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Determinants of exercise capacity in the hypertensive elderly--a study based on the assessment of cardiac reserve by dipyridamole radionuclide angiography.

To evaluate the determinants of exercise capacity in the hypertensive elderly with an assessment of cardiac reserve by dipyridamole radionuclide angiography, 31 elderly subjects (aged 62 to 78 years, 15 hypertensive and 16 normotensive) underwent symptom-limited maximum treadmill exercise with measurement of maximal oxygen consumption along with radionuclide angiography in list mode at rest and after dipyridamole infusion. In the normotensive elderly, maximal oxygen consumption correlated with relative filling volume during the rapid filling period at rest (r = 0.58; p < 0.05), and correlated inversely with the percent change in the peak ejection rate with dipyridamole (r = -0.63; p < 0.01). In contrast, maximal oxygen consumption correlated with atrial contribution at rest (r = 0.69; p < 0.005), and correlated inversely with the percent change in atrial contribution with dipyridamole (r = -0.87; p < 0.0001) in the hypertensive elderly. These results indicate that the mechanisms for maintaining exercise capacity are different in elderly subjects with or without hypertension.

Aged↗

Modification of angiotensin II-induced relaxation by dipyridamole, phthalazinol and aspirin in isolated dog renal arteries.

Angiotensin (ANG) II-induced relaxations in isolated dog renal and cerebral arteries are postulated to be mediated by the release of prostaglandin (PG) I2 from the arterial wall. In helical strips of dog renal arteries treated with dipyridamole, relaxations induced by ANG II (10(-7) M) and exogenously applied PGI2 (10(-8) M) were potentiated; the potentiation was appreciably greater in the ANG-induced relaxation. Treatment with phthalazinol did not alter the response to ANG II, but significantly potentiated the relaxation induced by PGI2. The ANG-induced relaxations were suppressed or reversed to contractions by aspirin or indomethacin. Combined treatment of dipyridamole with aspirin or indomethacin restored the relaxant response to ANG II, while phthalazinol in combination with aspirin did not restore the response. It may be concluded that the potentiation of responses to ANG II by dipyridamole is associated with increments in the release of PGI2 from the arterial wall and potentiations of the response of arterial smooth muscle to PGI2. Dipyridamole appears to increase the production of PGI2 even in the presence of PG synthesis inhibition by aspirin or indomethacin.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effects of prostaglandin E1 and dipyridamole on disposal of colloidal carbon via glomerular mesangial channels.

We investigated the effects of prostaglandin E1 (PGE1) and dipyridamole on the disposal of macromolecules via mesangial channels to understand the antinephritic effect of PGE1. To increase glomerular carbon, rats were injected i.v. first with anti-glomerular basement membrane (GBM) serum and then with 30 mg/100 g body weight of carbon. Carbon in the glomerulus was detected with an image analyzer. Administration of anti-GBM serum resulted in about a 2 to 3-fold increase in glomerular uptake of carbon in the normal rats. To investigate the day-to-day situation of glomerular carbon, the right kidney was removed the day after carbon injection, and the left kidney was isolated on days 7, 14 and 21. By day 21, glomerular carbon had decreased significantly. Rats with carbon received PGE1 0.1 x 2 and 1.0 x 2 mg/kg, s.c., and dipyridamole 200 and 400 mg/kg, p.o., for 10 days after the isolation of the right kidney. PGE1 administration did not cause a decrease in the amount of glomerular carbon compared with that of the control. However, the dipyridamole group showed a more rapid decrease of glomerular carbon. It is concluded that PGE1 has no effect on the mesangial channels, but dipyridamole can accelerate the disposal of glomerular carbon by way of the mesangial channels.

Alprostadil↗

Regional myocardial blood flow in man during dipyridamole coronary vasodilation.

