Publications by authors named "Dávid Garbaisz"

16 Publications

  • Page 1 of 1

Cryopreservation moderates the thrombogenicity of arterial allografts during storage.

PLoS One 2021 22;16(7):e0255114. Epub 2021 Jul 22.

Department of Vascular and Endovascular Surgery, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.

Introduction: Management of vascular infections represents a major challenge in vascular surgery. The use of cryopreserved vascular allografts could be a feasible therapeutic option, but the optimal conditions for their production and use are not precisely defined.

Aims: To evaluate the effects of cryopreservation and the duration of storage on the thrombogenicity of femoral artery allografts.

Methods: In our prospective study, eleven multi-organ-donation-harvested human femoral arteries were examined at five time points during storage at -80°C: before cryopreservation as a fresh native sample and immediately, one, twelve and twenty-four weeks after the cryopreservation. Cross-sections of allografts were perfused with heparin-anticoagulated blood at shear-rates relevant to medium-sized arteries. The deposited platelets and fibrin were immunostained. The thrombogenicity of the intima, media and adventitia layers of the artery grafts was assessed quantitatively from the relative area covered by fibrin- and platelet-related fluorescent signal in the confocal micrographs.

Results: Regression analysis of the fibrin and platelet coverage in the course of the 24-week storage excluded the possibility for increase in the graft thrombogenicity in the course of time and supported the hypothesis for a descending trend in fibrin generation and platelet deposition on the arterial wall. The fibrin deposition in the cryopreserved samples did not exceed the level detected in any of the three layers of the native graft. However, an early (up to week 12) shift above the native sample level was observed in the platelet adhesion to the media.

Conclusions: The hemostatic potential of cryopreserved arterial allografts was retained, whereas their thrombogenic potential declined during the 6-month storage. The only transient prothrombotic change was observed in the media layer, where the platelet deposition exceeded that of the fresh native grafts in the initial twelve weeks after cryopreservation, suggesting a potential clinical benefit from antiplatelet therapy in this time-window.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255114PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297765PMC
July 2021

[The use of HeRO (Hemodialysis Reliable Outflow) graft in hemodialysis].

Orv Hetil 2019 Aug;160(31):1231-1234

Városmajori Szív- és Érgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Városmajor u. 68., 1122.

Creating durable vascular access has become more complicated with the improvement of the management and with the increasing survival of patients with end-stage renal disease. HeRO (Hemodialysis Reliable Outflow) graft allows to maintain vascular access on the upper limb in patients with the presence of bilateral central venous occlusion. Our institute was the first in Hungary to perform a HeRO graft implantation in a patient receiving regular hemodialysis. Our objective was to present our findings with this recent innovation. Case report, medical documentation and imaging studies were reviewed. The patient (73-year-old, female) has been receiving hemodialysis since 12 years with the history of several arteriovenous fistula (AVF) creations, thrombectomies, use of central venous catheter in both sides. Following the occlusion of a left cubital arterio-venous fistula, none of the conventional vascular access types could have been performed due to bilateral subclavian vein occlusion. Successful HeRO graft implantation was performed. The patient underwent graft thrombectomy and endovascular intervention 7 and 12 months after the original procedure. After both reoperations, the graft functioned well for hemodialysis. HeRO graft can be a good alternative to central venous catheters and lower limb arterio-venous grafts in cases of bilateral central venous occlusion. Orv Hetil. 2019; 160(31): 1231-1234.
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http://dx.doi.org/10.1556/650.2019.31450DOI Listing
August 2019

[Open and endovascular repair of iliac artery aneurysms].

Orv Hetil 2018 Apr;159(13):520-525

Városmajori Szív- és Érgyógyászati Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Városmajor u. 68., 1122.

Introduction And Aim: Iliac artery aneurysms make up 2% of all aneurysms. There are only a few data available on the results of surgical treatment, therefore the optimal treatment is unclear. Our objective was the retrospective analysis of the perioperative morbidity and mortality of patients who underwent iliac artery surgery as well as the comparison of elective open surgery and endovascular iliac aneurysm repair (EVIAR).

Method: Retrospective analysis of patients who underwent surgery for iliac artery aneurysm between 1 January 2005 and 31 December 2014.

