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Effect of beta-adrenoceptor blockade on dipyridamole-induced myocardial asynergies in coronary artery disease.

Twenty-one patients with angiographic evidence of significant coronary artery disease, and positive dipyridamole echocardiographic test results at basal condition and after 7 days of placebo treatment were prospectively studied to see whether beta blockade modifies the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to propranolol (120 mg/day) or placebo treatment in 3 divided doses for 7 days, after which each patient crossed over to the alternate regimen. Dipyridamole-echocardiographic testing was repeated at the end of each treatment. Propranolol abolished new mechanical signs of transient dipyridamole-induced ischemia (new wall motion abnormalities or an increase in degree of basal asynergies, or both) in 13 of 21 patients. The remaining 8 patients had positive results on dipyridamole echocardiographic testing after the propranolol treatment period. At basal conditions both heart rate and rate-pressure product were significantly reduced with propranolol; there was also a significant decrease in these parameters at peak dipyridamole infusion. At peak dipyridamole infusion heart rate and rate-pressure product were significantly lower in patients with negative than in those with positive echocardiographic test results after propranolol. Our data show that administration of beta blockade significantly reduces the development of transient dipyridamole-induced myocardial asynergies, the earliest markers of acute myocardial ischemia, detected with 2-dimensional echocardiography.

Adrenergic beta-Antagonists↗

Effect of dipyridamole-like compound (R-E 244) on aggregation and cyclic AMP accumulation in human platelets.

The aim of this in vitro study was to evaluate the effect of a clinical concentration (2 microM) of dipyridamole alone or in combination with adenosine, 5'-N-ethyl-carboxamido-adenosine (NECA), or prostaglandin E2 on ADP-induced whole blood aggregability. Cyclic AMP accumulation in platelet-rich plasma was also evaluated. For comparison, R-E 244 (a dipyridamole analogue with low phosphodiesterase inhibition) was examined. In whole blood, dipyridamole (2 microM), but not R-E 244 (2 microM), had a small inhibitory effect (16% +/- 5%, p less than 0.01) on aggregation. Adenosine (1 or 5 microM) had an inhibitory effect that was enhanced by the combination with dipyridamole or R-E 244. Adenosine + dipyridamole produced an inhibition almost equal to that of adenosine + R-E 244. Dipyridamole and R-E 244 had no influence on the antiaggregatory effect of NECA and prostaglandin E2. In platelet-rich plasma, dipyridamole and R-E 244 did not enhance cyclic AMP, nor did they reinforce the cyclic AMP production during treatment with adenosine, NECA, and prostaglandin E2. Our results suggest that inhibition of the uptake of adenosine into red blood cells may play a more important role than the inhibition of phosphodiesterase as the pharmacological mechanism for the antiaggregatory effect of dipyridamole in clinical treatment.

Adenosine↗

Detection of coronary artery disease by digital stress echocardiography: comparison of exercise, transesophageal atrial pacing and dipyridamole echocardiography.

OBJECTIVES: This study assessed and compared the diagnostic potential of exercise, transesophageal atrial pacing and dipyridamole stress echocardiography in a clinical setting. BACKGROUND: Although they have been widely studied, no data exist with regard to comparisons of these procedures in a head-to-head study in different clinical settings. METHODS: One hundred four consecutive patients with suspected coronary artery disease undergoing coronary angiography and with no previous myocardial infarction or rest left ventricular wall motion abnormalities underwent digital posttreadmill, transesophageal atrial pacing and dipyridamole echocardiography. RESULTS: Feasibility of digital exercise echocardiography was 84%; 8 of 88 remaining patients had a nondiagnostic exercise echocardiographic test (inadequate exercise or imaging). In 80 patients with feasible and diagnostic digital exercise echocardiography, sensitivity, specificity and accuracy were, respectively, 89%, 91% and 90%. Eighty of the 104 patients underwent transesophageal atrial pacing and dipyridamole echocardiography. Feasibility of the alternative stress procedures was 77% for transesophageal atrial pacing and 96% for dipyridamole. In 60 patients successfully undergoing both alternative stress procedures, sensitivity and specificity were 83% and 76% for atrial pacing and 43% and 92% for dipyridamole echocardiography, respectively. In the group of 24 patients with nondiagnostic exercise echocardiography and consequent indication to alternative stress procedures, accuracy of transesophageal atrial pacing was higher than that of dipyridamole echocardiography (73% vs. 45%, p = 0.06). CONCLUSIONS: Because of its higher diagnostic potential and additional functional information, exercise is the stress of choice when stress echocardiography is used to detect the presence of coronary artery disease. Alternative stresses can be used in patients with nondiagnostic exercise echocardiography. Transesophageal and dipyridamole echocardiography differ in feasibility and diagnostic reliability (higher sensitivity of transesophageal atrial pacing, higher specificity of dipyridamole). These characteristics must be considered when selecting procedures to be used as alternatives to exercise.