Regional myocardial blood flow before and after intravenous dipyridamole (0.56 mg/kg) was measured during cardiac catheterization in 11 patients using the 133Xe washout technique. Significant increases in heart rate (75 +/- 4 vs 87 +/- 6, p less than 0.004) and decreases in systolic blood pressure (144 +/- 8 vs 131 +/- 7, p less than 0.02) were observed with dipyridamole infusion. However, double product and cardiac output did not differ before or after drug infusion. Regional myocardial blood flow increased from 67 +/- 3 (SEM) to 117 +/- 3 ml/100 mg/min in myocardial segments supplied by nonobstructed coronary arteries. In stenotic coronary arteries, flow increased from 57 +/- 5 to 79 +/- 9 ml/100 mg/min with dipyridamole. We conclude that dipyridamole infusion results in flow differences which discriminate stenotic from nonstenotic coronary arteries.

Blood Pressure↗

Combined dipyridamole and aspirin pellet formulation for improved oral drug delivery. Part 1: Development pharmaceutics.

The dissolution profile of various weight fractions of dipyridamole: hydropropylmethylcellulose acetate succinate (HPMC-AS) and dipyridamole: hydroxypropylmethylcellulose phthalate co-precipitates lead to the choice of 1:2 dipyridamole: HPMC-AS as the controlled-release component. It was deposited to form two-third of the total dose as an inner layer on inert sucrose cores by air suspension coating for release mainly in the small intestine. Further examination of this material by IR spectroscopy, differential scanning calorimetry and X-ray diffraction indicated some free drug, preferentially soluble under gastric pH conditions. One-third of the total dose was applied by pan coating as an outer layer of micronized dipyridamole around the inner enteric co-precipitate layer. Aspirin-loaded cores were prepared also by pan coating for use in the final product, which contained both anti-platelet drugs.

Aspirin↗

[The dipyridamole test in coronary disease diagnosis].

One of the coronary disease diagnostic methods of big sensitivity and specificity is perfusive effort scintrigraphy of myocardium by means of thallium-201. For few years the dipyridamole test has been applied instead of the effort test. Perfusive scintigraphy of myocardium after provocative treatment by means of dipyridamole and then selective coronary arteriography of coronary vessels, have been carried out at 25 patients with ischemia. These studies showed almost 100% of conformability with exposing the ischemia zones in scintigraphy and coronary arteriography in cases of coronary vessels contraction over 50%. The dipyridamole test also revealed the ischemzones in myocardium that are in agreement with coronary vascularization deficiency. That test can be utilized in revealing the coronary disease and is helpful in qualifying patients for coronary arteriography. At the same time studies that have been carried out prove that applying dipyridamole is absolutely contraindicated in treating of coronary disease of the organic background.

Adult↗

Drug utilization review: dipyridamole plus aspirin antiplatelet therapy.

To assess whether dipyridamole was being used appropriately in providing antiplatelet therapy at the San Diego VAMC, a drug utilization review was conducted. Concomitant aspirin therapy was required for dipyridamole to be considered effective in the disease states reviewed. Seventy-three patients on antiplatelet therapy were evaluated, using dosing criteria established through a literature review. Our data indicated tht based on the criteria, only 11% of patients received dipyridamole in appropriate doses; it was underdosed in 89% of patients, and in 19% of patients, it was used when not indicated. In addition, 19% of patients did not receive concomitant aspirin therapy. Results suggest hat dipyridamole is not used optimally in providing antiplatelet therapy to patients in this institution.

Aspirin↗

A comparison of the modulation of antiblastics cytotoxicity by verapamil and dipyridamole in a human colon carcinoma cell line.

This study was designed to compare the activity of two MDR modulators, verapamil and dipyridamole, on the in vitro growth of a human colon carcinoma cell line. The aims were: a) to investigate the different sensitivity of the parental cell line (LoVo S) and the doxorubicin-resistant one (LoVo R) towards the treatment with several antiblastics and their associations with verapamil or dipyridamole; b) to evaluate if the combined use of these drugs with verapamil or dipyridamole increases their cytotoxicity; c) to understand whether the mechanism of action of each modulator is the same. Idarubicin and vinblastine were the most active drugs on both cell lines. LoVo R cells showed cross-resistance to vinblastine, teniposide and mitoxantrone, while chemosensitivity towards cisplatin and cyclophosphamide was almost the same in both cell lines. The inhibitory effect on cell growth was enhanced when the drugs were associated with verapamil, but no difference was detected with cisplatin and cyclophosphamide. Verapamil is thus an effective MDR modulator when used with drugs actively pumped out of tumour cells by P-glycoprotein, while it is ineffective with drugs that induce resistance by different mechanisms. When combined with dipyridamole, a significant result was observed in the case of cisplatin, where a marked increase of cytotoxicity was detected.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effects of dipyridamole, nitroglycerin, and nitroprusside on coronary vascular resistance in rabbits: measurement with pulsed Doppler velocimetry.