Results: During the 10-year period, 62 patients with a mean age of 68.9 years underwent elective surgery for iliac artery aneurysm (54 males, 87.1%). In 10 cases acute surgery was performed due to aneurysm ruptures (13.9%), 3 patients died within the perioperative period (30%). Regarding anatomical localisation, aneurysm developed mostly on the common iliac artery (80.6%). As an elective surgery, 35 patients (56.5%) underwent open surgery, 25 (40.3%) underwent EVIAR and other endovascular interventions were performed in 2 cases (3.2%). Postoperative complications (1 patient [4.0%] vs. 17 patients [48.5%]; p<0.001) and intensive care treatment (29 patients [82.8%] vs. 2 patients [8.0%]; p<0.001) were significantly rarer after EVIAR than after open surgery. Furthermore, EVIAR resulted in considerably shorter postoperative hospital stays (4.7 ± 2.3 days vs. 11.8 ± 12.2 days; p = 0.006) and significantly less blood transfusion demand (1 patient [4.0%] vs. 26 patients [74.2%]; p<0.001). There were no significant differences regarding long-term survival rates between EVIAR and open surgery (81.4% vs. 71.4%; p = 0.95).

Conclusion: In case of the surgical treatment of iliac artery aneurysms, owing to the lower complication rates and shorter postoperative length of stay, EVIAR is primarily recommended. Orv Hetil. 2018; 159(13): 520-525.
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http://dx.doi.org/10.1556/650.2018.30968DOI Listing
April 2018

[Role of the homograft bypass in extremity inferior's reconstructions].

Magy Seb 2017 03;70(1):5-12

Városmajori Szív- és Érgyógyászati Klinika, Semmelweis Egyetem 1122 Budapest, Városmajor utca 68.

Introduction: Vascular homografts are used for limb salvage in cases of graft infection after previous reconstructive vascular surgery or inadequate autologous veins. During multi-organ donation the thoracic aorta segment, aortic bifurcation, iliac arteries, femoral arteries, popliteal arteries, femoral veins and greater saphenous veins can be harvested. Our aim was to optimize the use of homografts by analyzing the results of previous procedures.

Methods: The patient information was processed retrospectively, using the clinical computer system. 162 procedures were performed on 144 patients between 2007 and 2014. The short- and long-term patency, hemorrhagic complication rate, amputation rate and mortality was examined in our study. The location, graft type and length of cryopreservation were taken into consideration. Aortoiliac and femoropopliteal reconstructions with arterial and venous homografts were examined.

Results: The mean age of the patients was 63.6 ± 10.7 years, the mean follow-up period was 36 ± 28 months. The primary patency rates at the postoperative 1, 3 and 6 months were 83.7%, 75.0% and 63.4%. In this study the arterial and deep venous homografts had better primary patency rates compared to the superficial venous homografts: at the postoperative 1, 3, 6 months the arterial homograft results were 85.6%, 78.6% and 74.3%, the greater saphenous vein homograft results were 81.4%, 70.4% and 47.7% in the same intervals.

Conclusion: The reconstructive surgical procedures in septic area mean serious challenge for the vascular surgeons. The AB0 compatibility of the graft and the recipient did not result better long-term outcomes compared to the non-compatible grafts. According to our data the ideal choice of homogenous graft is an arterial homograft which was not cryopreserved longer than 6 months.
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http://dx.doi.org/10.1556/1046.70.2017.1.1DOI Listing
March 2017

Postconditioning in major vascular surgery: prevention of renal failure.

J Transl Med 2015 Jan 27;13:21. Epub 2015 Jan 27.

1st Department of Surgery, Semmelweis University, Budapest, Hungary.

Background: Postconditioning is a novel reperfusion technique to reduce ischemia-reperfusion injuries. The aim of the study was to investigate this method in an animal model of lower limb revascularization for purpose of preventing postoperative renal failure.

Methods: Bilateral lower limb ischemia was induced in male Wistar rats for 3 hours by infrarenal aorta clamping under narcosis. Revascularization was allowed by declamping the aorta. Postconditioning (additional 10 sec reocclusion, 10 sec reperfusion in 6 cycles) was induced at the onset of revascularization. Myocyte injury and renal function changes were assessed 4, 24 and 72 hours postoperatively. Hemodynamic monitoring was performed by invasive arterial blood pressure registering and a kidney surface laser Doppler flowmeter.

