The Shear Stress of Busting Blood Clots

Department of Mechanical Engineering and the Maurice Kanbar Center for Biomedical Engineering, the Cooper Union for the Advancement of Science and Art, New York, USA.
New England Journal of Medicine (Impact Factor: 55.87). 10/2012; 367(14):1361-3. DOI: 10.1056/NEJMcibr1207994
Source: PubMed


Systemic delivery of tissue-type plasminogen activator (t-PA) to dissolve a thrombus after a heart attack or stroke is accompanied by the risk of hemorrhage. A recent study shows the use of nanoaggregates to target t-PA to the thrombus in mouse models of mesenteric injury and pulmonary embolism.

30 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most targeted drug delivery approaches utilize molecular targets or regional variations in chemical or structural properties of the tissue microenvironment to localize drug at disease sites. Here we briefly describe a novel nanotherapeutic drug delivery platform that relies upon local mechanical activation by high fluid shear stresses to selectively target drugs to sites of vascular obstruction. This strategy is based on the use of microscale aggregates of nanoparticles that are shear sensitive and break up into individual nanoscale components that adhere to the surface of stenotic vessels in regions of abnormally high fluid shear stress, much as natural platelets do. This biomimetic approach to targeted drug delivery offers a potential new therapeutic approach for treatment of pulmonary embolism, stroke, atherosclerosis, and other hemodynamic-related disorders that are caused by vascular clots, stenosis or obstruction.
    Israel Journal of Chemistry (Online) 08/2013; 53(9‐10). DOI:10.1002/ijch.201300052 · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Preclinical ResearchAtherosclerosis and its sequelae are key contributors to overall human morbidity and mortality worldwide. Substantial effort has been made toward the understanding of disease mechanisms and particularly treatment options. Drugs for primary and secondary prevention of atherosclerosis and in particular its complications, e.g., myocardial infarction, are widely used therapeutics. However, those drugs typically act nonspecifically, thus affecting not only target cells and atherosclerotic lesions but also causing unwanted side effects. One of the most promising recent developments are drugs that exclusively act at the site where they are needed and thereby minimize deleterious side effects. This review focuses on new approaches for targeted drug delivery, emphasizing single‐chain antibody constructs, liposomal formulations, and microRNAs/gene delivery to sites of atherosclerosis and thrombosis.
    Drug Development Research 11/2013; 74(7). DOI:10.1002/ddr.21103 · 0.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 'Septal bounce' is a pathognomonic sign of constrictive pericarditis (CP). The objectives of the study are to resolve the etiology of the septal bounce, to generate septal bounce-related diagnostic tools, and to prove that its presence is related to the mechanical interaction between the atrioventricular inflow and the inter-ventricular septum. We compared steady state free precession four-chamber images between 11 CP patients and 11 controls via cardiac magnetic resonance. The septal bounce was composed of two movements observed during every cardiac cycle, simultaneous with the rapid filling and atrial systole respectively. Three parameters (measured at end-systole) were generated: right ventricular (RV) clamp (compression ratio of the RV)-greater in CP (0.88 ± 0.03) than controls (0.85 ± 0.03, p = 0.02), tri-septal angle between the tricuspid valve annulus plane and the interventricular septum (81° ± 9° vs. 91° ± 7°, p = 0.01), and impact angle between the tricuspid inflow vector and septum (8.6° ± 8.7° vs. 0° ± 6.6°, p = 0.01). The accuracy, positive predictive value, sensitivity and specificity of these parameters in differentiating CP from controls ranged from 100 to 82 %. A forth parameter-septal flow ratio, gauging the proportion of tricuspid inflow impacting the septum, was markedly higher in CP than controls (0.38 ± 0.19 vs. 0.01 ± 0.03, p < 0.0001) with 100 % sensitivity, specificity, positive and negative predictive value. The septal bounce consists of two sequential movements during each cardiac cycle, is time-related with the rapid ventricular filling and atrial systole, and likely represents a result of the tricuspid blood inflow impacting the interventricular septum. Four septal bounce-derived parameters have a good accuracy in differentiating CP from volunteers.
    The International Journal of Cardiovascular Imaging 09/2014; 31(1). DOI:10.1007/s10554-014-0537-2 · 1.81 Impact Factor
Show more