TY - THES AU - Barnucz, Enikö TI - Possibilities for protecting cardiac and vascular function against ischaemia-reperfusion injury PB - Semmelweis Egyetem PY - 2017 DO - 10.14753/SE.2017.2241 UR - https://m2.mtmt.hu/api/publication/3387520 ID - 3387520 LA - English DB - MTMT ER - TY - JOUR AU - Veres, Gábor AU - Hegedűs, Péter AU - Barnucz, Enikö AU - Schmidt, H AU - Radovits, Tamás AU - Zoller, R AU - Karck, M AU - Szabó, Gábor Balázs TI - TiProtec preserves endothelial function in a rat model JF - JOURNAL OF SURGICAL RESEARCH J2 - J SURG RES VL - 200 PY - 2016 IS - 1 SP - 346 EP - 355 PG - 10 SN - 0022-4804 DO - 10.1016/j.jss.2015.06.062 UR - https://m2.mtmt.hu/api/publication/2939940 ID - 2939940 N1 - Összes idézések száma a WoS-ban: 0 AB - BACKGROUND: Coronary artery bypass surgery provides excellent patency rates; however, the early and/or late graft failure reduces the long-term benefit of myocardial revascularization. We investigated the effectiveness of generally used saline, Custodiol solutions and a new solution (TiProtec) at preserving endothelium after cold ischemia and warm reperfusion injury. MATERIALS AND METHODS: Aortic transplantations were performed in Lewis rats. Aortic arches were stored in saline, Custodiol, and TiProtec solutions for 2 h then were transplanted into the abdominal aorta. Two, 24 hours and 1 week after transplantation, the implanted grafts were harvested. Endothelium-dependent and -independent vasorelaxations were investigated in organ bath. DNA strand breaks were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-method, messenger RNA expressions by quantitative real-time polymerase chain reaction, and the expression of CD-31 and alpha smooth muscle actin by immunochemistry. RESULTS: Severely impaired endothelial function and integrity of implanted aortic grafts were shown after 2 h in the saline, Custodiol group (maximal vasorelaxation to acetylcholine: control: 91 +/- 2%, saline: 26 +/- 5%, Custodiol: 24 +/- 5%, CD-31-positive area control: 96 +/- 2%, saline: 35 +/- 13% Custodiol: 54 +/- 5%, P < 0.05, respectively); however, a preserved endothelial function was observed in the TiProtec group when compared with the saline and Custodiol group (maximal vasorelaxation: 46 +/- 7%, CD-31-positive area: 54 +/- 10%, P < 0.05). After 1 wk, endothelial function was partially recovered in all groups; however, it was significantly better in the TiProtec group (maximal vasorelaxation to acetylcholine: saline: 42 +/- 3%, Custodiol: 48 +/- 3%, TiProtec: 56 +/- 3%, CD-31-positive area: saline: 56 +/- 5%, Custodiol: 54 +/- 4%; TiProtec: 83 +/- 6%, P < 0.05, respectively). In addition, messenger RNA levels of Bax, B-cell lymphoma-2, endothelial NOS, vascular endothelial growth factor 2, and caspase-3 were significantly altered in both groups. CONCLUSIONS: TiProtec appears to be superior for the preservation of endothelial- and smooth muscle cells of bypass graft after cold storage and warm reperfusion in our murine model. LA - English DB - MTMT ER - TY - JOUR AU - Loganathan, S AU - Korkmaz-Icoz, S AU - Radovits, Tamás AU - Li, S AU - Mikles, B AU - Barnucz, Enikö AU - Hirschberg, Kristóf AU - Karck, M AU - Szabó, Gábor Balázs TI - Effects of soluble guanylate cyclase activation on heart transplantation in a rat model JF - JOURNAL OF HEART AND LUNG TRANSPLANTATION J2 - J HEART LUNG TRANSPL VL - 34 PY - 2015 IS - 10 SP - 1346 EP - 1353 PG - 8 SN - 1053-2498 DO - 10.1016/j.healun.2015.05.006 UR - https://m2.mtmt.hu/api/publication/2961301 ID - 2961301 N1 - The first two authors contributed equally to this study. AB - BACKGROUND: The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is an important key mechanism to protect the heart from ischemia/reperfusion injury. However, this pathway is disrupted in several cardiovascular diseases as a result of decreased NO bioavailability and increased NO-insensitive forms of sGC. Cinaciguat preferentially activates these NO-insensitive, oxidized forms of sGC. METHODS: We assessed the hypothesis that targeting