1. The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
1
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. Ventricular Arrhythmias: !
Major Cause of Death!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
3
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. Krasnoyarsk-26: A Cold War
High-Tech Center in Siberia!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
5
6. Krasnoyarsk-26:!
Still not on the
map !
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
6
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. 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. 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. 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. Cardiovascular Research Pendulum: !
From Reductionism to Integration!
integration
reduction
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
11
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. 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. 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
16. The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
16
17. The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
17
18. The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
18
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. 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. 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. 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. Functional and Molecular Anatomy !
of the Canine SAN!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
23
24. Molecular Definition of the
Human Atrio-Ventricular Node!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
24
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. Optical Mapping of Ventricular
Tachycardia in Infarcted Hearts!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
27
29. Virtual Electrode Induced Phase
Singularity: Cause of Arrhythmia!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
29
30. Defibrillation with a Biphasic Shock!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
30
31. The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
31
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. 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. 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. Thank you!!
The Lucy & Stanley Lopata Distinguished
11/25/08
Professorship in Biomedical Engineering
35