Aged↗

Cellular pharmacokinetics and pharmacodynamics of dipyridamole in vascular smooth muscle cells.

Hemodialysis arteriovenous grafts are often plagued by stenosis at the vein-graft anastomosis, which is due to the proliferation of venous smooth muscle cells (SMCs). Perivascular delivery of dipyridamole, a potent antiproliferative agent, has been proposed for the prevention of graft stenosis. In order to develop an optimal delivery system for dipyridamole, we examined its pharmacokinetics and pharmacodynamics in human and porcine venous and arterial SMCs in vitro. SMCs were incubated with dipyridamole for various durations, and visualized for the uptake and release by fluorescence microscopy, which were further quantified by fluorospectrometry. The antiproliferative effect of dipyridamole was examined by cell counting or the methylthiazoletetrazolium (MTT) dye-reduction assay. Cytotoxicity was examined by the lactate dehydrogenase (LDH)-release assay. The kinetics of dipyridamole transport through the cell membrane was compatible with a passive diffusion mechanism. Dipyridamole inhibited SMC proliferation in a dose-dependent manner and was more effective in venous than arterial cells in both species. The inhibition was completely reversible at 15microg/ml upon drug removal from the medium. At 25microg/ml, however, the effect was partially irreversible, which might be attributed to the cytotoxicity of dipyridamole. These data support the need for sustained delivery of dipyridamole to achieve the long-term inhibition of SMC proliferation in the prevention of stenosis since SMCs are continuously stimulated at the anastomosis of hemodialysis arteriovenous grafts.

Animals↗

Dipyridamole protects the liver against warm ischemia and reperfusion injury.

BACKGROUND: Adenosine, a metabolite of adenosine triphosphate degradation during ischemia, is reported to attenuate ischemia and reperfusion injury in several tissues. Dipyridamole is a nucleoside transport inhibitor that augments endogenous adenosine. In this study, we tested whether dipyridamole would attenuate hepatic I/R injury. For this purpose, dipyridamole was applied to a 2-hour total hepatic vascular exclusion model in dogs. STUDY DESIGN: Dipyridamole (DYP) was given by continuous intravenous infusion for 1 hour before ischemia at a dose of 0.25 mg/kg (high-DYP, n = 6), 0.1 mg/kg (medium-DYP, n = 6), or 0.05 mg/kg (low-DYP, n = 6). Nontreated animals were used as ischemic controls (CT, n = 12). Two-week survival, systemic and hepatic hemodynamics, liver function tests, energy metabolism, adenosine 3', 5'-cyclic monophosphate (cyclic AMP) levels, platelet numbers, arachidonic acid metabolites, and histopathology were analyzed. RESULTS: Two-week animal survival was 25% in CT, 17% in high-DYP, 100% in medium-DYP, and 17% in low-DYP. Dipyridamole significantly improved postreperfusion hepatic blood flow and energy metabolism, attenuated liver enzyme release and purine catabolite production, and augmented cyclic AMP levels. The medium dose of dipyridamole lessened platelet aggregation, thromboxane B2 production, and polymorphonuclear neutrophil infiltration, and improved survival. CONCLUSIONS: We demonstrated marked hepatoprotective effects of dipyridamole against severe ischemia and reperfusion injury in canine livers. Dipyridamole is a promising agent for liver surgery and transplantation.

