Background In this work, we report a novel targetable ultrasonic contrast agent with the potential to noninvasively define and localize myriad pathological tissues for diagnosis or therapy. The is biotinylated, lipid-coated, perfluorocarbon emulsion that has low inherent echogenicity unless bound surface itself. Methods Results study 1, emulsions without biotin were suspended in buffered saline imaged 7.5-MHz linear-array transducer. Neither manifested significant backscatter until avidin...

Background— Restenosis is a serious complication of coronary angioplasty that involves the proliferation and migration vascular smooth muscle cells (VSMCs) from media to intima, synthesis extracellular matrix, remodeling. We have previously demonstrated tissue factor–targeted nanoparticles can penetrate bind stretch-activated muscles in after balloon injury. In present study, concept VSMC-targeted as drug-delivery platform for prevention restenosis studied. Methods Results— Tissue containing...

Abstract Before molecular imaging with MRI can be applied clinically, certain problems, such as the potential sparseness of epitopes on targeted cell surfaces, and relative weakness conventional MR contrast agents, must overcome. Accordingly, conditions for diagnostic conspicuity that apply to any paramagnetic agent known intrinsic relaxivity were examined in this study. A highly potent liquid perfluorocarbon nanoparticle (∼250 nm diameter, >90000 Gd 3+ /particle) was imaged at 1.5 T used...

Recently, we have identified the dramatic depletion of cardiolipin (CL) in diabetic myocardium 6 weeks after streptozotocin (STZ) injection that was accompanied by increases triacylglycerol content and multiple changes polar lipid molecular species. However, state, predominant hallmarks cardiomyopathy were each present concomitantly, thus, it impossible to identify temporal course alterations myocardium. Using newly developed enhanced shotgun lipidomics approach, demonstrated loss abundant...

A biodegradable positron-emitting dendritic nanoprobe targeted at α v β 3 integrin, a biological marker known to modulate angiogenesis, was developed for the noninvasive imaging of angiogenesis. The has modular multivalent core-shell architecture consisting heterobifunctional core chemoselectively functionalized with polyethylene oxide (PEO) chains that form protective shell, which imparts stealth and dictates pharmacokinetics. Each 8 branches labeling radiohalogens. Placement radioactive...

Criteria for the retrospective diagnosis of acute myocardial infarction rely heavily on increases in lactate dehydrogenase (LD) isoenzymes. However, LD isoenzyme activities are not specific injury. Recently, increased concentrations cardiac troponin I (cTnI) have been shown to be highly damage and sensitivity comparable with that creatine kinase MB detecting Furthermore, cTnI persist plasma at least several days. The present study was designed determine relative sensitivities isoenzymes over...

We investigated the mechanism(s) responsible for decreased cardiac output during continuous positive-pressure ventilation (CPPV). Seven dogs were anesthetized with chloralose-urethane, intubated, and ventilated using a volume ventilator. measured heart rate, stroke volume, determinants of volume: left right ventricular end-diastolic volumes, isovolumic ejection phase indices myocardial contractility, pulmonary systemic arterial pressures. Myocardial blood flow was estimated radioactive...

Diabetic cardiomyopathy is characterized by excessive utilization of fatty acid substrate, diminished glucose transport, and mitochondrial dysfunction. However, the chemical mechanisms linking altered substrate to dysfunction are unknown. Herein, we use shotgun lipidomics multidimensional mass spectrometry identify dramatic decreases in critical inner membrane lipid, cardiolipin, diabetic murine myocardium (from 7.2 ± 0.3 nmol/mg protein control hearts 3.1 0.1 myocardium; p < 0.001, n = 7)....

The binding of thrombin to fibrin is thought be an important mechanism by which thrombi exhibit procoagulant activity; however, the extent other procoagulants are associated with has not been previously defined. This study was designed determine whether clotting factors than bound whole-blood clots and can thereby contribute significant activity. Clots formed in vitro from human blood exhibited minimal activity when incubated plasma depleted vitamin K-dependent barium-citrate adsorption, as...

BACKGROUND Optimal coronary thrombolysis should be prompt and persistent. Although activation of platelets increased thrombin activity have been associated with clinical thrombolysis, the role each in delaying or inducing early reocclusion has difficult to define. METHODS AND RESULTS In conscious dogs thrombosis induced by electrical current, we assessed impact on rapidity incidence two types adjunctive treatment given concomitantly intravenous tissue-type plasminogen activator (t-PA): 1)...

Diabetic cardiomyopathy is the result of maladaptive changes in energy homeostasis. However, biochemical mechanisms underlying dysfunctional lipid metabolism diabetic myocardium are incompletely understood. Herein, we exploit shotgun lipidomics to demonstrate a 4-fold increase acylcarnitines myocardium, which was reversible upon insulin treatment. Analysis acylcarnitine molecular species unexpectedly identified containing mass shift 16 amu comparison anticipated species. Synthesis 3-hydroxy...

