Addition Of Dipyridamole Research Articles

Structure and Properties of Fibrous Materials Based on Poly(-3-Hydroxybutyrate)

The article studies the supramolecular structure of polymer matrices for sustained isolation of drugs based on ultrathin fibers of polyhydroxybutyrate obtained by electrospinning method. Dipyridamole was chosen as a model drug. The concentration of dipyridamole in the fibers ranged from 1 to 5%. The morphology of nonwoven fibrous materials was investigated by scanning electron microscopy, differential scanning calorimetry, electron paramagnetic resonance. It was shown that the addition of the dipyridamole leads to a change in the fiber geometry. Fibers based on polyhydroxybutyrate are characterized by non-equilibrium molecular structure. In the current work, it was found that the addition of dipyridamole causes extra crystallization processes and the molecular mobility in the amorphous regions of the polymer slows down

Analysis of structure and dynamics of superfine polyhydroxybutyrate fibers for targeted drug delivery

Creation of polymer matrix systems for targeted drug delivery into a living organism is a challenging problem of modern treatment of various diseases and injuries. Poly-3-hydroxybutyrate (PHB) is commonly used for development of therapeutic systems. The aim of this article is to examine the changes in structure and morphology of fibers in presence of dipyridamole (DPD) as model drug for controlled release. It was found that addition of dipyridamole led to disappearance of spindle-shaped nodules on fibers of PHB in comparison with pure PHB. The research of thermophysical parameters showed that specific melting enthalpy (and the degree of crystallinity) of PHB fibers increased with the addition of DPD. With the increasing of DPD content in PHB fibers, more perfect and equilibrium crystal structure was formed. According to analysis of intercrystalline regions of PHB fibers, it was found that as the crystallinity of PHB in intergranular regions rose, the corresponding decrease of radical rotation speed was observed. It was concluded that fibers of PHB can be used for creating therapeutic systems for targeted and prolonged drug delivery.

A New Tool to Study Ribavirin-Induced Haemolysis

Today, treatment of chronic hepatitis C is based on a synergistic combination of pegylated interferon and ribavirin with antiprotease inhibitors. Haemolytic anaemia, which is the major side effect of ribavirin treatment, disrupts ribavirin treatment compliance and varies significantly from one patient to another. There is an individual susceptibility to ribavirin haemolysis. With a view to studying haemolysis, and thus optimizing the treatment response, we have developed a new in vitro tool for analysing the ribavirin-induced lysis of red blood cells. Resuspended red blood cells were incubated with isotonic buffer and a range of concentrations of ribavirin. Haemolysis was quantified by spectrophotometric measurement of the supernatant at 540 nm. The assay was used to test the effects of various compounds and to investigate the susceptibility of patients to haemolytic anaemia. In our assay, the degree of haemolysis is dependent on the ribavirin concentration used and can be inhibited by the addition of dipyridamole (50% inhibitory concentration [IC(50)] 30 μM), ATP or glutathione (IC(50) 1.63 mM and 767 μM, respectively). We observed a strong decrease in red blood cell haemolysis in the presence of the ribavirin prodrug viramidine (Taribavirin(®)). When testing the performance of this assay with blood from 24 patients before treatment, we observed a strong correlation between in vitro haemolysis before treatment and the decrease in haemoglobin levels seen in vivo during subsequent treatment (P<0.001). With this new tool it is possible to better evaluate individual susceptibility to ribavirin-induced haemolysis before the start of treatment. In addition, this model will enable the mechanism of ribavirin-induced anaemia to be further explored and allow molecules that could reduce ribavirin haemolysis to be screened and tested in vitro. This approach could help optimize current and future therapeutic strategies involving ribavirin in the treatment of chronic hepatitis C.

Effects of dipyridamole on Plasmodium falciparum-infected erythrocytes.

This study assessed the antimalarial activity of dipyridamole, a well-known vasodilator and inhibitor of platelet aggregation. Dipyridamole was effective against all of the erythrocytic stages such as rings, trophozoites and schizonts, and induced ultrastructural changes during the transition from trophozoite to schizont in vitro. Merozoites were also inhibited from invading dipyridamole-treated erythrocytes. It seems that dipyridamole binds to the erythrocyte membrane blocking the receptors for the merozoite. The 50% inhibitory concentration (IC(50)) of dipyridamole against Plasmodium falciparum infection was 30 nM. The IC(50) of chloroquine decreased from 97.0 nM to 13.7 nM when combined with dipyridamole (0.1 nM). Therefore, we suggest that dipyridamole has antiplasmodial activity due to its ability to arrest parasite development and by inhibiting merozoite invasion of the erythrocytes. Chloroquine activity against P. falciparum is also enhanced by the addition of dipyridamole. Treatment with a combination of chloroquine and dipyridamole may lead to a more effective treatment for chloroquine-resistant strains of P. falciparum.

