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Lopata Chair Presentation

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Lopata Chair Presentation

  1. 1. The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 1
  2. 2. Failure of SA and AV nodes are Indications for Implantable Pacemakers! Annual US diagnosed Atrioventricular 50,000 block Sinus 200,000 bradicardia AV node 20,000 ablation The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 2
  3. 3. Ventricular Arrhythmias: ! Major Cause of Death! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 3
  4. 4. Winston Churchill’s “Iron Curtain” speech, Fulton, Missouri, March 5, 1946! “I have a strong admiration and regard for the valiant Russian people and for my wartime comrade, Marshal Stalin. There is deep sympathy and goodwill in Britain -- and I doubt not here also -- toward the peoples of all the Russias and a resolve to persevere through many differences and rebuffs in establishing lasting friendships. It is my duty, however, to place before you certain facts about the present position in Europe. From Stettin in the Baltic to Trieste in the Adriatic an iron curtain has descended across the Continent. Behind that line lie all the capitals of the ancient states of Central and Eastern Europe. Warsaw, Berlin, Prague, Vienna, Budapest, Belgrade, Bucharest and Sofia; all these famous cities and the populations around them lie in what I must call the Soviet sphere, and all are subject, in one form or another, not only to Soviet influence but to a very high and in some cases increasing measure of control from Moscow”. Sir Winston Churchill, March 5, 1946 Westminster College, Fulton, Missouri The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 4
  5. 5. Krasnoyarsk-26: A Cold War High-Tech Center in Siberia! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 5
  6. 6. Krasnoyarsk-26:! Still not on the map ! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 6
  7. 7. From Plutonium and Spy Satellites to the Gore-Chernomyrdin Commission! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 7
  8. 8. Alma Mater: Moscow Institute of Physics and Technology!   1934. Peter Kapitsa (British citizen, FRC, Director of the Mond Laboratory and Professor, Cambridge University, UK) was forcefully detained by Stalin during his vacation in Russia. On requests of the British Government, Stalin replied: “Send me Rutherford and then we will send Kapitsa back to England”   1938. Lev Landau was arrested. Released after Peter Kapitsa sends a letter to Stalin, requesting Landau’s liberation.   October 23, 1945. Dr. Peter Kapitsa sends a proposal to Premier-Minister Georgy Malenkov to establish an Institute of Physics and Technology that would employ innovative methods for selection and training the future elite physicists and engineers   March 10, 1946 (5 days after the “Iron Curtain” speech) Stalin’s government approves establishment of the Higher School of Physics and Technology The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 8
  9. 9. My “exciting” undergraduate and graduate school years (1980-1992)! Leonid Brezhnev Yuri Andropov Konstantin Chernenko Mikhail Gorbachev Boris Yeltsin (1964-1982) (1982-1984) (1984-1985) (1985-1991) (1991-…) I moved to the United States in 1992 The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 9
  10. 10. Journey to Heart Physiology!   1963, Born in Krasnoyarsk-26, a.k.a. “Iron City” – a high-tech “closed” city in Siberia   1978-1980, Krasnoyarsk Summer School for Natural Sciences   1980-1986, Moscow Institute of Physics and Technology, M.Sc. in Nuclear Physics   1986-1992, Institute of Biophysics, Russian Academy of Sciences, Ph.D. in Biophysics. Laboratory of Professor Valentin Krinsky   1992-1994, Postdoctoral training in University of Pittsburgh. Laboratory of Professor Guy Salama   1994-2000, Department of Cardiology, Cleveland Clinic Foundation   2000-2004, Department of Biomedical Engineering, Case Western Reserve University   2004, Washington University in Saint Louis The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 10
  11. 11. Cardiovascular Research Pendulum: ! From Reductionism to Integration! integration reduction The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 11
  12. 12. Projects!   Cardiac protection in hibernating species   Mechanisms of physiological cardiac pacing by the Sino- Atrial and Atrio-Ventricular nodes   Tissue-engineered cardiac pacemaking structures   Mechanisms of conduction and arrhythmia in the settings of infarction   Mechanisms of electric pacing and defibrillation   Mechanisms of electroporation and associated cardiac dysfunction   Low-voltage implantable device therapy for atrial and ventricular arrhythmias The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 12
  13. 13. Projects!   Cardiac protection in hibernating species   Mechanisms of physiological cardiac pacing by the Sino- Atrial and Atrio-Ventricular nodes   Tissue-engineered cardiac pacemaking structures   Mechanisms of conduction and arrhythmia in the settings of infarction   Mechanisms of electric pacing and defibrillation   Mechanisms of electroporation and associated cardiac dysfunction   Low-voltage implantable device therapy for atrial and ventricular arrhythmias The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 13