Dipyridamole, nitroglycerin, and nitroprusside are all effective vasodilators. However, few studies have compared their in vivo coronary vasodilatation effects. The purpose of this study was to compare the effects of these agents on coronary blood flow velocity and vascular resistance in anesthetized, open-chest rabbits. Male New Zealand white rabbits were anesthetized, and a 3-mm, suction-type, pulsed Doppler velocimeter probe was applied to the proximal part of the left anterior descending coronary artery after median sternotomy. The rabbits received infusion of various doses of dipyridamole (0.1 mg/kg, n = 5; 1 mg/kg, n = 5; 10 mg/kg, n = 9), nitroglycerin (0.01 mg/kg, n = 8; 0.1 mg/kg, n = 5; 1 mg/kg, n = 5; 10 mg/kg, n = 7), or nitroprusside (0.01 mg/kg, n = 5; 0.1 mg/kg, n = 5; 1 mg/kg, n = 5). The percent changes in coronary blood flow velocity and coronary vascular resistance were measured. All three vasodilators increased coronary blood flow velocity significantly and decreased coronary vascular resistance dose-dependently. The dose-response curves of dipyridamole, nitroglycerin, and nitroprusside were significantly different from one another (p < 0.01). Dipyridamole at a dose of 10 mg/kg produced the greatest increase in coronary blood flow velocity and the greatest reduction in coronary vascular resistance in anesthetized, open-chest rabbits.

Analysis of Variance↗

Slowing of proton transport processes in the structure of bacterial reaction centers and bacteriorhodopsin in the presence of dipyridamole.

Dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido(5, 4-d)pyrimidine, is employed in clinical practice as a vasodilator. It can also inhibit a specific membrane protein (glycoprotein P) which pumps anticancer drugs out of tumor cells. Dipyridamole (10-4 M) markedly slows down the kinetics of the electrogenic phase of the photoelectric response in Rhodobacter sphaeroides chromatophores. This phase is due to proton transfer from the external medium to the secondary quinone acceptor in the reaction center. In purple membranes of bacterium Halobacterium salinarium containing bacteriorhodopsin dipyridamole (in its charged state) significantly slowed the kinetics of proton transfer from the primary donor, Asp-96 (in membranes from bacteria of wild type), or from the external medium (in D96N mutant) to the Schiff base. It is suggested that dipyridamole can influence the structural-dynamic state of membrane proteins including modification of the structure of their hydrogen bonds involved in proton-transport processes.

Bacteriorhodopsins↗

[Usefulness of spect with 99mTc-tetrofosmin and stimulus with dipyridamole in patients with left bundle branch block of His].

BACKGROUND: In patients with left bundle branch block, the 201Tl scintigraphic studies show high sensitivity, but with low specificity, in the diagnosis of coronary artery disease. OBJECTIVE: [corrected] To assess the value of 99mTc-tetrofosmin Single Photon Emission Computed Tomography (SPECT) and dipyridamole administration in patients with left bundle branch block. METHODS: 22 patients with angina and left bundle branch block were retrospectively studied by cardiac catheterization and Tc-Tf after dipyridamole administration (0,142 mg/kg/min. i.v.) and at rest. RESULTS: The mean number of territories with perfusion defects was 1.5+/-1.0, and the average number of diseased vessels in the coronariographic study was 1.6+/-1.3 (r = 0.77, p<0.001). Sensitivity, specificity, positive predictive value, negative predictive value, total predictive value and Kappa index in the diagnosis of multivessel disease were 92%, 90%, 92%, 90%, 91% and 0.82, respectively. In the diagnosis of anterior descending artery disease, these values were 83%, 70%, 77%, 78%, 77%, and 0.54, respectively. CONCLUSION: In patients with angina and left bundle branch block, SPECT with Tc-Tf-dipyridamole is of great value in the study of coronary artery disease extension. Sensitivity and specificity for the diagnosis of anterior descending artery disease were similar to that shown in series with thallium-dipyridamole.