Animals↗

Dipyridamole-induced abnormal Tl-201 lung uptake in patients with normal myocardial perfusion: a marker of increased left ventricular filling pressures.

BACKGROUND: The mechanism of dipyridamole-induced abnormal increased T1-201 lung uptake in patients without coronary artery disease is poorly understood. The purpose of this study was to evaluate the relation between dipyridamole-induced abnormal T1-201 lung uptake and left ventricular (LV) diastolic indexes using Doppler, color M-mode and Tissue Doppler modalities at rest, and at dipyridamole stress echocardiograpy (DSE) in patients with normal myocardial perfusion and LV function. METHODS AND RESULTS: 18 consecutive patients (mean age 64 +/- 7 years) with normal myocardial perfusion and increased lung T1-201 uptake on dipyridamole stress-redistribution single photon emission computed tomography (SPECT) were included in our study. These patients were compared with 18 age-matched control patients with normal perfusion and normal T1-201 lung uptake. All patients underwent DSE. A good correlation was found between the T-201 lung uptake, the peak early velocity of mitral inflow (E, r = 0.57) and estimated pulmonary capillary wedge pressure (PCWP = 1.24[E/Ea] + 1.9, r = 0.68). In patients with increased L/H ratio compared to control group, the E and the PCWP were significantly higher at baseline 81 +/- 18 vs 68 +/- 11 (cm/s) and 13 +/- 3 vs 10.2 +/- 2 (mmHg). An additional significant increase of E to 91 +/- 23 (cm/s (P = 0.001)) and PCWP to 14.8 +/- 3 (P = 0.005) after dipyridamole administration was seen; in contrast to a nonsignificant change observed in control group. For the detection of a dipyridamole induced PCWP >12 mmHg, a L/H ratio of >/=50% had a sensitivity of 72% and a specificity of 83%, resulting in a positive and a negative predictive value of 81% and 75%, respectively. CONCLUSIONS: A dipyridamole-induced abnormal T1-201 lung uptake in patients with normal myocardial perfusion and systolic function is predictive of elevated filling pressures at rest and in response to dipyridamole administration, probably reflecting an intrinsic resting diastolic dysfunction and a further abnormal response to vasodilatation.

Aged↗

Dipyridamole thallium imaging.

Dipyridamole cardiac imaging is a useful alternative to exercise stress testing in the evaluation of patients with ischemic heart disease. Intravenous dipyridamole has been approved recently for clinical use. Oral dipyridamole is widely available. The hemodynamic effects of dipyridamole include an increase in coronary blood flow in excess of the increase in myocardial oxygen consumption and cardiac output. The quality of the thallium images is better or similar to that of exercise thallium images. The optimal dose of intravenous dipyridamole is 0.56 mg/kg and the optimal oral dose is 300-375 mg, although higher doses may be necessary in some patients. The sensitivity and specificity of dipyridamole-thallium imaging, whether intravenous or oral, have been shown in a number of studies to be quite adequate and comparable to that achieved during exercise thallium imaging. Dipyridamole-thallium imaging has also been useful in identifying high-risk patients undergoing major elective vascular surgery. The relative merits of dipyridamole imaging versus exercise testing after acute myocardial infarction require further studies.

Coronary Vessels↗

Comparison of bicycle, heavy isometric, dipyridamole-atropine and dobutamine stress echocardiography for diagnosis of myocardial ischemia.