Low-dose and high-dose acetylsalicylic acid, with and without dipyridamole: a review of clinical trial results.

Publication of the results of the second European Stroke Prevention Study (ESPS-2) provided the incentive for an update of the meta-analyses of aspirin and dipyridamole in the secondary prevention of stroke. After review of published randomized trials of prolonged treatment with aspirin, dipyridamole, or their combination in patients with a history of stroke or transient ischemic attack (TIA), data on the occurrence of stroke, myocardial infarction, and vascular death were used to calculate overall relative risk reductions. The relative risk reduction for aspirin versus placebo was 13%. The same relative risk reduction was found in separate meta-analyses of trials with high (1,000-1,500 mg), medium (250-500 mg), and low (50-100 mg) doses of aspirin. Trials in which different doses were compared showed no difference in the occurrence of vascular events. The addition of dipyridamole to low-dose aspirin further reduced the risk for vascular events by 15%. We conclude from current trials that low-dose aspirin alone reduced the risk of vascular events in patients with prior stroke or TIA by 13%. There is no evidence of a dose-effect relationship. An additional reduction of the risk by 15% can be obtained by adding dipyridamole to aspirin. The overall evidence for the relative effects of the combination of dipyridamole and aspirin versus aspirin alone or placebo is highly consistent. The clinical evidence now favors the two agents in combination over aspirin alone.

Apoptosis by 2-chloro-2′-deoxy-adenosine and 2-chloro-adenosine in human peripheral blood mononuclear cells

Adenosine has profound effects on immune cells and has been implicated in the intrathymic apoptotic deletion of T-cells during development. In order to characterize adenosine effects on quiescent peripheral blood mononuclear cells (PBMC), we have evaluated the ability of the previously characterized adenosine receptor agonist 2-chloro-adenosine (2CA; Ceruti, Barbieri et al., 1997) and of the antineoplastic drug 2-chloro-2'-deoxy-adenosine (2CdA, cladribine) to trigger apoptosis of PBMC. Apoptosis was assessed by morphological changes, DNA fragmentation by agarose gel electrophoresis and appearance of hypodiploid DNA peak by flow cytometry. 2CA (10 microM) and 2CdA (1 microM) induced apoptosis in human PBMC, which are relatively insensitive to apoptosis. For both agents, the effect was concentration- and time-dependent, although 2CdA induced apoptosis more potently than 2CA. Evaluation of mitochondrial function in parallel samples using the mitochondrial membrane-potential-specific dye JC-1 showed that mitochondrial damage followed the same kinetics as apoptosis, hence an early damage of mitochondria is likely not responsible for adenosine-induced death of PBMC. The effect of 2CA was partially prevented by addition of dipyridamole (DP), a nucleoside transport inhibitor, hence some of the apoptotic effect of this nucleoside is, at least in part, due to intracellular action. Alternatively, DP did not affect 2CdA-induced apoptosis, suggesting that 2CdA may enter cells via a DP-insensitive transporter. 5-Iodotubercidin (5-Itu), a nucleoside kinase inhibitor, was also able to partially prevent the action of 2CA and was not able to affect 2CdA-induced apoptosis, suggesting a different role for phosphorylation in 2CA- vs 2CdA-induced apoptosis. To test the role of P1 receptors, agonists and antagonists selective at various P1 receptor subtypes were used. Data suggest that, for 2CA, apoptosis is partially sustained by activation of the A2A receptor subtype, whereas no role is exerted by P1 receptors in 2CdA-dependent apoptosis. Moreover, in these cells, apoptosis could also be triggered through intense activation of the A3 receptor via selective agonists such as 2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), but this mechanism plays no role in either 2CA- or 2CdA-induced apoptosis. On the whole, our results suggest that 2CA and 2CdA follow different pathways in inducing apoptosis of immune cells. Moreover, our data also suggest that there are at least three different ways by which adenosine derivatives may induce apoptosis of human PBMC: (i) through an A2A-like extracellular membrane receptor; (ii) through entry of nucleosides into cells and direct activation of intracellular events involved in the apoptotic process; or (iii) through activation of the A3 receptor.

