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11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 1
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 2
Failure of SA and AV nodes are Indications for Implantable Pacemakers!
Annual US diagnosed
Atrioventricular block
50,000
Sinus bradicardia
200,000
AV node ablation
20,000
Ventricular Arrhythmias: !Major Cause of Death!
11/25/08 3 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
Winston Churchill’s “Iron Curtain” speech, Fulton, Missouri, March 5, 1946!
11/25/08 4 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
“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
Krasnoyarsk-26: A Cold War High-Tech Center in Siberia!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 5
Krasnoyarsk-26:!
Still not on the map !
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 6
From Plutonium and Spy Satellites to the Gore-Chernomyrdin Commission!
11/25/08 7 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
Alma Mater: Moscow Institute of Physics and Technology!
11/25/08 8 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
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
My “exciting” undergraduate and graduate school years (1980-1992)!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 9
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
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
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 10
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 11
Cardiovascular Research Pendulum: !From Reductionism to Integration!
integration
reduction
Projects!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 12
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
Projects!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 13
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
Projects!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 14
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 Professorship in Biomedical Engineering 15
Cardiac Protection during Hibernation!
11/25/08
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 16
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 17
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 18
Connexin 43 forms cell-cell communication channels!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 19
Human failing heart
Connexin 43 α-actinin
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 20
5 0 m
µ
1 0 m
µ
0
1 SA WA WH
0 2 4 6 8
10 12 14 16 18 20
Summer Active
Winter Hibernating
Winter Active
Projects!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 21
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
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 22
We Use Transgenic Mouse Approach to Study Ionic Mechanisms of SA Node !
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 23
Functional and Molecular Anatomy !of the Canine SAN!
Molecular Definition of the Human Atrio-Ventricular Node!
11/25/08 24 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
11/25/08 25
Engineering Cardiac Pacemaking Structures of the SA and AV Nodes!
The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
Projects!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 26
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
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 27
Optical Mapping of Ventricular Tachycardia in Infarcted Hearts!
Virtual Electrode Polarization!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 28
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 29
Virtual Electrode Induced Phase Singularity: Cause of Arrhythmia!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 30
Defibrillation with a Biphasic Shock!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 31
Cardialen Low-energy pain-free defibrillation
Low-energy Painless !Atrial Defibrillation!
11/25/08 32 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
• 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
D. Graeme Thomas, President and CEO
Ongoing Grant projects!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 33
NIH R01 HL085369, “Structure/function of the pacemaking and conduction system of the heart”
NIH R01 HL67322 "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
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
11/25/08 34 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering
Thank you!!
11/25/08 The Lucy & Stanley Lopata Distinguished Professorship in Biomedical Engineering 35