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Mark H Schoenfisch - One of the best experts on this subject based on the ideXlab platform.
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dual action antimicrobials Nitric Oxide Release from quaternary ammonium functionalized silica nanoparticles
Biomacromolecules, 2012Co-Authors: Alexis W Carpenter, Brittany V Worley, Danielle L Slomberg, Mark H SchoenfischAbstract:The synthesis of quaternary ammonium (QA)-functionalized silica nanoparticles with and without Nitric Oxide (NO) Release capabilities is described. Glycidyltrialkylammonium chlorides of varied alkyl chain lengths (i.e., methyl, butyl, octyl, and dodecyl) were tethered to the surface of amine-containing silica nanoparticles via a ring-opening reaction. Secondary amines throughout the particle were then functionalized with N-diazeniumdiolate NO donors to yield dual functional nanomaterials with surface QAs and total NO payloads of 0.3 μmol/mg. The bactericidal activities of singly (i.e., only NO-releasing or only QA-functionalized) and dual (i.e., NO-releasing and QA-functionalized) functional nanoparticles were tested against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. Particles with only NO Release capabilities alone were found to be more effective against P. aeruginosa, while particles with only QA-functionalities exhibited greater toxicity toward S. aureus. The minimum ...
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Nitric Oxide Release part iii measurement and reporting
Chemical Society Reviews, 2012Co-Authors: Peter N Coneski, Mark H SchoenfischAbstract:Nitric Oxide's expansive physiological and regulatory roles have driven the development of therapies for human disease that would benefit from exogenous NO administration. Already a number of therapies utilizing gaseous NO or NO donors capable of storing and delivering NO have been proposed and designed to exploit NO's influence on the cardiovascular system, cancer biology, the immune response, and wound healing. As described in Nitric Oxide Release: Part I. Macromolecular scaffolds and Part II. Therapeutic applications, the preparation of new NO-Release strategies/formulations and the study of their therapeutic utility are increasing rapidly. However, comparison of such studies remains difficult due to the diversity of scaffolds, NO measurement strategies, and reporting methods employed across disciplines. This tutorial review highlights useful analytical techniques for the detection and measurement of NO. We also stress the importance of reporting NO delivery characteristics to allow appropriate comparison of NO between studies as a function of material and intended application.
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Nitric Oxide Release part ii therapeutic applications
Chemical Society Reviews, 2012Co-Authors: Alexis W Carpenter, Mark H SchoenfischAbstract:A wide range of Nitric Oxide (NO)-releasing materials has emerged as potential therapeutics that exploit NO's vast biological roles. Macromolecular NO-releasing scaffolds are particularly promising due to their ability to store and deliver larger NO payloads in a more controlled and effective manner compared to low molecular weight NO donors. While a variety of scaffolds (e.g., particles, dendrimers, and polymers/films) have been cleverly designed, the ultimate clinical utility of most NO-releasing macromolecules remains unrealized. Although not wholly predictive of clinical success, in vitro and in vivo investigations have enabled a preliminary evaluation of the therapeutic potential of such materials. In this tutorial review, we review the application of macromolecular NO therapies for cardiovascular disease, cancer, bacterial infections, and wound healing.
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Nitric Oxide Release part i macromolecular scaffolds
Chemical Society Reviews, 2012Co-Authors: Daniel A Riccio, Mark H SchoenfischAbstract:The roles of Nitric Oxide (NO) in physiology and pathophysiology merit the use of NO as a therapeutic for certain biomedical applications. Unfortunately, limited NO payloads, too rapid NO Release, and the lack of targeted NO delivery have hindered the clinical utility of NO gas and low molecular weight NO donor compounds. A wide-variety of NO-releasing macromolecular scaffolds has thus been developed to improve NO's pharmacological potential. In this tutorial review, we provide an overview of the most promising NO Release scaffolds including protein, organic, inorganic, and hybrid organic-inorganic systems. The NO Release vehicles selected for discussion were chosen based on their enhanced NO storage, tunable NO Release characteristics, and potential as therapeutics.