It has generally been assumed, from assessment of myocardial metabolism with [1(-11)C]palmitate and positron emission tomography, that clearance the radiolabel myocardium is attributable solely to efflux products oxidative metabolism. However, interpretations would differ if this assumption were unfulfilled. Furthermore, metabolized nonmetabolized tracer not quantified. Accordingly, in study, was perfused extracorporeally 21 open-chest anesthetized dogs, extraction characterized under...

BACKGROUND This study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological of tissue factor-induced mediated the extrinsic pathway. METHODS AND RESULTS Thrombosis induced in femoral arteries anesthetized dogs with use anodal current elicit extensive vascular injury and formation platelet-rich thrombi one artery thrombogenic copper wire fibrin-rich without appreciable contralateral...

Accurate delineation of the volumetric motion left ventricle (LV) heart from tagged magnetic resonance imaging (MRI) is an important area research. The authors have built a system that takes extracted tag line features short axis (SA) and long (LA) image sequences as input fits four-dimensional (4-D) time-varying B-spline model to data by simultaneously fitting knot solids MRI frames via matching three solid planes LV for 4-D tracking. Important advantages are reconstruction surfaces,...

Intrinsic cardiac dysfunction during the diabetic state has been causally linked to changes in myocardial lipid metabolism. However, precise alterations molecular species of polar and non-polar lipids their responses insulin have not investigated. Herein we demonstrate four specific rat after induction by streptozotocin treatment: (i) a massive remodelling triacylglycerol including >5-fold increase tripalmitin mass 60% decrease polyunsaturated (i.e. triacylglycerols containing at least one...

Aim: To develop a fibrin-specific urokinase nanomedicine thrombolytic agent. Materials & Methods:In vitro fibrin-clot dissolution studies were utilized to and characterize simultaneous coupling loading of anti-fibrin monoclonal antibody onto perfluorocarbon nanoparticle (NP) surface. In vivo pharmacokinetics targeting the nanolytic agent was studied in dogs. Results: Simultaneous up 40 antibodies 400 enzymes per NP produced an effective targeted with no significant surface protein–protein...

Background Exposure and upregulation of tissue factor in the wall balloon-injured arteries may result prolonged activation coagulation contributing to restenosis. This study was designed determine whether brief or more inhibition factor–mediated with pathway inhibitor (TFPI) attenuates neointimal formation luminal stenosis after balloon-induced arterial injury. Methods Results The carotid artery minipigs fed an atherogenic diet injured by repetitive balloon hyperinflations, a procedure that...

Lanza GM, Abendschein DR, Hall CS, et al. Molecular imaging of stretch-induced tissue factor expression in carotid arteries with intravascular ultrasound. Invest Radiol 2000;35:227–234. RATIONALE AND OBJECTIVES. targeted contrast agents enables tissues to be distinguished by detecting specific cell-surface receptors. In the present study, a ligand-targeted acoustic nanoparticle system is used identify angioplasty-induced smooth muscle cells within arteries. METHODS. Pig were overstretched...

Background Activation of coagulation has been implicated in both acute thrombotic occlusion and restenosis after balloon angioplasty. However, concomitant administration antithrombotic agents thus far failed to prevent these complications. Importantly, the factors contributing procoagulant activity balloon-injured arteries over time have not defined. This study was designed determine duration on luminal surface relative roles tissue factor thrombin this response. Methods Results Abdominal...

Murine myocardium contains diminutive amounts of calcium-independent phospholipase A2 (iPLA2) activity (<5% that human heart), and malignant ventricular tachyarrhythmias are infrequent during acute murine myocardial ischemia. Accordingly we considered the possibility mouse was a species-specific knockdown pathologic phenotype ischemiainduced lethal tachyarrhythmias. Transgenic mice were generated expressing iPLA2β comparable to present in myocardium. Coronary artery occlusion Langendorff...

Thrombi are known to induce activation of the coagulation system, which may be a mechanism for progression thrombosis and its recurrence after thrombolysis. This study was designed characterize relative role thrombin activated factor X (factor Xa) as mediators procoagulant activity whole blood clots in plasma.Clots formed from human were incubated recalcified (25 mmol/L CaCl2) citrated plasma or nonanticoagulated with increasing concentrations recombinant desulfatohirudin (hirudin) inhibit...

Using an isoelectric-focusing (IEF) method developed to quantitate MM isoenzyme-creatine kinase (CK) sub-band activity, we identified a reproducible time-varying pattern of these sub-bands in the serum eight patients with acute myocardial infarction (MI). Our observations are consistent view that MM3-CK (the M2-CK dimer, pure gene product) is converted intravascularly MM2-CK, and then MM1-CK M1-CK postsynthetic sub-band). The reaches peak first, 16 hours after infarction, followed by MM1-CK....