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In 1990, the II. Department of Surgery (today Department of Cardiothoracic Surgery, AKH Wien, Universitaet Wien) decided to set up an isolated heart model. Until 1991 the money was raised and a postdoc, Bruno Podesser, was sent to the laboratory of Prof. Pierce at the Milton Hershey Medical School at Penn State University to learn how to hang hearts.

After two months Dr. Podesser returned to Vienna and set up the experimental equipment, that had been shipped before, at the newly founded Center for Biomedical Research. The experimental goal was to study ischemia-reperfusion with respect to intraoperative myocardial protection. The first painful steps were performed without the expected success. Therefore Dr. Podesser looked for other researches in Vienna that had experience with the isolated heart preparation. Prof. Rahberger from the Department of Pharmacology was one of them.
He became the major sparing partner during the first two years and laid the grounds for the first methodical publication. Prof. Schlag and Dr. Hallstroem from the Ludwig Boltzmann Institute of experimental and clinical Traumatology were another group of researchers, with whom a co-operation was build up, which is still ongoing.

However, the most important step towards success was the acquisition of a second fellow for the lab, Martin Zegner, who by that time had almost finished medical school. Both, Bruno Podesser and Martin Zegner knew each other from the Department of Anatomy, where they worked as tutors in the afternoons. Together they were able to standardize the procedures
and establish the so-called good laboratory practice under the guidance of Prof. Rahberger.
This was only feasible because of the excellent staff and conditions that were provided by the Center of Biomedical Research (Prof. Losert).

After the first publications and abstracts had been accepted, a further fellow was searched. Out of 20 applicants Gerda Koci was chosen and stayed for the next couple of years in the lab.

In a first attempt the cardioprotective efficacy of oxygenated crystalloid cardioplegic solutions was evaluated. The next group of publications dealed with the possible advantage of brief infusions of phosphodiestease-inhibitors in the setting of ischemia-reperfusion.
So far the experiments had all been performed with crystalloid perfusion buffers. But with increasing interest in the early reperfusion period it became evident, that only a perfusion fluid containing red blood cells would be close enough to physiologic conditions to study the changes after ischemia. According to a paper by Eberli and Apstein the perfusion apparatus was adopted. A light barrier-controlled hose pump was introduced, the volumes of the tubes had to be minimized and a special oxygenator was inserted into the circuit. Initially blood from donor rabbits was used, centrifuged and diluted. However, it became quickly evident, that this would be very costly due to exorbitant numbers of animals.

Again, alternatives were found in the paper of Eberli, where bovine blood that was collected from the local slaughterhouse and washed several times. The method was adopted, using the good connections to the veterinarians.


Ever since then the youngest fellow prepares the red blood cell concentrates from freshly collected cow blood once a week. The adaptation of the apparatus took almost a year. During this time a fellow from Germany, Jutta Weisser, was working in the laboratory.
It became her job to describe the changes of the model in detail in her thesis, the first thesis ever written in the laboratory.

A publication describing the new erythrocyte-perfused model followed, while other members of the laboratory focused on the anatomy of the coronary arteries in the rabbit. This seemed to be necessary because data from literature were sparse, but a detailed anatomical picture should be important for further studies of temporary and permanent occlusion. In parallel a new protocol, diltiazem administered during reperfusion only, was started, another fellow from Germany, Alexander Kunold, should write his thesis. The period was characterized by a close collaboration between the biochemists (Dr. Hallstroem) and new collaborations including the Department of Histology II (Prof. Mallinger, Dr. Schmiedberger), where biopsies were analyzed by electron microscopy.


Finally Dr. Podesser successfully organized a symposium on ischemia-reperfusion along with the common meeting of cardiothoracic surgeons from Germany, Austria and Switzerland.

