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PubMed1994

Dipyridamole is superior to dobutamine for thallium stress imaging: a randomised crossover study.

OBJECTIVE: To assess the value of dobutamine over dipyridamole as a pharmacological stressing agent in myocardial perfusion imaging with thallium-201. DESIGN: Stress and redistribution tomographic images were taken in a group of patients in a randomised crossover study of both agents. The scans were scored to give a value for the stress and redistribution images and a reversibility score (redistribution--stress). All patients had coronary angiography that was also scored. Differences between the two agents were compared by a paired t test. PATIENTS: 30 patients aged 51-70 years with chest pain thought to be caused by myocardial ischaemia. 11 had had previously myocardial infarction. RESULTS: Dipyridamole caused adverse symptoms in six patients whereas dobutamine caused symptoms in 21 patients (chi 2 = 15.15, p < 0.0001). Dobutamine stress took considerably longer than dipyridamole (31 v 6 minutes) and cost more (17 pounds v 1.50 pounds). There were no significant differences between the agents in terms of total stress or redistribution scores, but regional analysis showed that dipyridamole showed significantly more defects during stress at the apex and lateral wall (p < 0.05), with no significant difference at redistribution. Dipyridamole stress also caused significantly more reversible defects at the apex (p < 0.05) and gave a better correlation than dobutamine with coronary score (dipyridamole r = 0.80, p < 0.001 v dobutamine r = 0.64, p < 0.001). In six patients who had continued to take beta blockers the results of dobutamine stress did not correlate with coronary score, r = 0.34 (NS), whereas dipyridamole studies were not affected. CONCLUSION: Compared with dobutamine, dipyridamole was as effective in producing overall perfusion defects and more effective in provoking defects at the apex and lateral segment. The dipyridamole study correlated better with coronary score and was not affected by concurrent beta blocker treatment. It was also better tolerated by the patients, was less time consuming, and was much cheaper.

Aged↗

PubMed1995

Dipyridamole, a cGMP phosphodiesterase inhibitor, causes pulmonary vasodilation in the ovine fetus.

Endogenous nitric oxide (NO) modulates fetal pulmonary vascular tone by stimulating guanosine 3',5'-cyclic monophosphate (cGMP) production in vascular smooth muscle. Because cGMP is hydrolyzed and inactivated by phosphodiesterase enzymes, we evaluated the hemodynamic effects of two cGMP-specific phosphodiesterase (PDE5) inhibitors, dipyridamole and zaprinast, in the near-term chronically prepared ovine fetus. Brief (10 min) intrapulmonary infusions of dipyridamole caused dose-dependent increases in left pulmonary artery flow and decreases in left pulmonary arterial resistance that persisted for > 40 min after termination of the infusion. Prolonged (2 h) infusions of dipyridamole caused sustained pulmonary vasodilation throughout the infusion period. To compare the hemodynamic effects of dipyridamole with the PDE5 antagonist zaprinast, we studied the responses to equimolar doses of both agents in four fetuses. Zaprinast caused dose-dependent pulmonary vasodilation that was equivalent to that noted with equimolar doses of dipyridamole. To determine whether adenosine is involved with dipyridamole-induced pulmonary vasodilation, we compared the hemodynamic response to dipyridamole before and after administration of the potent adenosine receptor (P1) antagonist 8-phenyltheophylline (8-PT). Pretreatment with 8-PT markedly attenuated adenosine-induced pulmonary vasodilation but had no effect on the hemodynamic response to dipyridamole. We conclude that cGMP-specific phosphodiesterase activity is important in regulating fetal pulmonary vascular tone. In addition, dipyridamole administration causes dose-dependent pulmonary vasodilation that is equivalent to zaprinast and not primarily due to its effects on adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1989

Prognostic importance of dipyridamole-echocardiography test in coronary artery disease.

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

Actuarial Analysis↗

PubMed1991

Inhibition of dipyridamole-induced ischemia by antianginal therapy in humans. Correlation with exercise electrocardiography.

