Dr. Ouafa Hamza wurde für Ihre Arbeiten mit den zweiten Platz der Österreichischen Gesellschaft für Chirurgische Forschung ausgezeichnet.
Wir gratulieren unserer geschätzten Kollegin Frau Dr. Ouafa Hamza für Ihre von der Österreichischen Gesellschaft für Chirurgische Forschung ausgezeichnete Arbeit:
Charecterizazion of a novel closed chest model of ischemic mitral regurgitation in pigs.
Ouafa Hamza, Attila Kiss, Anne-Margarethe Kramer, Sandra Trojanek, Katharina Tillmann, Inês Fonseca Gonçalves, Eylem Acar, Verna Tretter, Klaus Ulrich3, Dietmar Abraham, Bruno K. Podesser
Background: Development of translational animal models of cardiovascular disease is crucial to understand the disease mechanism and pathophysiology and provide a unique platform to test novel therapies and devices. The European heart survey showed that 49% of patients with severe symptomatic mitral regurgitation were denied surgery. This patient population was characterized by one particularly recurrent parameter: Secondary mitral regurgitation. Surgical treatment of secondary mitral regurgitation remains a subject of controversy and still doesn't show a clear impact on the mortality. In addition, there is unmet need to establish less invasive approaches in patients with secondary mitral regurgitation. Aims: therefore, the aim of the present study was to establish a clinically reliable large animal model of mitral valve regurgitation.
Methods and Results: Young female domestic pigs were used for this model establishment (n=12, weight =60 +/- 12kg)). The induction of mitral valve regurgitation was performed by localized posteromedial papillary muscle (PMPM) myocardial infarction. The PMPM irrigating branches are first identified by selectively injecting contrast media in the circumflex branches while performing echocardiography. Then a 2ml of pure Ethanol are injected in the identified branches. The evaluation of the mitral valve regurgitation and cardiac function was assessed by echocardiography. Tissue samples from the papillary muscles and the mitral leaflets were analyzed by RT-qPCR.
Seven pigs survived the 6 weeks follow up period. Ethanol injection resulted in postero-inferior wall and PMPM dyskinesia. Significant left ventricle enlargement was noticed (End diastolic diameter at baseline: 50,04 ± 4.34mm vs at 6 weeks 62,12 ± 3.92mm; p<0.001) as well as left atrium enlargement (left atrium area at baseline: 7.75 ±0.95cm² vs at 6 weeks 17.65 ± 3.2cm²; p<0.001). Mitral regurgitation jet area significantly increased (jet area at baseline 0.03±0.015 cm² vs at 6 weeks 3.22 ± 0.53cm²). A significant tenting area developed over the follow up period (Tenting area at baseline 0.35 ± 0.21cm² vs 2.17 ± 0.63cm² at 6weeks; p<0.001). The posterior leaflet tethering resulted in a marked upregulation of inflammatory biomarkers such as TGFß, MMP9, IL1ß as well as TLR2 and 4.
Conclusion: Our results clearly provided significant evidence about a totally percutaneous clinical relevant model of ischemic mitral valve regurgitation in pigs that could be a platform for new mitral repair devices development and testing. Besides, ischemic mitral regurgitation was associated with a moderate remodeling at the valvular level as a consequence of valvular tethering.
Dr. Maximilian Kreibich wurde mit dem renommierten Helmut Denk Preis ausgezeichnet
Auch heuer konnte der "Helmut Denk Preis 2018" wie schon 2017 von einem Forscher unserer Abteilung eingefahren werden.
Für seine Publikation im Journal of Hypertension mit dem Titel "Tenascin-C promotes chronic pressure overload-induced cardiac dysfunction,
hypertrophy and myocardial fibrosis" erhielt Maximilian Kreibich aus der Arbeitsgruppe Podesser diesen begehrten Preis der Österreichischen Gesellschaft
für Herzchirurgie und Chirurgie der Thorakalen Aorta. Dr. Kreibich war im Rahmen eines Erasmusstipendiumst im ZBF und ist seit 2016 an der Abteilung für Herz- und
Gefäßchirurgie der Universität Freiburg tätig.