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dendrimers as a scaffold for Nitric Oxide Release
Journal of the American Chemical Society, 2006Co-Authors: Nathan Stasko, Mark H SchoenfischAbstract:The preparation and characterization of Nitric Oxide (NO)-releasing dendrimer conjugates are reported. Generation 3 and 5 polypropylenimine dendrimers (DAB-Am-16 and DAB-Am-64) were modified at the exterior to impart different amine functionalities. The ability to store NO on a dendritic scaffold using N-diazeniumdiolate NO donors was examined via the reaction of primary amine, secondary amine, and amide functionalities with high pressures of NO (5 atm). The secondary amine dendrimer conjugates exhibited a high storage capacity for NO (up to 5.6 μmol NO/mg), greatly increasing the “payload” of Released NO over existing macromolecular NO donors. The mechanism of diazeniumdiolate decomposition was proton initiated, generating NO spontaneously under physiological conditions (pH 7.4, 37 °C). The NO Release durations (>16 h) observed for the secondary amine dendrimers were significantly longer compared to small molecule alkyl secondary amine diazeniumdiolates, thus illustrating a dendritic effect on NO Release...
Thomas F Luscher - One of the best experts on this subject based on the ideXlab platform.
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tetrahydrobiopterin alters superOxide and Nitric Oxide Release in prehypertensive rats
Journal of Clinical Investigation, 1998Co-Authors: Francesco Cosentino, S Patton, Livius V Duscio, Ernst R Werner, Gabriele Wernerfelmayer, Pierre Moreau, T Malinski, Thomas F LuscherAbstract:Constitutive Nitric Oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H4B) may generate damaging superOxide (O2-). This study was designed to determine whether cNOS-dependent generation of O2- occurs in spontaneously hypertensive rats (SHR) before the onset of hypertension. Aortas from 4-wk-old SHR and Wistar-Kyoto rats were used. cNOS was stimulated by calcium ionophore A23187. In situ measurements of Nitric Oxide and hydrogen perOxide by electrochemical sensors and O2- production by chemiluminescence method were performed. Isometric tension was continuously recorded. H4B by high performance liquid chromatography and [3H]citrulline assay were determined in homogenized tissue. The {"type":"entrez-nucleotide","attrs":{"text":"A23187","term_id":"833253","term_text":"A23187"}}A23187-stimulated production of O2- and its superOxide dismutase product hydrogen perOxide were significantly higher, whereas Nitric Oxide Release was reduced in SHR aortas, with opposite results in the presence of exogenous H4B. Furthermore, NG-monomethyl-L-arginine inhibited the generation of cNOS-dependent O2- by approximately 70%. Natural H4B levels were similar in both strains; however, equivalent cNOS activity required additional H4B in SHR. The endothelium-dependent relaxations to {"type":"entrez-nucleotide","attrs":{"text":"A23187","term_id":"833253","term_text":"A23187"}}A23187 were significantly inhibited by catalase, and enhanced by superOxide dismutase, only in SHR; however, these enzymes had no effect in the presence of H4B. Thus, dysfunctional cNOS may be a source of O2- in prehypertensive SHR and contribute to the development of hypertension and its vascular complications.
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effect of age on kinetics of Nitric Oxide Release in rat aorta and pulmonary artery
Journal of Clinical Investigation, 1996Co-Authors: M Tschudi, Francesco Cosentino, Pierre Moreau, T Malinski, Matthias Barton, N A Bersinger, Georg Noll, Thomas F LuscherAbstract:Aging is an important determinant of vascular disease. Endothelium-derived Nitric Oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO Release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO Release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO Release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO Release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO Release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO Release was unaffected by superOxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO Release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.
Michael S. Goligorsky - One of the best experts on this subject based on the ideXlab platform.
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carbon monOxide induces vasodilation and Nitric Oxide Release but suppresses endothelial nos
American Journal of Physiology-renal Physiology, 1999Co-Authors: Christian Thorup, Caroline L Jones, Steven S Gross, Leon C Moore, Michael S. GoligorskyAbstract:The vascular effects of carbon monOxide (CO) resemble those of Nitric Oxide (NO), but it is unknown whether the two messengers converge or exhibit reciprocal feedback regulation. These questions we...
