1. Cardiac Output

2. Which Hearts Are Healthy?

3. Stroke Volume? End-systolic volume Stroke volume Left Ventricle Volume (ml) End-diastolic volume

4. Cardiac Output? HR X SV Heart Rate (beats/min) Stroke Volume (ml) Cardiac Output (L/min) ABCDE 88159817075 92100677970 8.115.95.45.55.3

5. What determines the stroke volume? Preload: how stretched the muscle is when it starts to contract. Afterload: the active stress the muscle has to generate in order to shorten Contractility: something else, but what?

6. Preload fulcrum

7. The effect of changing preload lowest preload highest preload

8. Afterload

9. The effect of changing afterload

10. Contractility Positive inotropism = contractility Negative inotropism = contractility Normal

11. Cellular Mechanism of Preload Effect on Strength of Contraction Length sensitivity of cardiac and skeletal muscle result from different mechanisms.

12. Myosin Heads Thin Filament Thick Filament 1.6 µm 1.0 µm 0.2 µm Optimum Overlap Length sensitivity of skeletal muscle

13. Cardiac Skeletal Length sensitivity of cardiac muscle

14. Muscle Length Force of Contraction Cytoplasmic [Ca ++ ] Force of Contraction Stretch Muscle How does preload affect force of cardiac muscle contraction?

15. Myosin Binding Site Myosin Head Troponin Complex Increased sensitivity of troponin C to Ca ++ Ca ++ Increased Ca ++ entry through Ca ++ L channels Length Sensitivity of Cardiac Muscle

16. Preload Afterload & Contractility in the Working Heart

17. 120 80 40 00 12 16 150 100 50 0 Left Ventricle Volume (ml) Pressure mmHgkPa 4 8 Preload depends on end-diastolic LV pressure and volume End-diastolic LV pressure End-diastolic LV volume

18. Preload depends on end-diastolic LV pressure and volume

19. Diastole Systole Right atrial pressure as a measure of preload P RA

20. Starling’s Law of the Heart Ventricular Function Curve The inflow equals the output

21. 120 80 40 00 12 16 150 100 50 0 Left Ventricle Volume (ml) Pressure mmHgkPa 4 8 Afterload depends on systolic ejection pressure LV Systolic ejection pressure Increased afterload reduced stroke volume shorter ejection time

22. Afterload depends on systolic ejection pressure 120 80 40 00 12 16 Pressure mmHgkPa 4 8 LV Systolic ejection pressure

23. Contractility Anything that influences stroke volume without acting through preload or afterload Sympathetic Nervous System Health of Heart Muscle Coronary Perfusion Drugs

24. Contractility “Squeezability”: How tightly can the ventricle squeeze by the end of ejection.

25. phosphorylates L-type Ca ++ channel Enhanced Contraction Enhanced Relaxation phosphorylates troponin to desensitize actin ß-adrenoceptor influence on contractility phosphorylates SR Ca ++ ATPase to increase Ca ++ reuptake

26. Left ventricular volume Pressure EKG Aortic Left ventricular Sympathetic Effect on the Heart

27. 150 50 0 100 Volume Left Ventricle (ml) End-Diastolic LV Volume End-Systolic LV Volume Stroke Volume Ejection Fraction = Stroke Volume End-Diastolic Volume Measuring Contractility A. Ejection Fraction

28. Ejection Fraction = Stroke Volume End-Diastolic Volume Measuring Contractility A. Ejection Fraction

29. 120 80 40 00 12 16 150 100 50 0 Left Ventricle Volume (ml) Pressure mmHgkPa 4 8 Measuring Contractility B. LV dP/dt Max Slope = LV dP/dt

30. Measuring Contractility B. LV dP/dt Max LV dP/dT ABCDE 1225170090012331209

31. 16 4 0 8 12 01 2 Right Atrial Pressure (kPa) (mm Hg) 48120 Cardiac Output (liters/min) Increased contractility Decreased contractility Measuring Contractility C. Ventricular Function Curve

32. 0 50 100 012 Left Atrial Pressure(kPa) (mm Hg) 8160 Stroke Volume (ml) Measuring Contractility C. Ventricular Function Curve A B C D 3 E

33. Measuring Contractility 1Ejection Fraction 2LV dP/dt max 3Ventricular Function Curve 4Maximal Systolic Elastance

34. Diastolic Pressure-Volume Curve Left Ventricular Volume (ml) Left Ventricular Pressure

35. Hypertrophy of Left Ventricle Eccentric (dilated) Stiff Ventricle Diastolic dysfunction Left Ventricular Volume (ml) Left Ventricular Pressure Normal stress = P x r 2h P x r 2h2h stress = Pressure Overload

36. End-systolic Pressure Volume Curve 050100150200 Left Ventricular Volume (ml) 300 200 100 40 30 20 10 0 Left Ventricular Pressure kPa mm Hg 0 Diastolic (relaxed myocardium) End-systolic (contracted myocardium)

37. The “time-varying elastance” model 050100150200 Left Ventricular Volume (ml) 300 200 100 40 30 20 10 0 Left Ventricular Pressure kPa mm Hg 0 minimum elastance elastance Emax

38. Measuring Contractility D. Emax 050100150200 Left Ventricular Volume (ml) 300 200 100 40 30 20 10 0 Left Ventricular Pressure kPa mm Hg 0 Emax Contractility (slope of end- systolic PV line) Preload “Afterload”

39. Left Ventricular Pressure Left Ventricular Volume (ml) Increased Preload Increased preload same afterload same contractility stroke volume

40. Left Ventricular Pressure Left Ventricular Volume (ml) Increased Afterload stroke volume same preload same contractility increase afterload

41. Left Ventricular Pressure Left Ventricular Volume (ml) Afterload compensation Preload increased increase afterload same contractility Stroke volume restored

42. Left Ventricular Pressure Left Ventricular Volume (ml) Afterload compensation Preload increased increase afterload same contractility Stroke volume restored

43. Left Ventricular Pressure Left Ventricular Volume (ml) Hypertension and Cardiac Work increase afterload External Work Contraction I Contraction 3

44. Left Ventricular Pressure Left Ventricular Volume (ml) Hypertension and Cardiac Work increase afterload Internal work

45. Left Ventricular Pressure Left Ventricular Volume (ml) Increased Contractility stroke volume same preload increased contractility same afterload

46. Left Ventricular Pressure Left Ventricular Volume (ml) Decreased Contractility same preload decreased contractility same afterload

47. Left Ventricular Pressure Left Ventricular Volume (ml) Preload compensation decreased contractility same afterload

48. Which Hearts Are Healthy?

49. Left Ventricular Pressure (mmHg)

50. Which Hearts Are Healthy? A. Pregnant 3 rd trimester

51. Which Hearts Are Healthy? B. Exercising

52. Which Hearts Are Healthy? C. Systolic Dysfunction

53. Which Hearts Are Healthy? D. Normal

54. Which Hearts Are Healthy? E. Diastolic Dysfunction