Administration Of Dipyridamole Research Articles

Antimanic-like effect of dipyridamole in the methylphenidate-induced hyperlocomotion.

Adenosinergic system has been implicated in the pathophysiology of bipolar disorder and drugs that affect adenosine neurotransmission have shown some efficacy as add-on therapy in manic patients. Thus, the aim of the present study was to screen adenosinergic drugs for antimanic-like effect in methylphenidate (MPH)-induced hyperlocomotion in mice. Male and female Swiss mice received a single allopurinol (50 and 200 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) administration before an acute MPH challenge (5mg/kg, sc). In experiments with repeated treatment, male mice received a daily administration of allopurinol (25 and 50 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) for 14 days. Finally, pretreatment with aminophylline (2mg/kg, sc), an unspecific adenosine receptor antagonist, was used to evaluate a putative adenosinergic mediation. Locomotor activity was measured in the automated activity chamber for 20 min. Acute and repeated dipyridamole reduced the increase in locomotor activity induced by MPH, while allopurinol and inosine had no effect. Aminophylline blocked the effect of dipyridamole in MPH-induced hyperlocomotion. The present results suggest that dipyridamole may have an antimanic-like effect through adenosine receptors and reinforce the proposal that the adenosine system may be an interesting target for new antimanic drugs.

Algorithm for Diagnosis of Patients with Ischemic Heart Disease Depending on the Presence of Significant Coronary Artery Lesions

The aim. To analyze the structure of ischemic heart disease and the prevalence of myocardial ischemia with no ob-structive coronary arteries among patients who underwent elective coronary angiography.
 Materials and methods. We examined 1,200 patients with a clinical diagnosis of ischemic heart disease. After coro-nary angiography all the patients with non-stenotic coronary arteries underwent hyperventilation challenge test to ex-clude vasospastic angina and echocardiographic study with intravenous administration of dipyridamole to assess the index of coronary reserve and longitudinal strain.
 Results. The mean age of the study participants was 59.1 ± 4.2 years. The number of male and female subjects was comparable, amounting to 493 (48.8%) and 517 (51.2%), respectively. Stenotic coronary arteries were detected in 699 patients (74.1%). The number of women without hemodynamically significant lesions was twice as large than that of men (210 [67.5%] vs. 101 [32.5%]). Among the examined patients with non-stenotic atherosclerosis of the coronary arteries, 241 patients (77.4%) were diagnosed with coronary microvascular dysfunction, 19 (6.1%) with vasospasm of the coronary arteries, and 2 patients (0.6%) were diagnosed with a combination of vasospastic and microvascular angina. In 36 (73.5%) of 49 patients, a segmental decrease in longitudinal strain of the apex/individual apical segments of the left ventricle was found. In patients without obvious micro- and macrovascular pathology, the interventricular septum was significant enlarged. In 9 (18.4%) of 49 patients, a diagnosis of hypertrophic cardiomyopathy was established.
 Conclusion. Patients with ischemia with no obstructive coronary arteries require careful examination and compari-son of clinical signs with the results of objective tests. Understanding the prevalence and mechanisms of the problem is a key to improving the diagnosis and treatment of cardiovascular complications in this group.

Coronary microcirculation and left ventricular diastolic function but not myocardial deformation indices are impaired early in patients with chronic kidney disease.

To investigate abnormalities in myocardial strain and classic echocardiographic indices and coronary flow reserve (CFR), in younger versus older CKD patients. Sixty consecutive CKD patients (<60 years old n=30, ≥60 years old n=30) and 30 healthy controls (age- and gender-matched with younger CKD patients) were recruited. An echocardiographic assessment including myocardial strain indices (i.e. global longitudinal strain -GLS -, TWIST, UNTWIST rate) was performed at baseline and following dipyridamole administration in all participants. Younger CKD patients had higher E/e', left ventricular mass index and relative wall thickness and lower E' (p< .005 for all) compared to healthy controls. Older CKD patients had lower E/A and E' (p< .05 for both) compared to younger CKD patients; these differences did not remain significant after adjustment for age. CFR was higher in healthy controls compared to younger and older CKD patients (p< .05 for both) without a significant difference between CKD groups. There were no significant differences in GLS, TWIST or UNTWIST values among the three groups of patients. Dipyridamole-induced changes did not differ significantly among the three groups. Compared to healthy controls, impaired coronary microcirculation and left ventricular diastolic function, but not myocardial strain abnormalities, are found in young CKD patients and deteriorate with aging.