NO-unresponsive sGC would protect the graft against ischemia/reperfusion injury in a rat heart transplantation model. Before explantation, donor Lewis rats received methylcellulose (1%) vehicle or cinaciguat 10 mg/kg. The hearts were excised, stored in cold preservation solution, and heterotopically transplanted. We evaluated in vivo left ventricular function of the graft. RESULTS: After transplantation, decreased left ventricular systolic pressure (77 +/- 3 mm Hg vs 123 +/- 13 mm Hg, p < 0.05), dP/dtmax (1,703 +/- 162 mm Hg vs 3,350 +/- 444 mm Hg, p < 0.05), and dP/dtmin (995 +/- 110 mm Hg vs 1,925 +/- 332 mm Hg, p < 0.05) were significantly increased by cinaciguat. Coronary blood flow was significantly higher in the cinaciguat group compared with the control group. Additionally, cinaciguat increased adenosine triphosphate levels (1.9 +/- 0.4 micromol/g vs 6.6 +/- 0.8 micromol/g, p < 0.05) and improved energy charge potential. After transplantation, increased c-jun messenger RNA expression was downregulated, whereas superoxide dismutase-1 and cytochrome-c oxidase mRNA levels were upregulated by cinaciguat. Cinaciguat also significantly decreased myocardial DNA strand breaks induced by ischemia/reperfusion during transplantation and reduced death of cardiomyocytes in a cellular model of oxidative stress. CONCLUSIONS: By interacting with NO-unresponsive sGC, cinaciguat enhances the protective effects of the NO/cGMP pathway at different steps of signal transduction after global myocardial ischemia/reperfusion. Its clinical use as pre-conditioning agent could be a novel approach in cardiac surgery. LA - English DB - MTMT ER - TY - JOUR AU - Korkmaz, S AU - Atmanli, A AU - Li, S AU - Radovits, Tamás AU - Hegedűs, Péter AU - Barnucz, Enikö AU - Hirschberg, Kristóf AU - Loganathan, S AU - Yoshikawa, Y AU - Yasui, H AU - Karck, M AU - Szabó, Gábor Balázs TI - Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction JF - EXPERIMENTAL BIOLOGY AND MEDICINE J2 - EXP BIOL MED VL - 240 PY - 2015 IS - 9 SP - 1247 EP - 1255 PG - 9 SN - 1535-3702 DO - 10.1177/1535370215570184 UR - https://m2.mtmt.hu/api/publication/2885973 ID - 2885973 N1 - Department of Cardiac Surgery, University of Heidelberg, Heidelberg, 69120, Germany Heart Center, Semmelweis University, Budapest, 1122, Hungary Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan Cited By :7 Export Date: 7 October 2021 CODEN: EBMMB Correspondence Address: Korkmaz, S.; Department of Cardiac Surgery, Germany; email: korkmaz@uni-heidelberg.de Chemicals/CAS: acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1; copper zinc superoxide dismutase, 149394-67-2; glyceraldehyde 3 phosphate dehydrogenase, 9001-50-7; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; phospholipid hydroperoxide glutathione peroxidase, 97089-70-8; troponin T, 60304-72-5; zinc, 7440-66-6, 14378-32-6; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; bis(aspirinato)zinc(II); Coordination Complexes; Isoproterenol; Troponin T; Zinc AB - The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17-22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 +/- 0.7 mmHg/microL vs. 4.6 +/- 0.5 mmHg/microL, P < 0.05), increased stroke volume (30 +/- 3 microL vs. 50 +/- 6 microL, P < 0.05), decreased systemic vascular resistance (7.2 +/- 0.7 mmHg/min/mL vs. 4.2 +/- 0.5 mmHg/min/mL, P < 0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 +/- 0.03 mV vs. 0.09 +/- 0.02 mV, P < 0.05) and prolonged QT-interval (79.2 +/- 3.2 ms vs. 69.5 +/- 2.5 ms, P < 0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 +/- 15%), glutathione peroxidase 4 (+44 +/- 12%), and transforming growth factor (TGF)-beta1 (+102 +/- 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical, mechanical, and histological changes after acute myocardial ischemia. The induction of antioxidant enzymes and the anti-inflammatory cytokine TGF-beta1 may play a pivotal role in the mechanism of action of Zn(ASA)2. LA - English DB - MTMT ER - TY - JOUR AU - Veres, Gábor AU - Hegedűs, Péter AU - Barnucz, Enikö AU - Zoller, R AU - Klein, S AU - Radovits, Tamás AU - Korkmaz, S AU - Karck, M AU - Szabó, Gábor Balázs TI - Graft preservation with heparinized blood/saline solution induces severe graft dysfunction JF - INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY J2 - INTERACT CARDIOVAS THOR SURG VL - 20 PY - 2015 IS - 5 SP - 594 EP - 600 PG - 7 SN - 1569-9293 DO - 10.1093/icvts/ivv010 UR - https://m2.mtmt.hu/api/publication/2885972 ID - 2885972 N1 - Összes idézések száma a WoS-ban: 0 AB - OBJECTIVES: Vascular grafts are often stored in cold physiological saline/heparinized blood preservation solution. Until now, only in vitro studies investigated the effect of the aforementioned preservation solutions on endothelial function. The main goal of our study was to compare the storage effect of physiological saline and heparinized blood after short-time cold storage and warm reperfusion in a rat model of aortic transplantation. METHODS: Aortic abdominal transplantations (n = 6-8/group) were performed in Lewis rats. The donor aortic arches were placed in cold physiological saline and heparinized blood solutions and stored for 2 h. After the 2 h ischaemia, the aortic arches were transplanted into the abdominal aorta of the recipient. Two, 24 h or 1 week after transplantation, implanted grafts were harvested. Endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasorelaxation were investigated in organ bath experiments. DNA strand breaks were assessed by transferase-mediated dUTP nick-end labelling-method and mRNA expression by quantitative real-time polymerase chain reaction. In addition, the expression of CD-31 was also investigated by immunochemistry. RESULTS: Severely impaired endothelial function and integrity of grafts were shown after 2 and 24 h reperfusion in both groups (maximal vasorelaxation control: 94 +/- 1%, heparinized blood: 27 +/- 4 and 17 +/- 3%, saline 34 +/- 5% and 28 +/- 5%; CD-31 positive area control: 96 +/- 1% blood: 38 +/- 8% and 41 +/- 6%, saline: 35 +/- 12% and 41 +/- 7%, respectively P < 0.05). After 1 week, endothelial function and integrity were partially recovered (maximal vasorelaxation: heparinized blood: 46 +/- 4%, saline: 46 +/- 2%, CD-31 positive area blood: 35 +/- 4%; saline: 56 +/- 5%, P < 0.05). In addition, mRNA levels of Bax, Bcl-2 and caspase-3 were significantly altered and DNA stand breaks were observed. CONCLUSIONS: Storage with the generally used physiological saline and heparinized blood solutions is unable to protect the endothelium against cold ischaemia and warm reperfusion injury. A similar weak preservation effect was observed. LA - English DB - MTMT ER - TY - JOUR AU - Veres, Gábor AU - Hegedűs, Péter AU - Barnucz, Enikö AU - Zoller, R AU - Klein, S AU - Schmidt, H AU - Radovits, Tamás AU - Korkmaz, S AU - Karck, M AU - Szabó, Gábor Balázs TI - Endothelial dysfunction of bypass graft: Direct comparison of In Vitro and In Vivo models of ischemia-reperfusion injury JF - PLOS ONE J2 - PLOS ONE VL - 10 PY - 2015 IS - 4 PG - 13 SN - 1932-6203 DO - 10.1371/journal.pone.0124025 UR - https://m2.mtmt.hu/api/publication/2885971 ID - 2885971 N1 - Összes idézések száma a WoS-ban: 0 AB - BACKGROUND: Although, ischemia/reperfusion induced vascular dysfunction has been widely described, no comparative study of in vivo- and in vitro-models exist. In this study, we provide a direct comparison between models (A) ischemic storage and in-vitro reoxygenation (B) ischemic storage and in vitro reperfusion (C) ischemic storage and in-vivo reperfusion. METHODS AND RESULTS: Aortic arches from rats were stored for 2 hours in saline. Arches were then (A) in vitro reoxygenated (B) in vitro incubated in hypochlorite for 30 minutes (C) in vivo reperfused after heterotransplantation (2, 24 hours and 7 days reperfusion). Endothelium-dependent and independent vasorelaxations were assessed in organ bath. DNA strand breaks were assessed by TUNEL-method, mRNA expressions (caspase-3, bax, bcl-2, eNOS) by quantitative real-time PCR, proteins by Western blot analysis and