Results: Muscle viability studies showed no significant improvement with the use of postconditioning in terms of ischemic rhabdomyolysis (4 h: ischemia-reperfusion (IR) group: 42.93 ± 19.20% vs. postconditioned (PostC) group: 43.27 ± 27.13%). At the same time, renal functional laboratory tests and kidney myoglobin immunohistochemistry demonstrated significantly less expressed kidney injury in postconditioned animals (renal failure index: 4 h: IR: 2.37 ± 1.43 mM vs. PostC: 0.92 ± 0.32 mM; 24 h: IR: 1.53 ± 0.45 mM vs. PostC: 0.77 ± 0.34 mM; 72 h: IR: 1.51 ± 0.36 mM vs. PostC: 0.43 ± 0.28 mM), while systemic hemodynamics and kidney microcirculation significantly improved (calculated reperfusion area: IR: 82.31 ± 12.23% vs. PostC: 99.01 ± 2.76%), and arterial blood gas analysis showed a lesser extent systemic acidic load after revascularization (a defined relative base excess parameter: 1(st) s: IR: 2.25 ± 1.14 vs. PostC: 1.80 ± 0.66; 2(nd) s: IR: 2.14 ± 1.44 vs. PostC: 2.44 ± 1.14, 3(rd) s: IR: 3.99 ± 3.09 vs. PostC: 2.07 ± 0.82; 4(th) s: IR: 3.28 ± 0.32 vs. PostC: 2.05 ± 0.56).

Conclusions: The results suggest a protective role for postconditioning in major vascular surgeries against renal complications through a possible alternative release of nephrotoxic agents and exerting a positive effect on hemodynamic stability.
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http://dx.doi.org/10.1186/s12967-014-0379-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314807PMC
January 2015

Attenuation of skeletal muscle and renal injury to the lower limb following ischemia-reperfusion using mPTP inhibitor NIM-811.

PLoS One 2014 26;9(6):e101067. Epub 2014 Jun 26.

Semmelweis University, 1st Department of Surgery, Budapest, Hungary.

Introduction: Operation on the infrarenal aorta and large arteries of the lower extremities may cause rhabdomyolysis of the skeletal muscle, which in turn may induce remote kidney injury. NIM-811 (N-metyl-4-isoleucine-cyclosporine) is a mitochondria specific drug, which can prevent ischemic-reperfusion (IR) injury, by inhibiting mitochondrial permeability transition pores (mPTP).

Objectives: Our aim was to reduce damages in the skeletal muscle and the kidney after IR of the lower limb with NIM-811.

Materials And Methods: Wistar rats underwent 180 minutes of bilateral lower limb ischemia and 240 minutes of reperfusion. Four animal groups were formed called Sham (receiving vehicle and sham surgery), NIM-Sham (receiving NIM-811 and sham surgery), IR (receiving vehicle and surgery), and NIM-IR (receiving NIM-811 and surgery). Serum, urine and histological samples were taken at the end of reperfusion. NADH-tetrazolium staining, muscle Wet/Dry (W/D) ratio calculations, laser Doppler-flowmetry (LDF) and mean arterial pressure (MAP) monitoring were performed. Renal peroxynitrite concentration, serum TNF-α and IL-6 levels were measured.

Results: Less significant histopathological changes were observable in the NIM-IR group as compared with the IR group. Serum K+ and necroenzyme levels were significantly lower in the NIM-IR group than in the IR group (LDH: p<0.001; CK: p<0.001; K+: p = 0.017). Muscle mitochondrial viability proved to be significantly higher (p = 0.001) and renal function parameters were significantly better (creatinine: p = 0.016; FENa: p<0.001) in the NIM-IR group in comparison to the IR group. Serum TNF-α and IL-6 levels were significantly lower (TNF-α: p = 0.003, IL-6: p = 0.040) as well as W/D ratio and peroxynitrite concentration were significantly lower (p = 0.014; p<0.001) in the NIM-IR group than in the IR group.

Conclusion: NIM-811 could have the potential of reducing rhabdomyolysis and impairment of the kidney after lower limb IR injury.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101067PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072765PMC
October 2015

Impaired intestinal mucosal barrier upon ischemia-reperfusion: "patching holes in the shield with a simple surgical method".

Biomed Res Int 2014 14;2014:210901. Epub 2014 May 14.

