Francis Fontan Prize Report of Dr. György Lang

Fellowship period 11/2004 – 2/2006   1. Clinical   Place:        Dept. of Cardiothoracic Surgery,                 University of Vienna, Austria Position:    Consultant Thoracic Surgeon Tutors:      W. Klepetko, W. Wisser, S. Taghavi

  

New experience:

1.      Human lung and heart-lung transplantation

2.      Experimental lung transplantation in a large animal model

3.      ECMO (central and peripheral cannulation, prolonged pre- and postoperative management)

4.      Clamshell, Hemi-Clamshell and Inverse-T thoracotomy

5.      Extended surgical procedures in thoracic malignancies

6.      Oesophageal surgery

7.      Rigid bronchoscopy, interventional bronchoscopy and stenting procedures

8.      Tracheobronchial resection and reconstruction

 

2. Research

 

Place:        Center of Biophysical Research, University of Vienna, Austria

       Dept. of Thoracic Surgery, Catholic University Leuven, Belgium

Position:     First Investigator

Tutors:       W. Klepetko, W. Wisser, D. van Raemdonck

 

Summary of research (Planned submission to 21st EACTS Annual Meeting in Geneva):

 

Prolonged veno-arterial ECMO after transplantation restores function of severely injured lung grafts in a pig model

 

György Lang MD, Clemens Aigner MD, Günther Winkler MD, Freddy Neurath MD, Keso Shkirdladze MD, Wilfried Wisser MD, Ernst Wolner MD, Dirk Van Raemdonck MD, and Walter Klepetko MD

 

Objective

Veno-arterial ECMO (vaECMO) support during transplantation prolonged into the early postoperative period provides reduction of pulmonary artery flow and allows for protective ventilation. This approach might have the potential to restore function of lung allografts which would otherwise be unsuitable for transplantation.

 

Methods

Isolated left lung transplantation was performed in 16 pairs of size matched pigs.  

In the donor animals, brain death was induced by intrathecal balloon inflation. Organs were harvested 4 hours later and stored for 18 – 24 hours at 4⁰C.

Recipients were divided in 2 groups with group A (n = 8) undergoing transplantation without any cardiopulmonary support followed by ventilation with 10 ml/kg BW tidal volume.

Animals of group B (n = 8) were transplanted on vaECMO, which was prolonged into the postoperative period for 24 hours (ECMO flow set at 50 % of initial cardiac output) and received protective low tidal volume (5 ml/kg BW) ventilation. 

One hour after transplantation the native right lung was functionally excluded in both groups. Graft function was compared between both groups by measuring PaO₂ at FiO₂=1,0 and  mPAP  immediately after exclusion of the contralateral lung (time point 1) and one hour after exclusion of the contralateral lung in group A and 1 hour after discontinuation of ECMO in group B (time point 2). In addition donor lungs were evaluated with regard to wet to dry ratio, lung compliance and histological signs of lung edema. 

 

Results

Animals of both groups were comparable with regard to donor and recipient weight, mean time between brain death and start of harvest, cold ischemic time as well as initial P/F ratio after reperfusion. 4 out of 8 animals in group A did not reach time point 2, all died due to severe, histological proven pulmonary edema. All animals transplanted in group B survived prolonged ECMO support and were successfully weaned from ECMO after 24 hours except one (hemodynamical instability).

 

Results are given in the following table.

 

	PaO2 at FiO2=1,0 (mmHg)		mPAP (mmHg)		w/d ratio		Lung compliance (ml/cmH2O)
Timepoint	1	2	1	2	1	2	1	2
Group A	155±102	96±30	38,4±5,2	45,2±2,7	4,9±0,3	4,8±0,6	16±6	11±1
Group B	150±71	334±60	32±5,6	24,1±4,3	4,6±0,8	4,4±1,3	13±2	16±3
P value	ns	<0,002	ns	<0,001	ns	ns	ns	0,034

 

 

Conclusions

Transplantation on ECMO with prolongation for 24 hours restores functional integrity of severely damaged donor lungs. This approach could help to expand the available donor pool by wider use of marginal donors.