Adenoviral vector-based COVID-19 vaccines-associated cerebral venous sinus thromboses: Are those adverse events related to the formation of neutrophil extracellular traps?

In March and April 2021 several countries temporarily suspended vaccinations with adenoviral vector-based COVID-19 vaccines. Concerns of national regulators particularly regarded very rare cases of cerebral venous sinus thrombosis after immunization with this type of vaccine. Until now, these adverse events were interpreted as standard hypercoagulable events, but their clinical characteristics suggest that they may actually represent unique thrombotic disorders referred to as immunothrombosis. In this paper it is speculated that it is possible that immunothrombosis after this type of vaccine results from formation of neutrophil extracellular traps (NETs) in veins affected by stagnant blood flow. Such a stasis occurs in individuals with anatomical variants of cerebral venous outflow, which may explain why these events are primarily seen in the cerebral veins. It has already been found that SARS-CoV-2 spike protein can evoke release of NETs. There is also a question if thrombotic events after adenoviral vector-based COVID-19 vaccines could be avoided. These vaccines will still be needed to curb COVID-19 worldwide, since they do not require transportation and storage at very low temperatures. Perhaps, vaccinations with these vaccines should be performed in combination with prophylactic administration of dipyridamole, which is an inexpensive pharmaceutical agent reducing the release of NETs.

Adenoviral vector-based COVID-19 vaccines-associated cerebral venous sinus thromboses: Are those adverse events related to the formation of neutrophil extracellular traps?

In March and April 2021 several countries temporarily suspended vaccinations with adenoviral vector-based COVID-19 vaccines. Concerns of national regulators particularly regarded very rare cases of cerebral venous sinus thrombosis after immunization with this type of vaccine. Until now, these adverse events were interpreted as standard hypercoagulable events, but their clinical characteristics suggest that they may actually represent unique thrombotic disorders referred to as immunothrombosis. In this paper it is speculated that it is possible that immunothrombosis after this type of vaccine results from formation of neutrophil extracellular traps (NETs) in veins affected by stagnant blood flow. Such a stasis occurs in individuals with anatomical variants of cerebral venous outflow, which may explain why these events are primarily seen in the cerebral veins. It has already been found that SARS-CoV-2 spike protein can evoke release of NETs. There is also a question if thrombotic events after adenoviral vector-based COVID-19 vaccines could be avoided. These vaccines will still be needed to curb COVID-19 worldwide, since they do not require transportation and storage at very low temperatures. Perhaps, vaccinations with these vaccines should be performed in combination with prophylactic administration of dipyridamole, which is an inexpensive pharmaceutical agent reducing the release of NETs.

Prolonged dipyridamole administration reduces myocardial perfusion defects in experimental chronic Chagas cardiomyopathy

