80 ms after the J point in leads V5 and V6 or leads II and Vf) and dipyridamole stress echo (new wall motion abnormalities) were observed in 38 and 30 patients, respectively. The result of tests was concordant in 69% of hypertensives and 92% of normotensives. The two tests shared the same sensitivity in hypertensives (82%) and normotensives (71%). Of 37 patients without coronary artery disease, 12 had a false-positive result during exercise electrocardiography and four during stress echo. The specificity was lower for exercise electrocardiography than for stress echo in hypertensives (50 versus 89%, P = 0.0006), while no difference was evidenced in normotensives (84 versus 89%, P = 0.4). In hypertensives, the accuracy, positive, and negative predictive values were 66, 61, and 75% for exercise electrocardiography, and 86, 87, and 84% for stress echo. Corresponding figures in normotensives were 78, 80, and 76% for exercise electrocardiography, and 81, 86, and 77% for stress echo. CONCLUSIONS: In chest-pain patients with right bundle branch block, dipyridamole stress echo was effective to diagnose coronary artery disease in both normotensives and hypertensives. Moreover, it exhibited superior diagnostic information than exercise electrocardiography in hypertensives, due to significantly higher specificity. However, the two tests had similar diagnostic value in normotensives.

Aged↗

The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography in patients with coronary artery disease.

The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography was evaluated in 12 patients with angiographically proven coronary artery disease. The patients had dipyridamole 201Tl tomography performed after 7 days treatment with 50 mg atenolol and then repeated after a further 7 days treatment with placebo. The images were interpreted qualitatively by two experienced observers and quantitatively using the Bullseye technique. Qualitative analysis of the images revealed that four of the 12 patients had larger defects on their scans whilst receiving atenolol compared to placebo. The remaining eight patients had defects which were the same size on both treatments. The severity of defects assessed qualitatively was not significantly influenced by atenolol therapy (P = 0.13, McNemera's test). The results obtained with the Bullseye method did not demonstrate significant statistical differences for defect size, degree of reversibility or percentage reversibility whilst the patients were receiving atenolol or placebo (Wilcoxon Rank Sum Test). Atenolol increased the size of perfusion defects on dipyridamole 201Tl tomography qualitatively and quantitatively for four patients in this group of 12 with proven coronary artery disease. Although this did not achieve a high level of statistical significance physicians should be aware that atenolol can influence the images obtained at dipyridamole 201Tl tomography.

Adult↗

The value and correlates of left ventricular cavity assessment in dipyridamole 201Tl SPET studies.

Left ventricular cavity (LVC) enlargement during SPET dipyridamole 201Tl myocardial perfusion imaging studies is a proven marker of severity of coronary artery disease. Nevertheless, the influence of the extent of myocardial infarct and ischaemia on the degree of LVC enlargement both at rest and with dipyridamole has not been clearly analysed. One hundred and one patients were studied by both dipyridamole myocardial perfusion imaging and radionuclide ventriculography within 1 week. The left ventricular ejection fraction (LVEF) was 57 +/- 9 in normal resting LVC patients (group I), 43 +/- 8 in mild LVC enlargement patients (group II) and 28 +/- 5 in moderate-to-severe LVC enlargement patients (group III). The number of fixed defects was increased in patients in group II and group III, but there was no significant differences in the number of ischaemic segments among groups. The number of ischaemic segments was much higher in patients with transient cavity dilatation than those without cavity change; nonetheless, both LVEF and the numbers of fixed segments were unchanged. The degree of LVC enlargement at rest strongly reflects the resting left ventricular systolic function as well as the extent of previous myocardial infarct. On the other hand, transient cavity dilatation during dipyridamole infusion can only reflect the extent of viable myocardium at risk.

Aged↗

Estimation of hydrogen peroxide plasma levels in patients evaluated for coronary heart disease using dipyridamole infusion followed by SPECT.

