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PubMed2004

Accuracy of dipyridamole myocardial contrast echocardiography for the detection of residual stenosis of the infarct-related artery and multivessel disease early after acute myocardial infarction.

OBJECTIVES: We aimed to evaluate the ability of vasodilator myocardial contrast echocardiography (MCE) to detect significant infarct-related artery (IRA) stenosis and multivessel disease (MVD) after thrombolysis. BACKGROUND: The detection of residual IRA stenosis subtending significant viable myocardium and the identification of MVD may help to triage patients who may benefit from mechanical revascularization after acute myocardial infarction (AMI) and thrombolysis. METHODS: Patients with AMI underwent low-power MCE at rest and after dipyridamole stress during SonoVue infusion seven to 10 days after thrombolysis. RESULTS: Of the 73 patients, 61 demonstrated significant myocardial viability, of whom 57 (93%) showed significant IRA stenosis. Sensitivities to detect >50% IRA stenosis and MVD were 88% and 72%, respectively. The accuracy of detecting significant coronary stenosis in the anterior (left anterior descending coronary artery) versus inferoposterior (right coronary artery/left circumflex artery) circulation was similar for both IRA (85% vs. 91%) and remote territories (91% vs. 81%). Quantitative peak contrast intensity (p = 0.02), microbubble velocity (p = 0.0001), and myocardial blood flow (p < 0.0001) were significantly lower in patients with significant coronary stenosis during dipyridamole compared with rest. Only beta reserve discriminated various grades of coronary stenosis. CONCLUSIONS: Use of MCE accurately predicted significant IRA stenosis and MVD after thrombolysis. This information is valuable for identifying patients who may benefit from mechanical revascularization.

Aged↗

PubMed1991

Dipyridamole perfusion scintigraphy.

Dipyridamole is one of several agents that may be infused intravenously to nonivasively evaluate coronary perfusion without dynamic exercise. Among such agents it is the most investigated, and it is associated with the greatest clinical experience. Its mechanism of action utilizes intrinsic adenosine and does not require the induction of ischemia. Rather, the method tests the coronary flow reserve by dilating the precapillary and arteriolar capillary beds. Vessels with a limited coronary flow reserve demonstrate reduced responsiveness with relative flow reduction and a resultant defect on perfusion scintigraphy. Side effects are common and generally benign, but deaths have been reported and they generally relate to severe hypotension, prolonged dense ischemia and resultant infarction, or bronchospasm. Severe complications are rare and can be avoided by the prompt administration of aminophylline, the dipyridample antedote. Diagnostic accuracy for the identification of coronary disease appears similar to that for exercise perfusion scintigraphy. It should be applied to patients with known or suspected coronary disease who require coronary evaluation, but who cannot exercise adequately for diagnostic or prognostic purposes. In such patients, the method is useful for the preoperative assessment of risk at peripheral vascular and other major noncardiac surgery. It may be of value as well in the assessment of the otherwise uncomplicated patient postinfarction. Not yet established is its application to the patient with unstable angina or in the acute setting, after coronary reperfusion. Similarly, its comparison with direct adenosine infusion or with pharmacological agents whose mechanism rests entirely on ischemia induction, as does dobutamine, has until now been limited. Unlike its use with perfusion scintigraphy, the application of dipyridamole with echocardiography and other functional ischemic indicators is totally dependent on the induction of ischemia. This is likely less frequent than the induction of nonischemic perfusion heterogeneity. The agent is now commonly available and will make a significant beneficial impact on patient evaluation and management.

Coronary Disease↗

PubMed1976

Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.

A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.

Acute Disease↗

PubMed2000

Evaluation of coronary flow reserve in hypertensive patients by dipyridamole transesophageal doppler echocardiography.

This study evaluates the coronary flow reserve (CFR) in hypertensive patients with and without left ventricular (LV) hypertrophy. CFR was assessed by transesophageal Doppler echocardiography in 15 normal subjects (group I), 21 hypertensive patients without LV hypertrophy (group II), and 27 hypertensive patients with LV hypertrophy (group III). All hypertensive patients were complaining of typical anginal pain and had normal coronary angiograms. The sample volume was placed at the bifurcation of the left main and left anterior descending coronary arteries. Coronary blood flow velocities were evaluated at rest, 2 minutes after dipyridamole infusion, and 2 minutes after intravenous aminophylline. The ratios of dipyridamole to rest peak diastolic and systolic velocities were considered as indexes of CFR. Peak diastolic velocity ratio was significantly lower in group III than in groups I and II (1.6 +/- 0.2, 2.7 +/- 0.4, and 2.1 +/- 0.2, respectively; p <0.05), and it was significantly lower in group II than I (p <0.05). The peak systolic velocity ratio was significantly lower in group III than in groups I and II (1.7 +/- 0.3, 2.8 +/- 0.3, and 2.1 +/- 0.2, respectively; p <0.05), and it was significantly lower in group II than I (p <0.05). The peak diastolic velocity ratio was inversely related to systolic blood pressure, diastolic blood pressure, and LV mass index (r = -0.48, -0. 51, and -0.37 respectively) in hypertensive patients. It is concluded that CFR is significantly impaired in hypertensive patients, especially those with LV hypertrophy, compared with healthy subjects. The degree of impairment of CFR is related to LV mass index.