Dr. David Santer wurde mit dem renommierten Helmut Denk Preis ausgezeichnet
Wir gratulieren unseren geschätzten Kooperationspartner Herrn Dr. David Santer für seine mit den Helmut Denk Preis ausgezeichnete Arbeit:
In vivo and ex vivo functional characterization of left ventricular remodelling after myocardial infarction in mice
David Santer, Felix Nagel, Maximilian Kreibich, Elda Dzilic, Philipp T. Moser, Gabriela Muschitz, Milat Inci, Martin Krssak, Roberto Plasenzotti, Helga Bergmeister, Karola Trescher and Bruno K. Podesser
Aims: The interest in cardiac remodelling (REM) has steadily increased during recent years. The aim of this study was to functionally characterize REM following myocardial infarction (MI) in mice using high-end in vivo and ex vivo methods.
Methods and Results:Myocardial infarction or sham operation was induced in A/J mice. Six weeks later, mice underwent cardiac magnetic resonance imaging and were subsequently sacrificed for ex vivo measurements on the isolated heart. Thereafter, hearts were trichrome stained for infarction size calculation. Magnetic resonance imaging showed significantly reduced ejection fraction (P < 0.01) as well as increased end-systolic and end-diastolic volumes (P < 0.01) after MI. The mean infarct size was 48.8 ± 6.9% of left ventricle. In the isolated working heart coronary flow (time point 20?: 6.6 ± 0.9 vs. 13.9 ± 1.6 mL/min, P < 0.01), cardiac output (time point 20?: 17.5 ± 2.6 vs. 36.1 ± 4.3 mL/min, P < 0.01) and pump function (80 mmHg: 2.15 ± 0.88 vs. 4.83 ± 0.76, P < 0.05) were significantly attenuated in MI hearts during all measurements. Systolic and diastolic wall stress were significantly elevated in MI animals.
Conclusion: This two-step approach is reasonable, since data quality increases while animals are not exposed to major additional interventions. Both the working heart and magnetic resonance imaging offer a reliable characterization of the functional changes that go along with the development of post-MI REM. By combining these two techniques, additional information such as wall stress can be evaluated.
Urkunde Helmut Denk Preis
Gewinner: 8th Joint Scandinavian Conference of Cardiothoracic Surgery, August 19th, 2016
Wir gratulieren unseren geschätzten Kooperationspartner Herrn Dr. Terje Aass zum C. Walton Lillehei Young Investigator’s Award für seine hervorragende Arbeit:
Myocardial energy status and ultrastructure with polarizing and depolarizing cardioplegic arrest in a porcine model
Terje Aass, Lodve Stangeland, David J. Chambers, Seth Hallström, Christine Rossmann, Bruno K. Podesser, Malte Urban, Knut Nesheim, Rune Haaverstad, Knut Matre and Ketil Grong
Background: Depolarizing St. Thomas´ Hospital cardioplegic solution No 2 (STH-2) administered as cold, repeated, oxygenated blood is considered as the optimal mode of protection during cardiac surgery. The novel St. Thomas´ Hospital polarizing cardioplegic solution (STH-POL) with esmolol/adenosine/magnesium offers comparable myocardial protection  and may further reduce demands for high-energy phosphates.
Methods: Twenty pigs on tepid cardiopulmonary bypass (CPB) were randomized to cardiac arrest for 60 min with antegrade freshly mixed, cold, oxygenated STH-POL or STH-2 blood cardioplegia every 20 min. Haemodynamic variables were recorded continuously and left ventricular biopsies, snap-frozen in liquid nitrogen, were obtained at baseline, 58 min after X-clamp and 20 and 180 min after weaning from CPB. Tissue levels of adenine nucleotides were evaluated by high-performance liquid chromatography, ultrastructure with morphometry.