BACKGROUND: Prolonged ischemia leads to myocardial infarction and increased formation of toxic oxygen radicals. These substances exert deleterious effects on myocardial cells, contributing to reperfusion injury and generation of arrhythmia. Little information is available, however, concerning the toxic oxygen species generated during transient ischemia. The purpose of our study was to estimate hydrogen peroxide plasma levels in patients subjected to short-lasting ischemia induced by a dipyridamole stress test used for the diagnosis of coronary artery disease. Evaluation of the performed test was carried out with 99mTc-SestaMIBI followed by single photon emission computed tomography (SPECT). METHODS: Blood was obtained from peripheral veins of 53 patients (37 men and 16 women, mean age 49 +/- 11 years). Plasma hydrogen peroxide levels were estimated by spectrophotometric methods: immediately before a dipyridamole challenge and after drug infusion. RESULTS: Hydrogen peroxide plasma levels in patients with a negative SPECT test were 23.5 +/- 3.0 mumol/l (mean +/- SEM) and 21.0 +/- 2.9 after the dipyridamole infusion (P = 0.474). Plasma concentrations of hydrogen peroxide in patients with a positive SPECT test were 30.5 +/- 4.6 and increased after dipyridamole challenge to 50.3 +/- 5.4 (P = 0.004). Further analysis revealed that the observed difference cannot be attributed to previous history of myocardial infarction. CONCLUSIONS: Even transient myocardial ischemia can generate toxic oxygen derivatives. Evaluation of plasma levels of hydrogen peroxide may be of clinical relevance in patients with suspected coronary artery disease.

Coronary Disease↗

High dose dipyridamole myocardial imaging: simultaneous sestamibi scintigraphy and two-dimensional echocardiography in the detection and evaluation of coronary artery disease. Italian Group of Nuclear Cardiology.

BACKGROUND: Dipyridamole stress combined with echocardiography or perfusion scintigraphy can be used to detect coronary artery disease, but head-to-head comparative data are lacking. The aim of this study was to compare the relative accuracy of high-dose dipyridamole stress imaging (up to 0.84 mg/kg over 10 min) with two-dimensional echocardiography and sestamibi perfusion scintigraphy in detecting coronary artery disease. METHODS: One-hundred and one patients with a history of chest pain and no previous myocardial infarction, were studied simultaneously using planar perfusion scintigraphy and echocardiography during a high-dose dipyridamole stress, at seven different institutions. RESULTS: During coronary angiography, 21 patients had non-significant lesions, and 80 had significant lesions (> or = 50% diameter reduction): 37 had single-, 19 double- and 24 triple-vessel disease. Sensitivity for disease detection was 78% [95% confidence interval (CI) 67-86%] for echocardiography and 79% (CI 68-87%) for scintigraphy. The specificity was 76% (CI 67-84%) for echocardiography and 90% (CI 83-95%) for scintigraphy. The inter-center variation in accuracy ranged from 50 to 100% for echocardiography (coefficient of variation 19.7%) and from 71 to 100% for scintigraphy (coefficient of variation 15%). The angiographically assessed extent and severity of coronary artery disease, evaluated using the Duke score, was correlated to the extent and severity of perfusion defects with scintigraphy (r = 0.65, P < 0.0001) and regional wall motion abnormalities by echocardiography (r = 0.57, P < 0.0001). CONCLUSIONS: Perfusion scintigraphy and echocardiography have similar accuracies for the non-invasive identification of angiographically assessed coronary artery disease during high-dose dipyridamole stress. Inter-center variability in diagnostic accuracy is higher for echocardiography than scintigraphy. Both methods allow a reasonably accurate estimation of extent and severity of disease, via a semiquantitative assessment of extent and severity of perfusion of functional defects.

Aged↗

Assessment of left ventricular ejection dynamics in patients with coronary artery disease during dipyridamole-stress Doppler echocardiography.