BackgroundMyocardial perfusion defects (MPD) due to coronary microvascular dysfunction is frequent in chronic Chagas cardiomyopathy (CCC) and may be involved with development of myocardial damage. We investigated whether MPD precedes left ventricular systolic dysfunction and tested the hypothesis that prolonged use of dipyridamole (DIPY) could reduce MPD in an experimental model of CCC in hamsters. Methods and resultsWe investigated female hamsters 6-months after T. cruzi infection (baseline condition) and control animals, divided into T. cruzi-infected animals treated with DIPY (CH + DIPY) or placebo (CH + PLB); and uninfected animals treated with DIPY (CO + DIPY) or placebo (CO + PLB). The animals were submitted to echocardiogram and rest SPECT-Sestamibi-Tc99m myocardial perfusion scintigraphy. Next, the animals were treated with DIPY (4 mg/kg bid, intraperitoneal) or saline for 30 days, and reevaluated with the same imaging methods. At baseline, the CH + PLB and CH + DIPY groups showed larger areas of perfusion defect (13.2 ± 13.2% and 17.3 ± 13.2%, respectively) compared with CO + PLB and CO + DIPY (3.8 ± 2.2% e 3.5 ± 2.7%, respectively), P < .05. After treatment, we observed: reduction of perfusion defects only in the CH + DIPY group (17.3 ± 13.2% to 6.8 ± 7.6%, P = .001) and reduction of LVEF in CH + DIPY and CH + PLB groups (from 65.3 ± 9.0% to 53.6 ± 6.9% and from 69.3 ± 5.0% to 54.4 ± 8.6%, respectively, P < .001). Quantitative histology revealed greater extents of inflammation and interstitial fibrosis in both Chagas groups, compared with control group (P < .001), but no difference between Chagas groups (P > .05). ConclusionsThe prolonged use of DIPY in this experimental model of CCC has reduced the rest myocardial perfusion defects, supporting the notion that those areas correspond to viable hypoperfused myocardium.

USING RESULTS OF FIRST-TRIMESTER BIOCHEMICAL SCREENING AND UTERINE ARTERY PULSATILITY INDEX FOR INCLUSION IN RISK GROUPS FOR FETAL GROWTH RESTRICTION

Objective: to study the combined use of first-trimester biochemical screening results and uterine artery pulsality index (PI) for inclusion in risk group for fetal growth restriction (FGR), improvement of pregnancy outcomes in women from the risk group for the development of FGR.Material and methods. The work is based on the results of studies conducted from 2009 to 2014 in the maternity unit of Republican Clinical Hospital № 2 MoH in the Republic of Tatarstan which is the clinical facility for the Department of Obstetrics and Gynecology № 1 of the Continuing Medical Education Institution “Kazan State Medical University” MoH RF, and maternity unit and prenatal clinic of the Volzhskaya Central City Hospital in the Mari El Republic. First-trimester biochemical screening results and uterine artery PI were the basis for the formation of FGR risk groups. Pregnancy and delivery outcomes in 156 pregnant women with a risk for the development of FGR and in 25 healthy controls were evaluated. In order to improve the placental blood flow based on the proven safety profile, all women with FGR received dipyridamole in the II trimester of pregnancy for at least 3 weeks.Conclusion: concomitant decrease in PAPP-A MoM and increase in uterine artery PI provide the most valuable information for forecasting FGR. Administration of dipyridamole by women with FGR helps to improve placental blood flow, prevents degenerative changes in the placenta, and promotes live births even in III degree FGR.

P4345Severe rest myocardial perfusion defects in experimental chronic Chagas cardiomyopathy correspond to viable hypoperfused myocardium: proof-of-concept study using prolonged dipyridamole administration

P4345Severe rest myocardial perfusion defects in experimental chronic Chagas cardiomyopathy correspond to viable hypoperfused myocardium: proof-of-concept study using prolonged dipyridamole administration

Does intravenous dipyridamole administration cause acute renal impairment?

Does intravenous dipyridamole administration cause acute renal impairment?

Effect of Dipyridamole Injected for Myocardial Perfusion Imaging on Blood Glucose Concentration; A Preliminary Study.