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Cannabinoid Receptors Are Coupled to Nitric Oxide Release in Invertebrate Immunocytes, Microglia, and Human Monocytes
Journal of Biological Chemistry, 1996Co-Authors: George B. Stefano, Michael S. GoligorskyAbstract:Abstract The present study demonstrates that stereoselective binding sites for anandamide, a naturally occurring cannabinoid substance, can be found in invertebrate immunocytes and microglia. The anandamide-binding site is monophasic and of high affinity, exhibiting a Kd of 34.3 nM with a Bmax of 441 fmol/mg protein. These sites are highly selective, as demonstrated by the inability of other types of signaling molecules to displace [3H]anandamide. Furthermore, this binding site is coupled to Nitric Oxide Release in the invertebrate tissues examined as well as in human monocytes. Interestingly, the cannabinoid-stimulated Release of Nitric Oxide initiates cell rounding. Thus, these cannabinoid actions resemble those of opiate alkaloids. In this regard, we demonstrate that these signaling systems use the same effector system, i.e. Nitric Oxide Release, but separate receptors. Last, the presence of a cannabinoid receptor in selected evolutionary diverse organisms indicates that this signaling system has been conserved for more than 500 million years.
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continuous monitoring of Nitric Oxide Release from human umbilical vein endothelial cells
Biochemical and Biophysical Research Communications, 1993Co-Authors: Hirokazu Tsukahara, D V Gordienko, Michael S. GoligorskyAbstract:Abstract Direct measurement of Nitric Oxide (NO) Release is pivotal for understanding its role in the regulation of vascular tone. However, data on the direct measurement of NO have been scarce. Recent description of NO-selective electrode has prompted us to examine NO Release from endothelial cells using this approach. In the present study, we continuously monitored [NO] in the incubation medium conditioned by cultured human umbilical vein endothelial cells (HUVEC) with an amperometric NO-sensor. The HUVEC Released NO on stimulation with several agonists such as α-thrombin, bradykinin, L-arginine and ionomycin; the responses were characterized by an initial rise and a subsequent sustained increase. Activation of Ca/calmodulin system resulted in a robust elevation in [NO], occasionally displaying an oscillatory component. Calmidazolium pretreatment attenuated the ionomycin-induced response. Pretreatment with phorbol ester suppressed the ionomycin-induced NO Release from HUVEC. Forskolin pretreatment did not modify NO Release elicited by ionomycin. These findings indicate that the synthesis/Release of NO in endothelial cells is a Ca/calmodulin dependent step. Activation of protein kinase C interferes with the Ca/calmodulin-induced activation of NOS in endothelial cells. Thus, the present study shows that NO synthase is a substrate for phosphorylation by different kinases which modulate the activity of the enzyme as determined by continuous monitoring of NO Release from endothelial cells using a specific NO-sensor.
George B. Stefano - One of the best experts on this subject based on the ideXlab platform.
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Morphine stimulates Nitric Oxide Release in human mitochondria
Journal of Bioenergetics and Biomembranes, 2015Co-Authors: George B. Stefano, Kirk J. Mantione, Lismary Capellan, Federico M. Casares, Sean Challenger, Rohina Ramin, Joshua M. Samuel, Christopher Snyder, Richard M. KreamAbstract:The expression of morphine by plants, invertebrate, and vertebrate cells and organ systems, strongly indicates a high level of evolutionary conservation of morphine and related morphinan alkaloids as required for life. The prototype catecholamine, dopamine, serves as an essential chemical intermediate in morphine biosynthesis, both in plants and animals. We surmise that, before the emergence of specialized plant and animal cells/organ systems, primordial multi-potential cell types required selective mechanisms to limit their responsiveness to environmental cues. Accordingly, cellular systems that emerged with the potential for recruitment of the free radical gas Nitric Oxide (NO) as a multi-faceted autocrine/paracrine signaling molecule, were provided with extremely positive evolutionary advantages. Endogenous morphinergic signaling, in concert with NO-coupled signaling systems, has evolved as an autocrine/paracrine regulator of metabolic homeostasis, energy metabolism, mitochondrial respiration and energy production. Basic physiological processes involving morphinergic/NO-coupled regulation of mitochondrial function, with special emphasis on the cardiovascular system, are critical to all organismic survival. Key to this concept may be the phenomenon of mitochondrial enslavement in eukaryotic evolution via endogenous morphine.