OBJECTIVES: To investigate the contribution of Doppler-echocardiographically derived aortic indexes of left ventricular systolic function during dipyridamole-stress to the diagnosis of coronary artery disease (CAD). DESIGN: This was a clinical study. METHODS: Echocardiographic studies under baseline and peak dipyridamole stresses were performed on 15 normal subjects and 32 patients with angiographically confirmed CAD. Peak Doppler velocity, acceleration, and acceleration time of the ascending aorta, as well as segmental left ventricular wall motion, were analyzed. RESULTS: The sensitivity, specificity and overall accuracy of wall-motion abnormalities induced by dipyridamole for the detection of CAD were 62.5, 100, and 74.5%, respectively. When wall-motion abnormalities were combined with the percentage changes in peak aortic velocity and acceleration, the overall sensitivities were 84.38 and 78.15%, respectively, the specificities were 66.7 and 80.00%, respectively, and the accuracy was 78.72% for both models. When all three parameters were combined, the sensitivity, specificity and overall accuracy of the method were 87.5, 86.7, and 87.2%, respectively. CONCLUSIONS: Doppler-echocardiographically derived aortic indexes of left ventricular systolic function during dipyridamole stress could be a useful adjunct to two-dimensional echocardiography by improving its sensitivity in the diagnosis of CAD.

Coronary Disease↗

The interaction of varying doses of dipyridamole and acetyl salicylic acid on the inhibition of platelet functions and their effect on bleeding time.

1 In normal volunteers maximum reductions in platelet functions, collagen aggregation, adhesion and PF4 availability, were achieved using combined doses of 50 mg three times daily dipyridamole + 180 mg ASA or 75 mg three times daily dipyridamole + 120 mg ASA daily. 2 These doses did not prolong the bleeding time. 3 A synergistic effect has been demonstrated with 25 mg dipyridamole three times daily and 60 mg ASA. 4 At higher doses the effects on platelet functions were additive up to the maximal response. 5 The effect of low doses of ASA on platelet function was cumulative. 6 As lower doses of ASA in the combination studied inhibit platelet functions maximally without altering the bleeding time and probably without inhibiting prostacyclin, we suggest that these combinations of dipyridamole and ASA merit consideration in future clinical trials.

Adult↗

Additive renal effects of indomethacin and dipyridamole in man.

The effect of dipyridamole alone and in combination with indomethacin was studied in 11 water loaded rheumatic patients with normal kidney function. The adenosine uptake inhibitor dipyridamole and the prostaglandin synthesis inhibitor indomethacin decreased diuresis by 25-50% when given alone and by approximately 80% when combined. These effects were not associated with changes in renal PAH-clearance, but may be partially related to a fall in GFR. Sodium excretion was decreased in parallel with the fall in GFR. In addition, both indomethacin and dipyridamole reduced the free water clearance. Theophylline at therapeutic plasma levels reversed the reduction in GFR and transiently counteracted the inhibition of tubular water and sodium excretion induced by combined dipyridamole and indomethacin treatment. The results suggest that endogenous adenosine and prostaglandins are both involved in the control of renal function in man, and that drugs that affect these two autocoids may interact to cause adverse effects in man.

Adenosine↗

The role of dipyridamole in addition to low dose aspirin in the prevention of occlusion of coronary artery bypass grafts.

One hundred and one subjects were randomised to receive either aspirin 100 mg or aspirin 100 mg + dipyridamole 300 mg daily before undergoing coronary bypass surgery. The drugs were commenced at least 36 hours before operation and patients were followed for one year. There were three perioperative deaths and 37 withdrawals, of which 14 were drug related (aspirin four, aspirin + dipyridamole ten). Cineangiocardiograms at nine weeks and one year showed vein graft patency rates of 93% and 87% for subjects treated with aspirin alone; and 90% and 89% in those who received aspirin+dipyridamole. During the follow-up period 14% of 232 coronary lesions in the aspirin treated group advanced by more than two grades compared with 15% of 315 lesions in the aspirin+dipyridamole group. The study did not establish superiority of one regimen over another in terms of graft patency or progress of lesions in native vessels. However, low dose aspirin was better tolerated than combination therapy.

Aged↗

The action of nitroglycerine and dipyridamole in normal and ischaemic dog heart.