Angina Pectoris↗

PubMed2003

Usefulness of coronary flow reserve over regional wall motion when added to dual-imaging dipyridamole echocardiography.

Vasodilator stress echocardiography allows semi-simultaneous imaging of left anterior descending (LAD) coronary flow and regional wall function. To assess the relative (and additive?) value of regional flow and function for noninvasive identification of angiographically assessed LAD disease in patients with chest pain syndrome, we studied 230 consecutive in-hospital patients (134 men, aged 63.5 +/- 11 years) with chest pain syndrome and normal regional and global left ventricular function. All patients underwent stress echocardiography with dipyridamole (up to 0.84 mg/kg over 10 minutes), including wall motion analysis by 2-dimensional echocardiography and coronary flow reserve (CFR) evaluation of the LAD artery by Doppler, with or without contrast injection. A new regional wall motion abnormality in >or=2 contiguous segments was required for 2-dimensional echocardiographic positivity. CFR was evaluated as the ratio of dipyridamole to peak diastolic coronary blood flow velocity at rest. All patients underwent coronary angiography within 60 days; a quantitatively assessed diameter reduction >50% of the LAD artery was considered significant. Of the 230 patients, 70 had LAD disease. A regional wall motion abnormality in LAD territory was present in 52 patients, and reduced CFR (<1.9) in 62 patients. Sensitivity for detecting LAD disease was 74% for 2-dimensional echocardiography (95% confidence interval [CI] 64% to 84%) and 81% for CFR <1.9 (95% CI 72% to 90%); specificity was 91% (95% CI 87% to 96%) for 2-dimensional echocardiography and 84% for CFR (95% CI 79% to 90%). Accuracy was 86% for 2-dimensional echocardiography (95% CI 82% to 91%) and 83.5% for CFR (95% CI 79% to 88%). When 2-dimensional echocardiography and CFR criteria were considered, sensitivity increased to 93% (95% CI 87% to 99%), with 80.6% specificity (95% CI 74.5% to 86.7%). CFR was assessed during vasodilator stress echocardiography. Its diagnostic accuracy for detecting LAD disease was comparable to regional wall motion abnormalities. However, the data for flow and function can be complementary in terms of predicting underlying angiographic anatomy, because abnormal wall motion can include coronary artery disease, and negative CFR can exclude it.

Chest Pain↗

PubMed2003

Usefulness of chronotropic incompetence to dipyridamole in predicting myocardial perfusion defects in heart transplant recipients.

The aim of this report was to assess the relation between heart rate response to dipyridamole infusion and perfusion defects at quantitative sestamibi single-photon emission computed tomographic imaging. We demonstrated in 166 heart transplant recipients that chronotropic incompetence to dipyridamole is the only significant and independent predictor of perfusion defects.

Case-Control Studies↗

PubMed1996

Comparison of the diagnostic potential of four echocardiographic stress tests shortly after acute myocardial infarction: submaximal exercise, transesophageal atrial pacing, dipyridamole, and dobutamine-atropine.