Results: With polarizing cardioplegia tissue levels of creatine phosphate were increased compared to STH-2 cardioplegia both at 58 min of X-clamp, 59.9±6.4 (SEM) vs. 44.5±7.4 nmol/mg protein (p<0.025), and at 20 min after reperfusion, 61.0±6.7 vs. 49.0±5.5 nmol/mg protein (p<0.05). Tissue levels of ATP was increased at 20 min of reperfusion in the STH-POL group, 35.4±1.1 vs. 32.4±1.2 nmol/mg protein (p<0.05). Mitochondrial surface-to-volume ratio was slightly decreased in the STH-POL compared to the STH-2 group at 20 min after reperfusion (6.74±0.14 vs. 7.46±0.13 ?m2/?m3, p=0.047). None of these differences were present at 180 min of reperfusion. From 150 min of reperfusion, however, Cardiac Index was increased with STH-POL cardioplegia.
Conclusion: These results demonstrate an improved energy status with STH-POL cardioplegia compared to the standard potassium-based depolarizing blood cardioplegia during cardioplegic arrest and early after reperfusion.
Reference: Aass T, Stangeland L, Moen CA, Salminen PR, Dahle GO, Chambers DJ, et al. Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass. Eur J Cardiothorac Surg (2016) doi: 10.1093/ejcts/ezv488.
Dr. Terje Aass
Gewinner: Poster Session Cardiovascular Research Days 2016
Characterization of left ventricle function in a relevant experimental model for human rheumatoid arthritis
Ines Fonseca Goncalves, Dr. Silvia Hayer, Milat Inci, Birgit Niederreiter, Tetyana Shvets, Prof. Kurt Redlich, Dr. Attila Kiss, Prof. Bruno Karl Podesser
Background: There is evidence that patients with rheumatoid arthritis (RA) have higher risk for cardiovascular disease as well as developed impaired left ventricle (LV) function. However, the mechanism behind the hemodynamic impairment is not completely understood. It is therefore an unmet need to characterize LV function in a relevant experimental model which ultimately give opportunity to develop treatment strategies that improve LV function in RA.
Aim: The present study was aimed to characterize LV function as well as inflammatory cytokines and chemokines in LV tissue
samples in a TNF-driven inflammatory, erosive arthritis mouse model.
Methods: Anaesthetized and intubated male and female human TNF-alpha transgenic (hTNFg; n=7 in
both sex) and their wild type littermates mice (n=7 in both sex) with age of 14-15 weeks were used.
Hemodynamic function was evaluated by insert the catheter tip retrograde into LV. The mRNA levels
of Interleukin 6 (IL-6), Interleukin-1? (IL-1?), Monocyte Chemoattractant Protein 1 (MCP-1),
Macrophage Inflammatory Protein 2 (MIP2), Neutrophil Chemokine (KC) in LV samples were
determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results:
hTNFg mice showed severe clinical signs of arthritis such as severe paw swelling and almost
complete loss of grip strength at week 14. In comparison to WT littermates, hTNFg mice significantly
showed smaller body weight and heart weight (P<0.01, respectively). LV systolic pressure (hTNFg;
male: 71±16; female: 69±8 vs. WT; male: 98±18; female: 89±16 in mmHg) and the rate of LV pressure
rise (+dP/dt; hTNFg; male: 5335±1287; female: 4109±910 vs. WT; male: 6816±567; female:
5822±1288 in mmHg/s) was markedly decline in hTNFg mice in comparison with WT littermates.
There was a tendency in increase of left ventricle end-diastolic pressure and -dP/dt in hTNFg mice.
However, there were no difference in mRNA expression of IL-6, IL-1? and MIP2 in heart tissue
between the groups. In contrast relatives mRNA expression of MCP-1 (WT vs. hTNFg; male: 1.02 ±
0.21 vs. 1.65±0.5; female: 1.44±0.38 vs. 2.38±0.43; P<0.05) and KC (WT vs. hTNFg; male: 1.05±0.3
vs. 2.60±0.81; females: 1.39±0.53 vs. 2.09±0.3 P<0.05) were significantly increased in hTNFg mice.
Conclusion: This is the first study to demonstrate that TNFg mice showed significant impairment in LV
systolic function in association with increase in tissue levels of MCP-1 and KC.
Winners of the Posterpresentations: Bruno Podesser (l), Ines Fonseca Goncalves (r)