1 Network and post-network resistances were measured together with heat clearance and heat production in the myocardium. 2 Nitroglycerine dilated all resistance vessels but was twice as effective on network as compared with post-network vessels. 3 Dipyridamole dilated network and post-network vessels equally. 4 Nitroglycerine had no effect on heat clearance or heat production in ischaemic myocardium. 5 Dipyridamole increased heat clearance in normal but not in ischaemic myocardium. 6 Dipyridamole depressed heat production in normal and ischaemic myocardium. 7 That the clinical effectiveness of nitroglycerine does not depend entirely on its coronary vasodilator properties is confirmed. 8 It is suggested that the action of dipyridamole in depressing myocardial heat production may be due to an action on the efficiency of oxygen utilization during cardiac contraction.

Animals↗

Dipyridamole: a potent stimulator of prostacyclin (PGI2) biosynthesis.

1 Dipyridamole (0.01 to 0.75 mM) increased prostacyclin (PGI2) biosynthesis from tritiated arachidonic acid in rat stomach fundus homogenates by 21 to 350%. The transformation of prostaglandin H2 (PGH2) to PGI2 by a microsomal fraction of pig aorta was stimulated by dipyridamole at 0.1 M by 63%. 2 In the isolated perfused heart of the rabbit dipyridamole at 1 and 5 micrograms/ml increased PGI2 release by 70% and 146% respectively. 3 Our results show a stimulation of the second step in PGI2 biosynthesis (from endoperoxides) by dipyridamole. This effect should be considered in relation to the therapeutic usage of the drug in myocardial infarction.

Animals↗

The acute hemodynamic effect of IV nitroglycerin and dipyridamole in patients with pulmonary arterial hypertension: comparison with IV epoprostenol.

Nitroglycerin and dipyridamole are two commonly available and well tolerated vasoactive medications. Their acute hemodynamic effects in patients with pulmonary arterial hypertension are not well defined in the current literature. The authors retrospectively analyzed the acute hemodynamic effects of IV nitroglycerin, dipyridamole, and epoprostenol in 59 patients with pulmonary arterial hypertension as determined by changes from baseline in systemic and pulmonary hemodynamic parameters. Statistical analysis was performed using the independent sample t test. A p value <0.05 was considered significant. Nitroglycerin is predominantly a vasodilator of the pulmonary vasculature with moderate systemic vasodilator effect, while dipyridamole is primarily a positive inotropic agent. Epoprostenol is a potent vasodilator of both pulmonary and systemic vessels and a strong positive inotropic agent. Nitroglycerin and dipyridamole may be useful in the acute management of pulmonary arterial hypertension.

Acute Disease↗

Prognostic value of dipyridamole thallium imaging after acute myocardial infarction in older patients.

OBJECTIVE: To assess the utility of intravenous dipyridamole thallium testing for predicting major cardiac events following acute myocardial infarction in older patients. DESIGN: Prospective cohort study with a median follow-up of 18 months. SETTING: A university teaching hospital. PARTICIPANTS: 73 patients aged 65 years and older with enzymatically confirmed acute myocardial infarction (mean age 75 years, 56% male, 71% white). MEASUREMENTS: All patients underwent a detailed clinical assessment, an echocardiogram, and an intravenous dipyridamole thallium stress test before hospital discharge. The study endpoint was death or nonfatal reinfarction during the follow-up period. RESULTS: Overall, 24 patients (33%) died or developed recurrent myocardial infarction during follow-up. Among 44 patients with a reversible thallium defect, 19 (43%) reached the study endpoint, compared with only five of 29 patients (17%) without reversible ischemia (P = .04). On multivariate analysis, independent prognostic variables included non-use of aspirin at hospital discharge (P = .002), decreased left ventricular systolic function (P = .009), non-use of a beta-blocker at hospital discharge (P = .013), and reversible ischemia on thallium scintigraphy (P = .025). The relative risks for death or reinfarction associated with non-use of aspirin, non-use of a beta-blocker, left ventricular dysfunction, and reversible ischemia were 2.65, 2.39, 2.01, and 2.51, respectively. Patients with three or four of these risk factors had an 83% probability of death or reinfarction, compared with 41% in patients with two risk factors and 6% in patients with one or no risk factor (P < .001). CONCLUSION: Intravenous dipyridamole thallium imaging provides independent prognostic information in older patients with acute myocardial infarction. Moreover, the combination of clinical, echocardiographic, and dipyridamole thallium variables effectively stratifies older postinfarction patients into high-, intermediate-, and low-risk categories for death or recurrent myocardial infarction.

