Organprotektion Lab

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Our group in 2007

Anesthetic-induced preconditioning

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 represents 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: volatile anesthetics reduce myocardial infarct size even when they are administered as late as during reperfusion of the occluded vessel (postconditioning).

The intracellular mechanisms underlying APC 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. 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 anesthesiology regime to alleviate cardiovascular mortality and apoplectic insults in the perioperative period.

Members

Head: Dr. Markus Lange

Research Fellows:

• Dr. Thorsten Smul
• Dr. Andreas Redel
• Dr. Christopher Lotz
• Dr. Jan Stumpner
• Christoph Blomeyer

Visiting Research Fellow

• Dr. Feng Gao

MD Students:

• Tobias Tischer-Zeitz
• Johannes Schmidt
• Verena Schnupp
• Anja Frank
• Tobias Nefzger

Technician:

• Katarina Pech

Methods

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

Publications

1. 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 pmid:18580175. PubMed HubMed [Paper1]
2. 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 pmid:18518784. PubMed HubMed [Paper2]
3. 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 pmid:18227289. PubMed HubMed [Paper3]
4. 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 pmid:18156310. PubMed HubMed [Paper4]
5. 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 pmid:17563879. PubMed HubMed [Paper5]
6. 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 pmid:17457146. PubMed HubMed [Paper6]
7. 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 pmid:17242104. PubMed HubMed [Paper7]
8. 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. pmid:17006071. PubMed HubMed [Paper8]
9. 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. pmid:16931983. PubMed HubMed [Paper9]
10. 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 pmid:16766632. PubMed HubMed [Paper10]
11. 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 pmid:16399333. PubMed HubMed [Paper11]
12. 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 pmid:16217658. PubMed HubMed [Paper12]
13. 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 pmid:12457251. PubMed HubMed [Paper13]

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