Dipyridamole inhibits adenosine reuptake and increases cyclic Adenosine Monophosphate (cAMP) levels in platelets, erythrocytes and endothelial cells, all of which influence blood glucose. Acute hyperglycaemia reduces endothelium-dependent vasodilation and suppresses coronary microcirculation; which, in theory, can alter the outcome of a radionuclide scan. The present study was conducted with the aim to investigate the changes in blood glucose level of patients receiving dipyridamole for cardiac scan. A total of 293 patients (85 men and 208 women, age: 60.59±10.43 years) were included in the study. Fasting Blood Glucose (FBG) was measured before and 8 min after dipyridamole (0.568 mg/kg) injection during myocardial perfusion imaging. The data in different groups were analysed by paired t-test. There was not a significant difference between first (106.89 ± 19.21mg/dL) and second (107.98 ± 17.57 mg/dL) FBG measurements (p= 0.293). However, when the patients were grouped based on the quartiles of first measurement, there was an increase in FBG following dipyridamole injection in the first quartile (mean difference: 7.15±21.27 mg/dL, p<0.01); in contrast, FBG levels showed a significant decrease after dipyridamole administration in the 4(th) quartile (mean difference: -9.53±18.20 mg/dL, p<0.001). The differences in 2(nd) and 3(rd) quartiles were negligible. The patients were divided into normal, ischemic and fixed lesions based on the outcome of scans, then the possible correlation of dipyridamole-induced FBG alteration and scan results were investigated. There were no significant difference between the FBG values before and after dipyridamole injection and the final outcome of scan. The effects of dipyridamole on blood glucose highly depend on the initial blood glucose level.

Successful percutaneous coronary intervention after transcatheter aortic valve implantation with CoreValve bioprosthesis.

We present a case of an 84-year-old male patient who was admitted to our department due to recurrent angina 17 months after transcatheter aortic valve implantation (TAVI) with a 29 mm CoreValve bioprosthesis (Figure 1). Symptoms were increasing in the past several weeks, and on admission the patient was in Canadian Cardiovascular Society class 3. His past medical history included hypertension and chronic atrial fibrillation. Non-invasive diagnostics was initially started with trans-thoracic echocardiography, which did not show signs of left ventricle wall motion abnormalities. Secondly, single-photon emission computed tomography (SPECT) was performed, showing a significant perfusion drop in the left ventricle anterior wall after dipyridamole administration. The patient was referred for coronary angiography. During the examination a critical ostial lesion of the left anterior descending (LAD) artery was discovered with impaired myocardial flow to the distal portion of the artery (TIMI 2). On examination performed 2 months prior to TAVI there were no significant lesions in coronary arteries. Percutaneous intervention (PCI) started with the positioning of a 6 Fr EBU 3.5 catheter between aortic bioprosthesis struts and into the ostium of the left coronary artery (LCA). Afterwards standard PCI with stent implantation was performed. Percutaneous coronary intervention result was good with no significant residual stenosis and restored normal TIMI flow. At discharge, triple antithrombotic therapy was recommended (aspirin, clopidogrel, vitamin K antagonist (VKA)) for 1 month, which should be followed by dual therapy for up to 1 year (aspirin/clopidogrel, VKA). Even though the nitinol frame of the CoreValve bioprosthesis extends to the ascending aorta, the space between the struts is wide enough to ensure coronary access. Navigating through the struts may be burdened with additional difficulties depending on the bioprosthesis final position in relation to the coronary ostia, which may be hidden behind the frame struts or behind the parts of the leaflets sewn to the nitinol frame. Crossing through the gaps may not be necessary when it comes to diagnostic angiography. In some cases sub-selective contrast injection may fully visualize the coronary sinus and coronary arteries, and may be helpful when struts are crossing the coronary ostia. In terms of TAVI, PCI performed prior to the valve implantation is believed to be gold standard, yet the optimal timing of PCI relative to TAVI is still uncertain and is the subject of constant discussion regardless of growing experience. However, due to improvement of long-term TAVI outcomes, increase of frequency of post-TAVI PCI dictated by the progression of coronary artery disease (CAD) is expected. The above-mentioned procedure is achievable, but may prove demanding – especially when valve prostheses’ elements/struts are in the close vicinity of the coronary ostia, making it difficult to gain optimal support. Different types of new generation bioprosthesis may have valve-specific crossing and support issues, which make intervention more challenging. Further investigations are necessary to assess the safety of post-TAVI PCI and to develop the best solutions for different patients [1–4]. Figure 1 Steps of the procedure: coronary angiography showing critical lesion in the proximal LAD (A); catheter placement and wire crossing (B); stent implantation (C); final result (D); *possibile locations of the coronary ostia (RCA – NCC); – ...

Ivabradine and Bisoprolol on Doppler-derived Coronary Flow Velocity Reserve in Patients with Stable Coronary Artery Disease: Beyond the Heart Rate.

