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  1. Article: Zinc-aspirin preconditioning reduces endothelial damage of arterial grafts in a rodent model of revascularization.

    Benke, Kálmán / Stengl, Roland / Stark, Klára Aliz / Bai, Yang / Radovits, Tamás / Loganathan, Sivakkanan / Korkmaz-Icöz, Sevil / Csonka, Máté / Karck, Matthias / Szabó, Gábor / Veres, Gábor

    Frontiers in cardiovascular medicine

    2024  Volume 10, Page(s) 1288128

    Abstract: Introduction: Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ... ...

    Abstract Introduction: Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ischemia-reperfusion injury (IRI), which occurs during the harvest and implantation of the grafts, is an important determinant of graft patency. Preconditioning with aspirin, a nonsteroidal anti-inflammatory drug has been shown to reduce the functional and molecular damage of arterial grafts in a rodent model. Studies have found that the zinc-aspirin complex may be able to exert an even better protective effect in pathological cardiovascular conditions. Thus, our aim was to characterize the protective effect of zinc-aspirin complex on free arterial grafts in a rodent model of revascularization.
    Methods: Donor Lewis rats were treated with either zinc-aspirin, aspirin, or placebo (
    Results: The endothelium dependent maximal vasorelaxation was improved (non-transplanted control group: 82% ± 3%, transplanted control group: 14% ± 2%, aspirin group: 31% ± 4%, zinc-aspirin group: 52% ± 4%), the nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the groups preconditioned with aspirin or zinc-aspirin. However, zinc-aspirin proved to be more effective in the reduction of IRI, than aspirin alone.
    Discussion: Preconditioning with zinc-aspirin could be a promising way to protect the function and structural integrity of free arterial grafts, thus improving the outcomes of CABG.
    Language English
    Publishing date 2024-01-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2023.1288128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Aspirin Reduces Ischemia-Reperfusion Injury Induced Endothelial Cell Damage of Arterial Grafts in a Rodent Model

    Veres, Gábor / Benke, Kálmán / Stengl, Roland / Bai, Yang / Stark, Klára Aliz / Sayour, Alex Ali / Radovits, Tamás / Loganathan, Sivakkanan / Korkmaz-Icöz, Sevil / Karck, Matthias / Szabó, Gábor

    Antioxidants. 2022 Jan. 18, v. 11, no. 2

    2022  

    Abstract: Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a ...

    Abstract Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a nonsteroidal anti-inflammatory drug improves the long-term patency of vein grafts. Whether aspirin has the same effect on arterial grafts is questionable. We aimed to characterize the beneficial effects of aspirin on arterial bypass grafts in a rodent revascularization model. We gave Lewis rats oral pretreatment of either aspirin (n = 8) or saline (n = 8) for 5 days, then aortic arches were explanted and stored in cold preservation solution. The third group (n = 8) was a non-ischemia-reperfusion control. Afterwards the aortic arches were implanted into the abdominal aorta of recipient rats followed by 2 h of reperfusion. Endothelium-dependent vasorelaxation was examined with organ bath experiments. Immunohistochemical staining were carried out. Endothelium-dependent maximal vasorelaxation improved, nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the aspirin preconditioned group, compared to the transplanted control group. Significantly improved endothelial function and reduced I/R injury induced structural damage were observed in free arterial grafts after oral administration of aspirin. Aspirin preconditioning before elective CABG might be beneficial on free arterial graft patency.
    Keywords animal models ; aorta ; apoptosis ; aspirin ; cold ; coronary vessels ; endothelial cells ; immunohistochemistry ; nonsteroidal anti-inflammatory agents ; oral administration ; prognosis ; vasodilation
    Language English
    Dates of publication 2022-0118
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11020177
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Pharmacological activation of soluble guanylate cyclase improves vascular graft function.

    Veres, Gábor / Bai, Yang / Stark, Klára Aliz / Schmidt, Harald / Radovits, Tamás / Loganathan, Sivakkanan / Korkmaz-Icöz, Sevil / Szabó, Gábor

    Interactive cardiovascular and thoracic surgery

    2021  Volume 32, Issue 5, Page(s) 803–811

    Abstract: Objectives: Ischaemia-reperfusion injury impairs the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate (cGMP) signalling pathway and leads to vascular dysfunction. We assessed the hypothesis that the soluble guanylate cyclase ... ...