BACKGROUND: Dipyridamole echocardiography test (DET: two-dimensional echocardiographic monitoring with dipyridamole infusion up to 0.84 mg/kg in 10 minutes) is a useful tool for the noninvasive diagnosis of coronary artery disease. Aims of the present study were to assess the effects of antianginal drugs on dipyridamole-induced ischemia and to evaluate whether drug-induced changes in DET response may predict variations in exercise tolerance. METHODS AND RESULTS: Fifty-seven patients with angiographically assessed significant coronary artery disease (greater than 70% lumen reduction in at least one major coronary vessel) performed a DET and an exercise electrocardiography test (EET) in random order both off treatment and on antianginal drugs (beta-blockers, calcium antagonists and nitrates, alone or in various combinations). The criterion for DET positivity was a transient dyssynergy of contraction absent or of a lesser degree in the baseline examination. In DET, two parameters were evaluated: the dipyridamole time (i.e., the time from onset of dipyridamole infusion to obvious dyssynergy) and the wall motion score index. DET sensitivity was 91% off therapy and fell to 65% under therapy (p less than 0.01). In the 37 patients who had a positive DET both off and on therapy, the dipyridamole time increased from 6 +/- 3 (off therapy) to 8 +/- 3 minutes (on therapy) (p less than 0.01). The wall motion score index at peak dipyridamole went from 1.38 +/- 0.14 to 1.31 +/- 0.14 (p less than 0.01). EET and DET yielded concordant (positive versus negative) results in 41 of 57 (71%) patients off and in 35 of 57 (61%) on therapy (p = NS). In the subgroup of 38 patients with both positive DET and EET without treatment, the therapy-induced variations in exercise time were significantly correlated with the variations in dipyridamole time (r = 0.5; p less than 0.01), not with variations in wall motion score index (r = 0.3; p = NS). CONCLUSIONS: 1) Antianginal therapy can protect from dipyridamole-induced ischemia and 2) the therapy-induced changes in DET response parallel variations in exercise tolerance and might be useful for the objective, exercise-independent assessment of the therapy efficacy.

Adrenergic beta-Antagonists↗

PubMed1994

Assessment of anatomic and physiological severity of single-vessel coronary artery lesions by dipyridamole echocardiography. Comparison with positron emission tomography and quantitative arteriography.

BACKGROUND: The aim of this study was to compare the results of dipyridamole-echocardiography test (DET: two-dimensional echo monitoring during dipyridamole infusion up to 0.84 mg/kg over a period of 10 minutes) with both anatomic and physiological parameters of coronary artery disease severity, assessed by computer-assisted quantitative coronary arteriography, and regional coronary flow reserve, measured by [13N]ammonia (13NH3) and dynamic positron emission tomography (PET), respectively. METHODS AND RESULTS: We studied 31 patients with a history of chest pain and neither previous myocardial infarction nor resting wall motion abnormalities. Eighteen patients had single-vessel disease (> 50% stenosis of one major coronary vessel), and 13 had normal coronary arteries. The criterion for DET positivity was the appearance of a new transient regional wall motion abnormality. In patients with a positive DET, two parameters were evaluated: the dipyridamole time (ie, the time from the beginning of drug infusion to the development of obvious dyssynergy) and the wall motion score index (WMSI, a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of segments interpreted. Quantification of regional myocardial blood flow was obtained by PET measurements of 13NH3 arterial input function and left ventricular myocardial tissue concentration both at control and after dipyridamole (0.56 mg/kg over 4 minutes). Maximal regional blood flow after dipyridamole in the region supplied by the stenotic vessel was significantly lower in the 11 patients with coronary artery disease and positive DET than in the 7 patients with coronary artery disease and negative DET (1.08 +/- 0.33 versus 1.98 +/- 0.37 mL.min-1.g-1, P < .01). In patients with a positive DET, regional coronary flow reserve correlated well with dipyridamole time (r = .87, P < .01) but not with peak WMSI (r = .25, P = NS). Patients with dipyridamole-induced akinesia or dyskinesia (n = 6) had a greater reduction in regional coronary flow reserve than did those showing hypokinesia (n = 5): 1.38 +/- 0.51 versus 2.17 +/- 0.42, P < .05. Percent area reduction was more severe in patients with DET positivity than in those with DET negativity (93.7 +/- 8.7% versus 77 +/- 10.3%, P < .01), and it correlated with regional coronary flow reserve (r = .64, P < .01) and dipyridamole time (r = -.59, P < .01). CONCLUSIONS: In patients with single-vessel disease, DET shows an excellent specificity but a limited sensitivity; in these patients, DET positivity is associated with a physiologically important coronary stenosis. Severity of the anatomic stenosis and impairment in regional flow reserve are greater when the dipyridamole-induced dyssynergy appears earlier during the test. Therefore, a stratification of the anatomo-physiological severity of coronary artery disease can be obtained with DET, based mainly on the temporal allocation of the transient dyssynergy.