IntroductionCoronary flow velocity reserve (CFVR) is an important prognostic marker in patients with stable coronary artery disease (CAD). Beta-blockers and ivabradine have been shown to improve CFVR in patients with stable CAD, but their effects were never compared. The aim of the current study was to compare the effects of bisoprolol and ivabradine on CFVR in patients with stable CAD.MethodsPatients in sinus rhythm with stable CAD were enrolled in this prospective, randomized, double-blind trial. Patients had to be in a stable condition for at least 15 days before enrollment, on their usual therapy. Patients who were receiving beta-blockers or ivabradine entered a 2-week washout period from these drugs before randomization. Transthoracic Doppler-derived CFVR was assessed in left anterior descending coronary artery, and was calculated as the ratio of hyperemic to baseline diastolic coronary flow velocity (CFV). Hyperemic CFV was obtained using dipyridamole administration using standard protocols. After CFVR assessment, patients were randomized to ivabradine or bisoprolol and entered an up-titration phase, and CFVR was assessed again 1 month after the end of the up-titration phase.ResultsFifty-nine patients (38 male, 21 female; mean age 69 ± 9 years) were enrolled. Transthoracic Doppler-derived assessment of CFV and CFVR was successfully performed in all patients. Baseline characteristics were similar between the bisoprolol and ivabradine groups. No patient dropped out during the study. At baseline, rest and hyperemic peak CFV as well as CFVR was not significantly different in the ivabradine and bisoprolol groups. After the therapy, resting peak CFV significantly decreased in both the ivabradine and bisoprolol groups, but there was no significant difference between the groups (ivabradine group 20.7 ± 4.6 vs. 22.8 ± 5.2, P < 0.001; bisoprolol group 20.1 ± 4.1 vs. 22.1 ± 4.3, P < 0.001). However, hyperemic peak CFV significantly increased in both groups, but to a greater extent in patients treated with ivabradine (ivabradine: 70.7 ± 9.4 vs. 58.8 ± 9.2, P < 0.001; bisoprolol: 65 ± 8.3 vs. 58.7 ± 8.2, P < 0.001). Accordingly, CFVR significantly increased in both groups (ivabradine 3.52 ± 0.64 vs. 2.67 ± 0.55, P < 0.001; bisoprolol 3.35 ± 0.70 vs. 2.72 ± 0.55, P < 0.001), but it was significantly higher in ivabradine group, despite a similar decrease in heart rate (63 ± 7 vs. 61 ± 6; P not significant).ConclusionIvabradine improves hyperemic peak CFV and CFVR to a greater extent than bisoprolol in patients with stable CAD, despite a similar decrease in heart rate. These data demonstrate that the benefits from ivabradine therapy go beyond the heart rate. This could be due to a different mechanism such as diastolic perfusion time, isovolumic ventricular relaxation, end-diastolic pressure, and collaterals.FundingServier.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0237-x) contains supplementary material, which is available to authorized users.

The neuron-astrocyte-microglia triad in a rat model of chronic cerebral hypoperfusion: protective effect of dipyridamole.

Chronic cerebral hypoperfusion during aging may cause progressive neurodegeneration as ischemic conditions persist. Proper functioning of the interplay between neurons and glia is fundamental for the functional organization of the brain. The aim of our research was to study the pathophysiological mechanisms, and particularly the derangement of the interplay between neurons and astrocytes-microglia with the formation of “triads,” in a model of chronic cerebral hypoperfusion induced by the two-vessel occlusion (2VO) in adult Wistar rats (n = 15). The protective effect of dipyridamole given during the early phases after 2VO (4 mg/kg/day i.v., the first 7 days after 2VO) was verified (n = 15). Sham-operated rats (n = 15) were used as controls. Immunofluorescent triple staining of neurons (NeuN), astrocytes (GFAP), and microglia (IBA1) was performed 90 days after 2VO. We found significantly higher amount of “ectopic” neurons, neuronal debris and apoptotic neurons in CA1 Str. Radiatum and Str. Pyramidale of 2VO rats. In CA1 Str. Radiatum of 2VO rats the amount of astrocytes (cells/mm2) did not increase. In some instances several astrocytes surrounded ectopic neurons and formed a “micro scar” around them. Astrocyte branches could infiltrate the cell body of ectopic neurons, and, together with activated microglia cells formed the “triads.” In the triad, significantly more numerous in CA1 Str. Radiatum of 2VO than in sham rats, astrocytes and microglia cooperated in the phagocytosis of ectopic neurons. These events might be common mechanisms underlying many neurodegenerative processes. The frequency to which they appear might depend upon, or might be the cause of, the burden and severity of neurodegeneration. Dypiridamole significantly reverted all the above described events. The protective effect of chronic administration of dipyridamole might be a consequence of its vasodilatory, antioxidant and anti-inflammatory role during the early phases after 2VO.

