2. Cardiac Pumping Qiang XIA (夏强), PhD Department of Physiology Room C518, Block C, Research Building, School of Medicine Tel: 88208252 Email: xiaqiang@zju.edu.cn

3. Case A 70-year-old man was admitted to the hospital with shortness of breath, severe fatigue and weakness, abdominal distension, and swelling of ankles. At night he requires four pillows and often wakes up because of acute air hunger. His history revealed episodes of angina pectoris and a progressive shortness of breath with exertion for several years. On examination the chief abnormalities were slight cyanosis (bluish cast to the skin), distension of the neck veins, rapid respirations (20/min), rales (crackling sounds) at the lung bases bilaterally, an enlarged heart with slight tachycardia (110 beats/min) and a diastolic gallop rhythm (sounds like galloping horse), enlarged liver, excess fluid in the abdomen, and edema at the ankles and over the lower tibias. His blood pressure was 115/80. The chest x-ray examination showed an enlarged heart and diffuse density (indicative of fluid in the lungs) at both lung bases. An electrocardiogram (ECG) showed normal sinus rhythm, Q waves, and left axis deviation. Treatment included bed rest and administration of digitalis and a diuretic.

4. The mechanism that couples excitation – an action potential in the plasma membrane of the muscle cell – and contraction of heart muscle Excitation-Contraction Coupling In Cardiac Muscle 兴奋 - 收缩偶联

5. Passage of an action potential along the transverse tubule opens nearby voltage-gated calcium channels, the “ryanodine receptor,” located on the sarcoplasmic reticulum, and calcium ions released into the cytosol bind to troponin. The calcium-troponin complex “pulls” tropomyosin off the myosin-binding site of actin, thus allowing the binding of the cross-bridge, followed by its flexing to slide the actin filament. Excitation-contraction coupling in skeletal muscle

6. Calcium ions regulate the contraction of cardiac muscle: the entry of extracellular calcium ions causes the release of calcium from the sarcoplasmic reticulum (calcium-induced calcium release [ 钙诱导的钙释放 ]), the source of about 95% of the calcium in the cytosol. Excitation-contraction coupling in cardiac muscle

8. Cardiac cycle （心动周期） The cardiac events that occur from beginning of one heartbeat to the beginning of the next are called the cardiac cycle

9. Pressure （压力） Volume （容积） Valves （瓣膜） Blood flow （血流） What happens in the heart during each cardiac cycle?

10. Systole: ventricles contracting Diastole: ventricles relaxed

11. Click here to play the Mechanical Events of the Cardiac Cycle Flash Animation Mechanical Events of the Cardiac Cycle

12. Summary of events in the left atrium, left ventricle, and aorta during the cardiac cycle

14. Pressure changes in the right heart during a contraction cycle.

15. Atria──primer pump （初级泵） Ventricles──major source of power Role of atria and ventricles during each cardiac cycle

16. Heart Sounds 心音 1 st sound –soft low-pitched lub –associated with closure of the AV valves –Marks the onset of systole 2 nd sound –louder dup –associated with closure of the PA and aortic valves –Occurs at the onset of diastole

17. Chest surface areas for auscultation of normal heart sounds Four traditional value areas – Aortic space: 2RIS – Pulmonic valve: 2LIS – Tricuspid valve: 4ICS LLSB – Mitral valve: Apex RIS--right intercostal space LIS—left intercostal space ICS--intercostal space LLSB--left lower sternal border

18. Phonocardiogram （心音图）

19. Heart valve defects causing turbulent blood flow and murmurs

20. Acute rheumatic fever Mitral stenosis -- Accentuated first sound Mitral stenosis – Presystolic murmur Mitral regurgitation -- systolic murmur Aortic insufficiency -- Loud systolic ejection murmur, third sound

21. Evaluation of Heart Pumping 1.Stroke volume (SV) （搏出量） : volume of blood pumped per beat SV = EDV – ESV EDV: end-diastolic volume （舒张末期容积） ESV: end-systolic volume （收缩末期容积） ~70ml (60~80ml)

22. heart enlargement Stroke volume for evaluating different patients?

