Organprotektion Lab

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Our group in 2007

Anesthetic-induced preconditioning and postconditioning

Volatile anesthetics not only induce anesthesia, but also render organs resistant against ischemic damage. For example, the magnitude of an experimentally induced myocardial infarct size can be reduced by more than 50% by the administration of volatile anesthetics, even if the administration has been discontinued prior to the ischemic injury (anesthetic-induced preconditioning, APC). These protective effects are also effective in other organ systems; e.g. the brain. APC is as effective as ischemic preconditioning and thus represent one of the most potent therapeutic strategies of infarct size reduction. Surgery-related temporary ischemia of the heart or the brain can be prevented using APC in the perioperative period.

However, infarct sparing therapies can often only be applied after the patient’s admission to the hospital. Even in this situation the patient can benefit from the application of volatile anesthetics.Recently, it has been described that volatile anesthetics also exert cardioprotective properties when administered after the ischemic injury (anesthetic-induced postconditioning, APOST). This might be of enormous therapeutical implications since myocardial ischemia is often unpredictable.

The intracellular mechanisms underlying APC and APOST are under intense investigation. The projects performed by our group aim to identify triggers, mediators and end-effectors of anesthetic-induced pre- and postconditioning and to characterize their complex intracellular interaction. Particularly, we focuse on ß1- and ß2-adrenergic receptors and their downstream targets. Given the large incidence of perioperative cardiovascular morbidity and mortality and the incidence of myocardial and cerebral infarction, the results of these projects are of high clinical relevance and might provide a better understanding of the cardioprotective properties of volatile anesthetics. They might help to choose the appropriate and protective anaesthesia regime to alleviate cardiovascular mortality and apoplectic insults in the perioperative period.

Members

Head: PD Dr. Markus Lange

Research Fellows:

• Dr. Thorsten Smul
• Dr. Christopher Lotz (currently at UC Los Angeles, USA)
• Dr. Jan Stumpner
• Dr. Christoph Blomeyer (currently at Medical College of Wisconsin, Milwaukee, USA)
• Tobias Tischer-Zeitz
• Dr. Sonja Maisch
• Anja Frank

External Collaborator

• Dr. Andreas Redel, Department of Anesthesiology, Hospital of the University of Regensburg

MD Students:

• Tobias Nefzger
• Tobias Tischer-Zeitz
• Johannes Schmidt
• Verena Schnupp
• Anja Frank
• Joanna Pociej
• Anna Kellermann
• Nadyia Virstyuk
• Johannes Richl
• Teresa Hilz
• Andreas Beck
• Andreas Neuwirth
• Julia Umminger
• Ulrike Kolar

Technician:

• Katerina Pech

Methods

• in vivo model of acute myocardial infarction in two rodent species
• Western Blot
• PCR
• ELISA