Adult↗

PubMed1993

Repeated dipyridamole administration enhances collateral-dependent flow and regional function during exercise. A role for adenosine.

Two main hypotheses concerning the mechanisms responsible for coronary collateral growth suggest the involvement of chemical or mechanical factors. Since we recently demonstrated that the development of the coronary collateral circulation is not closely related to the extent or duration of myocardial ischemia, we hypothesized that chronic repeated vasodilation and increased myocardial blood flow using dipyridamole would enhance collateral development in miniswine with an ameroid-occluded left circumflex coronary artery (LCx). Two days after surgical instrumentation, the animals received dipyridamole (n = 9), diltiazem as an adenosine-independent vasodilator (n = 8), or control vehicle (n = 7) 90 minutes per day, 5 days per week for 8 weeks. At 5 and 8 weeks, transmural blood flow and systolic wall thickening were measured during infusion of dipyridamole, diltiazem, or vehicle. Transmural blood flow increased similarly in the LCx and nonoccluded regions at 30 and 60 minutes during infusion of either vasodilator. Thus, we believe that similar mechanical stimulation resulted from dipyridamole and diltiazem infusion. There was no change in blood flow during administration of the vehicle. Systolic wall thickening in the collateral-dependent region was not altered by infusion of dipyridamole, diltiazem, or vehicle. Therefore, both vasodilators increased blood flow without eliciting ischemia. After 8 weeks of repeated treatment with each pharmacological agent, at least 24 hours after the last drug infusion, near maximal physiological capacity of the coronary collateral vessels was assessed during treadmill running (approximately 240 beats per minute). Transmural myocardial blood flow ratios, expressed as flow in the LCx divided by flow in the nonoccluded region of the left ventricle, were similar at rest for animals treated with dipyridamole (0.90 +/- 0.03), diltiazem (0.97 +/- 0.05), and control vehicle (0.89 +/- 0.02). However, collateral-dependent myocardial blood flow during exercise was greater (P < .05) in the dipyridamole-treated animals (0.78 +/- 0.04) than in either diltiazem-treated (0.63 +/- 0.09) or vehicle-treated (0.62 +/- 0.02) animals. LCx systolic wall thickening at rest was similar in animals treated with dipyridamole (44.4 +/- 6.3%), diltiazem (42.2 +/- 3.0%), and control vehicle (38.1 +/- 2.8%). During exercise, however, myocardial function in the collateral-dependent region was greater (P < .05) in the dipyridamole-treated (39.2 +/- 5.2%) compared with diltiazem-treated (23.9 +/- 4.0%) and vehicle-treated (26.9 +/- 2.9%) animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

PubMed2003

Cochrane review: dipyridamole for preventing major vascular events in patients with vascular disease.

BACKGROUND: Patients enrolled in clinical trials after nondisabling cerebral ischemia have an annual risk of vascular events (death from all vascular causes, nonfatal stroke, or nonfatal myocardial infarction) of 4% to 11%. Aspirin reduces the incidence by 13%. Many trials in patients presenting with vascular disease investigated the efficacy of (addition of) dipyridamole in secondary prevention. We systematically compared the efficacy and safety of dipyridamole versus control in the presence and absence of other antiplatelet drugs in clinical trials on the secondary prevention of vascular events in patients with vascular disease. SUMMARY OF REVIEW: Randomized trials with concealed treatment allocation in patients with a nonembolic arterial vascular disease were selected. Therapy consisted of dipyridamole in the presence or absence of other antiplatelet drugs compared with no drug or an antiplatelet drug(s) other than dipyridamole. Twenty-six trials were included, with a total of 19 842 patients. Dipyridamole was not more efficacious in the prevention of vascular death (relative risk [RR], 1.02; 95% CI, 0.90 to 1.17). It appeared more efficacious in the prevention of vascular events (RR, 0.90; 95% CI, 0.83 to 0.98), but this result only reached statistical significance because of 1 large trial in patients presenting with cerebral ischemia. Combination treatment of dipyridamole and aspirin compared with aspirin had an RR of 1.03 (95% CI, 0.87 to 1.22) for vascular death and an RR of 0.90 (95% CI, 0.80 to 1.00) for vascular events. CONCLUSIONS: For patients who presented with arterial vascular disease, there was no evidence that dipyridamole, in the presence or absence of another antiplatelet drug (chiefly aspirin), reduced the risk of vascular death, although it may reduce the risk of further vascular events. However, this benefit was found only in a single large trial and only in patients presenting after cerebral ischemia. There was no evidence that dipyridamole alone was more efficacious than aspirin. Further trials comparing the effects of the combination of dipyridamole plus aspirin with aspirin alone are justified.