Bundle of His↗

Synergistic effect of prochlorperazine and dipyridamole on the cellular retention and cytotoxicity of doxorubicin.

Incubation of drug-resistant human tumor cells with a combination of prochlorperazine and dipyridamole has additive/synergistic effect on the cellular retention and cytotoxicity of doxorubicin. In patients administered a fixed dose of doxorubicin and prochlorperazine with escalating doses of dipyridamole, mean plasma levels of dipyridamole and prochlorperazine achieved were as high as 3.01 +/- 0.41 microm and 0.94 +/- 0.09 microm, respectively. Plasma samples from patients were analyzed in an in vitro assay to monitor the effect on the cellular retention of tritium-labeled daunorubicin in MDR1-transfected P388 cells. In 22 of 49 of the plasma samples analyzed, the daunorubicin in efflux blocking activity was one-half or greater than that of cells incubated with 12.5 microM verapamil, a well-known efflux blocker. These observations suggest that a combination of prochlorperazine and dipyridamole may enhance cellular doxorubicin retention by blocking efflux while reducing normal tissue toxicity and unwanted side effects in vivo.

Animals↗

Inhibition of intravascular fibrin deposition by dipyridamole in experimental animals.

Intravascular fibrin deposition was induced in rabbits by endotoxin, the infusion of fibrin monomer (FM), and by the infusion of thrombin and EACA. A previously developed radioisotope technique was used to measure the fibrin deposits in various organs. Dipyridamole treatment of rabbits caused significant inhibition of fibrin deposition in all three experimental models. The drug also inhibited platelet consumption and, in the thrombin- and EACA-infused animals, fibrinogen consumption as well. The results obtained with dipyridamole were compared with the effect of thorotrast. It was concluded from this comparison that the effect of dipyridamole could not be attributed to inhibition of the reticuloendothelial system. It is postulated that dipyridamole inhibits the final step at which soluble FM is precipitated as fibrin in vivo.

Aminocaproates↗

[Effect of dipyridamole on recombination of photooxidized bacteriochlorophylla and photoreduced primary quinone in reactive centers of purple bacteria and degradation of form M412 of bacteriorhodopsin].

It is shown that the addition of dipyridamole (2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4d]py rim idine) (up to 10(-4) M) leads to a drastic acceleration of the dark recombination reaction between photooxidized bacteriochlorophyll and photoreduced primary quinone in reaction centers of Rhodobacter sphaeroides. The value of the acceleration is similar to that registered under cryogenic temperatures. The extent of the effect of dipyridamole derivatives depended on their structure. In wild-type bacteriorhodopsin and D96N mutant, dipyridamole slowed down the Schiff base reprotonation (the kinetics of M412 form decay was registered). It is suggested that dipyridamole can influence the structural and dynamic state of membrane proteins by affecting the system of their hydrogen-bonds and thus modify electron and proton transport processes.

Bacteriochlorophylls↗

The value of dipyridamole thallium scintigraphy and dobutamine stress echocardiography as predictors of cardiac complications following reconstruction of the abdominal aorta.

BACKGROUND: The aim of this study was to evaluate the ability of dipyridamole thallium scintigraphy and dobutamine stress echocardiography to predict cardiac complications following elective reconstruction of the abdominal aorta in patients with a stable preoperative cardiac condition and to compare this with information obtained from the medical history, ECG and resting echocardiography alone. METHODS: This evaluation was performed from January 1993 until December 1995 as part of a prospective, randomised study in 200 patients, with a mean age of 65 (5% women). Dipyridamole thallium scintigraphy was performed on 195 patients and dobutamine stress echocardiography was added to the protocol in the last 83 patients. Cardiac complications were defined before the start of the study. RESULTS: In the postoperative period 62 cardiac complications occurred (31%). In patients clinically suspected of having coronary artery disease the incidence of complications was 40% (51/126), compared to 15% (11/74) when no coronary pathology was suspected (p<0.001). When reversible defects were present on dipyridamole thallium scintigraphy the incidence of complications was 36% (20/55), compared to 29% (41/140) when no reversible defects had been found (NS). Dobutamine stress echocardiography was impossible or contraindicated in 21 patients. In the remaining patients the incidence of complications was 71% (5/7) when new regional wall motion abnormalities were found, compared to 16% (9/55) when such abnormalities had not been detected (p<0.005). CONCLUSIONS: These data suggest that cardiac complications following reconstruction of the abdominal aorta in patients with a stable cardiac condition are best predicted by dobutamine stress echocardiography. Dipyridamole thallium scintigraphy, however, does not seem to be useful in this respect.