Several stress echocardiography (SE) modalities have been introduced for diagnosing coronary artery disease (CAD). Exercise and dobutamine SE are considered to have better diagnostic accuracy than vasodilator or isometric SE, but there are no studies in a single group of patients comparing these 3 tests with heavy 2-arm isometric SE. The purpose of this study was to determine the diagnostic characteristics of 4 SE methods in patients with chest pain. Altogether, 60 patients (age +/- SD 55.1 +/- 2.1 years) were tested with bicycle, heavy 2-arm isometric, dipyridamole-atropine and dobutamine SE. CAD (>50% stenosis) was present in 44 patients; 26 patients had 1-vessel disease. During bicycle SE, the double product at peak stress was higher than during dobutamine and dipyridamole-atropine SE (26.5 x 10(3), p <0.005 vs dobutamine and dipyridamole-atropine SE), and peak wall motion score index (1.40) was higher than during dipyridamole-atropine and isometric SE (1.26 and 1.07, respectively, p <0.05 vs bicycle SE). Bicycle, dipyridamole-atropine, and dobutamine SE had higher sensitivity than isometric SE (90%, 93%, 95%, and 30%, respectively, p <0.05 isometric SE vs others). There were no statistically significant differences with regard to specificity. Similarly, bicycle, dipyridamole-atropine, and dobutamine SE had a higher diagnostic accuracy than isometric SE (78%, 88%, 87% and 47%, respectively, p <0.05 isometric SE vs others). We conclude that bicycle, dipyridamole-atropine, and dobutamine SE have an equal diagnostic accuracy in detecting CAD despite higher double product and ischemic burden at peak stress during bicycle and dobutamine SE over dipyridamole-atropine SE. Heavy isometric SE is inaccurate.

Adult↗

Blood conservation with membrane oxygenators and dipyridamole.

Cardiopulmonary bypass induces platelet activation and dysfunction, which result in platelet deposition and depletion. Reduced platelet numbers and abnormal platelet function may contribute to postoperative bleeding. A membrane oxygenator may preserve platelets and reduce bleeding more than a bubble oxygenator, and the antiplatelet agent dipyridamole may protect platelets intraoperatively and reduce bleeding postoperatively. A prospective randomized trial was performed in 44 patients undergoing elective coronary artery bypass grafting to assess the effects of the membrane oxygenator and dipyridamole on platelet counts, platelet activation products, and postoperative bleeding. Patients who were randomized to receive a bubble oxygenator and no dipyridamole had the lowest postoperative platelet counts, the greatest blood loss, and the most blood products transfused. Platelet counts were highest and blood loss was least in patients randomized to receive a membrane oxygenator and dipyridamole (p less than .05). A bubble oxygenator with dipyridamole and a membrane oxygenator without dipyridamole resulted in intermediate postoperative platelet counts and blood loss. Arterial thromboxane B2 and platelet factor 4 concentrations were elevated on cardiopulmonary bypass in all groups. Both the membrane oxygenator and dipyridamole were independently effective (by multivariate analysis) in preserving platelets. Optimal blood conservation was achieved with a membrane oxygenator and dipyridamole.

6-Ketoprostaglandin F1 alpha↗

Effect of i.v. dipyridamole on cerebral blood flow, blood pressure, plasma adenosine and cAMP levels in rabbits.

In response to intravenous administration of dipyridamole, the quantitative and temporal changes in plasma adenosine and cyclic AMP (cAMP) levels in relation to the changes in cerebral blood flow (CBF) and mean arterial blood pressure (MABP) have not been studied. Therefore, we investigated simultaneously the changes in CBF (hydrogen and thermal clearance methods), MABP, plasma adenosine (HPLC) and cAMP (radioimmunoassay) levels for 1 h after intravenous injection of 0.7 and 1.4 mg/kg dipyridamole in rabbits. In separate experiments, only plasma adenosine concentrations were measured to determine how and for how long intravenous administration of 0.7 mg/kg dipyridamole is able to inhibit the removal of plasma adenosine. Dipyridamole decreased MABP, increased plasma adenosine and cAMP levels in a dose-dependent manner. The dose-dependency of increases in CBF could not be demonstrated owing to the marked hypotension. The increase in plasma adenosine concentrations was biphasic. The first peak could be detected at the end of the dipyridamole injection. The second peak occurred 20 min after drug administration, simultaneously with the maximal increases in plasma cAMP level and CBF, whereas the maximal fall in MABP developed earlier. Intravenous administration of 0.7 mg/kg dipyridamole inhibited adenosine uptake only by 25%, which lasted less than 10 min. We concluded that intravenously given dipyridamole is responsible only for the initial short-lasting elevation of plasma adenosine concentration, and is able to induce vasodilation without either dipyridamole itself or adenosine necessarily gaining access to the muscular layer.