From summer 1996 until fall 1997, Dr. Podesser left Vienna and went to the Cardiac Muscle Research Laboratory at Boston University, USA. The laboratory was lead by Prof. Apstein and Dr. Eberli. The goal of this research year was to learn new technologies. Besides perfusing hearts, Dr. Podesser got to know an infarct model in the rat and rabbit, and some basics in molecular biology at Prof. Colucci's lab. Most importantly he had the chance to learn about the organization of a research laboratory. In Vienna, in the meanwhile Dr. Zegner and Dr. Koci continued to work with rabbit hearts.

After his return, Dr. Podesser took over the laboratory again. The new technologies were quickly implemented: the fellows were instructed to the infarct models, the still existing collaborations were refreshed and new for molecular biology established. For the first time the animals investigated on the isolated heart had conditions that were similar to patients. New fellows came to the lab, Andy Kroener, Jan Schirnhofer and another fellow from Germany, Peter Korn.
The new organizational concept gave every fellow his own experimental study, according to priority the fellows collaborate.


Andy Kroener and Jan Schirnhofer were trained well, so when Dr. Koci and Dr. Zegner left the laboratory neither the standards nor the output of the lab decreased. With this highly motivated group of fellows a new protocol was started, ACE-inhibitors during ischemia and reperfusion, studied on normal and failing myocardium. P. Korn has finished his thesis on the normal myocardium, J. Schirnhofer his on the failing heart protocol.

Dr. Podessers clinical career involved him in the transplant program of the department. This opened a wide field of research with respect to ischemia and reperfusion injury. Therefore two new animal model had to be established, a transplant model in the pig and a model of brief warm ischemia. Strategies to increase the ischemic period tolerated by the explanted heart are currently under investigation, new drugs such as NO-donors and endothelin-receptor blockers were tested. The studies on NO-doners became the background for the theses of Max Franz and Severin Semsroth.


In 2001 Dr. Podesser became Associate Professor of Surgery at the Medical University of Vienna and Attending Surgeon at the Landesklinikum St. Pölten, Lower Austria.

 In 2002 Prof. Wolner asked him to take over the position of Scientific Coordinator of the Ludwig Boltzmann Institute of Cardiosurgical Research. This job involved all preclinical programs at the Department of Cardiothoracic Surgery, Medical University of Vienna.

 

Ludwig Boltzmann Cluster for Cardiovascular Research:

First period 2006-08:

 

In 2005 Dr. Podesser convinced Professor Wolner that only a cluster of scientifically related institutes can survive in the more competitive scientific community. Together with the Department of Internal Medicine II (Prof. G. Maurer) and the 3rd  Department of Internal Medicine at the Wilhelminen Spital (Prof. K. Huber) the Cluster for Cardiovascular Research was formed. Between 2006-2008, Dr. Podesser became the first coordinator and one of the 6 PIs of the cluster. His area of research was cardiac function and remodeling with a special focus on gender differences. The postdocs Wolfgang Dietl and Michael Bauer focused in their theses on gender differences in postMI remodeling.

 

The Cardiovascular Research Days

In 2006 Dr. Podesser founded an annual and later biannual platform, the Cardiovascular Research Days, where young scientists present their work in front of international experts in the field of cardiovascular medicine. So far Dr. Podesser and his team have organized this meeting 5 times under the patronage of the Societies of Cardiothoracic Surgery and Cardiology of Austria, Germany, Switzerland, and Italy with participants coming from all over Europe and the US. The best abstracts are selected for the “Carl Apstein” Prize.

 

Visiting Professorship

In 2007 Dr. Podesser went back to Boston to the Cardiac Muscle Research Lab (CMRL) for a 2 months visiting professorship at the Brigham and Women’s Hospital, Harvard Medical School (Prof. J. Loscazo and Prof. L. Cohn), focusing on cell transplantation in a mouse model of infarction. Dr. Liao, who is leading the CMRL, and Dr. Podesser started an exchange program for postdocs and fellows that is still existing and so far has brought students from Vienna to Boston and reverse (Dr. M. Bauer, K. Sereti, A. Iconomopoulos, A. Loscalzo).