Death, Sudden, Cardiac↗

PubMed1998

Pulmonary and systemic effects of the phosphodiesterase inhibitor dipyridamole in newborn lambs with persistent pulmonary hypertension.

Nitric oxide (NO) relaxes vascular smooth muscle by increasing the intracellular concentration of cGMP. In the pulmonary circulation, cGMP is inactivated by specific phosphodiesterases (PDE5). Dipyridamole, a clinically approved drug, has inhibitory activity against PDE5 and has been reported to augment the response to inhaled NO in persistent pulmonary hypertension of the newborn (PPHN). We wished to determine whether dipyridamole alone, or in combination with NO, can be used to treat a newborn lamb model of PPHN. In newborn lambs with PPHN, dipyridamole infused at 0.02 mg/kg/min for 45 min alone, or in combination with 5 ppm of inhaled NO for the final 15 min, significantly decreased pulmonary and systemic blood pressure, decreased pulmonary vascular resistance, and increased pulmonary blood flow. There was no significant difference between the pulmonary vascular effects of 5 ppm NO alone compared with the effects of NO combined with dipyridamole. In control lambs, the 45-min infusion of dipyridamole did not change pulmonary pressure whereas systemic pressure decreased by 28 +/- 3%. These systemic effects in control lambs persisted 90 min after discontinuing the dipyridamole infusion. Systemic arteries isolated from both control and PPHN lambs were significantly more sensitive to dipyridamole than pulmonary arteries. We conclude that dipyridamole has significant hemodynamic effects in both the pulmonary and systemic circulations of newborn lambs with pulmonary hypertension as well as in the systemic circulation of newborn control lambs. The pronounced effects of dipyridamole on the systemic circulation limits its utility as an adjunct to inhaled NO in the treatment of PPHN.

Animals↗

PubMed1996

Dipyridamole and dobutamine-atropine stress echocardiography in the diagnosis of coronary artery disease. Comparison with exercise stress test, analysis of agreement, and impact of antianginal treatment.

STUDY OBJECTIVES: To compare the usefulness of dipyridamole echocardiography, dobutamine-atropine echocardiography, and exercise stress testing in the diagnosis of coronary artery disease and to analyze the agreement among the tests. DESIGN: Performance of these three tests in random order on a consecutive cohort of patients. SETTING: A tertiary care and university center. PATIENTS: One hundred two consecutive patients with chest pain and no history of coronary artery disease. INTERVENTIONS: Dipyridamole echocardiography, dobutamine-atropine echocardiography, exercise stress testing, and coronary angiography. MEASUREMENTS AND RESULTS: Dobutamine-atropine test was positive in 49 (77%) of 63 patients with coronary artery disease, dipyridamole test in 49 (77%), and exercise stress test in 44 (68%; p = NS). Both echocardiographic tests showed an overall specificity (dipyridamole, 97%; dobutamine, 95%) higher than exercise stress test (79%; p < 0.05). Sensitivity of dipyridamole testing decreased from 93 to 61% (p = 0.002) if patients were receiving antianginal treatment but sensitivity of dobutamine-atropine testing was not affected (77% in patients receiving and not receiving treatment). When results were considered as positive-negative, agreement between dipyridamole and dobutamine-atropine echocardiography was 85% (kappa = 0.70). With regards to regional analysis, concordance was good (93% for segments, kappa = 0.76; and 95% for coronary arteries, kappa = 0.92). Major complications were more frequent during dobutamine-atropine (n = 7) than during dipyridamole infusion (n = 2) (p = 0.06). CONCLUSIONS: Dobutamine-atropine and dipyridamole echocardiography have a similar sensitivity and a higher specificity than that obtained by exercise ECG for the diagnosis of coronary artery disease. Similar information is obtained with dipyridamole and dobutamine-atropine echocardiography. It is our thought that pharmacologic stress echocardiography should be used as a first-step test to rule out coronary artery disease in patients not capable of exercising.