23. 2. Ejection fraction (EF) （射血分数） EF=(SV/EDV) x 100% 55~65%

24. 3. Cardiac output (CO) （心输出量） : the total volume of blood pumped by each ventricle per minute CO=SV x heart rate (HR) 5 L/min (4.5~6.0 L/min)

25. What parameters for comparison of people in different size?

26. 4. Cardiac index (CI) （心指数） : cardiac output per square meter of body surface area 3.0~ 3.5 L/minm 2

27. 5. Cardiac reserve （心力储备） : the maximum percentage that the cardiac output can increase above the normal level In the normal young adult the cardiac reserve is 300 to 400 percent Achieved by an increase in either stroke volume (SV) or heart rate (HR) or both

28. Measurement of Cardiac Function Echocardiography

29. Cardiac angiography Coronary Angiography from a 56-year-old man presented with unstable angina and acute pulmonary edema Rerkpattanapipat P, et al. Circulation. 1999;99:2965

30. Regulation of heart pumping

31. Regulation of stroke volume 1. Preload – Frank-Starling mechanism Preload （前负荷） of ventricles: end-diastolic volume (EDV) end-diastolic pressure (EDP)

32. Frank-Starling mechanism (Intrinsic regulation or heterometric regulation) （内在调节，或，异长调节） The fundamental principle of cardiac behavior which states that the force of contraction of the cardiac muscle is proportional to its initial length Significance: Precise regulation of SV

33. To increase the heart’s stroke volume: fill it more fully with blood. The increased stretch of the ventricle will align its actin and myosin in a more optimal pattern of overlap. Control of stroke volume Frank-Starling mechanism

34. Ventricular function curve (Frank-Starling curve)

36. Factors affecting preload (EDV) (1) Venous return Filling time Venous return rate Compliance (2) Residual blood in ventricles after ejection

37. Ernest Starling Ernest Henry Starling (17 April 1866 – 2 May 1927) was an English physiologist. He worked mainly at University College London, although he also worked for many years in Germany and France. His main collaborator in London was his brother-in-law, Sir William Maddock Bayliss. Starling is most famous for developing the "Frank–Starling law of the heart", presented in 1915 and modified in 1919. He is also known for his involvement along with Bayliss in the Brown Dog affair, a controversy relating to vivisection. In 1891, when he was 25, Starling married Florence Amelia Wooldridge, the widow of Leonard Charles Wooldridge, who had been his physiology teacher at Guy's and died at the age of 32. She was a great support to Starling as a sounding board, secretary, and manager of his affairs as well as mother of their four children. Other major contributions to physiology were: –The Starling equation, describing fluid shifts in the body (1896) –The discovery of peristalsis, with Bayliss –The discovery of secretin, the first hormone, with Bayliss (1902) and the introduction of the concept of hormones (1905) –The discovery that the distal convoluted tubule of the kidney reabsorbs water and various electrolytes –Starling was elected fellow of the Royal Society in 1899. http://en.wikipedia.org/wiki/Ernest_Starling

38. Otto Frank Otto Frank (June 21, 1865 - November 12, 1944) was a German doctor and an important figure in the history of cardiac physiology. Frank's initial research was related to fat absorption. But, in his postdoctoral work (Habilitationsschrift) Frank investigated the isometric and isotonic contractile behaviour of the heart and it is this work that he is best known for. Frank's work on this topic preceded that of Ernest Starling, but both are usually credited with providing the foundations of what is termed the Frank–Starling law of the heart. This law states that "Within physiological limits, the force of contraction is directly proportional to the initial length of the muscle fiber". Frank also undertook important work into the physiological basis of the arterial pulse waveform and may have coined the term essential hypertension in 1911. His work on the Windkessel extended the original ideas of Stephen Hales and provided a sound mathematical framework for this approach. Frank also published on waves in the arterial system but his attempts to produce a theory that incorporated waves and the Windkessel are not considered to have been successful. Frank also did work on the oscillatory characteristics of the auditory apparatus of the ear and the thermodynamics of muscle. He also worked extensively on developing accurate methods to measure blood pressure and other physiological phenomena (e.g. Frank's capsule (Frank-Kapsel), optical Spiegelsphygmograph). http://en.wikipedia.org/wiki/Otto_Frank_(physiologist)

39. Who Discovered the Frank- Starling Mechanism? Author: Heinz-Gerd Zimmer (http://physiologyonline.physiology.org/content/17/5/181.full) ABSTRACT In 1866 at Carl Ludwig’s Physiological Institute at Leipzig, Elias Cyon described the influence of diastolic filling of the isolated perfused frog heart on ejection volume. A study performed at the institute of the effect of filling pressure on contraction amplitude was published in 1869 by Joseph Coats, based on a recording made by Henry P. Bowditch.

