Cardiovascular Pharmacology

  Prof. Dr. Marcus C. Schaub (MD, PhD)
  Institute of Pharmacology and Toxicology
  Cardiovascular Research
  University of Zurich, Switzerland
  Winterthurerstrasse 190
  CH-8057 ZURICH

  Tel. :    +41 44 362 21 91
  email:  schaub@pharma.uzh.ch

In collaboration with the Dept. of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB, T6G 2G3, Canada

 Prof. Dr. Michael Zaugg (MD) Tel.  +1 780 248 1543 michael.zaugg@ualberta.ca 
 Dr. Eliana Lucchinetti (PhD) Tel.  +1 780 248 1543 lucchine@ualberta.ca  

Further collaborations with

PD Dr. Anna Y. Bogdanova (PhD), Institute of Veterinary Physioloy,
University of Zurich, 8057 Zurich, Switzerland
Tel. +41 44 635 88 11annab@access.uzh.ch
Dr. Fabio Zobi (PhD), Institute of Inorganic Chemistry,
University of Zürich, 8057 Zurich, Switzerland
Tel. +41 44 635 46 23fzobi@aci.uzh.ch

Main Field of Research: Cardioprotection

Cardioprotection by pharmacological and ischemic pre-and post-conditioning

Ischemic and pharmacological (in particular volatile anesthetics) pre- (before a severe ischemic period) and post-conditioning (immediately after a severe ischemic period) afford potent means of salvaging cardiomyocytes from irreversible damage following the ischemia-reperfusion injury. Using live cell microscopy with isolated cardiomyocytes, we evaluate the effects of anesthetics on the signaling pathways and cytoprotective mechanisms of cardiac conditioning. In addition, functional parameters, immunohistochemistry, biochemistry and gene expression and proteomic profiling is being done on isolated hearts in the Langendorff apparatus. We were able to show that post-conditioning with volatile anesthetics enhances the activity of the survival kinase PKB/Akt at the time of reperfusion, thereby preventing mitochondrial permeability transition and reducing infarct size. The cardioprotective effects of volatile versus intravenous anesthetics is also assessed in randomised placebo-controlled clinical studies of patients undergoing elective cardiovascular surgery.

Special Techniques and Equipment

  • Rat and Mouse Langendorff, Live Cell Microscopy
  • Gene Chip Analysis, Cardiomyocyte Cultures
  • Transcriptomic and proteomic analyses

