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Surgical therapies in HF, New Developments

Surgical therapies in HF, New Developments. Magdi Yacoub FRS. . Madrid May 6. 2010. Surgical therapies in HF, New Developments. Procedures. Revascularization Correcting Mechanical Lesions Surgical Remodeling Transplantation LVAD Combinations.

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Surgical therapies in HF, New Developments

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  1. Surgical therapies in HF, New Developments Magdi Yacoub FRS . Madrid May 6. 2010

  2. Surgical therapies in HF, New Developments Procedures • Revascularization • Correcting Mechanical Lesions • Surgical Remodeling • Transplantation • LVAD • Combinations

  3. Surgical therapies in HF, New Developments Correcting Mechanical Lesions • Rupture of IV Septum • MR result depend on pathophysiology • LV aneurysmectomy • DOR (Stitch trial) • ACCORN (prevent dilatation)

  4. Surgical therapies in HF, New Developments Transplantation • Dealing with donor shortage • Legislation • Ex vivo perfusion (transmedics) • Inducing specific immune tolerance • Several trial in Renal and liver TX

  5. Surgical therapies in HF, New Developments LVAD • Bridge to transplantation • Destination therapy • Bridge to recovery • Platfom for other form of therapy

  6. Surgical therapies in HF, New Developments Systems: RAS Organ: Changes in ventricular shape; laplace vs starling Multicellular: Connexins, Matrix abnormalities Cellular: CICR; Metabolic dysfunction; Cell loss etc Molecular: Ion Channel abnormalities…

  7. Surgical therapies in HF, New Developments LVAD -Bridge to Transplantation Reduced late Survival after bridge to transplantaion Shuhiber, BMj 2010 Left ventricular assist devices.  From an imaginative leap to clinical decision making M Yacoub, Nature reviews April 2010

  8. Surgical therapies in HF, New Developments LVAD - Bridge to Recovery • Defining mechanism of revascular remodeling • Benifetial and harmful effect of unloading

  9. The t-tubule system

  10. A site of concentration of ion channels Gu et al FASEBJ

  11. * Z Orientation 100 K X (TEM-Padmini)

  12. Calcium-induced calcium release (Cesare Terracciano)

  13. Techniques: patch clamping APs (current-clamp) A pulse of current triggers the AP and the voltage trace is recorded L-type current (voltage-clamp) -- 40mV to + 40mV +/- Cd

  14. F/Fo 10 µm 50 ms Techniques: Confocal

  15. FS

  16. CICR after prolonged overload Gomez et al 1997 Science Song et al 2006PNAS Lyon et al 2009 PNAS

  17. T-tubule disruption in HF

  18. T-tubules are critical for synchronous calcium release Human Atrial Cell few Rat Ventricle abundant HF Lost/disordered

  19. Conclusions • Continued development in many aspect of Heart Failure • Emphasis on combination therapies

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