In Memoriam Harry A. Fozzard, MD 1931–2014 Timothy J. Kamp, Craig T. January

D

r Harry A. Fozzard, Otho S.A. Sprague Distinguished Service Professor Emeritus in the Department of Medicine at the University of Chicago and former editor-inchief of Circulation Research, passed away in his sleep on December 9, 2014 at the age of 83. Dr Fozzard’s career and life reflected the emergence and evolution of cardiac electrophysiology as research and clinical disciplines. It is remarkable to reflect on the advances that have occurred in cardiac electrophysiology and the interwoven role Fozzard played in those advances.1 Dr Fozzard attended medical school at Washington University in St. Louis where he had the good fortune of having his first serious research experience in the laboratory of Earl Sutherland, a future Nobel Prize winner for the discovery of adenylyl cyclase and cAMP as a second messenger system. This triggered Fozzard’s interest in the cell membrane and associated signaling pathways. He subsequently did his internship at Yale University before serving in the US Navy Medical Corps. He returned to Washington University where he completed his internal medicine residency and cardiology training. Dr Fozzard’s research on membrane proteins initially focused on the Na/K ATAPase which resulted in 1964 in his first Circulation Research publication.2 Dr Fozzard wanted to pursue cardiac electrophysiology research, but he felt poorly prepared. It was an exciting time as Hodgkin and Huxley had just been award the Nobel Prize in Medicine in 1963 for their work defining ionic currents underlying neuronal excitability. Thus, he traveled to Bern, Switzerland, in 1963 to work in the laboratory of Silvio Weidmann, the scientist credited with first recording the cardiac action potential and one of the fathers of cardiac electrophysiology.3 During his time in Bern, he designed a voltage clamp allowing him to perform a detailed study of the membrane capacitance properties of the Purkinje fiber.4 The Purkinje fiber was an early

favorite of cardiac electrophysiologists given its defined geometry and small size enabling the first voltage clamp studies of cardiac muscle. In 1964, Fozzard returned to Washington University and was appointed assistant professor of medicine and physiology, and he established and directed the first coronary care unit at Barnes Hospital. With the advent of the coronary care unit, he realized the importance of real-time arrhythmia monitoring and collaboratively developed a digital computer system for this purpose.5 In 1966, he was recruited to the University of Chicago to join an outstanding group of cardiovascular researchers led by Hans Hecht, another pioneer in cardiac electrophysiology. Dr Fozzard spent the rest of his remarkable career at the University of Chicago; however, his research reflected no geographical boundaries as he readily collaborated with and exchanged trainees and ideas with researchers from around the world including Europe, Russia, Japan, and Uruguay among other places. He published nearly 250 original papers, reviews, editorials, and book chapters. He earned continuous National Institutes of Health funding for greater than 4 decades. At the same time, he remained active as a clinical cardiologist with many devoted patients. Dr Fozzard’s research primarily examined the roles of the Na/K ATPase, Na/Ca exchanger, Na channels, and Ca channels in cardiac physiology. His group perfected ion sensitive microelectrodes and used them to determine intracellular concentrations of Na, K, Ca, and Cl in cardiac preparations and how those concentrations changed in response to stimulation, development, and pharmacological intervention such as cardiac glycosides.6–11 As methodology to isolate single cardiomyocytes emerged in the early 1980s, Fozzard’s group isolated single canine Purkinje cells and went on to provide detailed characterization of Na and Ca currents in those cells as well as taking advantage of the new patch clamp technique

From the Division of Cardiovascular Medicine, University of Wisconsin—Madison. Correspondence to Timothy J. Kamp, MD, PhD, Division of Cardiovascular Medicine, 8459 WIMR2, 1111 Highland Ave, University of Wisconsin— Madison, Madison, WI 53705. E-mail [email protected] (Circ Res. 2015;116:552-553. DOI: 10.1161/CIRCRESAHA.115.306038.) © 2015 American Heart Association, Inc. Circulation Research is available at http://circres.ahajournals.org DOI: 10.1161/CIRCRESAHA.115.306038

Downloaded from http://circres.ahajournals.org/ at University of Hawaii--Manoa on June 8, 2015 552

Kamp and January   In Memoriam: Harry A. Fozzard   553 to measure single channel properties of Na channels in Purkinje cells.12–14 After the cloning of the voltage-gated Na channel, Fozzard and colleagues made major advances spanning 20 years in structure function studies of the channel helping to define the sites of local anesthetic block and well as toxin modulation of the channels.15–17 In addition, Fozzard and colleagues provided detailed studies of L-type and T-type Ca channels in cardiac muscle and provided one of the first studies defining the effect of phosphatases on L-type Ca channels.18 Thus, Fozzard performed pioneering research impacting many aspects of cardiac electrophysiology, arrhythmias, and the regulation of contraction in heart muscle. Perhaps Fozzard’s greatest impact was as a leader and mentor. He served as vice president for research for the American Heart Association and was editor in chief of Circulation Research from 1986 to 1991. In addition, over the years he served both as a clinical division Chief of Cardiology and later a basic science Chair of the Department of Pharmacological and Physiological Sciences. He mentored greater than 60 PhD and MD/PhD candidates, postdoctoral fellows, and other visiting scientist during his career. He was an inspiring teacher and supported the career development of many young scientists in his laboratory and beyond it. For example, a first year medical student sitting in his lecture on cardiac physiology who had planned a career in internal medicine suddenly became hooked on the heart and remarkable proteins called ion channels. For many, Dr Fozzard pointed us in new and exciting directions while providing sage advice and friendship. He was also an avid sailboat racer and outdoorsman as well as talented in scherenschnitte, a Swiss-German folk-art. The legacy of Dr Fozzard continues as those trained and mentored by him follow his example of rigorous science leading in ever surprising directions to unmask the mysteries of cardiac excitation and tame arrhythmias. Dr Fozzard is survived by his wife Lyn, their 2 sons Richard and Peter, 4 grandchildren, and his brother George.