List of Peer reviewed publications

  • Zobi F, Blacque O, Jacobs R, Schaub MC, Bogdanova AY: 17 e- Rhenium dicarbonyl CO-releasing molecules on a cobalamin scaffold for biological application. Dalton Trans 41: 370-378. 2012
  • Schaub MC: Artificial muscle: facts and fiction. Swiss Med Wkly. 19;141:w13319. 2011
  • Zuellig RA, Bornhauser BC, Amstutz R, Constantin B, Schaub MC: Tissue expression and actin binding of a novel N-terminal utrophin isoform. J Biomed Biotech 2011: 904547. 2011
  • Zobi F, Degonda A, Schaub MC, Bogdanova AY: CO releasing properties and cytoprotective effect of cis-trans- [ReII(CO)2Br2L2]n complexes. Inorg Chem 49: 7313-7322. 2010
  • Feng J, Lucchinetti E, Enkavi G, Wang Y, Gehrig P, Roschitzki B, Schaub MC, Tajkhorshid E, Zaugg K, Zaugg M: Tyrosine phosphorylation by Src within the cavity of the adenine nucleotide translocase 1 regulates ADP/ATP exchange in mitochondria. Am J Physiol Cell Physiol 298: C740-C748. 2010
  • Schaub MC, Lucchinetti E, Zaugg M: Genomics, transcriptomics, and proteomics of the ischemic heart. Heart Metab 42: 4-9. 2009
  • Zaugg M, Schaub MC: beta3-Adrenergic receptor subtype signaling in senescent heart. Nitric oxide intoxication or "endogenous" beta blockade for protection? Anesthesiology 109:956-959.2008 
  • Feng J, Zhu M, Schaub MC, Gehrig P, Roschitzki B, Lucchinetti E, Zaugg M: Phosphoproteome analysis of isoflurane-protected heart mitochondria: phosphorylation of adenine nucleotide translocator-1 on Tyr194 regulates mitochondrial function. Cardiovasc Res 80:20-29.2008
  • Samuel JL, Schaub MC, Zaugg M, Mamas M, Dunn WB, Swynghedauw B: Genomics in cardiac metabolism. Cardiovasc Res 79:218-227.2008
  • Feng J, Lucchinetti E, Fischer G, Zhu M, Zaugg K, Schaub MC, Zaugg M: Cardiac remodeling hinders activation of cyclooxygenase-2, diminishing protection by delayed pharmacologic preconditioning: Role of HIF1alpha and CREB. Cardiovasc Res 78:98-107.2008
  • Schaub MC, Heizmann CW: Calcium, troponin, calmodulin, S100 proteins: From myocardial basics to new therapeutic strategies. Biochem Biophys Res Commun 369:247-264.2008
  • Schaub MC, Lucchinetti E, Zaugg M: Genome reprogramming by triggering cardioprotective mechanisms. Basic Applied Myology 17: 151-160. 2007
  • Lucchinetti E, Hofer C, Bestmann L, Hersberger M, Feng J, Zhu M, Furrer L, Schaub MC, Tavakoli R, Genoni M, Zollinger A, Zaugg M: Gene Regulatory Control of Myocardial Energy Metabolism Predicts Postoperative Cardiac Function in Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery: Inhalational versus Intravenous Anesthetics. Anesthesiology 106:444-457.2007
  • Schaub MC, Hefti MA: The PGE2-Stat3 connection in cardiac hypertrophy. Cardiovasc Res 73: 3-5. 2007
  • Cook S, Togni M, Schaub MC, Wenaweser P, Hess OM: High heart rate; a cardiovascular risk factor. Eur Heart J 27:2387-2393.2006
  • Zhu M, Feng J, Lucchinetti E, Fischer G, Xu L, Pedrazzini T, Schaub MC, Zaugg M. Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway. Cardiovasc Res 72:152-62.2006
  • Tokarska-Schlattner M, Zaugg M, Zuppinger C, Wallimann T, Schlattner U: New insights into doxorubicin-induced cardiotoxicity: The critical role of cellular energetics. J Mol Cell Cardiol 41:389-405. 2006
  • Schaub MC. Hefti MA. Zaugg M. Integration of calcium with the signaling network in cardiac myocytes. J Mol Cell Cardiol 41:183-214.2006
  • Dyntar D, Sergeev P, Klisic E, Ambuhl P, Schaub MC, Donath MY: High glucose alters cardiomyocyte contacts and inhibits myofibrillar formation. J Clin Endocr Metab 91:1961-1967.2006
  • Feng J, Fischer G, Lucchinetti E, Zhu M, Bestmann L, Jegger D, Arras M, Pasch T, Perriard JC, Schaub MC, Zaugg M: Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of Akt/PKB signaling. Anesthesiology 104:1004-1014.2006
  • Lucchinetti E, Feng J, da Silva R, Tolstonog GV, Schaub MC, Schumann GG, Zaugg M: Inhibition of LINE-1 Expression in the Heart Decreases Ischemic Damage by Activation of Akt/PKB Signaling. Physiol Genomics 25:314-324.2006