1st Department of Surgery, Semmelweis University, Ulloi Street 78, Budapest 1082, Hungary.

Unlabelled: Mesenteric ischemia-reperfusion (IR) is associated with impairment of the gut barrier function and the initiation of a proinflammatory cascade with life-threatening results. Therefore methods directed to ameliorate IR injury are of great importance. We aimed at describing the effects of postconditioning (PC) on the alterations of the intestinal mucosal function and the inflammatory response upon mesenteric IR.

Methods: Male Wistar rats were gavaged with green fluorescent protein-expressing E. coli suspensions. Animals were randomized into three groups (n = 15), sham-operated, IR-, and PC-groups, and underwent 60 minutes of superior mesenteric artery occlusion, followed by 6 hours of reperfusion. Postconditioning was performed at the onset of reperfusion. Blood and tissue samples were taken at the end of reperfusion, for histological, bacteriological, and plasma examinations.

Results: The PC-group presented a more favorable claudin-2, claudin-3, claudin-4, and zonula occludens-1 membrane expression profile, and significantly lower rates of bacterial translocation to distant organs and plasma D-lactate levels compared to the IR-group. Histopathological lesions, plasma I-FABP, IL-6, and TNF- α levels were significantly lower in the PC-group compared to the IR-group.

Conclusion: The use of postconditioning improved the integrity of the intestinal mucosal barrier upon mesenteric IR, and thus reduced the incidence of bacterial translocation and development of a systemic inflammatory response.
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http://dx.doi.org/10.1155/2014/210901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053295PMC
February 2015

Postconditioning protects skeletal muscle against a long-lasting vascular occlusion.

J Invest Surg 2014 Oct 15;27(5):282-90. Epub 2014 May 15.

11st Department of Surgery, Semmelweis University, Budapest, Hungary.

Purpose/aim Of The Study: Long-lasting lower limb arterial occlusion is a condition with high incidence and complication rates. With the absence of appropriate treatment to cure advanced complications, mortality rates are high. Postconditioning (PC) might be capable of limiting the degree of ischemic-reperfusion (IR) injuries, thus reducing complications and mortality rates. The aim of this study was to evaluate the impact of postconditioning during the first postoperative day on skeletal muscle after a long-lasting arterial occlusion.

Materials And Methods: Male Wistar rats (n = 72) underwent 8 hr of infrarenal aortic occlusion followed by 2, 6, 12, or 24 hr of reperfusion. In one group of each reperfusion period, postconditioning was applied. Muscle samples were collected for histological examinations. Furthermore, muscle fiber viability and muscle wet-to-dry ratio were assessed. Blood samples were taken for creatine-kinase measurements.

Results: Postconditioning strongly reduced morphological injury compared to the corresponding ischemic-reperfusion group (p < .001). Serum creatine-kinase levels showed a peak at 6 hr post-ischemia (IR: 6702.2 ± 797.5; PC: 5523.3 ± 769.3 IU/l) and decreased to normal level by the end of the experiment (Sham: 171.5 ± 71.6; IR: 186.2 ± 82.7; PC: 174.2 ± 72.4 IU/l). Creatine-kinase levels were significantly reduced by postconditioning (p2hr = .028; p6hr = .06; p12hr = .042). A marked decrease in viability was observed in the ischemic-reperfusion groups (2 hr: 11.0 ± 4.1; 6 hr: 10.3 ± 3.6; 12 hr: 9.4 ± 3.3; 24 hr: 8.6 ± 2.8%), whereas with postconditioning, viability was preserved (2 hr: 26.4 ± 5.5; 6 hr: 24.6 ± 4.5; 12 hr: 24.5 ± 6.8; 24 hr: 26.2 ± 6.1%; p < .001); moreover, a significant decrease in the wet-to-dry ratio was achieved (p < .001).

Conclusion: Postconditioning was able to reduce local complications after a long-lasting lower limb vascular occlusion.
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http://dx.doi.org/10.3109/08941939.2014.916367DOI Listing
October 2014

Muscle fiber viability, a novel method for the fast detection of ischemic muscle injury in rats.

PLoS One 2014 13;9(1):e84783. Epub 2014 Jan 13.

1st Department of Surgery, Semmelweis University, Budapest, Hungary.