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Role of amygdala in mediating sexual and emotional behavior via coupled Nitric Oxide Release
Acta Pharmacologica Sinica, 2005Co-Authors: Elliott Salamon, Tobias Esch, George B. StefanoAbstract:Although the anatomical configuration of the amygdala has been studied a great deal, very little research has been conducted on understanding the precise mechanism by which this emotional regulatory center exerts its control on emotional and sexual behavior. By applying research methodology from the Neuroscience Research Institute, State University of New York, College at Old Westbury, we intended to demonstrate that much of the mediated effects of the amygdala, specifically the regulation of the male and female sexual response cycles, as well as related emotional considerations, exert their effects coupled to Nitric Oxide (NO) Release. Furthermore, by using current anatomical and histological data, we demonstrated that amygdalar tissue rich in endocannabinoid and opiate, as well as catecholamine, receptors could exert its neurochemical effects within an NO-mediated paradigm. This paradigm, together with the existence of estrogen and androgen signaling within the amygdala, further lends credence to our theoretical framework. We begin with a brief anatomical and functional review of amygdalar function, and then proceed to demonstrate its relationship with NO.
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cell surface estrogen receptors mediate calcium dependent Nitric Oxide Release in human endothelia
Circulation, 2000Co-Authors: George B. Stefano, Vincent Prevot, Jeanclaude Beauvillain, Patrick Cadet, Caterina Fimiani, I Welters, Gregory L Fricchione, Christophe Breton, Philippe Lassalle, Michel SalzetAbstract:Background—Although estrogen replacement therapy has been associated with reduction of cardiovascular events in postmenopausal women, the mechanism for this benefit remains unclear. Because Nitric Oxide (NO) is considered an important endothelium-derived relaxing factor and may function to protect blood vessels against atherosclerotic development, we investigated the acute effects of physiological levels of estrogen on NO Release from human internal thoracic artery endothelia and human arterial endothelia in culture. Methods and Results—We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase activity in human endothelial cells by acting on a cell-surface receptor. NO Release was measured in real time with an amperometric probe. 17β-Estradiol exposure to internal thoracic artery endothelia and human arterial endothelia in culture stimulated NO Release within seconds in a concentration-dependent manner. 17β-Estradiol conjugated to bovine serum albumin also stimulated NO Release, s...
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Autoimmunovascular regulation: morphine and ancondamide and ancondamide stimulated Nitric Oxide Release
Journal of Neuroimmunology, 1998Co-Authors: George B. StefanoAbstract:Abstract The hypothesis concerning morphine as an endogenous signal molecule has been strengthened with the recent discovery of a new opiate receptor subtype, designated μ 3 . This opiate receptor is opiate alkaloid sensitive and opioid peptide insensitive, including peptides previously shown to have affinities for μ opiate receptors. This receptor is coupled to Nitric Oxide Release in human endothelial cells, granulocytes and monocytes and in invertebrate immunocytes and microglia. In relation to the endothelium, it has also been coupled to vasodilation via Nitric Oxide. Given the known influence of Nitric Oxide in downregulating cell adhesion, the role of this compound has now been investigated in also diminishing endothelial–immunocyte interaction. Morphine, via Nitric Oxide, has the potential to diminish adhesion molecule expression and in so doing calm an inflammatory process between immunocytes and the endothelial surface. In this regard, the potential for abuse is also present.
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HUMAN MONOCYTE ADHESION IS MODULATED BY ENDOTHELIN B RECEPTOR-COUPLED Nitric Oxide Release
Journal of Immunology, 1997Co-Authors: Jonathan M. King, Kamal D. Srivastava, George B. Stefano, Thomas V. Bilfinger, Wadie F Bahou, Harold I. MagazineAbstract:Human monocytes have the capacity to produce both endothelin 1 (ET-1) and Nitric Oxide (NO), yet the roles of these mediators in monocyte function remain unclear. The relationship of ET-1 and NO Release to monocyte adhesion was explored using peripheral blood monocytes (PBM) and the human monocytic cell lines THP-1 and U937. Specific binding of 125I-labeled ET-1 to THP-1 was abrogated by pretreatment with the endothelin B (ET(B)) receptor antagonist, BQ-788, but not by the endothelin A (ET(A)) receptor antagonist, BQ-123, consistent with predominant ET(B) receptor expression. Direct measurement of NO with an amperometric probe demonstrated the production of nanomolar concentrations of NO by PBM and THP-1 cells upon treatment with ET-1, which was abrogated by BQ-788, but not BQ-123, pretreatment, suggesting functional coupling of ET(B) receptors to NO Release. Indeed, the presence of ET(B) receptor mRNA transcripts was detected in THP-1 and is consistent with previous reports that have demonstrated functional coupling of ET(B) receptors to constitutive NO synthase activation. In contrast, U937 cells did not Release NO in response to ET-1 treatment, and mRNA transcripts were not detected in these cells, consistent their failure to bind 125I-labeled ET-1, as previously determined. Exposure of PBM to ET-1 markedly reduced the adhesion of these cells to human saphenous vein, whereas PBM adhesion in the presence of BQ-788 was restored to control levels. These data demonstrate that PBM interactions with the vascular wall can be reduced by autocrine production of NO and suggest that ET(B) receptors may attenuate monocyte activity at sites of inflammation.