Adenosine↗

Photo-immobilization of dipyridamole (Persantin) at the surface of polyurethane biomaterials: reduction of in-vitro thrombogenicity.

Dipyridamole is a well-known vasodilator and a powerful inhibitor of activation and aggregation of blood platelets. Moreover, dipyridamole is essentially non-toxic. The drug is used extensively in clinical anti-coagulation regimes, for example pre- and post-coronary angioplasty procedures. Recently, we have found that photochemical, covalent coupling of dipyridamole to polyurethane surfaces leads to improved thromboresistance in vitro. This phenomenon is now studied in more detail. Both qualitative and more quantitative biochemical experiments were performed in order to characterize the in vitro blood compatibility of a set of polyurethane surfaces onto which dipyridamole was immobilized. First, scanning electron microscopy was used to examine the morphology of platelets which adhered during incubation with platelet-rich plasma. These experiments showed that immobilization of dipyridamole leads to a clearly decreased number of adherent platelets and to a largely diminished propensity of the surface to activate adherent platelets. Secondly, an in vitro thrombogenicity assay was run. These experiments showed that the thromboresistance increased with increasing surface density of immobilized dipyridamole. A short spacer chain separating dipyridamole from the polymer surface, was found to improve the thromboresistance further. Such a spacer chain apparently increases the efficacy of the immobilized drug. Collectively, the present results further substantiate the idea that dipyridamole retains its inhibitory activity with respect to activation and aggregation of blood platelets, when the compound is covalently attached to a polymer surface. The possible utility of these findings with respect to the development of an artificial blood vessel prosthesis is discussed briefly.

Biocompatible Materials↗

Comparison of myocardial blood flow during dobutamine-atropine infusion with that after dipyridamole administration in normal men.

OBJECTIVES: The present study was designed to compare the absolute myocardial blood flow (MBF) after intravenous dipyridamole infusion with that during dobutamine-atropine administration in normal healthy male volunteers. BACKGROUND: Both safety and usefulness of dobutamine-atropine stress in myocardial perfusion imaging have been reported. However, no information exists on whether the magnitude ofhyperemia achieved with dipyridamole and dobutamine-atropine is comparable. METHODS: Myocardial blood flow was measured with positron emission tomography and 15O-labeled water in 20 healthy young men (23 +/- 3 years) 1) at baseline, 2) after dipyridamole infusion (0.56 mg/kg over 4 min), and 3) during dobutamine (40 microg/kg/min) and atropine (0.25 to 1.0 mg) infusion. RESULTS: The MBF was significantly increased during dipyridamole infusion and during dobutamine-atropine stress compared with at rest (4.33 +/- 1.23 and 5.89 +/- 1.58 vs. 0.67 +/- 0.16 ml/min/g, respectively, p < 0.0001). Moreover, dobutamine-atropine infusion produced greater MBF compared with dipyridamole (p = 0.0011), while coronary vascular resistance did not differ significantly after dipyridamole administration and during dobutamine-atropine infusion (17.6 +/- 7.9 vs. 18.6 +/- 5.6 mm Hg/[ml/min/g], respectively). CONCLUSIONS: Near maximal coronary vasodilatation caused by dipyridamole is attainable using dobutamine and atropine in young healthy volunteers. Dobutamine in conjunction with atropine is no less effective than dipyridamole in producing myocardial hyperemia.