Acute lower extremity ischemia is a limb- and life-threatening clinical problem. Rapid detection of the degree of injury is crucial, however at present there are no exact diagnostic tests available to achieve this purpose. Our goal was to examine a novel technique - which has the potential to accurately assess the degree of ischemic muscle injury within a short period of time - in a clinically relevant rodent model. Male Wistar rats were exposed to 4, 6, 8 and 9 hours of bilateral lower limb ischemia induced by the occlusion of the infrarenal aorta. Additional animals underwent 8 and 9 hours of ischemia followed by 2 hours of reperfusion to examine the effects of revascularization. Muscle samples were collected from the left anterior tibial muscle for viability assessment. The degree of muscle damage (muscle fiber viability) was assessed by morphometric evaluation of NADH-tetrazolium reductase reaction on frozen sections. Right hind limbs were perfusion-fixed with paraformaldehyde and glutaraldehyde for light and electron microscopic examinations. Muscle fiber viability decreased progressively over the time of ischemia, with significant differences found between the consecutive times. High correlation was detected between the length of ischemia and the values of muscle fiber viability. After reperfusion, viability showed significant reduction in the 8-hour-ischemia and 2-hour-reperfusion group compared to the 8-hour-ischemia-only group, and decreased further after 9 hours of ischemia and 2 hours of reperfusion. Light- and electron microscopic findings correlated strongly with the values of muscle fiber viability: lesser viability values represented higher degree of ultrastructural injury while similar viability results corresponded to similar morphological injury. Muscle fiber viability was capable of accurately determining the degree of muscle injury in our rat model. Our method might therefore be useful in clinical settings in the diagnostics of acute ischemic muscle injury.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084783PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890280PMC
September 2014

Collateral circulation of the rat lower limb and its significance in ischemia-reperfusion studies.

Surg Today 2014 Dec 29;44(12):2345-53. Epub 2013 Dec 29.

1st Department of Surgery, Semmelweis University, 78 Ulloi Street, Budapest, 1082, Hungary,

Purpose: Rats are the most commonly used animal model for studies of acute lower limb ischemia-reperfusion. The ischemia induced by arterial clamping may cause milder damage than the application of a tourniquet if the presence of a possible collateral system is considered.

Methods: Male Wistar rats were randomized into three groups: in group A, the muscle weight affected by ischemia was measured; in group B, the severity of muscle damage caused by the application of a tourniquet and by infrarenal aortic occlusion was examined. Blood and muscle samples were taken from group B to assess the serum necroenzyme, potassium and TNF-α levels, as well as the muscle fiber viability and for histological examinations. In group C, the identification of the lower limb collateral system was performed using corrosion casting.

Results: Tourniquet application affected the lower muscle mass and resulted in significantly more severe injury compared to infrarenal aortic occlusion. This difference was reflected in the serum necroenzyme, potassium and TNF-α levels. The histological examination and viability assay confirmed these findings. The corrosion casts showed several anastomoses capable of supplying the lower limb.

Conclusion: Tourniquet application proved to be capable of inducing absolute lower limb ischemia, in contrast to infrarenal aortic ligation, where a rich collateral system is considered to help mitigate the injury.
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http://dx.doi.org/10.1007/s00595-013-0822-zDOI Listing
December 2014

Postconditioning of the small intestine: which is the most effective algorithm in a rat model?

J Surg Res 2014 Apr 21;187(2):427-37. Epub 2013 Oct 21.

1st Department of Surgery, Semmelweis University, Budapest, Hungary.

Background: Mesenteric ischemia is a serious clinical condition requiring immediate surgical intervention. The unavoidable ischemic-reperfusion (IR) injury may be ameliorated using the appropriate postconditioning protocol. The aim of the present study was to investigate the optimal postconditioning algorithm in a rat model of intestinal ischemic-reperfusion injury.

Materials And Methods: Male Wistar rats were randomized into five groups (n = 10), one sham-operated, one IR, and three postconditioned groups, each with different protocols. The animals were subjected to 60 min of mesenteric ischemia, followed by 60 min of reperfusion. Postconditioning was applied at the onset of reperfusion using three different algorithms. Arterial pressure and mucosal microcirculation were monitored throughout the experiment. Mesenteric pH was determined at the early phase of reperfusion. Blood and tissue samples were taken at the end of reperfusion for histologic evaluation, serum lactate dehydrogenase, serum creatine kinase, serum tumor necrosis factor-α, serum interleukin-6, detailed mucosal antioxidant, and scavenger capacity assays.