Mark E Meyerhoff - One of the best experts on this subject based on the ideXlab platform.
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controlled light induced gas phase Nitric Oxide Release from s nitrosothiol doped silicone rubber films
Nitric Oxide, 2019Co-Authors: Gergely Lautner, Blake Stringer, Elizabeth J Brisbois, Mark E Meyerhoff, Steven P SchwendemanAbstract:Abstract The light induced Nitric Oxide (NO) Release properties of S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) NO donors doped within polydimethylsiloxane (PDMS) films (PDMS-SNAP and PDMS-GSNO respectively) for potential inhaled NO (iNO) applications is examined. To achieve photolytic Release of gas phase NO from the PDMS-SNAP and PDMS-GSNO films, narrow-band LED light sources are employed and the NO concentration in a N2 sweep gas above the film is monitored with an electrochemical NO sensor. The NO Release kinetics using LED sources with different nominal wavelengths and optical power densities are reported. The effect of the NO donor loading within the PDMS films is also examined. The NO Release levels can be controlled by the LED triggered Release from the NO donor-doped silicone rubber films in order to generate therapeutic levels in a sweep gas for suitable durations potentially useful for iNO therapy. Hence this work may lay the groundwork for future development of a highly portable iNO system for treatment of patients with pulmonary hypertension, hypoxemia, and cystic fibrosis.
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thromboresistant anti biofilm catheters via electrochemically modulated Nitric Oxide Release
Bioelectrochemistry, 2015Co-Authors: Alessandro Colletta, Dipankar Koley, Jianfeng Wu, Chuanwu Xi, Terry C Major, Robert H Bartlett, Mark E MeyerhoffAbstract:Abstract Inexpensive Nitric Oxide (NO) Release strategies to prevent thrombosis and bacterial infections are desirable for implantable medical devices. Herein, we demonstrate the utility of electrochemically modulated NO Release from a catheter model using an inner copper wire working electrode and an inorganic nitrite salt solution reservoir. These catheters generate NO surface fluxes of > 1.0 × 10 − 10 mol min − 1 cm − 2 for more than 60 h. Catheters with an NO flux of 1.1 × 10 − 10 mol min − 1 cm − 2 are shown to significantly reduce surface thrombus formation when implanted in rabbit veins for 7 h. Further, the ability of these catheters to exhibit anti-biofilm properties against bacterial species commonly causing bloodstream and urinary catheter infections is examined. Catheters releasing NO continuously during the 2 d growth of Staphylococcus aureus exhibit a 6 log-unit reduction in viable surface bacteria. We also demonstrate that catheters generating NO for only 3 h at a flux of 1.0 × 10 − 10 mol min − 1 cm − 2 lower the live bacterial counts of both 2 d and 4 d pre-formed Escherichia coli biofilms by > 99.9%. Overall, the new electrochemical NO-Release devices could provide a cost-effective strategy to greatly enhance the biocompatibility and antimicrobial properties of intravascular and urinary catheters, as well as other implantable medical devices.