The effect of eplerenone on adenosine formation in humans in vivo: a double-blinded randomised controlled study.

BackgroundIt has been suggested that mineralocorticoid receptor antagonists have direct cardioprotective properties, because these drugs reduce mortality in patients with heart failure. In murine models of myocardial infarction, mineralocorticoid receptor antagonists reduce infarct size. Using gene deletion and pharmacological approaches, it has been shown that extracellular formation of the endogenous nucleoside adenosine is crucial for this protective effect. We now aim to translate this finding to humans, by investigating the effects of the selective mineralocorticoid receptor antagonist eplerenone on the vasodilator effect of the adenosine uptake inhibitor dipyridamole, which is a well-validated surrogate marker for extracellular adenosine formation.Methods and ResultsIn a randomised, double-blinded, placebo-controlled, cross-over study we measured the forearm blood flow response to the intrabrachial administration of dipyridamole in 14 healthy male subjects before and after treatment with placebo or eplerenone (50 mg bid for 8 days). The forearm blood flow during administration of dipyridamole (10, 30 and 100 µg·min−1·dl−1) was 1.63 (0.60), 2.13 (1.51) and 2.71 (1.32) ml·dl−1·min−1 during placebo use, versus 2.00 (1.45), 2.68 (1.87) and 3.22 (1.94) ml·dl−1·min−1 during eplerenone treatment (median (interquartile range); P = 0.51). Concomitant administration of the adenosine receptor antagonist caffeine attenuated dipyridamole-induced vasodilation to a similar extent in both groups. The forearm blood flow response to forearm ischemia, as a stimulus for increased formation of adenosine, was similar during both conditions.ConclusionIn a dosage of 50 mg bid, eplerenone does not augment extracellular adenosine formation in healthy human subjects. Therefore, it is unlikely that an increased extracellular adenosine formation contributes to the cardioprotective effect of mineralocorticoid receptor antagonists.Trial RegistrationClinicalTrials.gov, NCT01837108

Low-dose dipyridamole treatment partially prevents diabetes mellitus-induced vascular endothelial and renal abnormalities in rats