Aged↗

The pyrimido-pyrimidine derivatives, dipyridamole and RA-642, reduce opacification of crystalline lens in diabetic rats.

We assessed the effect of dipyridamole, RA-642 and mopidamol, on lenticular opacities in a model of experimental diabetic cataracts in rats. All three pyrimido-pyrimidine derivatives caused a statistically significant reduction of opacification in crystalline lens as compared with untreated diabetic animals. The production of superoxide anions (phenazine methosulphate [PMS]-induced nitroblue tetrazolium [NBT] reduction) showed a decrease of 81.6%, 78.9% and 1.8% in lens tissue homogenates from rats treated with dipyridamole, RA-642 and mopidamol, respectively. Dipyridamole and RA-642 produced a statistically significant inhibition (50% and 64.8%, respectively) of lipid peroxidation (ferrous sulphate and ascorbic acid [FeAs]-induced malondialdehyde [MDA] production) as compared with the group of untreated diabetic rats. Mopidamol did not exert any inhibitory effect on lipid peroxidation. There was a statistically significant correlation between opacification of lens and PMS-induced NBT reduction and FeAs-induced MDA production. We conclude that the protective effect of dipyridamole and RA-642 from free radical damage to crystalline lens in the model of experimental diabetes used in this study, is the result of the antioxidant action of these compounds. The effect exerted by mopidamol, however, suggest a possible complementary effect of the pyrimido-pyrimidine derivatives through interaction with other mechanisms (e.g., the sorbitol pathway) implicated in the development of cataracts.

Animals↗

Differential inhibition of 2'-deoxycytidine salvage as a possible mechanism for potentiation of the anti-human immunodeficiency virus activity of 2',3'-dideoxycytidine by dipyridamole.

Dipyridamole, a commonly used coronary vasodilator and antithrombotic drug, was recently shown to potentiate the activity of 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine against the human immunodeficiency virus type 1 (HIV-1) in human monocyte-macrophages in vitro. We report in the present paper that in uninfected monocyte-macrophages dipyridamole significantly inhibits cellular salvage of [3H]deoxycytidine, whereas it does not affect the salvage of [3H]dideoxycytidine. Similar differential inhibition by dipyridamole of the salvage of thymidine, as opposed to 3'-azido-3'-deoxythymidine, was reported previously (G. V. Betageri, J. Szebeni, K. Hung, S. S. Patel, L. M. Wahl, M. Corcoran, and J. N. Weinstein, Biochem. Pharmacol. 40:867-870, 1990). Taken together, these observations suggest that inhibition of the salvage of competing physiological nucleosides may explain or contribute to the potentiating effect of dipyridamole on these antiviral dideoxynucleoside drugs.

Antiviral Agents↗

Absence of effect of dipyridamole on renal and platelet function in diabetes mellitus.