Sources of Funding T.J.K. and C.T.J. are supported by NIH R01 HL078878.

Disclosures None.

References 1. Fozzard HA. Fifty years of cardiovascular science together. Circ Res. 2003;92:4–5. 2. Krespi V, Fozzard HA, Sleator W, Jr. An adenosine triphosphatase preparation from a membrane-sarcotubular fraction of guinea pig heart muscle. Cir Res. 1964;15:545–551. 3. Coraboeuf E, Weidmann S. Potential de repos et potentiels d’action du muscle cardiaque, mesures a l’aide d’electrodes intracellulariares. . CR Soc Biol Paris. 1949;143:1329–1331. 4. Fozzard HA. Membrane capacity of the cardiac Purkinje fibre. J Physiol. 1966;182:255–267. 5. Cox JR, Nolle FM, Fozzard HA, Oliver GC Jr. AZTEC, a preprocessing program for real-time ECG rhythm analysis. IEEE Trans Biomed Eng. 1968;15:128–129. 6. Lee CO, Fozzard HA. Activities of potassium and sodium ions in rabbit heart muscle. J Gen Physiol. 1975;65:695–708. 7. Fozzard HA, Sheu SS. Intracellular potassium and sodium activities of chick ventricular muscle during embryonic development. J Physiol. 1980;306:579–586. 8. Sheu SS, Korth M, Lathrop DA, Fozzard HA. Intra- and extracellular K+ and Na+ activities and resting membrane potential in sheep cardiac purkinje strands. Circ Res. 1980;47:692–700. 9. Wasserstrom JA, Schwartz DJ, Fozzard HA. Catecholamine effects on intracellular sodium activity and tension in dog heart. Am J Physiol. 1982;243:H670–H675. 10. Baumgarten CM, Fozzard HA. Intracellular chloride activity in mammalian ventricular muscle. Am J Physiol. 1981;241:C121–C129. 11. January CT, Fozzard HA. The effects of membrane potential, extracellular potassium, and tetrodotoxin on the intracellular sodium ion activity of sheep cardiac muscle. Circ Res. 1984;54:652–665. 12. Scanley BE, Hanck DA, Chay T, Fozzard HA. Kinetic analysis of single sodium channels from canine cardiac Purkinje cells. J Gen Physiol. 1990;95:411–437. 13. Sheets MF, January CT, Fozzard HA. Isolation and characterization of single canine cardiac purkinje cells. Circ Res. 1983;53:544–548. 14. Makielski JC, Sheets MF, Hanck DA, January CT, Fozzard HA. Sodium current in voltage clamped internally perfused canine cardiac Purkinje cells. Biophys J. 1987;52:1–11. doi: 10.1016/S0006-3495(87)83182-X. 15. Satin J, Kyle JW, Chen M, Bell P, Cribbs LL, Fozzard HA, Rogart RB. A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties. Science. 1992;256:1202–1205. 16. Sunami A, Dudley SC Jr, Fozzard HA. Sodium channel selectivity filter regulates antiarrhythmic drug binding. Proc Natl Acad Sci U S A. 1997;94:14126–14131. 17. Hanck DA, Nikitina E, McNulty MM, Fozzard HA, Lipkind GM, Sheets MF. Using lidocaine and benzocaine to link sodium channel molecular conformations to state-dependent antiarrhythmic drug affinity. Circ Res. 2009;105:492–499. doi: 10.1161/CIRCRESAHA.109.198572. 18. Ono K, Fozzard HA. Two phosphatase sites on the Ca2+ channel affecting different kinetic functions. J Physiol. 1993;470:73–84. Key Words: calcium channel ◼ cardiac electrophysiology ◼ excitationcontraction coupling ◼ ion channels ◼ ion-sensitive microelectrodes ◼ sodium channel

Downloaded from http://circres.ahajournals.org/ at University of Hawaii--Manoa on June 8, 2015

Harry A. Fozzard, MD: 1931−2014 Timothy J. Kamp and Craig T. January Circ Res. 2015;116:552-553 doi: 10.1161/CIRCRESAHA.115.306038 Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7330. Online ISSN: 1524-4571

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circres.ahajournals.org/content/116/4/552

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation Research is online at: http://circres.ahajournals.org//subscriptions/

Downloaded from http://circres.ahajournals.org/ at University of Hawaii--Manoa on June 8, 2015

Harry A. Fozzard, MD: 1931–2014.

Harry A. Fozzard, MD: 1931–2014. - PDF Download Free
633KB Sizes 0 Downloads 8 Views