Dipyridamole is a conventionally used platelet inhibitor employed for the secondary prevention of transient ischemic attack. Dipyridamole could potentiate some of the vascular protective effects of nitric oxide (NO) [1]. Intriguingly, the vascular protective action of dipyridamole was reported to be mediated by its stimulatory action on endothelial nitric oxide synthase (eNOS) activity [2]. However, the effect of dipyridamole in diabetes mellitus-induced vascular endothelial dysfunction (VED) is not yet known. There are strong associations between diabetic VED and nephropathy [3,4]. Administration of dipyridamole either alone or in combination with aspirin reduced the incidence of proteinuria in patients with diabetic nephropathy [5]. Dipyridamole at high-dose is considered proischemic, and it could cause a marked coronary steal effect. Dipyridamole, however, at lowdose orallymight have aminimal hemodynamic effect [6]. The present study investigated the effect of low-dose dipyridamole in diabetes mellitus-induced VED and nephropathy in rats. The experimental protocol of this study was approved by the ‘Institutional Animal Ethics Committee’. Wistar albino rats of either sex (n = 6) weighing about 250 to 350 g were used. Group I (Normal Control), rats were maintained on standard food and water, and no treatment was given. Group II (Diabetic Control), rats were administered streptozotocin (STZ) (50 mg/kg, i.p., once), andwere allowed for 8 weeks to develop experimental VED and nephropathy (rats showing blood glucose level of greater than 200 mg/dl after 72 h of STZ administration were selected and named as diabetics). Group III (Dipyridamole per se), normal rats were administered low-dose dipyridamole (30 mg/kg/day, p.o.) for 4 weeks. Group IV (Dipyrida), the diabetic rats after 4 weeks of STZ-administration were treated with low-dose dipyridamole (30 mg/kg/day, p.o.) for 4 weeks. Groups V and VI (Wortmannin or L-NAME Incubated Aortic Ring of Dipyridamole Treated), the diabetic rats were treated with low-dose dipyridamole (30 mg/kg/day, p.o., 4 weeks) as mentioned in group IV. The in vitro effects of wortmannin (100 nM) or L-NAME (100 μM) (the aortic ring was incubated with either wortmannin or L-NAME for 30-min) on endothelium-dependent and -independent relaxation in the phenylephrine (3 × 10−6 M)-precontracted isolated aortic ring preparation were evaluated. One way ANOVA, followed by Tukey's multiple comparison test was employed to analyse the data. STZ-induced diabetic rats developed VED and nephropathy in 8 weeks. Diabetes mellitus-induced VED was associated with marked reduction in acetylcholine-induced endothelium-dependent relaxation, decrease in aortic and serum nitrite/nitrate concentration, and induction of oxidative stress and lipid alteration. Scanning electron microscopic and histological studies on thoracic aorta revealed a marked impairment in vascular endothelial integrity. Moreover, elevation of serum creatinine and blood urea nitrogen, and induction of proteinuria accompanying with renal oxidative stress were noted in diabetic rats. However, treatment with low-dose dipyridamole partially, but substantially prevented aforementioned vascular endothelial and renal abnormalities in diabetic rats without affecting the elevated glucose concentration. Interestingly, incubation of aortic rings, isolated from dipyridamole-treated diabetic rats, with either wortmannin (inhibitor of phosphatidylinositide 3-kinase, PI3-K) or LNAME (inhibitor of nitric oxide synthase, NOS) markedly abolished dipyridamole-associated improvement in acetylcholine-induced endothelium-dependent relaxation (Table 1, Figs. 1 and 2). To summarize, dipyridamole in low-dose partially, but significantly prevents diabetes mellitus-induced VED by activating endothelial PI3K-eNOS-NO signalling pathways. The renovascular reduction of oxidative stress might explain the mechanism pertaining to the partial renoprotective action of low-dose dipyridamole in diabetes mellitus. We express our gratitude to the management of RITS, Sirsa, Haryana, India for the support. The authors of this manuscript have certified that

Qtc Prolongation after a Negative Dipyridamole Pharmacological Stress Study

QTc interval prolongation after dipyridamole administration was reported only in patients who had positive pharmacological stress test results. We report a case of QTc prolongation after dipyridamole administration with no evidence of myocardial ischemia.

Coronary Autoregulation Is Abnormal in Syndrome X: Insights Using Myocardial Contrast Echocardiography

Syndrome X in women is thought to be caused by coronary microvascular dysfunction, the exact site of which is unknown. The aim of this study was to characterize the microvascular site of dysfunction in these patients using myocardial contrast echocardiography. Women with exertional angina, positive test results on stress imaging, but no coronary artery disease (the study group, n = 18) and age-matched control women also with no coronary artery disease (n = 17) were enrolled. Myocardial contrast echocardiography was performed at rest and during dipyridamole-induced hyperemia. Mean microbubble velocity (β) and myocardial blood volume (A) were measured, and myocardial blood flow (A · β) was computed. In addition, plasma concentrations of eicosanoids, female sex hormones, and C-reactive protein were measured. Rest β and myocardial blood flow (A · β) were higher in the study compared with the control women (1.61 ± 0.68 vs. 0.74 ± 0.44, P = .0001, and 157 ± 121 vs. 54 ± 54, P = 0.0001, respectively) despite similar heart rates and systolic blood pressures. After the administration of dipyridamole, whereas the changes in A and A · β were not significantly different between the two groups, β reserve (the ratio of stress β to rest β) was markedly lower in the study group (1.48 ± 0.62 vs. 2.78 ± 0.94, P = .0001). Blood hematocrit, eicosanoids, female sex hormones, glucose, and C-reactive protein were not different between the two groups. Coronary autoregulation is abnormal in patients with syndrome X (higher resting β and myocardial blood flow and lower β reserve), which suggests that the coronary resistance vessels are the site of microvascular abnormality.