Adrenergic beta-Antagonists↗

PubMed1991

Relation between the incidence of arrhythmias and ischemic ST-segment depression during dipyridamole electrocardiography test in patients with coronary artery disease.

To examine the incidence of arrhythmias in dipyridamole infusion and the relation between dipyridamole-induced arrhythmias and ST-segment depression, dipyridamole electrocardiography tests were performed on 100 patients with coronary artery disease. Dipyridamole was infused at a rate of 0.568 mg/kg for 4 min, and 87-lead body surface mapping was performed to determine ischemic ST-segment depression. Positive ischemic response was defined as greater than or equal to 0.10 mV horizontal or downsloping ST-segment depression below the baseline, lasting 80 msec after the J point. Arrhythmias were observed by continuous electrocardiographic monitoring using a CM-5 lead electrocardiography. With respect to ventricular premature contractions (VPC), a group of patients with previous myocardial infarction (MI group) had a significantly higher incidence than a group of patients without previous myocardial infarction (non-MI group) before (16.7% vs. 1.7%, p less than 0.01) and after (38.1% vs. 3.4%, p less than 0.005) the dipyridamole infusion. The incidence of supraventricular premature contractions (SVPC), however, was not significantly different between the MI and non-MI groups. A group of patients with positive ischemic response had a significantly higher incidence of SVPC after the dipyridamole infusion than a group of patients with negative ischemic response (p less than 0.005). However, there was no significant difference in the incidence of VPC between the negative and positive ischemic response groups. These results suggest that dipyridamole-induced VPC is not always associated with ischemic ST-segment depression, but dipyridamole-induced SVPC is associated with dipyridamole-induced ischemic ST-segment depression in patients with coronary artery disease.

Adult↗

PubMed1992

Comparison of adenosine, dipyridamole, and dobutamine in stress echocardiography.

OBJECTIVE: To compare adenosine, dipyridamole, and dobutamine in stress echocardiography with regard to sensitivity, specificity, accuracy, and side effects. DESIGN: Crossover, blinded comparison, with coronary angiography serving as the criterion standard. SETTING: U.S. Army tertiary care hospital. PARTICIPANTS: Forty participants, 25 with coronary disease and 15 without coronary disease. Patients were eligible if they had coronary angiography within 6 weeks of stress testing or if they had a risk for coronary disease of less than 5%. MEASUREMENTS: Left ventricular wall motion was recorded after dobutamine (0.38 mg/kg body weight), adenosine (0.84 mg/kg body weight), and dipyridamole (0.84 mg/kg body weight) stress testing. Stress echocardiographic evaluation was considered to be abnormal if the patient developed new or progressive wall motion abnormalities. The rate of side effects for the types of echocardiography and the patient preference were recorded. MAIN RESULTS: The sensitivity of dobutamine stress echocardiography (76%; 95% CI, 59% to 93%) was significantly higher than that of adenosine echocardiography (40%; CI, 21% to 59%; P less than 0.001) and that of dipyridamole echocardiography (56%; CI, 37% to 75%; P = 0.019). The specificity of adenosine testing (93%; CI, 80% to 100%) was significantly higher than that of dobutamine echocardiography (60%; CI, 35% to 85%; P = 0.008) and that of dipyridamole echocardiography (67%; CI, 43% to 91%; P = 0.028). Symptoms were more frequent with adenosine echocardiography (100%) than with dipyridamole (88%; P less than 0.001) or dobutamine (80%; P less than 0.001) echocardiography. Treatment for persistent symptoms was required in more patients after dipyridamole echocardiography (40%) than after dobutamine (12%; P less than 0.001) or adenosine (0%; P less than 0.001) echocardiography. More patients preferred dobutamine (48%) or dipyridamole (40%) echocardiography to adenosine echocardiography (12%; P less than 0.001). CONCLUSIONS: Dobutamine stress echocardiography is more sensitive and is better tolerated than adenosine or dipyridamole stress echocardiography. Adenosine echocardiography is more specific than dobutamine or dipyridamole echocardiography and is less likely to cause persistent symptoms.