 

3. Summary of new knowledge disseminated in Hungary

 

Invited Lectures hold in Hungary

 

-         A tüdõtranszplantáció magyarországi helyzete. A Semmelweis Egyetem Transzplantációs- és Sebészeti Klinika Továbbképzõ Tanfolyama, 2005. május 27

-         Tüdõátültetés – Donor gondozás. Hungarotransplant Transzplantációs Tanfolyam, Budapest, 29. September 2005

-         A tüdõtranszplantáció magyarországi helyzete. Magyar Tudományos Akadémia Orvosi Osztály ülése, 2006. március 21.

-         Tüdõátültetés. Semmelweis Egyetem Pulmonológiai Klinika Szakorvosi Továbbképzõ Tanfolyam. Budapest, 2006. március 22.

-         Tüdõátültetés – Donor gondozás. Hungarotransplant Transzplantációs Tanfolyam, Budapest, 3. April 2006

-         Tüdõtranszplantáció. Semmelweis Egyetem Mellkassebészeti Tanszéki Csoport Továbbképzõ Tanfolyam, 14. April 2006

 

Book abstracts:

-    Az általános mellkassebészet tankönyve. Semmelweis Kiadó, Budapest, 2006

-    Szervátültetés (in press)

 

Presentations on Congresses/Meetings in Hungary

 

1.      Lang G, Furák J, Oláh Cs, Czebe K, Csekeõ A, Klepetko W. Tüdõtranszplantáció non-heart-beating donorból. MTT VI. Kongresszusa, Szeged, 2004. november 24

2.      Lang G. Magyar betegek tüdõátültetése a Bécsi Egyetem Szív- és Mellkassebészeti Klinikáján. NTTVB és NSZTVB ülése, Budapest, 2005 december 16.

3.      Lang G. Tüdõtranszplantáció – 2005. évi beszámoló. Magyar transzplantációs Társaság Kongresszusa, Lajosmizse, 7-9. Mai 2006

4.      Lang G, Aigner C, Jaksch P, Wisser W, Taghavi S, Czebe K, Klepetko W.Tüdõtranszplantáció során alkalmazott extracorporalis membránoxigenizációval (ECMO) szerzett intézeti tapasztalataink. Magyar Transzplantációs Társaság VIII. Kongresszusa, Zalakaros, 23-25 November 2006 

 

4. Articles and Abstracts / Peer Reviewed Journals

 

1. Lang Gy, Klepetko W. Lung transplantation for end-stage primary pulmonary hypertension. Ann Transplant. 2004;9(3):25-32. Review.
2. Taghavi S, Marta GM, Lang G, Seebacher G, Winkler G, Schmid K, Klepetko W.  Bronchial stump coverage with a pedicled pericardial flap: an effective method for prevention of postpneumonectomy bronchopleural fistula. Ann Thorac Surg. 2005 Jan;79(1):284-8. Review.
3. Aigner C, Winkler G, Jaksch P, Seebacher G, Lang G, Taghavi S, Wisser W, Klepetko W. Extended donor criteria for lung transplantation--a clinical reality. Eur J Cardiothorac Surg. 2005 May;27(5):757-61.
4. Zochbauer-Muller S, Fong KM, Geradts J, Xu X, Seidl S, End-Pfutzenreuter A, Lang G, Heller G, Zielinski CC, Gazdar AF, Minna JD. Expression of the candidate tumor suppressor gene hSRBC is frequently lost in primary lung cancers with and without DNA methylation. Oncogene. 2005 Sep 15;24(41):6249-55.
5. C Aigner, G Winkler, P Jaksch, G Seebacher, G Lang, S Taghavi, W Wisser, W Klepetko Extended donor criteria for lung transplantation – a clinical reality Eur J Cardiothorac Surg. 2005 May;27(5):757-61.
6. K Krenn, W Klepetko, S Taghavi, G Lang, B Schneider, S Aharinejad. Recipient Vascular Endothelial Growth Factor Serum Levels Predict Primary Lung Graft Dysfunction. American Journal of Transplantation 2006;7:1-7
7. CC Bauer, P Jaksch, SW Aberle, H Haber, G Lang, W Klepetko, H Hoffmann, E Puchhammer-Stöckl. Relationship between CMV DNA load in epithelial lining fluid and plasma of lung transplant recipients and analysis of coinfection with EBV and HHV-6 in the lung compartment. J Clin Microbiol, 2006 Dec 6