The addition of dipyridamole to dobutamine is not recommended

The addition of dipyridamole to dobutamine is not recommended

Effects of dipyridamole in combination with anticoagulant therapy on survival and thromboembolic events in patients with prosthetic heart valves: A meta-analysis of the randomized trials

The addition of dipyridamole, an antiplatelet agent, to conventional anticoagulant regimens has been shown to reduce the frequency of embolization after valve replacement with a mechanical prosthesis. The purpose of this meta-analysis was to reevaluate the benefit of dipyridamole by analyzing the evidence from all randomized clinical trials. Summary data were extracted from the application to the Food and Drug Administration. Six randomized clinical trials had accrued 1141 patients, of whom 582 received anticoagulant therapy alone and 559 received additional dipyridamole at dosages ranging from 225 to 400 mg per day. The events analyzed were all thromboembolic events, both fatal and nonfatal; hemorrhagic events, both fatal and nonfatal; and the overall mortality. The combination of dipyridamole with anticoagulants reduced the risk of thromboembolic events (fatal or nonfatal) by 56% when compared with the use of anticoagulants alone ( p = 0.0001). The risk reduction was seen in fatal and in nonfatal thromboembolic events (risk reduction for fatal events, 64%, p = 0.008; for nonfatal events, 50%, p = 0.005). The overall mortality rate was also significantly reduced by 40% in the group receiving dipyridamole ( p = 0.013). There was no difference between treatment groups with respect to hemorrhagic events (risk reduction, -1%, p = 0.94). This meta-analysis supports the use of dipyridamole in this setting and warrants further trials with new antiplatelet agents. (J T HORAC C ARDIOVASC S URG 1995;110:463-72)

Effect of dipyridamole on glomerular mesangial cell ecto-5'-nucleotidase expression.

Although dipyridamole has been extensively studied as an anti-aggregating agent, its mechanism of action has not been elucidated. Cultured mesangial cells were treated with dipyridamole 1-100 microM from 6-72 h. Ecto-5'-nucleotidase activity approximately doubled (from 115 +/- 11 to 226 +/- 14 nmol/min/mg) after treatment with 100 microM dipyridamole for 72 h. This effect was concentration- and time-dependent. Cycloheximide, an inhibitor of protein synthesis, did not alter basal 5'-nucleotidase activity. However, it prevented stimulation by 5 microM dipyridamole. Adenosine availability at the receptor sites was increased by dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), which inhibit adenosine uptake into the cell. Addition of dipyridamole or NBTI to the adenosine-treated mesangial cells produced an additive increase in ecto-5'-nucleotidase activity. Dipyridamole, through its effect on extracellular adenosine and ecto-5'-nucleotidase, may have an influence upon regulation of the glomerular microcirculation.

Effect of K + depolarization, tetrodotoxin, and NMDA receptor inhibition on extracellular adenosine levels in rat striatum

Extracellular adenosine in the striatum of adult male rats was measured by the use of a microdialysis fibre inserted transversely in the striatum. The adenosine concentration in samples of perfusate was determined by HPLC coupled to U.V. detection. The adenosine concentration (corrected for recovery) decreased after implantation of the probe. Two hours later it was 1.83 ± 0.22 in anaesthetized rats, whereas it was 40% higher in rats in which anaesthesia had been discontinued. Twenty-four hours later the adenosine concentration was 0.124 ± 0.09 μM; the addition of dipyridamole (100 μM), an adenosine uptake blocker, to the perfusate resulted in a 76% increase in adenosine concentration in the effluent, whereas addition of the adenosine deaminase inhibitor erythro-2-(hydroxy-3-nonyl) adenine (100 μM) caused a 260% increase. The addition of tetrodotoxin (1 μM) was followed by a decrease in basal adenosine concentration and a partial inhibition of the increase in adenosine evoked by K + depolarization. The increase induced by high K + was markedly inhibited by the NMDA receptor antagonist D(−)-amino-7-phosphoeptanoic acid (1 mM, D-AP7). These findings indicate that the extracellular adenosine level is influenced by neuronal activity, and that under strong depolarizing conditions the increase in adenosine level involves NMDA receptor activation.

