Cardiac Pumping

Qiang XIA (夏强 ), PhDDepartment of Physiology

Room C518, Block C, Research Building, School of MedicineTel: 88208252

Email: xiaqiang@zju.edu.cn

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.

The mechanism that couples excitation – an

action potential in the plasma membrane of

the muscle cell – and contraction of heart

muscle

Excitation-Contraction CouplingIn Cardiac Muscle 兴奋 -收缩偶联

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

Calcium ions regulate thecontraction 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

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

• Pressure（压力）• Volume（容积）• Valves（瓣膜）• Blood flow（血流）

What happens in the heart during each cardiac cycle?

Systole:ventricles contracting

Diastole:ventricles relaxed

Click here to play theMechanical Events

of the Cardiac CycleFlash Animation

Mechanical Events of the Cardiac Cycle

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

Pressure changes in the right heart during a contraction cycle.

• Atria──primer pump（初级泵）

• Ventricles──major source of power

Role of atria and ventricles during each cardiac cycle

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

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 spaceLIS—left intercostal space ICS--intercostal space LLSB--left lower sternal border

Phonocardiogram（心音图）

Heart valve defects causing turbulent blood flow and murmurs

Acute rheumatic fever

Mitral stenosis -- Accentuated first sound

Mitral stenosis – Presystolic murmur

Mitral regurgitation -- systolic murmur

Aortic insufficiency -- Loud systolic ejection murmur,third sound

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)

heart enlargement

Stroke volume for evaluating different patients?

2. Ejection fraction (EF)（射血分数）

EF=(SV/EDV) x 100%

55~65%

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)

What parameters for comparison of people in different size?

4. Cardiac index (CI)（心指数

） : cardiac output per

square meter of body surface

area

3.0~ 3.5 L/min•m2

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

Measurement of Cardiac Function

• Echocardiography

• 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

Regulation of heart pumping

Regulation of stroke volume

1. Preload – Frank-Starling mechanism

Preload（前负荷） of ventricles:

end-diastolic volume (EDV)

end-diastolic pressure (EDP)

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

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

Ventricular function curve (Frank-Starling curve)

Ventricular function curve (Frank-Starling curve)

Factors affecting preload (EDV)

• (1) Venous return

• Filling time

• Venous return rate

• Compliance

• (2) Residual blood in ventricles after ejection

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

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)

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.

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, GermanyLeipzig, Germany; Munich, Germany

London, England

Animal used Frog 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 volumePressure, cardiac output, and heart volume

Aim of studyEffect of temperature (3); Vagus stimulation (2)

Heart as muscle and reliable pressure recording

Application to the mammalian heart

New findingEjection (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

Effectdescribed (3); recorded (2)

quantified and visualized as a graph (5)

designated "the law of the heart" (11)

Continued research focusing on the mechanism?

No No Yes

TABLE 1. Comparison of the experimental studies describing the effect of filling of the heart on contraction and ejection

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

Afterload has very little effect on the normal ventricleHowever, as systolic failure develops even small increases in

afterload have significant effects on compromised ventricular

systolic functionConversely, small reductions in afterload in a failing ventricle can

have significant beneficial effects on impaired contractility

Congestive heart failure (CHF)

3. Myocardial contractility (Inotropic state)

（心肌收缩性 [变力状态 ]）

Homometric regulation

（等长调节）

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.

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

Factors regulating contractility

• HRCO (CO = SV x HR)

• HRContractility (Treppe effect)

• HR diastolic filling time

Regulation of heart rate

40~180 /min ， HRCO >180 /min ， or <40/min ， CO

Control of heart rate

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

Staircase phenomenon (Treppe effect , Force-frequency relationship)

Increase in rate of contraction (heart rate) causes increase in contractility

To increase SV, increase:end-diastolic volume,norepinephrine delivery from sympathetic neurons, andepinephrine delivery from the adrenal medulla.

To increase HR, increase:norepinephrine delivery from

sympathetic neurons, andepinephrine

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.

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.

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.

……

The End.