  • Lucchinetti E, da Silva R, Pasch T, Schaub MC, Zaugg M: Anaesthetic preconditioning but not postconditioning prevents early activation of the deleterious cardiac remodelling programme: evidence of opposing genomic responses in cardioprotection by pre- and postconditioning. Brit J Anaesth 95:140-152.2005
  • Tokarska-Schlattner M, Zaugg M, da Silva R, Lucchinetti E, Schaub MC, Wallimann T, Schlattner U: Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply. Am J Physiol Heart Circ Physiol 289:H37-H47.2005
  • Wacker J, Pasch T, Schaub MC, Zaugg M: Perioperative Strategien zur Regulierung des Sympathikotonus. Anaesthesist 54:303-318.2005
  • Feng J, Lucchinetti E, Ahuja P, Pasch T, Perriard JC, Zaugg M: Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3beta. Anesthesiology 103:987-995.2005
  • Haenggi T, Schaub MC, Fritschy JM: Molecular heterogeneity of the dystrophin-associated protein complex in the mouse kidney nephron: differential alterations in the absence of utrophin and dystrophin. Cell Tissue Res 319:299-313.2005
  • Garcia C, Julier K, Bestmann L, Zollinger A, von Segesser LK, Pasch T, Spahn DR, Zaugg M. Preconditioning with sevoflurane decreases PECAM-1 expression and improves one-year cardiovascular outcome in coronary artery bypass graft surgery. Br J Anaesth 94:159-165.2005
  • da Silva R, Lucchinetti E, Pasch T, Schaub MC, Zaugg M: Ischemic but not pharmacologic preconditioning elicits a gene expression profile similar to unprotected myocardium. Physiological Genomics 20:117-130.2004
  • Haenggi T, Soontornmalai A, Schaub MC, Fritschy JM: The role of utrophin and Dp71 for assembly of different dystrophin-associated protein complexes (DPCs) in the choroid plexus and microvaculature of the brain. Neuroscience 129:403-413.2004
  • Zaugg M, Schulz C, Wacker J, Schaub MC: Sympatho-modulatory therapies in perioperative medicine. Brit J Anaesth 93:53-62.2004
  • Zaugg M, Schaub MC, Foëx P: Myocardial injury and its prevention in the perioperative setting. Brit J Anaesth 93:21-33.2004
  • Sergeev P, da Silva R, Lucchinetti E, Zaugg K, Pasch T, Schaub MC, Zaugg M: Trigger-dependent gene expression profiles in cardiac preconditioning. Evidence for distinct genetic programs in ischemic and anesthetic preconditioning. Anesthesiology 100:474-488.2004
  • Zaugg M, Schaub MC: Cellular mechanisms in sympatho-modulation of the heart. Brit J Anaesth 93:34-52.2004Zaugg M, Schaub MC: Genetic modulation of adrenergic activity in the heart and vasculature: implications for perioperative medicine. Anesthesiology 102:429-446.200London MJ, Zaugg M, Schaub MC, Spahn DR: Perioperative beta-adrenergic receptor blockade. Physiologic foundations and clinical controversies. Anesthesiology 100:170-175.2004
  • Da Silva R, Grampp T, Pasch T, Schaub MC, Zaugg M: Differential activation of mitogen-activated protein kinases in ischemic and anesthetic preconditioning. Anesthesiology 100:59-69.2004
  • London MJ, Zaugg M, Schaub MC, Spahn DR: Perioperative beta-adrenergic receptor blockade. Physiologic foundations and clinical controversies. Anesthesiology 100:170-175.2004
  • Zaugg M, Schaub MC: Signaling and cellular mechanisms in cardiac protection by ischemic and pharmacological preconditioning. J Muscle Res Cell Motil 24:219-249.2003
  • Zaugg M, Lucchinetti E, Uecker M, Pasch T, Schaub MC: Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms. Brit J Anaesth 91:551-565.2003
  • Zaugg M, Lucchinetti E, Garcia C, Pasch T, Spahn DR, Schaub MC: Anaesthetics and cardiac preconditioning. Part II. Clinical implications. Brit J Anaesth 91:566-576.2003
  • Uecker M, da Silva R, Grampp T, Pasch T, Schaub MC, Zaugg M: Translocation of protein kinase-C isoforms to subcellular targets in ischemic and anesthetic preconditioning. Anesthesiology 99:138-147.2003