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Asymmetric Anion‐selective Membrane Electrode for Determining Nitric Oxide Release Rates from Ppolymeric Films/Electrochemical Devices
Electroanalysis, 2015Co-Authors: Joanna Zajda, Natalie R. Crist, Elżbieta Malinowska, Mark E MeyerhoffAbstract:A novel potentiometric method for the determination of Nitric Oxide (NO) is presented. The assessment of NO levels is based on the rapid reaction of NO with oxyhemoglobin, during which nitrate is formed and then detected potentiometrically using a polymeric membrane anion-selective electrode. The composition of the anion-selective membrane is optimized to eliminate the response to high levels of oxyhemoglobin reagent used to react with NO to form NO3−. The practical utility of the method is demonstrated by determining the NO Release rates from NO donor-doped polymeric films, as well as from a new electrochemical NO generation system within the range of 10 to 55×10−10 mol ⋅ min−1. The values measured with the new assay system are shown to correlate well with a chemiluminescence reference method after accounting for the trapping efficiency of NO by the oxyhemoglobin solution.
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reduced platelet activation and thrombosis in extracorporeal circuits coated with Nitric Oxide Release polymers
Critical Care Medicine, 2000Co-Authors: Gail M Annich, Mark E Meyerhoff, Kelly A Mowery, Jurgen P Meinhardt, Brian A Ashton, Scott I Merz, Ronald B Hirschl, Robert H BartlettAbstract:Objective: To determine whether the use of Nitric Oxide (NO)-releasing polymers coated onto the inner surface of extracorporeal circuits can reduce platelet consumption and activation in the absence of systemic heparinization using a rabbit model of veno-venous extracorporeal circulation. Design: Prospective, controlled trial Setting: Research laboratory at an academic medical institution. Subjects: New Zealand White Rabbits Interventions: Anesthetized, tracheotomized, and ventilated New Zealand White rabbits were injected with freshly prepared, 111 In(oxine) 3 labeled single donor platelets through the external jugular vein. After baseline measurements, these animals were placed on venovenous extracorporeal circulation through a 1-m control circuit or NO test circuit for 4 hrs at a blood flow rate of 109-118 mL/min via roller pump. Four groups were studied: systemically heparinized control circuits, systemically heparinized NO test circuits, nonheparinized control circuits, and nonheparinized NO test circuits. Platelet counts, fibrinogen levels, and plasma free indium levels were measured hourly. Circuits were rinsed and retained for gamma counting after the 4-hr run or when the circuit clotted. Four animals, one from each group, did not receive radiolabeled platelets so that the circuits could be preserved for scanning electron microscopic examination after the 4-hr study. Measurements and Main Results: Platelet consumption was significantly reduced in both the heparinized and nonheparinized NO test groups when compared with the controls (p <.0001 and p <.0004, respectively). Platelet adhesion to the extracorporeal circuits was significantly reduced in the nonheparinized test circuits when compared with the controls (p <.05). Scanning electron microscopic examination of the circuits revealed that in the absence of heparin and in the presence of a NO-releasing surface, platelets retained their spherical nonactivated shape. Conclusions: The incorporation of NO into the surface of extracorporeal circuits reduces platelet consumption and eliminates the need for systemic heparinization in a rabbit model of extracorporeal circulation.
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preparation and characterization of hydrophobic polymeric films that are thromboresistant via Nitric Oxide Release
Biomaterials, 2000Co-Authors: Kelly A Mowery, Mark H Schoenfisch, Joseph E Saavedra, Larry K Keefer, Mark E MeyerhoffAbstract:Abstract The preparation of hydrophobic polymer films (polyurethane and poly(vinyl chloride)) containing Nitric Oxide (NO)-releasing diazeniumdiolate functions is reported as a basis for improving the thromboresistivity of such polymeric materials for biomedical applications. Several different approaches for preparing NO-releasing polymer films are presented, including: (1) dispersion of diazeniumdiolate molecules within the polymer matrix; (2) covalent attachment of the diazeniumdiolate to the polymer backbone; and (3) ion-pairing of a diazeniumdiolated heparin species to form an organic soluble complex that can be blended into the polymer. Each approach is characterized in terms of NO Release rates and in vitro biocompatibility. Results presented indicate that the polymer films prepared by each approach Release NO for variable periods of time (10–72 h), although they differ in the mechanism, location and amount of NO Released. In vitro platelet adhesion studies demonstrate that the localized NO Release may prove to be an effective strategy for improving blood compatibility of polymer materials for a wide range of medical devices.