Adenosine↗

PubMed1999

Prevention of thymidine and hypoxanthine rescue from MTA (LY231514) growth inhibition by dipyridamole in human lung cancer cell lines.

The novel multitargeted antifolate, MTA (N-[4[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-ethy l]-benzoyl]-L-glutamic acid; LY23 1514) inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. The resultant inhibition of the de novo thymidylate and purine biosynthesis can be circumvented by salvage of extracellular thymidine and hypoxanthine. The first step in the salvage pathway is the transport of nucleosides and bases across the cell membrane. Dipyridamole inhibits nucleoside transport and in vitro studies have demonstrated that dipyridamole can prevent thymidine salvage rescue from antifolate thymidylate synthase inhibitors. More recently, dipyridamole also has been shown to prevent hypoxanthine rescue from antipurine antifolates in some cell lines but not others. The effects of dipyridamole on MTA growth inhibition and end product reversal by thymidine and hypoxanthine was investigated in two lung cancer cell lines with (A549) and without (COR L23) dipyridamole-sensitive hypoxanthine rescue. The IC50 values for MTA-induced growth inhibition were 28 and 640 nmol/L for COR L23 and A549 cells, respectively. End product reversal studies show that thymidine can completely reverse growth inhibition by IC50 concentration of MTA but only partially rescue cells from 10 times the IC50 concentration of MTA. The combination of thymidine and hypoxanthine was required for complete reversal from MTA at 10 times the IC50 concentration. Dipyridamole blocked the partial rescue from MTA-induced growth inhibition by thymidine alone as well as the complete rescue by thymidine plus hypoxanthine not only in A549 cells, which have dipyridamole-sensitive hypoxanthine transport, but also in COR L23 cells, in which hypoxanthine uptake is insensitive to dipyridamole. These studies demonstrate that nucleoside and base salvage can compromise the activity of MTA in human tumor cell lines, but that dipyridamole can readily prevent salvage and restore growth inhibition.

Antimetabolites, Antineoplastic↗

PubMed2002

Serum caffeine levels after 24-hour abstention: clinical implications on dipyridamole (201)Tl myocardial perfusion imaging.

BACKGROUND: Caffeine binds to the A2 receptors and inhibits adenosine's action of vasodilation or dipyridamole-induced vasodilation. Patients scheduled for (201)Tl myocardial perfusion using pharmacologic stress with dipyridamole or adenosine are advised to abstain from caffeine for 24 h before the test. This article reports on the residual serum caffeine levels of 36 patients after 24-h caffeine abstention and the clinical implications on dipyridamole (201)Tl myocardial perfusion imaging. METHODS AND RESULTS: Heart rate, diastolic blood pressure, and systolic blood pressure were recorded before and after dipyridamole infusion. Sixty-six percent of the patients had detectable plasma caffeine but all values were within the range of 0.1-0.8 mg/L. No statistically significant change in diastolic and systolic blood pressures after dipyridamole infusion has been observed. The mean heart rate was increased by 18% after dipyridamole infusion in patients with zero caffeine, and the heart rate increase was inversely correlated with the serum caffeine levels (r = -0.22) with 81% confidence. CONCLUSION: A serum caffeine level of 2 mg/L is predicted to be the lower limit for false-negative dipyridamole (201)Tl myocardial perfusion. The increase of heart rate after dipyridamole infusion could be the simple indicator for the serum caffeine level. Rescheduling of the patient study or further adenosine challenge is necessary only if the heart rate increase is <5% after dipyridamole or adenosine infusion.

Aged↗

PubMed2004

Effect of caffeine intake on myocardial hyperemic flow induced by adenosine triphosphate and dipyridamole.