 

5. Presentations and Abstracts / International

 

1. Lang G, Marta G, Aigner C, Jaksch P, Wisser W, Taghavi S, Klepetko W. The hemodinamically instable lung donor: a case for non-heart beating donation. 12^th Congress of ESOT, Geneva, 15-19 October 2005
2. C Aigner, S Taghavi, G Lang, G Marta, E Wolner, W Klepetko. Hemi-Clamshell and Inverse-T Incision - improved approach for extended tumor resections. 47. Österreichischer Chirurgenkongress, Wien, 15-17 Juni 2006
3. G Marta, G Lang, S Taghavi, W Wisser, W Klepetko. International Cooperation in Lung Transplantation: 5 years of experience with the Austrian-Hungarian Bilateral Agreement. The Vth National Congress Romtransplant, June 28-July 1, 2006, Cluj-Napoca, Romania
4. C Aigner, W Wisser, S Taghavi, G Lang, S Guth, A Abrahim, W Klepetko. Institutional experience with extracorporeal membrane oxygenation in lung transplantation. EACTS, Stockholm, 9-13 September 2006
5. Aigner, S Taghavi, G Lang, G Marta, H Baumgartner, W Klepetko. Haemodynamic complications after pneumonectomy: Reopening of the foramen ovale and atrial inflow obstruction. 11^th International Thoracic Surgery Congress, St. Wolfgang, 5-7 Oktober 2006
6. C Aigner, P Jaksch, S Taghavi, G Lang, A Hoda, W Wisser, W Klepetko. Pulmonary Retransplantation Is It Worth The Effort? A Long Term Analysis Of 46 Cases. Akzeptiert bei ISHLT 2007, San Francisco, 25-28 April 2007
7. C Aigner, W Wisser, S Taghavi, G Lang, W Klepetko. Outcome after lung transplantation with intra- and postoperatively prolonged ECMO support. Submitted to AATS 2007
8. M Korfei; C Ruppert; P Mahavadi, M Koch, P Markart; H Witt; G Lang; W Seeger, T Weaver, A Guenther. Abnormal accumulation of unprocessed surfactant protein (SP)-B and activation of the ER stress pathway in lungs of patients with Idiopathic Pulmonary Fibrosis (IPF) and Non-specific Interstitial Pneumonia (NSIP) Submitted and accepted for  ATS Meeting, San Francisco, 18-23 May 2007 and for the Keystone Meeting, Tahoe City, Mar 11-15,  2007
9. T Nkyimbeng, C Ruppert, G Lang, W Seeger  A Günther. Characterization of matrix metalloproteinase (MMP) expression and activity in the lungs of patients with Idiopathic Pulmonary Fibrosis (IPF). Submitted and accepted for the Keystone Meeting, Tahoe City, Mar 11-15,  2007
10. J Wilhelm, L Fink, RM Bohle, C Ruppert, P Markart, M Königshoff, M Wygrecka, O Amarie, M Hecker, M Korfei, P Mahavadi, G Lang, W Seeger, O Eickelberg, A Guenther. Expression profiling of Idiopathic Pulmonary Fibrosis (IPF) lungs reveals considerable differences in homogenate, septae from fibrotic lung regions, and septae from regular appearing lung regions Submitted and accepted for  ATS Meeting, San Francisco, 18-23 May 2007
11. M Korfei; C Ruppert P Markart; GS Schmitt; G Lang; PW Seeger and Andreas Guenther Proteomics of lung tissue from patients with Idiopathic Pulmonary Fibrosis (IPF) Submitted and accepted for  ATS Meeting, San Francisco, 18-23 May 2007