Postirradiation administration of adenosine monophosphate combined with dipyridamole reduces early cellular damage in mice

The administration of dipyridamole and adenosine 5′-monophosphate (AMP) to mice 5 to 25 min after 1 Gy of total-body gamma irradiation was found to decrease cellular damage, as indicated by the thymidine level in plasma and the amount of saline soluble polynucleotides in the thymus. The drug combination used did not influence similar cytotoxic effects of hydrocortisone. Furthermore, it was shown that the addition of dipyridamole and AMP to in vitro irradiated suspensions of thymocytes enhanced the rejoining processes of DNA strand breaks. Receptor-mediated action of extracellular adenosine may be responsible for the therapeutic effects observed.

In vitro and in vivo studies on the combination of Brequinar sodium (DUP-785; NSC 368390) with 5-fluorouracil; effects of uridine

Brequinar sodium (DUP-785; Brequinar) is a potent inhibitor of the pyrimidine de novo enzyme dihydroorotate dehydrogenase (DHO-DH), leading to a depletion of pyrimidine nucleotides, which could be reversed by uridine. In in vitro studies we investigated the effect of different physiological concentrations of uridine on the growth-inhibition by Brequinar, the effect of the nucleoside transport inhibitor, dipyridamole, and the combination of Brequinar and 5-fluorouracil (5FU). Uridine at 1 microM slightly reversed the growth inhibition by Brequinar, while the effect of 5-500 microM was greater. However, at Brequinar concentrations greater than 30 microM, uridine could not reverse the growth-inhibitory effects. Addition of dipyridamole could only partially prevent the reversing effects of uridine. The combination of Brequinar and 5FU was more than additive in the absence of uridine in the culture medium, but not in the presence of uridine. The combination of Brequinar and 5FU was tested in vivo in two murine colon tumour models, Colon 26 and Colon 38. Scheduling of both compounds appeared to be very important. In Colon 38 no potentiating effect of Brequinar could be observed. In contrast in Colon 26 a more than additive effect could be observed. Since uridine concentrations are considerably different in these tumours (higher in Colon 38), it was concluded from both the in vitro and in vivo experiments that uridine is an important determinant in combinations of Brequinar and 5FU.

Metabolism and Toxicity of Electroporated 1‐β‐d‐Arabinofuranosylcytosine Triphosphate in a Human Leukemia Cell Line

The metabolism and toxicity of 1‐β‐d‐arabinofuranosylcytosine triphosphate (ara‐CTP) directly injected into cells by electroporation was studied in human leukemia cell lines. The intracellular accumulation of ara‐CTP (ara‐CTP‐Ep) was dependent on the cell type, extracellular ara‐CTP concentration and pulse voltage on electroporation. In a promyelocytic leukemia cell line, HL‐60, ara‐CTP‐Ep revealed a cytotoxic effect in a dose‐dependent manner, although electroporation alone did not have any significant toxicity. Furthermore, simultaneous injection of dCTP, or continuous exposure to deoxycytidine, but not to other deoxyribonucleosides, immediately after electroporation rescued the cells from the toxicity of ara‐CTP‐Ep. The degradation of ara‐CTP‐Ep consisted of an early rapid phase followed by a slower phase with a half life of 1.5 h. The addition of dipyridamole (10 μM), an inhibitor of nucleoside transport, retarded this degradation process. These data indicate that transfer of ara‐CTP by electroporation is a useful method for the study of ara‐CTP metabolism.

14 Antithrombotic treatment of cerebrovascular disease

The most common type of cerebrovascular disease is ischaemia or infarction from atherothrombosis or cardiac embolism. Antithrombotic treatment with an antiplatelet agent or anticoagulant assumes a prior clinical classification into categories of transient ischaemic attack (TIA) or minor stroke, acute partial stable stroke, stroke-in-progression, and completed stroke. Aspirin reduces the risk of stroke, myocardial infarction, and death after TIA or minor stroke secondary to atherothrombosis. Aspirin is effective in both sexes at a dose of 300 or 1200 mg/day. Ticlopidine (500 mg/day), a new antiplatelet agent, is more effective than aspirin in preventing stroke and death in patients with TIA or minor stroke. Ticlopidine (500 mg/day) is effective in preventing recurrent stroke, myocardial infarction, or vascular death in patients with completed stroke. Aspirin has not been directly shown to be effective after completed stroke. No clear evidence exists for the use of anticoagulants in atherothrombotic cerebral vascular disease in patients presenting with TIA or minor stroke, acute partial stable stroke, stroke-in-progression, or completed stroke. Anticoagulation for rheumatic valvular heart disease is effective in preventing recurrent embolism. Long-term anticoagulation of patients with mechanical prosthetic valves protects against initial embolism and prevents recurrent embolism. The addition of aspirin (500-1000 mg/day) to warfarin reduces the rate of cerebral embolism from mechanical prosthetic heart valves but is associated with increased bleeding. The addition of dipyridamole (400 mg/day) to warfarin may be more effective than aspirin in reducing the rate of cerebral embolism from mechanical prosthetic heart valves and has fewer bleeding side-effects. Anticoagulation during the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke. Long-term anticoagulation of patients after the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke, recurrent myocardial infarction and death. Prophylactic anticoagulant treatment of patients with non-valvular atrial fibrillation reduces the incidence of embolism, but the optimal duration of treatment is not known. Immediate anticoagulation of patients with completed cardioembolic stroke is safe and effective in preventing recurrent embolism.