This study assessed and compared the diagnostic potential of submaximal exercise, transesophageal atrial pacing, dipyridamole, and dobutamine-atropine stress echocardiography tests shortly after acute myocardial infarction. In 121 study patients, 325 digital echocardiographic stress tests were attempted 10 to 11 days after acute myocardial infarction: 83 submaximal exercise tests, 121 high-dose dipyridamole echocardiography tests (DET), 69 transesophageal atrial pacing tests (< 150 beats/min), and 52 dobutamine tests, starting at 10 microgram/kg per minute, increasing stepwise to 40 microgram kg/min, and coadministering atropine in 12 patients (dobutamine-atropine stress echocardiography [DASE]). Results were correlated to a coronary artery diameter stenosis > or = 50% as determined by quantitative angiography. Feasibility to perform submaximal exercise echocardiography, atrial pacing echocardiography, DET, and DASE was 89%, 52%, 98%, and 88%, respectively. Atrial pacing was not tolerated by 18 patients and refused by 6 (9%). Severe but not life-threatening side effects were hypotension in DET (2%) and tachyarrhythmias in DASE (6%). Test positivity in multivessel disease with submaximal exercise, DET, and DASE was 55%, 93%, and 90%, respectively, and in 1-vessel disease 47%, 65%, 71%, and for atrial pacing, 82%, respectively. We conclude that submaximal exercise has limited sensitivity and atrial pacing limited feasibility. The pharmacologic stressors provide a useful, safe diagnostic approach: DET with slightly lower sensitivity in 1-vessel disease and DASE with insignificantly less feasibility.

Atropine↗

PubMed1997

Comparison of the prognostic value of dipyridamole and dobutamine stress echocardiography in patients with known or suspected coronary artery disease.

Direct comparison of the utility of dipyridamole stress echocardiography and dobutamine stress echocardiography was performed to identify patients at risk of future cardiac events in 134 patients with suspected or known coronary artery disease. The predictive values of dobutamine and dipyridamole were remarkably similar.

Adrenergic beta-Agonists↗

PubMed1997

Assessment of left internal mammary artery grafts using dipyridamole Doppler echocardiography.

Color Doppler echocardiography of the left mammary artery was combined with dipyridamole testing in order to assess the presence of significant (>70%) graft stenosis in 87 patients with a mammary artery graft to the left anterior descending coronary artery presenting with chest pain. Occluded grafts are detected by absent diastolic flow velocities at baseline, whereas the response of the diastolic flow velocity to dipyridamole distinguishes patients with critical versus noncritical stenosis of a patent graft.

Blood Flow Velocity↗

PubMed1998

Dipyridamole-dobutamine stress with Tc-99m sestamibi tomographic myocardial perfusion imaging.

In 66 patients unable to exercise referred for pharmacologic stress single-photon emission computed tomographic myocardial perfusion imaging, a moderate dose of dobutamine was combined with intravenous dipyridamole and the results were compared with standard intravenous dipyridamole stress. The combined stress protocol resulted in increased defect size and reversibility with technetium-99m sestamibi single-photon emission computed tomographic myocardial perfusion imaging.

Aged↗

PubMed1999

Long-term prognostic value of preoperative dipyridamole thallium imaging and clinical indexes in patients with diabetes mellitus undergoing peripheral vascular surgery.

The objective of this study is to assess the prognostic impact of preoperative dipyridamole thallium imaging and clinical variables on the long-term outcome of diabetic patients undergoing peripheral vascular surgery. Complete follow-up was obtained in 101 consecutive patients with diabetes mellitus undergoing routine dipyridamole thallium scintigraphy before vascular surgery (mean 4.2 +/- 3.2 years, range 1 month to 11 years). Low risk was defined by diabetes alone with a normal resting electrocardiogram. High risk was defined as a history of angina, myocardial infarction, congestive heart failure, or resting electrocardiogram abnormalities. There were 71 deaths in 98 patients discharged alive from the hospital (median survival 4.4 years). Age, the presence of resting electrocardiogram abnormalities, and an abnormal thallium scan were independent predictors of late death. After adjusting for age >70 years and thallium abnormalities, high-risk patients had a death rate 4.8 times (95% confidence interval 1.7 to 13.4, p <0.002) greater than low-risk patients. The presence of >2 reversible thallium defects was useful in further risk stratification of both low- and high-risk patients. Low-risk patients with >2 reversible defects had a median survival of 4.0 years compared with 9.4 years in those with < or =2 reversible defects (p <0.001). Similarly, high-risk patients with < or =2 reversible defects had an intermediate median survival rate of 4.7 years compared with 1.8 years in the group with >2 reversible defects (p <0.001). Therefore, advanced age and the presence of resting electrocardiographic or thallium abnormalities identifies a subset of diabetic patients with a poor long-term outcome after vascular surgery. Combined clinical and thallium variables may identify a population in whom intensive medical or surgical interventions may be warranted to reduce both perioperative and late cardiac events.

Aged↗

PubMed1981

Influence of aspirin and dipyridamole on patency of coronary artery bypass grafts.