the expression of CD-31 by immunochemistry. Endothelium-dependent maximal relaxation was drastically reduced in the in-vivo models compared to ischemic storage and in-vitro reperfusion group, and no difference showed between ischemic storage and control group. CD31-staining showed significantly lower endothelium surface ratio in-vivo, which correlated with TUNEL-positive ratio. Increased mRNA and protein levels of pro- and anti-apoptotic gens indicated a significantly higher damage in the in-vivo models. CONCLUSION: Even short-period of ischemia induces severe endothelial damage (in-vivo reperfusion model). In-vitro models of ischemia-reperfusion injury can be limitedly suited for reliable investigations. Time course of endothelial stunning is also described. LA - English DB - MTMT ER - TY - JOUR AU - Radovits, Tamás AU - Korkmaz, S AU - Mátyás, Csaba AU - Oláh, Attila AU - Németh, Balázs Tamás AU - Pali, S AU - Hirschberg, Kristóf AU - Zubarevich, A AU - Gwanmesia, PN AU - Li, S AU - Loganathan, S AU - Barnucz, Enikö AU - Merkely, Béla Péter AU - Szabó, Gábor Balázs TI - An altered pattern of myocardial histopathological and molecular changes underlies the different characteristics of type-1 and type-2 diabetic cardiac dysfunction JF - JOURNAL OF DIABETES RESEARCH J2 - J DIABETES RES VL - 2015 PY - 2015 PG - 12 SN - 2314-6745 DO - 10.1155/2015/728741 UR - https://m2.mtmt.hu/api/publication/2845088 ID - 2845088 N1 - * Megosztott szerzőség AB - Increasing evidence suggests that both types of diabetes mellitus (DM) lead to cardiac structural and functional changes. In this study we investigated and compared functional characteristics and underlying subcellular pathological features in rat models of type-1 and type-2 diabetic cardiomyopathy. Type-1 DM was induced by streptozotocin. For type-2 DM, Zucker Diabetic Fatty (ZDF) rats were used. Left ventricular pressure-volume analysis was performed to assess cardiac function. Myocardial nitrotyrosine immunohistochemistry, TUNEL assay, hematoxylin-eosin, and Masson's trichrome staining were performed. mRNA and protein expression were quantified by qRT-PCR and Western blot. Marked systolic dysfunction in type-1 DM was associated with severe nitrooxidative stress, apoptosis, and fibrosis. These pathological features were less pronounced or absent, while cardiomyocyte hypertrophy was comparable in type-2 DM, which was associated with unaltered systolic function and increased diastolic stiffness. mRNA-expression of hypertrophy markers c-fos, c-jun, and beta-MHC, as well as pro-apoptotic caspase-12, was elevated in type-1, while it remained unaltered or only slightly increased in type-2 DM. Expression of the profibrotic TGF-beta 1 was upregulated in type-1 and showed a decrease in type-2 DM. We compared type-1 and type-2 diabetic cardiomyopathy in standard rat models and described an altered pattern of key pathophysiological features in the diabetic heart and corresponding functional consequences. LA - English DB - MTMT ER - TY - JOUR AU - Rylova, SN AU - Barnucz, Enikö AU - Fani, M AU - Braun, F AU - Werner, M AU - Lassmann, S AU - Maecke, HR AU - Weber, WA TI - Does imaging alphavbeta3 integrin expression with PET detect changes in angiogenesis during bevacizumab therapy? JF - JOURNAL OF NUCLEAR MEDICINE J2 - J NUCL MED VL - 55 PY - 2014 IS - 11 SP - 1878 EP - 1884 PG - 7 SN - 0161-5505 DO - 10.2967/jnumed.114.137570 UR - https://m2.mtmt.hu/api/publication/2929487 ID - 2929487 N1 - Hiányzó Besorolás: 'Journal Article\n\nResearch Support, Non-U.S. Gov\'t',24 AB - In recent years, there has been a growing interest in molecular imaging markers of tumor-induced angiogenesis. Several radiolabeled RGD (arginine, glycine, aspartate) peptides have been developed for PET imaging of alphavbeta3 integrins in the tumor vasculature, but there are only limited data on how angiogenesis inhibitors affect the tumor uptake of these peptides. METHODS: Changes in (68)Ga-NODAGA-c(RGDfK) peptide uptake were measured using PET during bevacizumab therapy of 2 