Adult↗

Myocardial uptake and clearance of thallium-201 in normal subjects: comparison of dipyridamole-induced hyperemia with exercise stress.

Thallium-201 uptake and clearance after dipyridamole infusion may differ from that after exercise stress because the hemodynamic effects of these two interventions are different. In this study of normal volunteers, thallium kinetics after dipyridamole (n = 13) were determined from three serial image sets (early, intermediate and delayed) and from serial blood samples and compared with thallium kinetics after exercise (n = 15). Absolute myocardial thallium uptake was greater after dipyridamole compared with exercise (p less than 0.0001), although the relative myocardial distribution was similar. The myocardial clearance (%/h) of thallium was slower after dipyridamole than it was after exercise. Comparing dipyridamole and exercise, the differences in clearance were large from the early to the intermediate image (anterior, -11 +/- 17 versus 24 +/- 5, p = 0.0005; 50 degrees left anterior oblique, -7 +/- 11 versus 15 +/- 8, p = 0.004; 70 degrees left anterior oblique, 3 +/- 9 versus 21 +/- 6, p = 0.001). In contrast, the differences in clearance were small from the intermediate to the delayed image (anterior, 15 +/- 4 versus 20 +/- 2, p = 0.025; 50 degrees left anterior oblique, 15 +/- 4 versus 19 +/- 3, p = 0.13; 70 degrees left anterior oblique, 15 +/- 3 versus 18 +/- 2, p = 0.047). Thallium uptake and clearance in the liver, splanchnic region and spleen were greater after dipyridamole (p less than 0.001). Blood thallium levels were greater after dipyridamole (p less than 0.05) and cleared more slowly (p = 0.07). Thus, myocardial thallium-201 uptake and clearance after dipyridamole infusion differ from thallium kinetics after exercise. This difference is, in part, related to associated differences in extracardiac and blood kinetics. Diagnostic criteria for the detection of abnormal thallium-201 clearance must be specific for the type of intervention.

Adult↗

Low-dose dipyridamole infusion acutely increases exercise capacity in angina pectoris: a double-blind, placebo controlled crossover stress echocardiographic study.

OBJECTIVES: The aim of this study was to assess whether endogenous accumulation of adenosine, induced by low-dose dipyridamole infusion, protects from exercise-induced ischemia. BACKGROUND: Adenosine is a recognized mediator of ischemic preconditioning in experimental settings. METHODS: Ten patients (all men: mean age 63.4 +/- 7.3 years) with chronic stable angina, angiographically assessed coronary artery disease (n = 7) or previous myocardial infarction (n = 3) and exercise-induced ischemia underwent on different days two exercise-stress echo tests after premedication with placebo or dipyridamole (15 mg in 30 min, stopped 5 min before testing) in a double-blind, placebo controlled, randomized crossover design. RESULTS: In comparison with placebo, dipyridamole less frequently induced chest pain (20% vs. 100%, p = 0.001) and >0.1 mV ST segment depression (50% vs. 100%, p < 0.05). Wall motion abnormalities during exercise-stress test were less frequent (placebo = 100% vs. dipyridamole = 70%, p = ns) and significantly less severe (wall motion score index at peak stress: placebo = 1.55 +/- 0.17 vs. dipyridamole = 1.27 +/- 0.2, p < 0.01) following dipyridamole, which also determined an increase in exercise time up to echocardiographic positivity (placebo = 385.9 +/- 51.4 vs. dipyridamole = 594.4 +/- 156.9 s, p < 0.01). CONCLUSIONS: Low-dose dipyridamole infusion increases exercise tolerance in chronic stable angina, possibly by endogenous adenosine accumulation acting on high affinity A1 myocardial receptors involved in preconditioning or positively modulating coronary flow through collaterals.

Adenosine↗

Prognostic value of contractile response during high-dose dipyridamole echocardiography test in heart transplant recipients.