A prospective randomized trial was performed to determine if the administration of inhibitors of platelet function would improve the patency of coronary artery bypass grafts. Patients were operated on for intractable angina with angiographically demonstrable lesions. The left internal mammary artery (IMA) was used for bypass of lesions of the left anterior descending coronary artery (LAD). Saphenous vein grafts were used for the LAD if the IMA was inadequate and for all other vessels. Treated patients received 1,300 mg of aspirin and 100 mg of dipyridamole (Persantine) orally each day. Control patients received neither drug. Patients returned 3 to 6 months after operation for repeat angiography. Results were analyzed by chi-square. One hundred seventy-four patients entered the study from June, 1973, through December, 1975, and 113 were analyzed. In the control group, 66 patients had 27 IMA-LAD grafts and 93 saphenous vein grafts. In the treatment group, 47 patients underwent 18 IMA-LAD grafts and 75 saphenous vein grafts. Ninety-eight of the 120 grafts (82%) were patent in the control group, and 87 of 93 grafts (94%) were patent in the treatment group (x2 = 6.34, p less than 0.02). Of the 45 IMA-LAD grafts in both groups, only 1 was occluded, a patency of 98%. In the control group, 72 of 93 saphenous vein grafts (77%) were patent. In the treatment group, 69 of 75 (92%) were patent (x2 = 6.54, p less than 0.02). The results of the study show a 15% difference between the two groups in the early patency of saphenous vein grafts. We continue to use aspirin and dipyridamole to improve the patency of saphenous vein bypass grafts.

Aspirin↗

PubMed1997

Binding of dipyridamole to phospholipid vesicles: a fluorescence study.

Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and one of its derivatives, RA25, to phospholipid vesicles of DMPC (dimyristoylphosphatidylcholine) and DPPC (dipalmitoylphosphatidylcholine) was studied using fluorescence spectroscopy as well as quenching of fluorescence. The analysis of fluorescence data indicates that neutral dipyridamole binds to the phospholipids in their liquid crystalline phase with an association constant of 950 M(-1) and 1150 M(-1) to DMPC and DPPC, respectively. Protonation of DIP leads to a 3-fold reduction of the association constant. For the gel phospholipid phase, the binding is smaller (a factor of 2), independently of pH, suggesting that the more flexible lipid packing in the liquid crystalline phase facilitates the binding of the drug. The association constant of RA25 neutral form is considerably lower than for DIP, being around 295 M(-1). Fluorescence quenching with nitroxides TEMPO and stearic acid doxyl derivatives suggests the localization of DIP to be closer to the 5th carbon of alkyl chain. The quenching effect of 5-DSA below the lipid phase transition suggests that a strong static quenching may be operative. The quenching effect of 16-DSA is almost as great as that for 5-DSA below the phase transition, being even higher above the phase transition. This effect is probably due to the trans-gauche isomerization of the stearic acid nitroxide, making the encounter of its paramagnetic fragment with the DIP chromophore possible. Our data are consistent with DIP location close to the bilayer surface in the border of hydrophobic-polar heads interface which is similar to the data in micellar systems. In the case of RA25, the drug is in the outer part of the head group interface being much exposed to the aqueous phase and being significantly less accessible to the membrane nitroxide quenchers.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1988

Heparin plus dipyridamole in childhood hemolytic-uremic syndrome: a prospective, randomized study.

From 1976 to 1985, a total of 58 infants and children with the hemolytic-uremic syndrome were randomly assigned to treatment either with heparin and dipyridamole or with supportive management only. In the treatment group, two patients died in the early weeks of the disease. Analysis of clinical and laboratory data showed no significant difference between either group of patients as to the evolution of their illness except for a significantly higher incidence of anuria and a significantly faster recovery from hypertension in the treated group. Renal biopsy studies showed no differences between the two groups in terms of incidence and severity of the histologic lesions. The long-term data on blood pressure and creatinine clearance values in the survivors were similar in both groups. This study indicates that treatment with heparin and dipyridamole has no benefit over symptomatic therapy alone in the typical form of childhood hemolytic-uremic syndrome.

Adolescent↗

PubMed2001

[Utility of SPECT with 99m Tc-tetrofosmin and stimulus with dipyridamole in patients with permanent ventricular pacemakers].