alphavbeta3-negative squamous cell carcinoma cell lines (A-431 and FaDu) that induce alphavbeta3-positive neovasculature when transplanted into nude mice. Tumor uptake of (68)Ga-NODAGA-c(RGDfK) was correlated to microvascular density, vascular morphology, and permeability as well as alphavbeta3 integrin expression. RESULTS: Bevacizumab significantly inhibited growth of A-431 tumors and caused a significant reduction in microvascular density and alphavbeta3 integrin expression within 7 d after start of therapy. Bevacizumab also caused a normalization of blood vessel morphology and decreased tumor necrosis. However, (68)Ga-NODAGA-c(RGDfK) uptake was significantly increased at day 7 of therapy and did not decrease until after 3 wk of treatment. In Fadu xenografts, bevacizumab therapy caused only a minor inhibition of tumor growth and minor changes in (68)Ga-NODAGA-c(RGDfK) uptake. CONCLUSION: Uptake of radiolabeled RGD peptides is not necessarily decreased by effective antiangiogenic therapy. Early in the course of therapy a decrease in the expression of alphavbeta3 integrins may not be reflected by a decrease in the uptake of RGD peptides. LA - English DB - MTMT ER - TY - JOUR AU - Hegedűs, Péter AU - Veres, Gábor AU - Radovits, Tamás AU - Barnucz, Enikö AU - Korkmaz, S AU - Székely, N AU - Kolonics, Ferenc AU - Merkely, Béla Péter AU - Szabó, Gábor Balázs TI - A foszfodiészteráz-5-inhibitor vardenafil hatása a hipoxia-reoxigenáció okozta endothel-diszfunkcióra patkányaortában. JF - CARDIOLOGIA HUNGARICA J2 - CARDIOL HUNG VL - 44 PY - 2014 IS - 4 SP - 224 EP - 230 PG - 7 SN - 0133-5596 UR - https://m2.mtmt.hu/api/publication/2824422 ID - 2824422 N1 - Ellenőrizve teljes szöveg alapján GT LA - Hungarian DB - MTMT ER - TY - JOUR AU - Veres, Gábor AU - Hegedűs, Péter AU - Barnucz, Enikö AU - Zoller, R AU - Radovits, Tamás AU - Korkmaz, S AU - Kolonics, Ferenc AU - Weymann, A AU - Karck, M AU - Szabó, Gábor Balázs TI - Addition of vardenafil into storage solution protects the endothelium in a hypoxia-reoxygenation model JF - EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY J2 - EUR J VASC ENDOVASC VL - 46 PY - 2013 IS - 2 SP - 242 EP - 248 PG - 7 SN - 1078-5884 DO - 10.1016/j.ejvs.2013.05.006 UR - https://m2.mtmt.hu/api/publication/2372522 ID - 2372522 N1 - Megosztott elsőszerzőség: Veres Gábor és Hegedűs Péter között. AB - OBJECTIVE: Based upon the well known protective effect of intracellular cyclic guanosine monophosphate (cGMP) accumulation, we tested the hypothesis that storage solution enriched with optimal concentration of the phosphodiestherase-5 inhibitor vardenafil could provide better protection of vascular grafts against reperfusion injury after long-term cold ischaemic storage. METHODS: Isolated thoracic aorta obtained from rats underwent 24-h cold ischaemic preservation in physiological saline or vardenafil (10(-11) M)-supplemented saline solution. Reperfusion injury was simulated by hypochlorite (200 muM) exposure for 30 minutes. Endothelium-dependent vasorelaxation was assessed, and histopathological and molecular-biological examination of the aortic tissue were performed. RESULTS: Compared with the control group, the saline group showed significantly attenuated endothelium-dependent maximal relaxation (Rmax) to acetylcholine after hypoxia-reoxygenation, which was significantly improved by vardenafil supplementation (Rmax control: 98 +/- 1%; saline: 48 +/- 6%; vardenafil: 75 +/- 4%; p < .05). Vardenafil treatment significantly reduced DNA strand breaks (control: 10.6 +/- 6.2%; saline: 72.5 +/- 4.0%; vardenafil: 14.2 +/- 5.2%; p < .05) and increased cGMP score in the aortic wall (control: 8.2 +/- 0.6; saline: 4.5 +/- 0.3; vardenafil: 6.7 +/- 0.6; p < .05). CONCLUSIONS: Our results support the view that impairment of intracellular cGMP signalling plays a role in the pathogenesis of the endothelial dysfunction induced by cold storage warm reperfusion, which can be effectively reversed by pharmacological phosphodiesterase-5 inhibition. LA - English DB - MTMT ER -