  14. 14. Projects!   Cardiac protection in hibernating species   Mechanisms of physiological cardiac pacing by the Sino- Atrial and Atrio-Ventricular nodes   Tissue-engineered cardiac pacemaking structures   Mechanisms of conduction and arrhythmia in the settings of infarction   Mechanisms of electric pacing and defibrillation   Mechanisms of electroporation and associated cardiac dysfunction   Low-voltage implantable device therapy for atrial and ventricular arrhythmias The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 14
  15. 15. Cardiac Protection during Hibernation! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 15
  16. 16. The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 16
  17. 17. The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 17
  18. 18. The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 18
  19. 19. Connexin 43 forms cell-cell communication channels! Human failing heart Connexin 43 α-actinin The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 19
  20. 20. Summer Winter Winter Active Active Hibernating SA WA WH 1 20 50 µm 18 16 14 12 10 8 6 4 2 1 0 µm 0 0 The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 20
  21. 21. Projects!   Cardiac protection in hibernating species   Mechanisms of physiological cardiac pacing by the Sino- Atrial and Atrio-Ventricular nodes   Tissue-engineering cardiac pacemaking structures   Mechanisms of conduction and arrhythmia in the settings of infarction   Mechanisms of electric pacing and defibrillation   Mechanisms of electroporation and associated cardiac dysfunction   Low-voltage implantable device therapy for atrial and ventricular arrhythmias The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 21
  22. 22. We Use Transgenic Mouse Approach to Study Ionic Mechanisms of SA Node ! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 22
  23. 23. Functional and Molecular Anatomy ! of the Canine SAN! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 23
  24. 24. Molecular Definition of the Human Atrio-Ventricular Node! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 24
  25. 25. Engineering Cardiac Pacemaking Structures of the SA and AV Nodes! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 25
  26. 26. Projects!   Cardiac protection in hibernating species   Mechanisms of physiological cardiac pacing by the Sino- Atrial and Atrio-Ventricular nodes   Tissue-engineering cardiac pacemaking structures   Mechanisms of conduction and arrhythmia in the settings of infarction   Mechanisms of electric pacing and defibrillation   Mechanisms of electroporation and associated cardiac dysfunction   Low-voltage implantable device therapy for atrial and ventricular arrhythmias The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 26
  27. 27. Optical Mapping of Ventricular Tachycardia in Infarcted Hearts! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 27
  28. 28. Virtual Electrode Polarization! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 28
  29. 29. Virtual Electrode Induced Phase Singularity: Cause of Arrhythmia! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 29
  30. 30. Defibrillation with a Biphasic Shock! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 30
  31. 31. The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 31
  32. 32. Low-energy Painless ! Atrial Defibrillation! D. Graeme Thomas, Cardialen Low-energy pain-free defibrillation President and CEO •  New approach to defibrillation:   Most arrhythmias maintained by reentrant activation   Reentry stabilizes at “anchor points”, e.g. scar tissue, etc   Low-energy shock attracted to same “anchor points”   Allows unpinning of reentrant circuit with low-energy monophasic shock using proprietary multiple-pulse protocol The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 32
  33. 33. Ongoing Grant projects!   NIH R01 HL085369, “Structure/function of the pacemaking and conduction system of the heart”   NIH R01 HL67322 quot;Virtual electrode hypothesis of defibrillation”   NIH R01 HL074283, “The role of electroporation in defibrillation”   AHA “Structure of the human AV junction”   NIH, R01 HL082729, Collaboration with Natalia Trayanova, Johns Hopkins University   NIH R01 HL083393 and GM075200, Collaboration with Larry Taber   NIH R01 EB008999, Collaboration with Cheri Deng, University of Michigan, Ann Arbor, MI   NIH R01 HL095010, Collaboration with Colin Nichols, Washington University in Saint Louis, MO The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 33
  34. 34. Acknowledgements: Vadim Fedorov Christina Ambrosi Qing Lou Alexey Glukhov Wenwen Li Ai-Li Cai Li Li Fujian Qu Kelley Foyil Bill Hucker Crystal Ripplinger Vladimir Nikolski Current Collaborators: • Richard Schuessler, Nader Moazami, Richard Gross, Colin Nichols, Larry Taber, Eliot Elson, Shelly Sakiyama-Elbert, Don Elbert, Yoram Rudy, Washington University in St. Louis • Andrew Rollins, Cheri Deng, Case Western Reserve University, Cleveland, OH • Halina Dobrzynski, Mark Boyett, University of Manchester, Manchester, UK • Natalia Trayanova, Johns Hopkins University, Baltimore MD • Patrick Tchou, David Van Wagoner, Yuanna Cheng, Cleveland Clinic Foundaiton, OH • Leo Rosenschtraukh, Yuri Egorov, Irina Shishkina, Tatiana Mikheeva, Cardiology Research Center, Moscow, Russia • Brian Barnes, Vadim Fedorov, University of Alaska, Fairbanks • Paul Iazzio, Matthew Andrews, University of Minnesota The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 34
  35. 35. Thank you!! The Lucy & Stanley Lopata Distinguished 11/25/08 Professorship in Biomedical Engineering 35

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