Aged↗

Evaluation of oral dipyridamole electrocardiography test in ischaemic heart disease.

Forty-three cases of ischaemic heart disease of the age group 35-72 yrs with positive treadmill test (TMT) results were administered dipyridamole in the morning on empty stomach. Heart rate, BP and ECG were recorded before and every 15 mins after oral dipyridamole upto 2 hrs. ECG was repeated every 5 mins when patients developed angina or ischaemic ECG changes. Oral dipyridamole electrocardiography test (ODET) was found to be positive in 21 (48.83%) cases and majority of them developed ST depression in 25-40 mins and persisted for less than 30 mins. While compared with TMT results patients having chest pain, lower target heart rate (< 75%), shorter time to onset (< 2 mins) of ST depression and longer duration (> 8 mins) of ST depression had significantly higher rates of positivity on ODET than those without these manifestations. There were minor changes in hemodynamic parameter (heart rate, systolic and diastolic blood pressure) and other minor side effects encountered include mild headache and benign unifocal VPCs. Oral dipyridamole is viewed as a safe drug and may be used as a substitute for TMT specially in economically poor and physically disabled patients with significant coronary artery disease.

Administration, Oral↗

[The yentl syndrome in women with arterial hypertension and positive findings on the echocardiography dipyridamole stress test].

UNLABELLED: The aim of this study was to assess the possible gender differences between positive (new wall motion abnormality) combined dipyridamole stress echocardiography and coronary angiography or myocardial revascularization procedures. We evaluated 127 consecutive patients (82 males, 53.5 years old and 45 females, 56.1 years old) with systemic hypertension and chest pain (angina or atypical chest pain) who underwent pharmacological stress echocardiography (dipyridamole-atropine or dipyridamole-dobutamine) for detection of myocardial ischaemia. Coronary angiography was carried out in 84 patients (58 males and 26 females). Diagnostic accuracy of the test was the same in women as in men (92.3 vs 89.1%, females vs males, respectively). Coronary angiography was done in 73.6% of male and 66.7% of female patients with positive test; the difference was not significant. Over a two-year follow-up there were 31 myocardial revascularization procedures (20 coronary surgery and 11 angioplasty), 25 in men and 6 in women (p = 0.028). There was a trend in women with positive test to have less surgery or angioplasty (28.6%) than in men (45.3%), but the difference was not significant. Cox multivariate regression analysis revealed that women were less likely to receive revascularization (relative risk for females RR = 0.1457, 95% CI 0.0416-0.5101). CONCLUSION: Although diagnostic accuracy of third generation dipyridamole stress echocardiography was not different between men and women, in patients with positive test there was a trend in women to undergo coronary angiography and coronary surgery or angioplasty in lesser degree than in men. Cox multivariate model showed low relative risk of females for revascularization procedures and possible Yentl's syndrome in studied population.

Coronary Angiography↗

Age, perfusion test results and dipyridamole reaction.

This retrospective study evaluated 933 patients referred for diagnostic nuclear medicine perfusion testing at 2 outpatient cardiology centers over a 7-month period. None of the patients were able to perform treadmill stress testing, and all received dipyridamole as a pharmacological stress. The authors found that 44% of the patients had an adverse reaction to dipyridamole. A correlational analysis of patients who did and did not have adverse reactions indicated that patients who exhibited some form of adverse reaction to dipyridamole were 10% more likely to have an abnormal perfusion test. In addition, age-group comparisons between patients 70 years or older and those younger than 70 years demonstrated that the younger group had a statistically greater probability of having an adverse reaction to dipyridamole.

Aged↗