Shoulders of Giants J. Hunter Mehaffey MD, MSc If I have seen - PowerPoint PPT Presentation

Surgeon-Scientist: Standing on the Shoulders of Giants J. Hunter Mehaffey MD, MSc

If I have seen further it is by standing on the shoulders of Giants. - Isaac Newton in 1675

“We [the Moderns] are like dwarves perched on the shoulders of giants [the Ancients], and thus we are able to see more and farther than the latter. And this is not at all because of the acuteness of our sight or the stature of our body, but because we are carried aloft and elevated by the magnitude of the giants.” - Bernard of Chartres 12 th Century

Nobel Laureate Surgeons 1. Theodor Kocher, 1909, Physiology, Pathology, and Surgery of the Thyroid 2. *Allvar Gullstrand, 1911, Dioptrics of the Eye 3. Alexis Carrel, 1912, Anastomosis of Vessels and Transplantation of Organs 4. Robert Barany, 1914, Vestibular System 5. Frederick Banting, 1923, Discovery of Insulin 6. *Walter Hess, 1949, Midbrain Function 7. Werner Forssmannn, 1956, Cardiac Catheterization 8. Charles Huggins, 1966, Hormones and Cancer 9. Joseph Murray, 1990, Organ Transplantation

Theodor Kocher

Alexis Carrel

Frederick Banting

…. if the science of surgery, then, requires genius, knowledge, and indefatigable application to render its professors truly respectable, what must we think of the insolence . . . of those who represent it as a low mechanical art which may be taught a butcher’s boy in a fortnight. . . . - John Jones (Surgeon US Army 1769) (Father of American Surgery and Author of America's First Medical Book)

John Gibbon

Irv Kron

E-CPR

Adenosine 2A Receptor

Methods • Sternotomy (n=15 pigs) • Electric Ventricular Fibrillation Arrest: 9V Battery • Randomized on Induction of ECMO (n=5 each) – Vehicle Control – Low Dose ATL1223 (0.3ng/kg/min) – High Dose ATL1223 (0.6ng/kg/min)

Systemic Injury

Fluid and Hemodynamics

Plasma Cytokines

Organ Injury

Meaningful bench research begins at the bedside and must be translated back to the bedside. - Irv Kron

Ex Vivo Lung Perfusion

Injury Model Compliance Oxygenation 500 100 100 ug/kg % Change Compliance 400 75 50 ug/kg PO 2 /FiO 2 Ratio Threshold (150) 300 50 200 100 ug/kg 25 100 50 ug/kg 0 0 0 60 120 180 240 0 60 120 180 240 Time (min) Time (min)

Superior Oxygenation in vivo Control 600 EVLP PO 2 /FiO 2 Ratio 450 300 150 Injury Perfusion 0 0 2 4 6 Hours

Rehabilitation on EVLP 800 p=0.02 30 p=0.02 Dynamic Compliance PO 2 /FiO 2 Ratio 600 (mL/cm H 2 O) 20 400 10 200 0 0 1 4 1 4 Duration of EVLP (hours) Duration of EVLP (hours) p = 0.002 8 p = 0.03 7 Wet / Dry Ratio 6 5 4 In Vivo Ex Vivo EVLP Control Control

In Vivo Lung Perfusion

Methods Injury - 8 pigs 2 Hours - 50 ul/kg Intravenous LPS - Central ECMO Cannulation Right Lung Left Lung (IVLP) 4 Hours - Systemic Circulation - Steen Solution - Standardized ECMO - Flow 8% Cardiac Output Reperfusion - IVLP Decannulation - Hourly ABG/Compliance 4 Hours - Wean ECMO - Tissue Sample

Superior Function 500 50 Injury IVLP Reperfusion 400 40 * * * * * * Compliance (mL/cm H 2 O) PO 2 /FiO 2 Ratio (mmHg) 300 30 200 20 100 10 * p<0.05 0 0 0 2 4 6 8 10 Hours Left Lung Oxygenation Systemic Oxygenation Total Lung Compliance Right Lung Oxygenation

Reduced Histologic Injury / Edema Left Lung Right Lung p=0.01 10 Wet / Dry Weight Ratio 8 6 4 2 0 Right Lung Left Lung

Cytokines

Adhesion Molecules P=0.03 P=0.12

Clinical Translation

It usually requires a considerable time to determine with certainty the virtues of a new method of treatment and usually still longer to ascertain the harmful effects. Alfred Blalock (1899 – 1964)

VADstent

LVAD Limitations

VADstent Development Length Volume 120.8 ± 2. Normal LV 8.99 2 348.5 ± 3. Diseased LV 10.77

VADstent Porcine Prototype

VADstent Modeling

VADstent Ovine Implant

VADstent

New ideas seldom have the simplicity of a switched on light bulb. Thomas Starzl (1926 – 2017)

Mentors

Colleagues

Family

Questions