    Abstract Objectives: Ischaemia-reperfusion injury impairs the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate (cGMP) signalling pathway and leads to vascular dysfunction. We assessed the hypothesis that the soluble guanylate cyclase activator cinaciguat would protect the vascular graft against ischaemia-reperfusion injury.
    Methods: In the treatment groups, rats (n = 8/group) were pretreated with either intravenous saline or intravenous cinaciguat (10 mg/kg) 2 h before an aortic transplant. Aortic grafts were stored for 2 h in saline and transplanted into the abdominal aorta of the recipients. Two hours after the transplant, the grafts were harvested and mounted in an organ bath. Vascular function of the grafts was investigated in the organ bath. Terminal deoxynucleotidyl transferase dUTP nick end labelling, cluster of differentiation 31, caspase-3, endothelial nitric oxide synthase, cGMP, nitrotyrosine and vascular cell adhesion molecule 1 immunochemical reactions were also investigated.
    Results: Pretreatment with cinaciguat significantly improved endothelium-dependent maximal relaxation 2 h after reperfusion compared with the saline group (maximal relaxation control: 96.5 ± 1%, saline: 40.4 ± 3% vs cinaciguat: 54.7 ± 2%; P < 0.05). Pretreatment with cinaciguat significantly reduced DNA fragmentation and nitro-oxidative stress; decreased the caspase-3 and vascular cell adhesion molecule 1 scores; and increased endothelial nitric oxide synthase, cGMP and cluster of differentiation 31 scores.
    Conclusions: Our results demonstrated that enhancement of cGMP signalling by pharmacological activation of the soluble guanylate cyclase activator cinaciguat might represent a beneficial therapy for treating endothelial dysfunction of arterial bypass graft during cardiac surgery.
    MeSH term(s) Animals ; Cyclic GMP ; Endothelium, Vascular ; Nitric Oxide ; Rats ; Reperfusion Injury/etiology ; Reperfusion Injury/prevention & control ; Soluble Guanylyl Cyclase ; Vascular Grafting
    Chemical Substances Nitric Oxide (31C4KY9ESH) ; Soluble Guanylyl Cyclase (EC 4.6.1.2) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2021-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2095298-3
    ISSN 1569-9285 ; 1569-9293
    ISSN (online) 1569-9285
    ISSN 1569-9293
    DOI 10.1093/icvts/ivaa329
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Aspirin Reduces Ischemia-Reperfusion Injury Induced Endothelial Cell Damage of Arterial Grafts in a Rodent Model.

    Veres, Gábor / Benke, Kálmán / Stengl, Roland / Bai, Yang / Stark, Klára Aliz / Sayour, Alex Ali / Radovits, Tamás / Loganathan, Sivakkanan / Korkmaz-Icöz, Sevil / Karck, Matthias / Szabó, Gábor

    Antioxidants (Basel, Switzerland)

    2022  Volume 11, Issue 2

    Abstract: Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a ...

    Abstract Long-term graft patency determines the prognosis of revascularization after coronary artery bypass grafting (CABG). Ischemia-reperfusion (I/R) injury of the graft suffered during harvesting and after implantation might influence graft patency. Aspirin, a nonsteroidal anti-inflammatory drug improves the long-term patency of vein grafts. Whether aspirin has the same effect on arterial grafts is questionable. We aimed to characterize the beneficial effects of aspirin on arterial bypass grafts in a rodent revascularization model. We gave Lewis rats oral pretreatment of either aspirin (
    Language English
    Publishing date 2022-01-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11020177
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation.

    Benke, Kálmán / Németh, Balázs Tamás / Sayour, Alex Ali / Stark, Klára Aliz / Oláh, Attila / Ruppert, Mihály / Szabó, Gábor / Korkmaz-Icöz, Sevil / Horváth, Eszter Mária / Benkő, Rita / Hartyánszky, István / Szabolcs, Zoltán / Merkely, Béla / Radovits, Tamás

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 5358

    Abstract: Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. ... ...

    Abstract Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dt
    MeSH term(s) Animals ; Antioxidants/metabolism ; Cardiotonic Agents/pharmacology ; Cyclic GMP/metabolism ; Cyclic GMP-Dependent Protein Kinases/metabolism ; Enzyme Activators/pharmacology ; Enzymes/genetics ; Enzymes/metabolism ; Heart Transplantation/methods ; Heart Ventricles/drug effects ; Male ; Nitric Oxide/metabolism ; Pyrazoles/pharmacology ; Pyrimidines/pharmacology ; Rats, Inbred Lew ; Signal Transduction/drug effects ; Soluble Guanylyl Cyclase/metabolism ; Tissue Donors ; Ventricular Function
    Chemical Substances Antioxidants ; Cardiotonic Agents ; Enzyme Activators ; Enzymes ; Pyrazoles ; Pyrimidines ; Nitric Oxide (31C4KY9ESH) ; Cyclic GMP-Dependent Protein Kinases (EC 2.7.11.12) ; Soluble Guanylyl Cyclase (EC 4.6.1.2) ; Cyclic GMP (H2D2X058MU) ; riociguat (RU3FE2Y4XI)
    Language English
    Publishing date 2020-03-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-62156-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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