UNLABELLED: The aims of this study were (a). to compare absolute myocardial blood flow (MBF) during adenosine triphosphate (ATP) infusion with that after dipyridamole administration without caffeine intake and (b). to evaluate the effect of caffeine intake on the hyperemic flow induced by these coronary vasodilator agents. METHODS: MBF was quantified with (15)O-labeled water and PET at rest, during ATP infusion (0.16 mg/kg/min for 9 min), and after dipyridamole administration (0.56 mg/kg over 4 min) after a 24-h abstinence from caffeine (baseline evaluation) in 10 healthy volunteers. Within 2 wk, the same PET studies were repeated after caffeine intake to evaluate the effect of caffeine on the hyperemic flow induced by these pharmacologic agents (caffeine study). Myocardial flow reserve (MFR), defined as the ratio of hyperemic to resting blood flow, was also evaluated. RESULTS: Resting MBF in baseline and caffeine studies did not differ significantly (0.79 +/- 0.29 vs. 0.75 +/- 0.31 mL/min/g, P = 0.88). Without caffeine intake, MBF during ATP infusion was significantly higher than that after dipyridamole administration (3.70 +/- 0.67 vs. 3.00 +/- 0.79 mL/min/g, P = 0.003), whereas there was no significant difference in MFR between ATP and dipyridamole stress (5.15 +/- 1.64 vs. 4.11 +/- 1.44, P = 0.07). After caffeine intake, the hyperemic flows induced by ATP and dipyridamole were not significantly different (1.68 +/- 0.37 vs. 1.52 +/- 0.40 mL/min/g, P = 0.50). MFR estimated by ATP and dipyridamole also did not differ significantly in the caffeine studies (2.44 +/- 0.88 vs. 2.25 +/- 0.94, P = 0.73). MBF during ATP infusion and after dipyridamole administration were significantly lower in the caffeine studies than that in the baseline evaluation (1.68 +/- 0.37 vs. 3.70 +/- 0.67 mL/min/g, P < 0.0001, and 1.52 +/- 0.40 vs. 3.00 +/- 0.79 mL/min/g, P < 0.0001, respectively). CONCLUSION: This study demonstrates that ATP has the potential to induce greater hyperemia than dipyridamole, whereas hyperemic responses to ATP and dipyridamole are similarly attenuated after caffeine intake. These findings suggest that abstinence from caffeine before ATP stress testing may be needed.

Adenosine Triphosphate↗

PubMed1991

Dipyridamole-induced myocardial ischaemia increases ANF release in man.

Atrial natriuretic factor (ANF) release is modulated by several haemodynamic factors, including ventricular and atrial wall stretch. Dipyridamole infusion, which is commonly used as a pharmacological stressor in patients with coronary artery disease, can acutely increase ventricular and atrial pressure via myocardial ischaemia. The aim of this study was to assess whether dipyridamole infusion (up to 0.84 mg kg-1 over 10') can affect ANF release in man. Nineteen patients (13 men, 6 women) with a history of chest pain were studied. Their drug regimen was interrupted and instead they were administered a dipyridamole infusion, combined with two-dimensional echocardiography and 12-lead ECG monitoring. Plasma ANF was measured by RIA while the patients rested, and after dipyridamole infusion. Eight patients had no evidence of myocardial ischaemia, as measured by electrocardiographic and/or echocardiographic criteria, during dipyridamole infusion: among them, ANF values were similar while they were at rest and at peak dipyridamole administration (23.9 +/- 9.5 vs 23.4 +/- 6.9 pg ml-1, P = ns). Eleven patients had dipyridamole-induced transient ischaemia (regional ventricular dyssynergy and/or ST segment depression): among them, ANF values rose significantly at peak dipyridamole administration (31.8 +/- 13.8 vs 65.5 +/- 36.4, P less than 0.01). We conclude that dipyridamole infusion does not increase ANF release in man in the absence of ischaemia. The induction of myocardial ischaemia acutely increases ANF release, probably through a rise in ventricular and atrial wall stress.

Atrial Natriuretic Factor↗

PubMed1985

Inhibitory effects of dipyridamole on growth, nucleoside incorporation, and platelet-activating capability in the U87MG and SKNMC human tumor cell lines.