Addition of dipyridamole to aspirin does not further reduce PTCA complications

Addition of dipyridamole to aspirin does not further reduce PTCA complications

Adenosine Receptor Activation and the Regulation of Tyrosine Hydroxylase Activity in PC 12 and PC 18 Cells

We compared the response of rat PC12 cells and a derivative PC18 cell line to the effects of adenosine receptor agonists, antagonists, and adenine nucleotide metabolizing enzymes. We found that theophylline (an adenosine receptor antagonist), adenosine deaminase, and AMP deaminase all decreased basal cyclic AMP content and tyrosine hydroxylase activity in the PC12 cells, but not in PC18 cells. Both cell lines responded to the addition of 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine, adenosine receptor agonists, by exhibiting an increase in tyrosine hydroxylase activity and cyclic AMP content. The latter finding indicates that both cell lines contained an adenosine receptor linked to adenylate cyclase. We found that the addition of dipyridamole, an inhibitor of adenosine uptake, produced an elevation of cyclic AMP and tyrosine hydroxylase activity in both cell lines. Deoxycoformycin, an inhibitor of adenosine deaminase, failed to alter the levels of cyclic AMP or tyrosine hydroxylase activity. This suggests that uptake was the primary inactivating mechanism of adenosine action in these cells. We conclude that both cell types generated adenine nucleotides which activate the adenosine receptor in an autocrine or paracrine fashion. We found that PC12 cells released ATP in a calcium-dependent process in response to activation of the nicotinic receptor. We also measured the rates of degradation of exogenous ATP, ADP, and AMP by PC12 cells. We found that the rates of metabolism of the former two were at least an order of magnitude greater than that of AMP. Any released ATP would be rapidly metabolized to AMP and then more slowly degraded to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECTS OF DIPYRIDAMOLE AND 8-AMINOGUANOSINE ON INOSINE AND GUANOSINE LEVELS IN RAT BLOOD: 68

The metabolism of inosine (Ino) and guanosine (Guo) was studied in rat blood and plasma in vitro. Nucleoside levels were determined using a modification of the HPLC method of Hartwick and Brown (1977). When heparinized whole blood was spiked with Ino and maintained at room temperature, the level of Ino declined in a linear manner from an initial concentration of 9.9 to 1.6 μg/ml after 60 min., giving a plasma half-life of 23.7 min. Blood spiked with Guo showed a similar linear decline in Guo levels, but in a faster manner (11.0 to 0.1 μg/ml at 60 min., half-life = 8.9 min.). The decline in nucleoside concentration was greatly retarded by maintaining blood and plasma on ice. Addition of dipyridamole (100 nmoles/ml) to whole blood, to block nucleoside uptake, retarded the disappearance of Ino and Guo 1.2 and 2.8-fold, respectively. Addition of 8-aminoguanosine (8-AG, 100 nmoles/ml), an inhibitor of purine nucleoside phosphorylase (PNP), had a slightly greater effect, increasing the half-lives of Ino and Guo 2.5 and 4.4-fold, respectively. Dipyridamole and 8-AG had an additive effect in whole blood. When rat plasma was spiked at room temperature with Ino and Guo (each at 1 μg/ml), neither nucleoside was detectable after 30 min. However, addition of 8-AG to spiked rat plasma totally inhibited the reduction in the levels of each nucleoside for at least 60 min. Thus, membrane transport and especially catabolism by PNP cause disappearance of Ino and Guo from rat blood in vitro.

Adenosine: a physiological modulator of superoxide anion generation by human neutrophils.