Results: The shorter and intermediate length cycles of postconditioning enhanced mucosal microcirculation and redox state and significantly delayed the normalization of mesenteric pH. Furthermore, milder histopathologic lesions and lower concentrations of serum necroenzymes and proinflammatory cytokines were detected compared with the IR group. The protective effect of postconditioning using longer cycles could only be seen in a tendentious manner.

Conclusions: In a rat model of intestinal ischemia-reperfusion, the shorter and intermediate length cycles of postconditioning proved to be more effective than the use of longer cycles.
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http://dx.doi.org/10.1016/j.jss.2013.10.035DOI Listing
April 2014

Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?

PLoS One 2013 11;8(9):e73758. Epub 2013 Sep 11.

1st Department of Surgery, Semmelweis University, Budapest, Hungary.

Introduction: Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury.

Material And Methods: Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured.

Results: In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (p early = 0.02; p late = 0.005), AST (p early = 0.02; p late = 0.004) and less DNA damage by TUNEL test (p early = 0.05; p late = 0.034) and PAR positivity (p early = 0.02; p late = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment.

Conclusion: Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073758PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770697PMC
July 2014

[Postconditioning can reduce long-term lung injury after lower limb ischemia-reperfusion].

Magy Seb 2013 Jun;66(3):146-54

Semmelweis Egyetem, I. sz. Sebészeti Klinika, 1082 Budapest, Üllői út. 78.

Introduction: Operation on the infrarenal aorta could cause ischemic-reperfusion (IR) injury in local tissues and remote organs (e.g. the lung).

Objectives: Our aim was to reduce long-term lung damage, after lower limb IR with postconditioning.

Materials And Methods: Male Wistar rats underwent 180 minutes of bilateral lower limb ischemia. Animals were divided into three groups: Sham-operated, IR, Postconditioned (PostC) and further to two subgroups according to reperfusion time: 24 h and 72 h. Serum free radical and IL-6 levels, histological changes, Wet/Dry (W/D) ratio, tissue myeloperoxidase (MPO) activity and Hsp72 levels were investigated.

Results: Postconditioning can reduce histological changes in the lung. Free radical levels are significantly lower in PostC groups than in IR groups (42.9 ± 8.0 vs. 6.4 ± 3.4; 27.3 ± 4.4 vs. 8.3 ± 4.0 RLU%; p < 0.05). IL-6 level (238.4 ± 31.1 vs. 209.1 ± 18.8; 190.0 ± 8.8 vs. 187.0 ± 14.9 pg/ml) and Hsp72 expression did not show any significant difference. Compared to the IR group, lung MPO activity did not change in the PostC groups. W/D ratio in PostC groups is significantly lower at all measured time-points (68% vs. 65%; 72% vs. 68%; p < 0.05).

Conclusion: Postconditioning may reduce long-term damages of the lung after lower limb ischemic-reperfusion injury.
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http://dx.doi.org/10.1556/MaSeb.66.2013.3.3DOI Listing
June 2013

Therapeutic option for managing lung injury induced by infrarenal aortic cross-clamping.

J Surg Res 2013 Nov 29;185(1):469-76. Epub 2013 May 29.

1(st) Department of Surgery, Semmelweis University, Budapest, Hungary.

Background: Operations on the infrarenal aorta can cause ischemic-reperfusion (IR) injury in local tissues, which could result in remote organ (e.g., lung) damage. Treatment of such injuries remains an unresolved problem.

Objectives: Our aim was to reduce remote lung damage after lower limb IR by means of postconditioning.

Materials And Methods: Male Wistar rats were divided into three groups: Sham-operated, IR, and Postconditioned (PostC). In the latter two groups rats underwent 180 min of exclusion of the infrarenal aorta. The reperfusion time was 4 h. Serum-free radical levels, tumor necrosis factor-α and interleukin-6 concentrations, histologic changes in the lung, wet/dry-ratio, myeloperoxidase activity, heat shock protein 72 level and blood gas changes were investigated.