40. Carl LudwigOtto FrankErnest H. Starling Year of publication1886 (3); 1869 (2)1895 (4); 1898 (5)1914 (8,9); 1926 (11) Performed atLeipzig, Germany Leipzig, Germany; Munich, Germany London, England Animal usedFrog Dog Heart preparation Working, recirculating (3); Closed system pumping into manometer (2) Working heart dependent on preload and afterload Heart-lung preparation Parameters measuredPressure (2)Pressure and volume Pressure, cardiac output, and heart volume Aim of study Effect of temperature (3); Vagus stimulation (2) Heart as muscle and reliable pressure recording Application to the mammalian heart New finding Ejection (3) and contraction amplitude dependent on filling (2) Curves of isovolumetric and isotonic maxima (5) Regulation of heart volume and output by preload and afterload Effect described (3); recorded (2) quantified and visualized as a graph (5) designated "the law of the heart" (11) Continued research focusing on the mechanism? No Yes TABLE 1. Comparison of the experimental studies describing the effect of filling of the heart on contraction and ejection

41. 2. Afterload （后负荷） ( Usually measured as arterial pressure )

43.  Afterload has very little effect on the normal ventricle  However, as systolic failure develops even small increases in afterload have significant effects on compromised ventricular systolic function  Conversely, small reductions in afterload in a failing ventricle can have significant beneficial effects on impaired contractility Congestive heart failure (CHF)

44. 3. Myocardial contractility (Inotropic state) （心肌收缩性 [ 变力状态 ] ） Homometric regulation （等长调节）

45. To further increase the stroke volume: fill it more fully with blood AND deliver sympathetic signals (norepinephrine and epinephrine); it will also relax more rapidly, allowing more time to refill.

46. Sympathetic signals (norepinephrine and epinephrine) cause a stronger and more rapid contraction and a more rapid relaxation.

48. Factors regulating contractility

50. HR  CO  (CO = SV x HR) HR  Contractility  (Treppe effect) HR  diastolic filling time  Regulation of heart rate ¤ 40~180 /min ， HR  CO  ¤ >180 /min ， or <40/min ， CO 

52. Control of heart rate

53. To speed up the heart rate: deliver the sympathetic hormone, epinephrine, and/or release more sympathetic neurotransmitter (norepinephrine), and/or reduce release of parasympathetic neurotransmitter (acetylcholine). T, ions, metabolites, other hormones

54. Staircase phenomenon (Treppe effect, Force- frequency relationship) Increase in rate of contraction (heart rate) causes increase in contractility

56. To increase SV, increase: end-diastolic volume, norepinephrine delivery from sympathetic neurons, and epinephrine delivery from the adrenal medulla. To increase HR, increase: norepinephrine delivery from sympathetic neurons, and epinephrine delivery from adrenal medulla (reduce parasympathetic). It is not possible, under normal circumstances, to increase one but not the other of these determinants of cardiac output.

57. Case A 70-year-old man was admitted to the hospital with shortness of breath, severe fatigue and weakness, abdominal distension, and swelling of ankles. At night he requires four pillows and often wakes up because of acute air hunger. His history revealed episodes of angina pectoris and a progressive shortness of breath with exertion for several years. On examination the chief abnormalities were slight cyanosis (bluish cast to the skin), distension of the neck veins, rapid respirations (20/min), rales (crackling sounds) at the lung bases bilaterally, an enlarged heart with slight tachycardia (110 beats/min) and a diastolic gallop rhythm (sounds like galloping horse), enlarged liver, excess fluid in the abdomen, and edema at the ankles and over the lower tibias. His blood pressure was 115/80. The chest x-ray examination showed an enlarged heart and diffuse density (indicative of fluid in the lungs) at both lung bases. An electrocardiogram (ECG) showed normal sinus rhythm, Q waves, and left axis deviation. Treatment included bed rest and administration of digitalis and a diuretic.

58. Questions 1. Would you expect cardiac output and stroke volume to be normal, high, or low? Why? 2. What do the distension of the neck veins and enlargement of the liver indicate? What is the mechanism? 3. Is the efficiency of the heart altered? If so, why? 4. What do you expect to find on measurement of ejection fraction and residual volume? Explain. ……

59. The End.