1. Department of Physiology
Cardiac Pumping
Qiang XIA (夏强), PhD
Department of Physiology
School of Medicine
Tel: ,

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

3. Excitation-contraction coupling in skeletal muscle
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

4. 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

6. 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

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

8. Systole:
ventricles contracting
Diastole:
ventricles relaxed

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

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

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

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

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

15. 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

16. Phonocardiogram（心音图）

17. Heart valve defects causing turbulent blood flow and murmurs

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

19. Evaluation of Heart Pumping
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)

20. Stroke volume for evaluating different patients?
heart enlargement

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

22. 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)

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

24. 4. Cardiac index (CI)（心指数）: cardiac output per square meter of body surface area
3.0~ 3.5 L/min•m2

25. 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

26. Measurement of Cardiac Function
Echocardiography

27. 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

28. Regulation of heart pumping

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

30. 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

31. Control of stroke volume
Frank-Starling mechanism
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.

32. Ventricular function curve (Frank-Starling curve)

33. Ventricular function curve (Frank-Starling curve)

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

35. 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 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.

36. Otto Frank
Otto Frank (June 21, 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 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).

37. Who Discovered the Frank-Starling Mechanism?
Author: Heinz-Gerd Zimmer (
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.

38. TABLE 1. Comparison of the experimental studies describing the effect of filling of the heart on contraction and ejection
Carl Ludwig
Otto Frank
Ernest H. Starling
Year of publication
1886 (3); 1869 (2)
1895 (4); 1898 (5)
1914 (8,9); 1926 (11)
Performed at
Leipzig, Germany
Leipzig, Germany; Munich, Germany
London, England
Animal used
Frog
Dog
Heart preparation
Working, recirculating (3); Closed system pumping into manometer (2)
Working heart dependent on preload and afterload
Heart-lung preparation
Parameters measured
Pressure (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

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

41. Afterload has very little effect on the normal ventricle
Congestive heart failure (CHF)
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

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

43. 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.

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

46. Factors regulating contractility

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

50. Control of heart rate

51. T, ions, metabolites, other hormones
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).

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

54. 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.

55. The End.