 

Ludwig Boltzmann Cluster for Cardiovascular Research

Second period 2009-12

Between 2009 and 2012, the second cluster period had been a very productive period. Dr. Karola Trescher has taken over much of the organisational work in the lab including lab meetings and internal trainings together with Wolfgang Dietl and Michael Bauer. The scientific focus was on postMi remodeling and volume overload. In her PhD thesis Gabriela Pomper together with our technician Christoph Milat Inci established a demanding brain death model in the mouse. This model enables us to test now the effects of brain death on heart function and to study potential protective drugs.

Andrea Baumgartner focused on the effects of NO-supplementation during septic shock in a chronic model in the rat and subsequent evaluation on the isolated heart. Based on the PhD work of Barbara Thometich, who studied the effect of extracellular matrix remodeling with special focus on tenascin C (TNC), we have established a TNC-KO colony of mice. The influence of myocardial infarction in these mice are the PhD theses of David Santer and Felix Nagel. Besides, these mice are also the fundament of an international collaboration with Prof. Zoltan Papp from the University of Debreceen, Hungary. Mathias Hasun worked in his thesis on protection strategies for failing hearts, using the newly developed HTKn46 from Dr. Köhler Chemie, Germany. Maximilian Kreibich and Elda Dzilic have taken over this program and focused more on acute ischemia/reperfusion. In a model of temporary occlusion of the LAD in the rat they currently study the effects of subsequent cardiac arrest, simulation the clinical situation of patients with unstable angina, who cannot be stabilized in the cathlab and need to undergo surgery. The differences of old and young myocardium during ischemia/reperfusion have been the thesis of Krista Adelmann. Her work was taken over by Philipp Moser and is still in progress.

In 2010 we received together with scientists from the University of Vienna (Prof. Th. Erker, Prof. Ch. Studenik and Dr. G. Brunhofer) a research grant from the Austrian Ministry of Industry and Technology (PRIZE PROGRAM). We have patented a newly described group of vasoactive compounds, so-called dithiocarbamide derivatives. In a series of experiments we try to determine optimal concentrations etc. and potential clinical use. This is the work of Joanna Krynicka and Paul Haller.

Finally, in our large animal program, we are studying the effects of a new approach to arrest the heart during cardiac surgery. The gold standard for myocardial protection for over 30 years has been hyperkalemic cardioplegia, inducing depolarized arrest. However, depolarized arrest can lead to ionic imbalance, enhanced energy utilization and ischemia-reperfusion injury. An alternative is to use ‘polarized’ arrest. In this study, the efficacy of the new clinically relevant polarizing cardioplegia, comprising esmolol, adenosine and magnesium in Ringers solution, is compared to conventional hyperkalemic St Thomas’ Hospital solution in pigs subjected to cardiopulmonary bypass and global ischemia-reperfusion. We perform these experiments in collaboration with the St. Thomas’ Hospital, King’s College London (Dr. D. Chambers) and we are especially happy and proud to do these experiments in Vienna because we are one of the few locations in Europe that are still able to do these experiments in terms of equipment and human resources.

 The long-lasting collaboration with Dr. Chambers also has been the base for a recent book that we both edited and published in 2011. It gives an overview of past and current work in myocardial protection and presents an outlook.

 

Ludwig Boltzmann Cluster for Cardiovascular Research

Third period 2013-16

For the next 4 years the group will continue to work on animal models of ischemia/reperfusion, brain death and heart failure in vivo and ex vivo. Thereby above mentioned programs will be continued and/or finalized. One of the new programs started is in collaboration with EATON Inc, a global industry that focuses on power supply and safety. The fibrillation threshold of mammalian hearts is addressed in this program. Thresholds become more and more clinically relevant because modern devices such as elevators use kHz frequencies. So far the effect of this range of frequency has not been evaluated systematically.

 

 

Last Updated ( Mittwoch, 27 Februar 2013 )