AIMS:

Although dipyridamole is a widely used pharmacological stress agent, the direct effects on myocardium are not entirely known. Diabetic cardiomyopathy can be investigated by 2D-strain echocardiography. The aim of this study was to assess myocardial functional reserve after dipyridamole infusion using speckle-tracking echocardiography.

METHODS:

Seventy-five patients referred for dipyridamole stress myocardial perfusion gated SPECT (MPGS) were examined by echocardiography to assess a new concept of longitudinal strain reserve (LSR) and longitudinal strain rate reserve (LSRR) respectively defined by the differences of global longitudinal strain (GLS) and longitudinal strain rate between peak stress after dipyridamole and rest. Twelve patients with myocardial ischemia were excluded on the basis of MPGS as gold standard.

RESULTS:

Mean LSR was -2.28+/-2.19 % and was more important in the 28 (44%) diabetic patients (-3.27+/-1.93 %; p = 0.001). After multivariate analyses, only diabetes improved LSR (p = 0.011) after dipyridamole infusion and was not associated with glycaemic control (p = 0.21), insulin therapy (p = 0.46) or duration of the disease (p = 0.80). Conversely, age (p = 0.002) remained associated with a decrease in LSR. LSSR was also correlated to age (p = 0.005). Patients with a LSR < 0% have a better survival after 15 months (log-rank p = 0.0012).

CONCLUSION:

LSR explored by 2D speckle-tracking echocardiography after dipyridamole infusion is a simple and new concept that provides new insights into the impact of diabetes and age on the myocardium with a potential prognostic value.

A 64-year-old man, with no history of trauma, presented with transient visual loss. He was diagnosed with amaurosis fugax and started on dipyridamole and simvastatin. An inconclusive ultrasound (US) Doppler was followed by CT angiogram (CTA) and MRI, which demonstrated free floating intraluminal thrombus in the distal right common carotid artery. ECG showed sinus rhythm and an echocardiogram showed no cardiac thrombus. Following discussion at the vascular multidisciplinary team the decision was made to treat with intravenous heparin followed by warfarin. He has been regularly followed up with CTA/USS, the most recent (Oct 2012) showing no evidence of thrombus. He has had no further symptoms. Despite no initial aetiology being found we suggest that his undiagnosed oesophageal carcinoma (diagnosed 5 months after initial presentation) could have been responsible for a hypercoagulability state giving an increased risk of thrombosis and leading to the thrombus in the common carotid artery.

BACKGROUND AND PURPOSE:

Our aim was to assess the spatiotemporal evolution of the cerebrovascular inflammation occurring after ischemic and hemorrhagic strokes using a recently developed, fast, and ultra-sensitive molecular MRI method.

METHODS:

We first assessed longitudinally the cerebrovascular inflammation triggered by collagenase-induced hemorrhage and by permanent/transient middle cerebral artery occlusion in mice, using MRI after injection of microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (MPIOs-αVCAM-1). Thereafter, we used this method to study the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole after stroke.

RESULTS:

Using multiparametric MRI, we demonstrated that the level and the kinetics of cerebrovascular VCAM-1 expression depend on several parameters, including stroke pathogenesis, the natural history of the disease, and the administration of inflammation-modulating drugs. Interestingly, in transient middle cerebral artery occlusion and intracranial hemorrhage models, VCAM-1 expression was maximal at 24 hours and almost returned to baseline 5 days after stroke onset. In contrast, after permanent middle cerebral artery occlusion, VCAM-1 overexpression was sustained between 24 hours and 5 days, and was particularly significant in the peri-infarct areas. Our results suggest that these perilesional areas expressing VCAM-1 constitute an inflammatory penumbra that is recruited by the ischemic core during the subacute phase. Using MPIOs-αVCAM-1-enhanced imaging, we also provided evidence that celecoxib and atorvastatin (but not dipyridamole) alleviate VCAM-1 overexpression after stroke and prevent formation of the inflammatory penumbra.

CONCLUSIONS:

MPIOs-αVCAM-1-enhanced imaging seems to be promising in the detection of individuals presenting with severe cerebrovascular responses after stroke, which could therefore benefit from anti-inflammatory treatments.

Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality of hepatic surgery or during liver transplantation. Previous studies had implicated extracellular adenosine signaling in liver protection. Based on the notion that extracellular adenosine signaling is terminated by uptake from the extracellular towards the intracellular compartment via equilibrative nucleoside transporters (ENTs), we hypothesized a functional role of ENTs in liver protection from ischemia. During orthotopic liver transplantation in humans, we observed higher expressional levels of ENT1 than ENT2, in conjunction with repression of ENT1 and ENT2 transcript and protein levels following warm ischemia and reperfusion. Treatment with the pharmacologic ENT inhibitor dipyridamole revealed elevations of hepatic adenosine levels and robust liver protection in a murine model of liver ischemia and reperfusion. Subsequent studies in gene-targeted mice for Ent1 or Ent2 demonstrated selective protection from liver injury in Ent1-/- mice. Treatment with selective adenosine receptor antagonists indicated a contribution of Adora2b receptor signaling in ENT-dependent liver protection. Taken together, these findings implicate ENT1 in liver-protection from ischemia and reperfusion injury and suggest ENT inhibitors in the prevention or treatment of ischemic liver injury. (HEPATOLOGY 2013.).

Quantification of myocardial perfusion scintigraphy is often performed to assist physicians in detecting coronary artery disease (CAD). Modern software and hardware packages provide improvements able to shorten scan time and/or reduce administered activity, without compromising image quality in radionuclide myocardial perfusion imaging (MPI). Recently, multifocal collimators were introduced with dedicated reconstruction software, named IQ-SPECT, able to shorten considerably scan time. The aim of our study was to compare this new protocol to the already validated standard ones. Patients, methods: We enrolled 43 patients with suspected or diagnosed CAD. All patients underwent a two-days protocol radionuclide myocardial perfusion scan at rest and after a standard stress test (exercise or dipyridamole) after administering 99mTc-tetrofosmin. Images were acquired on a 2-head gamma camera and reconstructed with attenuation correction. All the images were scored using a 17-segments model by three experienced physicians, blind to clinical data and to acquisition and processing modality. Results, conclusion: No significant differences were recorded in perfusion scores on paired t-test and Wilcoxon among the full-time images reconstructed with standard protocol or IQ-SPECT, both overall on a 17-segments evaluation and when considering different territories of distribution. MPI with IQ-SPECT protocol can be acquired at about a quarter scan time without disagreement compared to full time scan acquisition performed with standard protocols.

Abstract The physical stability of amorphous solid dispersions (SDs) is influenced by their storage conditions. The goal of this work was to investigate the factors affecting the recrystallization of drugs in SDs after storage under conditions of high temperature and high humidity. SDs of three drugs (dipyridamole, nifedipine and indomethacin) with different functional groups (amino, carbonyl and hydroxyl) and onset times for crystallization of the amorphous state were prepared using crospovidone (CrosPVP). All of the drugs in the SDs remained in an amorphous state at 25 °C/50% relative humidity (RH) in closed glass bottles for at least six months. Under conditions of high temperature (40 °C/75%RH/closed and 60 °C/open), differences in interactions between the hydrogen bond donors of the drugs and the amide carbonyl group of CrosPVP are essential factors for recrystallization of the drugs in the SDs. On the other hand, under condition of high humidity (40 °C/75%RH/open), in addition to the difference in the interaction between the drug and CrosPVP, the rate of increase in moisture content affects their recrystallization in SDs.