Heart and skeletal muscle insulin resistance but not myocardial blood flow reserve could be related to chronic use of thiazolidione in patients with type-2 diabetes

Heart and skeletal muscle insulin resistance and abnormal myocardial flow reserve (MFR) occurs in patients with type-II diabetes. Improvement of heart and skeletal muscle insulin resistance with rosiglitazone use over 16 weeks have been reported. However, it is not clear whether chronic use of troglitazone can improve heart and skeletal muscle insulin resistance and MFR. Materials and Methods: To test the hypothesis whether effects of troglitazone on heart and skeletal muscle insulin resistance and MFR in patients with type-II diabetes, rest and dipyridamole stress perfusion positron emission tomography (PET) with 13N-ammonia and heart and skeletal muscle 18FDG PET scans under insulin clamping were undertaken before and 12 month after the initiation of troglitazone therapy (400 mg/day) in 23 patients with type-II diabetes. Twenty patients with type-II diabetes without CAD and without medications were served as controls. In controls, any medications were not added from the first PET study and 12 months after the second PET study. Results: Baseline myocardial blood flow (MBF) was comparable before and after the troglitazone group as was the controls. MBF during dipyridamole administration (0.56 mg/min/kg) was not significantly improved in troglitazone group and controls. MFR was not improved in troglitazone group and controls. In troglitazone group, whole body glucose disposal rate (GDR; μmole/min/kg) significantly improved (pre; 19.0 ± 9.55, post; 28.7 ± 15.3, p as did the skeletal muscle glucose utilization rate (SMGU (μmole/min/kg); pre; 20.3 ± 12.0, post; 34.8 ± 10.6, p insulin resistance is implicated in patients with type-II diabetes and impaired MFR is uncoupled with insulin resistance in the whole body and heart and skeletal muscle in patients with type-II diabetes.

The Presence of Left Ventricular Inotropic Reserve Correlates With Improvement of Left Ventricular Systolic Function in Non-Ischemic Cardiomyopathy Patients after Long-Term Oral Administration of Dipyridamole

The determination of the left ventricular inotropic reserve (LVIR) is meaningful for prognostic purposes and for the prediction of the response to treatment in heart failure (HF) patients. Purpose: We aimed at assessing the effect of long-term administration of dipyridamole (a microvasculature vasodilator) over rest left ventricular (LV) systolic function in patients with HF due to non-ischemic cardiomyopathy and its correlation to the presence of LVIR in the baseline evaluation.

Cerebrovascular steal phenomenon in a patient undergoing dipyridamole nuclear perfusion cardiac imaging

Transient ischemic neurological deficits following intravenous dipyridamole administration during pharmacological cardiac stress test are seldom reported, but there can be serious vascular complications. We report a case of a 58-year-old Caucasian male who developed expressive aphasia after dipyridamole infusion during an elective dipyridamole-technetium cardiac stress test performed for chest pain. Computed tomography angiogram of the neck revealed a known total occlusion of the right internal carotid artery and 50% stenosis of the left internal carotid artery. The patient's aphasia spontaneously resolved within 24h. In this paper, we report a unique case in which the administration of intravenous dipyridamole precipitated transient ischemic attack in a patient with stable asymptomatic bilateral carotid artery disease and prior carotid endarterectomy. We also discuss the intracerebral vascular steal phenomenon as a possible pathophysiological mechanism in this patient.