We evaluated the effect of dipyridamole (5 mg/kg/day) for 12 months on renal and platelet function in 53 children with insulin dependent diabetes mellitus (IDDM) in a prospective double blind placebo controlled trial. Urine albumin excretion (expressed as the geometric mean albumin to creatinine concentration ratio (UA/UC) was measured every three months throughout the study. At 12 months, the geometric mean UA/UC was no different in diabetic children receiving dipyridamole, 0.60 mg/mmol, when compared with those receiving placebo, 0.87 mg/mmol. Glomerular filtration rate, urinary excretion of retinol binding protein, and N-acetyl-beta-D-glucosaminidase (NAG), blood pressure, and spontaneous platelet aggregation in response to stirring whole blood did not differ between the two groups at 12 months. Subgroup analysis to include only those children with high UA/UC before entry into the study also failed to show an effect of the drug on UA/UC. Eleven children had either persistently high UA/UC (n = 8: four on dipyridamole, four on placebo) or progression to high UA/UC (n = 3: two on dipyridamole, one on placebo). These children had significantly higher urinary excretion of retinol binding protein and NAG, bigger kidneys, and higher diastolic blood pressure both before and after treatment than the remaining 42 children, whereas there was no difference in spontaneous platelet aggregation between the two groups. These observations on the associations between UA/UC and other parameters of renal function suggest that measurement of 'tubular' proteins and diastolic blood pressure as well as UA/UC may contribute to the identification of those at risk of developing nephropathy.

Adolescent↗

Long term clinical outcome of coronary surgery and assessment of the benefit obtained with postoperative aspirin and dipyridamole.

Three hundred and twenty patients originally entered into a randomised study to assess the effect of aspirin and dipyridamole on the patency of coronary bypass grafts one year after operation were clinically reassessed a mean of 6.6 years (range 4.3-8.6) after operation. Patients were recruited between 1978 and 1982 after the present policy of total revascularisation had been adopted. During the follow up period there were 25 deaths of which 17 were due to cardiac causes (average annual cardiac mortality 0.8%). Of 280 patients available for contact, 250 (89.3%) attended an outpatient interview. Ninety four (37.6%) patients complained of recurrent angina but in only 23 (9.2%) was this severe. Two hundred and eleven (84.4%) of the 250 patients underwent exercise stress testing. There were 73 (34.6%) abnormal tests of which 52 were in the group of 94 patients with recurrent angina. Myocardial infarction occurred in nine of the 250 patients during the follow up period. Twenty six patients (10.4%) had reinvestigation for symptoms. This group had a graft occlusion rate of 52%. Half these patients have required reoperation and 20 of 22 occluded or severely stenosed grafts were replaced. In only two instances were vein grafts inserted into vessels with new disease. Half of the original group were given aspirin (330 mg three times a day) plus dipyridamole (75 mg three times a day). Of the 250 patients interviewed, 122 took aspirin and dipyridamole from the second postoperative day for a mean of 25 months, with warfarin for three months. The other 128 patients took placebo for a mean of 23 months together with warfarin for three months. This long term treatment with aspirin plus dipyridamole conferred no significant benefit for all clinical outcomes measured at a mean of 6.6 years.

Angina Pectoris↗

High dose dipyridamole as a pharmacological stress test during cardiac catheterisation in patients with coronary artery disease.

AIM: To validate dipyridamole as a pharmacological stress test during cardiac catheterisation, allowing both functional and morphological estimation of stenosis severity. METHODS: The study encompassed 74 patients: 62 patients with significant coronary artery disease (age 61 (SD 8) years; seven women, 55 men) and 12 controls. Regional wall motion, left ventricular ejection fraction and end diastolic pressure were analysed in the resting state and after high dose intravenous dipyridamole. Patients were subdivided into four groups: group I (n = 32, 43%) had stopped all anti-ischaemic treatment for > 24 h, group II (n = 14, 19%) was under treatment, group III (n = 16, 22%) had significant coronary artery disease only in regions with regional wall motion abnormalities at rest, and group IV consisted of 12 control patients (16%) with no significant coronary artery disease (age 62 (8) years, three women, nine men). RESULTS: The sensitivity of dipyridamole testing in patients with coronary artery disease was poor. The best sensitivity was obtained with regional wall motion analysis (26/62 = 42%) and with global left ventricular ejection fraction (25/62 = 40%). Specificity was 100% for regional wall motion and 100% for ejection fraction. Calculated positive and negative predictive values for regional wall motion were 100% and 63%, respectively. CONCLUSIONS: Although safe, handy, and inexpensive, dipyridamole is not an adequate pharmacological stress test during cardiac catheterisation because of its low sensitivity.

Cardiac Catheterization↗