Multiple myeloma (MM) is characterized by osteolytic bone lesions with uncoupled bone remodeling. In this study, we examined the effects of adenosine and its receptors (A1R, A2AR, A2BR, and A3R) on osteoblast and osteoclast differentiation of cells derived from patients with MM and healthy control subjects. Mesenchymal stem cells and bone marrow-derived mononuclear cells were isolated from bone marrow and differentiated into osteoblasts and osteoclasts, respectively. A1R antagonist rolofylline and A2BR agonist BAY60-6583 inhibit osteoclast differentiation of cells from patients with MM in a dose-dependent manner, as shown by TRAP staining (IC50: 10 and ∼10 nM, respectively). BAY60-6583 and dipyridamole, a nucleoside transport inhibitor, stimulate osteoblast differentiation of cells from patients with MM, as measured by ALP activity at d 14 and Alizarin Red staining at d 21 (by 1.57±0.03- and 1.71±0.45-fold, respectively), which can be blocked by A2BR antagonist MRS1754. Consistently, real-time PCR showed a significant increase of mRNA of osteocalcin and osterix at d 14. The effect of adenosine and its receptors is consistent in patients with MM and healthy subjects, suggesting an intrinsic mechanism that is important in both MM bone metabolism and normal physiology. Furthermore, the effect of dipyridamole on osteoblast differentiation is diminished in both A2BR- and CD39-knockout mice. These results indicate that adenosine receptors may be useful targets for the treatment of MM-induced bone disease.-He, W., Mazumder, A., Wilder, T., Cronstein. B. N. Adenosine regulates bone metabolism via A1, A2A, and A2B receptors in bone marrow cells from normal humans and patients with multiple myeloma.

False-positive findings with myocardial perfusion imaging (MPI) have frequently been identified in the presence of left bundle branch block (LBBB) and tend to lower the accuracy of MPI in individuals with normal coronary angiographs. Pharmacologic stress is recognized as the preferred method for MPI in patients with LBBB. In contrast, very few studies have evaluated the effect of right bundle branch block (RBBB) on MPI, and there is no consensus regarding the selection of pharmacologic versus exercise stress during MPI for the RBBB patient. In this study, we present a 45-year-old man with RBBB, who has a normal coronary artery angiography, but who showed abnormal myocardial perfusion with exercise MPI, and normal perfusion on dipyridamole MPI. The aim of the study is to stimulate awareness that the stress method selected for patients with RBBB can potentially interfere with the accuracy of the data.

ABSTRACT

Dipyridamole/technetium sestamibi scans (more commonly known as MIBI scans, an acronym for methoxyisobutyl isonitrile) are used commonly for the diagnosis and risk stratification of coronary artery disease. Adverse events from MIBI scans are extremely rare. We present the case of a 64-year-old man who was successfully resuscitated after two asystolic episodes following dipyridamole infusion for a MIBI scan. The second asystolic episode occurred in the emergency department 40 minutes after the patient had been transferred from the Cardiac Stress Test Laboratory. To our knowledge, there are no previous reports of patients having two discrete asystolic episodes or an asystolic episode as delayed as we report after a MIBI scan. Our case illustrates why emergency physicians should be aware of the potential for asystole following MIBI scanning and why aminophylline, the antidote for dipyridamole, should be readily available in emergency departments that could see patients after pharmacologic stress testing. Patients who become asystolic following dipyridamole infusion likely require prolonged cardiac monitoring, given the potential for further episodes after periods of hemodynamic stability.

We report an extremely rare case of thebesian vein microfistulae to both ventricles. A 65-year-old woman, with no major cardiovascular risk factors, presented with multiple episodes of chest pain. The resting electrocardiogram showed T-wave inversion in leads V1 -V4 . A Dipyridamole myocardial perfusion imaging revealed large and severe inferior defect with complete reversibility. Coronary angiography showed no coronary artery disease. On contrast injection, an exaggerated capillary blush from the distal portions of the right and left coronary artery systems was seen in both ventricles, mimicking the image of ventriculography. This appearance suggests prominent thebesian vessels, a congenital communication between the coronaries and the two ventricles. The clinical relevance of these myocardial sinusoids is still not well established. Although the majority of these fistulas are small in size and with no clinical significance, they can rarely present with chest pain, cardiac arrhythmia, syncope, myocardial infarction, and/or pulmonary hypertension. These fistulae when excessive can cause significant shunting of blood to the ventricles, leading to coronary steal phenomena and ischemia. This phenomenon is facilitated by the low resistance in these microfistulae as opposed to the higher resistance in the normal coronary circulation. Due to the diffuse nature of these microfistulae, neither surgery nor transcatheter therapy is feasible. This condition can only be managed medically; however, it should be noted that vasodilator agents, such as nitrates, can worsen the coronary steal phenomenon. Our patient was treated with ranolazine with significant improvement in her symptoms, which was not reported previously. Multiple coronary artery microfistulae could be an underestimated condition of angina in patient with normal coronaries.