BACKGROUND: Coronary allograft vasculopathy (CAV) remains a main factor limiting long-term survival after heart transplantation (HTX). The diagnosis of CAV is still based on serial coronary angiography. In this study, we evaluated the prognostic value of high-dose dipyridamole echocardiography in HTX. METHODS: Sixty-eight patients underwent dipyridamole echocardiography within 48 hours of their scheduled annual coronary angiography. Coronary allograft vasculopathy was defined as CAV 1 (focal or diffuse stenosis <50%) or CAV 2 (focal or diffuse stenosis >or=50%). Wall-motion score index (WMSI) was evaluated at rest and after dipyridamole administration. RESULTS: Results of coronary angiography were normal in 43 patients (63%), showed CAV 1 in 11 (16%), and showed CAV 2 in 14 (21%). Rest wall motion was normal in 39 patients and abnormal in 29. After dipyridamole administration, wall motion remained normal in all 39 (Group 1, no CAV in 34 and CAV 1 in 5). Of 29 patients with rest wall-motion abnormalities, all reversed to normal after dipyridamole in 8 patients (Group 2, no CAV in 7 and CAV 1 in 1) and remained or worsened in 21 (Group 3, CAV 2 in 14 and no CAV or CAV 1 in 7). During follow-up (6 +/- 3 years), 15 patients had major cardiac events: 11 occurred in Group 3, whereas 4 occurred in Groups 1 and 2. Wall motion at rest and after dipyridamole administration and CAV were independent predictors for cardiac events; only dipyridamole WMSI >1 remained significant (p < 0.0001) at multivariate analysis. CONCLUSIONS: Dipyridamole echocardiography is a simple, non-invasive test that after HTX may identify patients with altered wall motion who deserve stricter surveillance.

Adult↗

Effects of dipyridamole on left ventricular function.

BACKGROUND: Changes induced by dipyridamole infusion on left ventricular function in healthy individuals have not been investigated by gated myocardial perfusion single photon emission computed tomographic (SPECT) imaging. METHODS AND RESULTS: This study examined the amplitude and duration of changes induced by dipyridamole infusion on left ventricular function as assessed by technetium 99m sestamibi gated SPECT in 18 subjects with a low likelihood of coronary artery disease. Twenty mCi (740 MBq) of Tc-99m sestamibi were injected at rest. Three different consecutive gated SPECT images were performed 60 minutes later: baseline at rest, during the infusion of 0.76 mg/kg of dipyridamole, and 1 hour later. No patient received aminophylline. Left ventricular ejection fraction (LVEF), end-diastolic volume, and end-systolic volume were automically computed. Heart rate (HR) and blood pressure were regularly monitored. Mean LVEF was 63.2% +/- 8.0% baseline at rest, increased to 73.8% +/- 8.2% (P = .0001) during dipyridamole infusion, and returned to baseline values (63.0% +/- 7.5%) 1 hour later. End-diastolic volume did not vary significantly, and end-systolic volume decreased (from 32.2 +/- 19.5 to 26.6 +/- 17.9 u, P = .002) and returned to baseline values (32.7 +/- 15.6 u) 1 hour later. Dipyridamole induced moderate HR acceleration (from 80.2 +/- 15.0 to 96.5 +/- 9.6 beats/min, P < .001) and a slight decrease in diastolic blood pressure (from 80.6 +/- 8.1 to 70.1 +/- 9.0 mm Hg, P < .001). However, 1 hour later, HR and blood pressure had returned to baseline values. CONCLUSIONS: Dipyridamole increases LVEF and HR and decreases diastolic blood pressure slightly in healthy individuals. Because dipyridamole gated SPECT imaging acquisition is usually started 60 minutes after dipyridamole infusion, LVEF is in fact estimated at rest.

Adult↗

Diagnostic accuracy of dipyridamole technetium 99m-labeled sestamibi myocardial tomography for detection of coronary artery disease.

