The current study reports the use of small amplitude oscillatory rheometry to investigate the dynamics of blood clot formation upon heparin neutralization under three different oscillatory frequencies, two of which were mimicking physiological heart rates. We utilized two different heparin antidotes, namely protamine and newly developed universal heparin reversal agent (UHRA-7), at different concentrations to determine the quality of blood clot formed upon heparin neutralization by analyzing several key rheological parameters. Scanning electron microscopy (SEM) was used to determine the morphology and microstructure of the blood clot after heparin neutralization to support the rheological observations. The current study revealed that the structure of blood clots formed had significant differences when an oscillatory frequency that mimicked the physiological heart rate was used in comparison to a lower frequency commonly used in current clinical measurements. The limited working dose range for protamine and its intrinsic anticoagulation behaviour was observed. The neutralization profile of UHRA-7 showed a large window of activity. The global assessment of rheological parameters and microstructure of the clot together revealed additional details describing anticoagulant reversal and blood coagulation dynamics by relating the blood clot's fiber thickness and the oscillatory measurements, including storage modulus and blood clot's contractile force. Additionally, a mechanical characterization was conducted to provide a further assessment of blood coagulation using the rheological data.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104851 | DOI Listing |
Eur J Pharm Sci
January 2025
Department of Ophthalmology, LMU University Hospital, LMU Munich, Munich, Germany. Electronic address:
Adeno-associated virus (AAV)-based vectors have emerged as an effective and widely used technology for somatic gene therapy approaches, including those targeting the retina. A major advantage of the AAV technology is the availability of a large number of serotypes that have either been isolated from nature or produced in the laboratory. These serotypes have different properties in terms of sensitivity to neutralizing antibodies, cellular transduction profile and efficiency.
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, P. R. China.
Multicharged cyclodextrins have attracted significant attention because of their applications in biology and pharmaceuticals. This study reports an aminoethoxy-phenyl-pyridinium-modified γ-cyclodextrin (PyA-γ-CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (K) between PyA-γ-CD and heparin as high as 9.
View Article and Find Full Text PDFJ Cardiothorac Surg
January 2025
Department of Anesthesiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 167, Beilishi Road, Xicheng District, China.
Background: Heparin, an anticoagulant used in cardiac surgery, can result in heparin rebound (HR), where it returns postoperatively despite being neutralized with protamine. This study was designed to investigate the prevalence of HR in patients undergoing off-pump coronary artery bypass grafting (OPCAB) and evaluate the impact of HR on their short-term outcomes.
Methods: HR was defined by a 10% increase in activated coagulation time (ACT) following two hours of heparin neutralization with protamine, bleeding over 200 mL/h, and abnormal laboratory coagulation examination results.
J Phys Chem B
December 2024
Institut für Chemie und Biochemie, Freie Universität Berlin, Berlin 14195, Germany.
The interaction of unfractionated heparin (UFH) with universal heparin reversal agent 7 (UHRA-7) is investigated. UHRA-7 is composed of a hyperbranched polyglycerol core onto which an array of methylated tris(2-aminoethylamine) (Me-TREN) charged groups is grafted, which in turn are shielded with a layer of small chain poly(ethylene glycol) methyl ether (mPEG) chains. This system has previously been shown to be biocompatible and to be effective at neutralizing heparin.
View Article and Find Full Text PDFACS Appl Bio Mater
January 2025
Department of Chemistry, Fudan University, 2205 Songhu Road, Shanghai 200438, China.
Although porous frameworks are structurally ideal for the development of biomaterials through drug adsorption, sequestration, and delivery, integration of multiple biofunctions into a biocompatible porous framework would greatly improve its potential for preclinical investigations by increasing both therapeutic value and research and development efficiency. Herein, we report the preparation of a highly biocompatible supramolecular organic framework from an imidazolium-derived tetrahedral monomer and cucurbit[8]uril. The supramolecular organic framework has been revealed to have regular intrinsic porosity and adsorb doxorubicin, photofrin, and heparins driven by hydrophobicity and/or ion-pairing electrostatic interactions.
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