The effects of adenosine were studied on human neutrophils with respect to their generation of superoxide anion, degranulation, and aggregation in response to soluble stimuli. Adenosine markedly inhibited superoxide anion generation by neutrophils stimulated with N-formyl methionyl leucyl phenylalanine (FMLP), concanavalin A (Con A), calcium ionophore A23187, and zymosan-treated serum; it inhibited this response to PMA to a far lesser extent. The effects of adenosine were evident at concentrations ranging from 1 to 1,000 microM with maximal inhibition at 100 microM. Cellular uptake of adenosine was not required for adenosine-induced inhibition since inhibition was maintained despite the addition of dipyridamole, which blocks nucleoside uptake. Nor was metabolism of adenosine required, since both deoxycoformycin (DCF) and erythro-9-(2-hydroxy-3-nonyl) adenine did not interfere with adenosine inhibition of superoxide anion generation. The finding that 2-chloroadenosine, which is not metabolized, resembled adenosine in its ability to inhibit superoxide anion generation added further evidence that adenosine metabolism was not required for inhibition of superoxide anion generation by neutrophils. Unexpectedly, endogenously generated adenosine was present in supernatants of neutrophil suspensions at 0.14-0.28 microM. Removal of endogenous adenosine by incubation of neutrophils with exogenous adenosine deaminase (ADA) led to marked enhancement of superoxide anion generation in response to FMLP. Inactivation of ADA with DCF abrogated the enhancement of superoxide anion generation. Thus, the enhancement was not due to a nonspecific effect of added protein. Nor was the enhancement due to the generation of hypoxanthine or inosine by deamination of adenosine, since addition of these compounds did not affect neutrophil function. Adenosine did not significantly affect either aggregation or lysozyme release and only modestly affected beta-glucuronidase release by neutrophils stimulated with FMLP. These data indicate that adenosine (at concentrations that are present in plasma) acting via cell surface receptors is a specific modulator of superoxide anion generation by neutrophils.

Studies on the progression and regression of coronary and peripheral atherosclerosis in the cynomolgus monkey: I. Effects of dipyridamole and aspirin

The morphological and biochemical changes in the arteries of the cynomolgus monkey were investigated during the induction and regression of atherosclerosis. During the feeding of an atherogenic diet containing 2% cholesterol and 10% butter for 5 months, the animals developed fibro-fatty plaques which involved the coronary and peripheral arteries and caused significant luminal narrowing of these vessels. The induced aortic lesions contained increased amounts of free and esterified cholesterol, collagen, elastin, and calcium. These changes were associated with an elevation of plasma cholesterol and an increased net influx of plasma cholesterol and LDL into the aorta. Dipyridamole (10 mg/kg) and aspirin (50 mg/kg) had no effect on the arterial uptake of plasma LDL and cholesterol and did not protect against atherosclerosis in any of the vessels examined. During the regression period (low cholesterol diet) of 12 months duration, the induced lesions became more fibrotic and calcified while the cellularity and lipid content of the same lesions decreased. As a result of these changes there were no significant decreases in the atherosclerotic narrowing of the coronary and peripheral vessels. The net influx of plasma LDL and cholesterol into the aorta returned to normal during the regression period. This finding together with the slow rate of aortic cholesterol equilibration suggests that the retention of cholesterol in the regressed aortic lesions is due to a defect in cholesterol transport rather than to an abnormality in intimal permeability. The addition of dipyridamole and aspirin to the regression diet did not alter the course of the atherosclerosis.

The effect of dipyridamole on the adenosine triphosphate level of stored human blood.

Abstract : The addition of dipyridamole, a synthetic deaminase inhibitor at a concentration of .0001 M to human Heparin-ACD blood fortified with adenosine, resulted in an increase in ATP above control levels during storage at 4 C, rising to a maximum of 130% at five days and falling to 20% at 30 days. Aliquots of the same blood fortified with adenine, adenosine or both incubated at 37 C for 30 hours showed levels at or slightly above the upper limit of +2 SD of normal. The addition of dipyridamole at a concentration of .0001M to similar aliquots showed significant increases in ATP above normal, rising to a maximum of 300, 350 and 400% in the aliquots fortified with adenine, adenosine and both respectively. Whereas the presence of adenine, adenosine or both in Heparin-ACD blood did not significantly alter the rise in whole blood inorganic phosphate during incubation at 37 C for 30 hours, the addition of dipyridamole to similar aliquots depressed the level by from 20 to 30% of control values. Protection of the amino group of the adenine constituent of adenosine and AMP is a means to conserve erythrocyte ATP. (Author)