BACKGROUND: The diagnostic accuracy of exercise 99mTc-labeled sestamibi and intravenous dipyridamole 201Tl-labeled myocardial tomography is established. The accuracy of dipyridamole stress 99mTc-labeled sestamibi myocardial tomography for the detection of coronary artery disease has not been reported. METHODS AND RESULTS: Our purpose was to determine the diagnostic accuracy of same-day, rest-dipyridamole stress 99mTc-labeled sestamibi myocardial single-photon emission computed tomography (SPECT) compared with coronary angiography. Two hundred forty-four patients who were unable to exercise adequately underwent both dipyridamole 99mTc-labeled sestamibi SPECT and coronary angiography within 6 months. Dipyridamole was administered intravenously in a standard dose of 0.56 mg/kg for 4 minutes. Cardiac and noncardiac side effects were recorded. The presence of coronary stenoses of 50% or greater diameter reduction in each of the major coronary arteries was compared with imaging data in corresponding myocardial perfusion beds. The patient population was predominately (98.8%) male with a mean age of 63 +/- 9 years (range 33 to 83 years). The majority of patients had stable angina (88%). Eighty-four patients (35%) gave a prior history of myocardial infarction; 44 patients (18%) had a history of congestire heart failure. The principal limitation to exercise stress was peripheral vascular disease in 62 patients (26%). No serious side effects occurred during dipyridamole stress; 14% of patients had chest pain and 8% of patients had 1 mm or greater ST segment depression. Of the 204 patients with documented coronary stenoses, 43 (21%) had single-vessel disease and 161 (79%) had multivessel disease. The sensitivity was 93% (40/43 in patients with single-vessel disease) and 91% (146/161 in patients with multivessel disease). Overall sensitivity was 91%. The specificity was 28% (11/40) in this population with a high prestest probability of coronary artery disease and posttest referral for cardiac catheterization. CONCLUSION: 99mTc-labeled sestamibi myocardial tomography in conjunction with intravenous dipyridamole stress is a safe and sensitive method for the detection of coronary artery disease. The diagnostic accuracy of dipyridamole stress 99mTc-labeled sestamibi SPECT for the detection of coronary artery disease is similar to that reported for exercise stress 99mTc-labeled sestamibi tomography, making this a suitable alternative for the evaluation of patients who are unable to exercise adequately.

Adult↗

Left bundle branch block and coronary artery disease: accuracy of dipyridamole thallium-201 single-photon emission computed tomography in patients with exercise anteroseptal perfusion defects.

BACKGROUND: Reduced septal or anteroseptal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) even in the absence of left anterior descending (LAD) coronary artery disease. The purpose of this study was to evaluate prospectively the accuracy of dipyridamole 201Tl single-photon emission computed tomography (SPECT) in detecting LAD coronary artery disease in patients with LBBB and septal or anteroseptal perfusion defects on exercise 201Tl SPECT. METHODS AND RESULTS: Twelve consecutive patients (10 men and two women) with complete LBBB and septal or anteroseptal perfusion defects on exercise 201Tl SPECT underwent dipyridamole 201Tl SPECT. The delay between dipyridamole and exercise was 2 to 30 days. Coronary angiography was performed during this period in all patients. Six (50%) of 12 patients with exercise perfusion defects showed normal perfusion after dipyridamole; all had normal coronary angiograms. The remaining six patients also had positive results of dipyridamole studies, two with moderate and four with severe septal or anteroseptal perfusion defects. Coronary angiography showed significant (> 50%) LAD coronary artery stenosis in three patients; three patients with severe septal or anteroseptal perfusion defects after dipyridamole had normal coronary angiograms. Neither the evaluation of apical involvement nor the presence of dilated ventricles, decreased left ventricular ejection fraction, or wall motion abnormalities could help to identify (or explain) false-positive results. CONCLUSION: This study confirms that dipyridamole is more accurate than exercise in excluding LAD coronary artery disease. However, there are still false-positive results and the severity of the septal or anteroseptal perfusion defect does not add additional information to identify LAD coronary artery disease. Coronary angiography is thus necessary for positive dipyridamole study results to identify coronary artery disease as a major prognostic factor in patients with LBBB.

Adult↗