  • Julier K, da Silva R, Carcia C, Bestmann L, Frascarolo P, Zollinger A, Chassot PG, Schmid ER, Turina MI, von Segesser LK, Pasch T, Spahn DR Zaugg M: Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology 98:1315-1327.2003
  • Zaugg M, Lucchinetti E, Spahn DR, Schaub MC: Volatile Anesthetics mimic cardiac preconditioning by priming the action of mitochondrial KATP channels via multiple signaling pathways. Anesthesiology 97:4-14.2002
  • Zaugg M, Lucchinetti E, Spahn DR, Pasch T, C Garcia, Schaub MC: Differential effects of anesthetics on mitochondrial KATP channel activity and cardiomyocyte protection. Anesthesiology 97:15-23.2002
  • Zaugg M, Schaub MC, Pasch T, Spahn DR: Modulation of beta-adrenergic receptor subtype activities in perioperative medicine: mechanisms and sites of action. Brit J Anaesthesia 88:101-123.2002
  • Knuesel I, Riban V, Zuellig RA, Schaub MC, Grady M, Sanes JR, Fritschy JM: Increased vulnerability to kainate-induced seizures in utrophin-knockout mice. Eur J Neuroscie 15:1474-1484.2002
  • Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, Kaiser N, Halban PA, Donath MY: Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110:851-860.2002
  • Maedler K, Fontana A, Ris F, Sergeev P, Toso C, Oberholzer J, Lehmann R, Bachmann F, Tasinato A, Spinas GA, Halban PA, Donath MY: FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. Proc Natl Acad Sci U S A 99:8236-41.2002
  • Knuesel I, Zuellig RA, Schaub MC, Fritschy JM: Alterations in dystrophin and utrophin expression parallel the reorganization of GABAergic synapses in a mouse model of temporal lobe epilepsy. Eur J Neuroscie 13:1113-1124.2001
  • Zaugg M, Jamali NZ, Lucchinetti E, Shafiq SA, Siddiqui MAQ: Norepinephrine-induced apoptosis is inhibited in adult rat ventricular myocytes exposed to volatile anesthetics. Anesthesiology 93:209-218.2000
  • Zaugg M, Xu W, Lucchinetti E, Jamali NZ, Shafiq S, Siddiqui MAQ: Beta-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes. Circulation 102:344-350.2000
  • Zuppinger C, Schaub MC, Eppenberger HM: Dynamics of early contact formation in cultured adult rat cardiomyocytes studied by N-cadherin fused to green fluorescent protein. J Mol Cell Cardiol 32:539-555.2000
  • Klainguti M, Aigner S, Kilo J, Eppenberger HM, Mandinova A, Aebi U, Schaub MC, Shaw SG, Lüscher TF, Atar D: Lack of nuclear apoptosis in cardiomyocytes and increased endothelin-1 levels in a rat heart model of myocardial stunning. Basic Res Cardiol 95:308-315.2000
  • Zuellig RA, Bornhauser BC, Knuesel I, Heller F, Fritschy JM, Schaub MC: Identification and characterisation of transcript and protein of a new short N-terminal utrophin isoform. J Cell Biochem 77:418-431.2000
  • Knuesel I, Bornhauser BC, Zuellig RA, Heller F, Schaub MC, Fritschy JM: Differential expression of utrophin and dystrophin in CNS neurons: an in situ hybridization and immunohistochemical study. J Comp Neurol 422:594-611.2000
  • Knuesel I, Mastrocola M, Zuellig RA, Bornhauser B, Schaub MC, Fritschy JM: Altered synaptic clustering of GABAa receptors in mice lacking dystrophin (mdx mice). Eur J Neurosci 11:4457-4462.1999
  • Zaugg M, Tagliente T, Lucchinetti E, Jacobs E, Krol M, Bodian C, Reich D, Silverstein HJ: Beneficial effects from b-adrenergic blockade in elderly patients undergoing noncardiac surgery. Anesthesiology 91:1674-1686.1999
  • Schaub MC, Hefti MA, Zuellig RA, Morano I: Modulation of contractility in human cardiac hypertrophy by myosin essential light chain isoforms. Cardiovasc Res 37:381-404.1998
  • Harder BA, Hefti MA, Eppenberger HM, Schaub MC: Differential protein localization in sarcomeric and nonsarcomeric contractile structures of cultured cardiomyocytes. J Struct Biol 122:162-175.1998
  • Schaub MC, Hefti MA, Harder BA, Eppenberger HM: Triiodothyronine restricts myofibrillar growth and enhances beating frequency in cultured adult rat cardiomyocytes. Basic Res Cardiol 93:391-395.1998