The effects of dipyridamole on tumor cell function were examined in cultures of two lines of human origin, the SKNMC neuroblastoma line that activates platelets by a mechanism which is dependent on the release of adenosine 5'-diphosphate and the U87MG glioblastoma line that induces platelet activation by the generation of thrombin. Cells grown in the presence of dipyridamole at 1 microM showed greater than 80% inhibition of uptake of adenosine, thymidine, and uridine with both lines. At 5 microM tumor cell growth was inhibited by 70% (U87MG) and 90% (SKNMC) but without concomitant cytotoxicity as determined by clonogenic assay (50% inhibitory concentration approximately 20 microM). At 10 microM dipyridamole cyclic adenosine 3':5'-monophosphate levels increased 150% with both cell lines but no changes above baseline values were seen at 2.5 microM. The two cell lines showed different responses to being cultured in the presence of dipyridamole in terms of their ability to subsequently activate platelets. U87MG cells cultured in 10 microM dipyridamole showed a doubling of the lag time as compared with cells grown in the absence of dipyridamole but with full aggregation; with SKNMC cells the aggregation rate was reduced and cells grown in 10 microM dipyridamole showed no reversible first wave, a 5-fold increase in lag time and a 75% inhibition in total aggregation. Since therapeutic doses of dipyridamole result in plasma concentrations of approximately 3.5 microM these results suggest that potential antimetastatic effects of dipyridamole could be direct arising from inhibition of important steps in tumor cell metabolism or indirect by suppressing one or more of the mechanisms involved in the ability of tumor cells to activate platelets.

Cell Division↗

PubMedDate not supplied

Correlation between the effects of aspirin and dipyridamole on platelet function and prevention of intimal hyperplasia in autologous vein grafts.

Fifty-four adult mongrel dogs receiving a lipid-supplemented diet were used to determine the effects of aspirin and dipyridamole on vein graft intimal hyperplasia. Twenty-one animals received the diet alone, 17 animals received a combination of dipyridamole and aspirin, while a further 16 animals received dipyridamole. Segments of undistended external jugular vein were anastomosed to bilaterally-divided femoral arteries. The vein grafts were harvested at six weeks and intimal thickness was measured with a Zeiss computerized microscope. Serum cholesterol, prothrombin time, partial thromboplastin time and clotting time was measured before the diet and at two, four and six weeks after operation. Plasma thromboxane B2 (TXB2) and the metabolite of prostacyclin I2 (6-keto PGF1 alpha) were determined by radioimmunoassay before and four weeks following operation. A similar and significant increase in serum cholesterol was observed in all animals receiving lipid supplementation. Platelet counts were significantly decreased in those animals receiving a combination of aspirin and dipyridamole while all other hematological parameters remained unchanged. Plasma TXB2 and 6-keto PGF1 alpha were unaffected by dipyridamole but were significantly decreased in those animals receiving the combined drug regimen. Intimal thickness measured 59 +/- 6 micron at six weeks in the controls. Dipyridamole reduced intimal thickness to 26 +/- 2 micron while aspirin and dipyridamole decreased intimal thickness to 28 +/- 2 micron. The data indicate that dipyridamole was as effective in reducing smooth muscle cell proliferation as the combination of aspirin and dipyridamole. Furthermore, the data suggest that antiplatelet drug regimens may reduce intimal thickening in autologous vein grafts by a mechanism other than affecting the thromboxane:prostacyclin ratio.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

Preservation of platelets and blood products by intravenously administered dipyridamole in patients who undergo coronary artery bypass grafting.

The combination of dipyridamole and acetylsalicylic acid has been proven effective in preventing coronary artery bypass graft occlusion, but the benefits of dipyridamole alone have not yet been evaluated. In order to assess the value of dipyridamole alone, the authors randomized 24 patients (age range from 47 to 76 years) who underwent coronary artery bypass grafting to treatment with either dipyridamole (120 mg/d) by constant intravenous infusion or isotonic dextrose solution. They recorded platelet counts and aggregates, hemoglobin levels, total blood loss, blood products and intravenous fluids given and dipyridamole plasma levels, starting 8 hours before operation and continuing for 3 days after. The two groups were similar with respect to pump time, cross-clamp time and baseline demographic factors. Platelet counts during cross-clamping and 1 hour postoperatively were similar, but those on days 1, 2 and 3 postoperatively were significantly (p = 0.01 to 0.02) higher in the dipyridamole group. Mean blood losses in this group were 22% to 30% lower, but the difference was not significant. However, administration of erythrocytes and plasma was 49% to 58% less in the dipyridamole group (p = 0.005 to 0.048) over the same period. Dipyridamole plasma concentrations varied from 0.37 micrograms/ml before and during bypass to 1.5 micrograms/ml in the 3 days after. The authors conclude that dipyridamole administered intravenously to patients who undergo coronary artery bypass grafting may preserve hemostatically effective platelets so that fewer blood products are required.

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