Publications

1. Stumpner J, Redel A, Kellermann A, Lotz CA, Blomeyer CA, Smul TM, Kehl F, Roewer N, and Lange M. Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction. Anesthesiology. 2009 Dec;111(6):1257-64. DOI:10.1097/ALN.0b013e3181bdf9f4 |
2. Redel A, Stumpner J, Tischer-Zeitz T, Lange M, Smul TM, Lotz C, Roewer N, and Kehl F. Comparison of isoflurane-, sevoflurane-, and desflurane-induced pre- and postconditioning against myocardial infarction in mice in vivo. Exp Biol Med (Maywood). 2009 Oct;234(10):1186-91. DOI:10.3181/0902-RM-58 |
3. Smul TM, Redel A, Stumpner J, Lange M, Lotz C, Roewer N, and Kehl F. Time course of desflurane-induced preconditioning in rabbits. J Cardiothorac Vasc Anesth. 2010 Feb;24(1):91-8. DOI:10.1053/j.jvca.2009.03.006 |
4. Lange M, Redel A, Smul TM, Lotz C, Nefzger T, Stumpner J, Blomeyer C, Gao F, Roewer N, and Kehl F. Desflurane-induced preconditioning has a threshold that is lowered by repetitive application and is mediated by beta 2-adrenergic receptors. J Cardiothorac Vasc Anesth. 2009 Oct;23(5):607-13. DOI:10.1053/j.jvca.2009.01.016 |
5. Smul TM, Lange M, Redel A, Stumpner J, Lotz CA, Roewer N, and Kehl F. Desflurane-induced cardioprotection against ischemia-reperfusion injury depends on timing. J Cardiothorac Vasc Anesth. 2009 Oct;23(5):600-6. DOI:10.1053/j.jvca.2008.11.004 |
6. Lange M, Redel A, Lotz C, Smul TM, Blomeyer C, Frank A, Stumpner J, Roewer N, and Kehl F. Desflurane-induced postconditioning is mediated by beta-adrenergic signaling: role of beta 1- and beta 2-adrenergic receptors, protein kinase A, and calcium/calmodulin-dependent protein kinase II. Anesthesiology. 2009 Mar;110(3):516-28. DOI:10.1097/ALN.0b013e318197ff62 |
7. Lange M, Smul TM, Redel A, Lotz C, Jazbutyte V, Schnupp V, Roewer N, and Kehl F. Differential role of calcium/calmodulin-dependent protein kinase II in desflurane-induced preconditioning and cardioprotection by metoprolol: metoprolol blocks desflurane-induced preconditioning. Anesthesiology. 2008 Jul;109(1):72-80. DOI:10.1097/ALN.0b013e31817be96c |
8. Kranke P, Redel A, Schuster F, Muellenbach R, and Eberhart LH. Pharmacological interventions and concepts of fast-track perioperative medical care for enhanced recovery programs. Expert Opin Pharmacother. 2008 Jun;9(9):1541-64. DOI:10.1517/14656566.9.9.1541 |
9. Redel A, Lange M, Jazbutyte V, Lotz C, Smul TM, Roewer N, and Kehl F. Activation of mitochondrial large-conductance calcium-activated K+ channels via protein kinase A mediates desflurane-induced preconditioning. Anesth Analg. 2008 Feb;106(2):384-91, table of contents. DOI:10.1213/ane.0b013e318160650f |
10. Redel A, Jazbutyte V, Smul TM, Lange M, Eckle T, Eltzschig H, Roewer N, and Kehl F. Impact of ischemia and reperfusion times on myocardial infarct size in mice in vivo. Exp Biol Med (Maywood). 2008 Jan;233(1):84-93. DOI:10.3181/0612-RM-308 |
11. Muellenbach RM, Kredel M, Said HM, Klosterhalfen B, Zollhoefer B, Wunder C, Redel A, Schmidt M, Roewer N, and Brederlau J. High-frequency oscillatory ventilation reduces lung inflammation: a large-animal 24-h model of respiratory distress. Intensive Care Med. 2007 Aug;33(8):1423-33. DOI:10.1007/s00134-007-0708-x |
12. Lange M, Redel A, Roewer N, and Kehl F. beta-Blockade Abolishes Anesthetic Preconditioning: Impact on Clinical Applicability. Anesthesiology. 2007 May;106(5):1062. DOI:10.1097/01.anes.0000265173.82995.e6 |
13. Lange M, Smul T, Zimmermann P, Kohlenberger R, Roewer N, and Kehl F. The effectiveness and patient comfort of the novel streamlined pharynx airway liner (SLIPA) compared with the conventional laryngeal mask airway in ophthalmic surgery. Anesth Analg. 2007 Feb;104(2):431-4. DOI:10.1213/01.ane.0000252460.94046.7c |
14. Smul TM, Lange M, Redel A, Burkhard N, Roewer N, and Kehl F. Desflurane-induced preconditioning against myocardial infarction is mediated by nitric oxide. Anesthesiology. 2006 Oct;105(4):719-25. DOI:10.1097/00000542-200610000-00018 |
15. Lange M, Smul TM, Blomeyer CA, Redel A, Klotz KN, Roewer N, and Kehl F. Role of the beta1-adrenergic pathway in anesthetic and ischemic preconditioning against myocardial infarction in the rabbit heart in vivo. Anesthesiology. 2006 Sep;105(3):503-10. DOI:10.1097/00000542-200609000-00014 |
16. Eckle T, Grenz A, Köhler D, Redel A, Falk M, Rolauffs B, Osswald H, Kehl F, and Eltzschig HK. Systematic evaluation of a novel model for cardiac ischemic preconditioning in mice. Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2533-40. DOI:10.1152/ajpheart.00472.2006 |
17. Lange M, Roewer N, and Kehl F. Anesthetic preconditioning as the alternative to ischemic preconditioning. J Thorac Cardiovasc Surg. 2006 Jan;131(1):252-3; author reply 253. DOI:10.1016/j.jtcvs.2005.09.002 |
18. Golenhofen N, Redel A, Wawrousek EF, and Drenckhahn D. Ischemia-induced increase of stiffness of alphaB-crystallin/HSPB2-deficient myocardium. Pflugers Arch. 2006 Jan;451(4):518-25. DOI:10.1007/s00424-005-1488-1 |
19. Redel A, Baumgartner W, Golenhofen K, Drenckhahn D, and Golenhofen N. Mechanical activity and force-frequency relationship of isolated mouse papillary muscle: effects of extracellular calcium concentration, temperature and contraction type. Pflugers Arch. 2002 Nov;445(2):297-304. DOI:10.1007/s00424-002-0931-9 |

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