Results: Postconditioning reduced histological damage in the lung (P < 0.05). Free radical levels and tumor necrosis factor-α concentrations were significantly lower in the PostC group than in the IR group (P < 0.05 and P < 0.01, respectively). Interleukin-6 concentrations did not significantly differ in the PostC group. Compared with the IR group, lung myeloperoxidase activity was lower in the PostC group. Decreased pulmonary heat shock protein 72 level was observed in the PostC group compared with the IR group and the wet/dry-ratio was also significantly lower in the PostC group (P < 0.05). A noticeably higher arterial pO2 level was manifest in the PostC group after 2 and 4 h of reperfusion (P < 0.05).

Conclusions: Postconditioning reduced lung damage under experimental conditions, in the early period of reperfusion after lower limb IR injury.
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http://dx.doi.org/10.1016/j.jss.2013.05.022DOI Listing
November 2013

[Postconditioning -- effective method against distant organ dysfunction?].

Magy Seb 2012 Aug;65(4):222-9

Semmelweis Egyetem, Általános Orvostudományi Kar I. sz. Sebészeti Klinika 1082 Budapest Üllői út 78.

Introduction: The ischemia-reperfusion injury of the small intestine is a condition of high mortality, which occurs following superior mesenteric artery (SMA) embolization or circulatory redistribution. The aim of the study was to evaluate the local and systemic effects of postconditioning in a rat model of small intestine ischemia-reperfusion.

Methods: Male Wistar rats underwent 60 min ischemia by the clamping of the SMA, followed by 6 hrs of reperfusion. The animals (n = 30) were randomized into three groups: sham-operated, control-, and postconditioned. Postconditioning was performed at the very onset of reperfusion by 6 alternating cycles of 10-10 seconds reperfusion/reocclusion, for a total of 2 min. At the end of the reperfusion blood and tissue (small intestine, lungs, kidney, liver) samples were taken for histological examination. The antioxidant status of small intestine was measured from intestinal homogenates.

Results: Histologic results revealed increased damage in control-group lungs, kidney, liver and small intestine in comparison with the postconditioned group. The injury was supported by significantly higher wet/dry weight ratio (p = 0.026), and serum levels of creatinine (p = 0.013), ASAT (p = 0.038), LDH (p = 0.028) and CK (p = 0.038) in the control group. The postconditioned group showed lower serum IL-6 levels (420 pg/ml vs. 188 pg/ml), as well as significantly higher mucosal antioxidant concentration.

Conclusions: Postconditioning was able to decrease not only local, but the systemic damage intensity also, after a small intestinal ischemic-reperfusion episode.
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http://dx.doi.org/10.1556/MaSeb.65.2012.4.9DOI Listing
August 2012

[Long ischemic period of the lower limb--study of skeletal muscle viability in experimental animal models].

Magy Seb 2010 Dec;63(6):374-9

Semmelweis Egyetem I. sz. Sebészeti Klinika 1082 Budapest Üllői út 78.

Introduction: Surgical treatment for acute limb ischemia is revascularization or - when the limb is in a critical stage - amputation. Correct staging of the disease is relatively difficult, therefore complication and mortality rates are extremely high. Our aim was to invesitigate acute critical ischemia in rats and to test postconditioning on this model.

Methods: Experiment I: male Wistar rats underwent 4, 6, 8 hours of bilateral lower limb ischemia without reperfusion. Experiment II: suspected critical ischemia was followed by 2 hours of reperfusion with or without postconditioning. Histological samples were collected for routine staining and nitroblue-tetrazolium (NBT) enzyme-histochemistry. In Experiment II the microcirculatory changes were measured by laser Doppler flowmetry and blood samples were collected for laboratory testing (kreatin-kinase, CK).

Results: Experiment I: After an eight-hour-obstruction, severe ischemic lesions were detectable, with rutine and NBT stainings, therefore 8 hours of ischemia was chosen for further testing. Experiment II: The CK levels showed significant (p < 0.05) drop, quantitative evaluation of enzyme-histochemisty resulted in significantly (p < 0.001) less viability depletion and microcirculation showed significant (p < 0.05) amelioration of the reperfusion parameters in the postconditioned group compared to the control.

Conclusions: Eight hours of lower limb ischemia is a suitable model to investigate acute critical ischemia in rats. Postconditioning could be a feasible technique to reduce IR injury associated with acute lower limb ischemia.
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http://dx.doi.org/10.1556/MaSeb.63.2010.6.4DOI Listing
December 2010
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