BACKGROUND AND OBJECTIVE: Patients with permanent ventricular pacemakers (PP) are a difficult subgroup to assess in the study of coronary artery disease. The objective of this study was to evaluate the diagnostic value of the myocardial perfusion scintigraphy with 99mTC-Tetrofosmin (Tc-Tf) and stimulus with dipyridamole in patients with PP and suspected coronary artery disease. PATIENTS AND METHODS: Fourteen patients with suspected coronary artery disease and without structural cardiopathy, who underwent Tc-Tf and cardiac catheterization, were studied retrospectively. Sensitivity, specificity, predictive values and Kappa index were calculated for the diagnosis of coronary artery disease, multivessel disease, and for each one of the coronary arteries (left anterior descending, right coronary, and circumflex). In addition, the correlation between the number of territories with perfusion defects and the number of diseased vessels was studied. RESULTS: In regards to the diagnosis of coronary artery disease, sensitivity, specificity, positive predictive value, negative predictive value and the Kappa index were 100%, 50%, 83%, 100% and 0.55, respectively. For multi-vessel disease, these values were 83%, 64%, 64%, 83% and 0.43 respectively. The correlation coefficient between the number of territories with perfusion defects and the number of diseased vessels was 0.61 (p = 0.02). In the diagnosis of anterior descending disease, sensitivity and specificity were 83% and 88% respectively. For the right coronary artery, these values were 100% and 44% and for the circumflex artery 38% and 83%, respectively. CONCLUSION: In patients with PP and suspected coronary artery disease, myocardial perfusion scintigraphy with Tc-Tf and stimulus with dipyridamole is of great value in the diagnosis of coronary artery disease and in the assessment of its extension.

Aged↗

PubMed1985

A double blind trial of dipyridamole in CAPD.

Since we had previously shown that dipyridamole augmented inulin and glucose clearance during intermittent peritoneal dialysis we sought to extend our study to the patient undergoing continuous ambulatory peritoneal dialysis. We carried out a double blind study in which patients received either 75 mg of active drug or placebo for a 2-week period. At the end of this period the mass transfer coefficients, between plasma and dialysate, were measured for selected solutes. We did not find any drug effect. The results of our first study together with the results of this study suggest that dipyridamole has no place in the chronic management of patients undergoing peritoneal dialysis.

Administration, Oral↗

PubMed1999

Dipyridamole stress echocardiography.

Dipyridamole stress is the forerunner and prototype of pharmacological stress echo tests in the diagnosis of coronary artery disease. The safety of this test has been conclusively demonstrated as a result of extensive experience in large-scale multicenter projects. The diagnostic accuracy of dipyridamole stress echo is comparable to dobutamine and largely a function of the employed dose. Higher dosages (up to 0.84 mg/kg) are being required to achieve good sensitivity. The prognostic value has been shown to be independent and additive to clinical, exercise echocardiogram, and angiographic data. The test positive response should be titrated on the basis of severity, extent, and timing of induced dyssynergy with low positivity being associated to more anatomically and functionally severe forms of disease. Multicenter, randomized, prospective, international studies on cost-effectiveness directly comparing a noninvasive strategy centered on stress echo versus an invasive strategy centered on coronary angiography are currently ongoing.

Adrenergic beta-Agonists↗

PubMed1998

Impaired myocardial vasodilation during hyperemic stress with dipyridamole in hypertriglyceridemia.

OBJECTIVES: This study sought to investigate the specific role of hypertriglyceridemia in the myocardial hyperemic stress with dipyridamole/rest flow ratio (MDR). BACKGROUND: Reduced MDR has been reported in hypercholesterolemic patients without evidence of ischemia. However, the specific role of hypertriglyceridemia in MDR has not been studied. METHODS: Fifteen nondiabetic normocholesterolemic hypertriglyceridemic patients and 13 age-matched control subjects were studied. Myocardial blood flow (MBF) during dipyridamole administration and baseline MBF in hypertriglyceridemic patients and control subjects were measured using positron emission tomography and nitrogen-13 ammonia, after which the MDR was calculated. RESULTS: Baseline MBF (ml/min per 100 g heart weight) in hypertriglyceridemic patients (mean +/- SD 73.6 +/- 24.1) did not differ significantly from that in control subjects (81.6 +/- 37.2). MBF during dipyridamole loading in hypertriglyceridemic patients (198 +/- 106) was significantly reduced compared with that in control subjects (313 +/- 176, p < 0.05), as was the MDR (2.71 +/- 1.07 vs. 3.73 +/- 1.14, respectively, p < 0.05). Spearman rank-order correlation analysis showed a significant relation between plasma triglyceride concentration and MDR (r = -0.466, asymptotic SE 0.157, p = 0.0125); however, no such significant relation was seen between total plasma cholesterol concentration and MDR (r = -0.369, asymptotic SE 0.130, p = 0.059). CONCLUSIONS: Impaired myocardial vasodilation was suggested in hypertriglyceridemic patients without symptoms and signs of ischemia.

Adult↗