1. Heart  as  a  Pump

2. Outline ‡ Overview of heart anatomy and function ‡ Cardiac cycle
‡ Volume-­‐Pressure  Diagram
‡ Cardiac  Output  and  Venous  Return ‡ Regulation  of  Cardiac  Output

3. Learning Objectives Describe the cardiac cycle by explaining Fig. 9-6
in Guyton and Hall
Analyze ventricular pumping with a volume ‐ pressure diagram
Understand  cardiac output and venous return - quantitatively know cardiac output
Know how cardiac output is regulated  - Frank- Starling mechanism and autonomic regulation

4. Cardiovascular System
Note, right side is the right side of the person or animal.
Two pumps in the heart:
Right side pumps blood through the lungs Left side through the peripheral organs
Each side has an atrium and a ventricle
Atrium is a primer pump for the ventricle Ventricle supplies the main pumping force

5. Heart  Anatomy
Atrioventricular valves: tricuspid (right) and mitral (left) Semilunar valves: pulmonary (right) and aortic (left)

6. Cardiac Cycle The cardiac cycle includes the events that
occur  from  the  beginning  of  one  heartbeat  to the  beginning  of  the  next
The  cardiac  cycle  consists  of  two  periods:
- Diastole  - period  of  relaxation  when  the  heart  fills with  blood
- Systole  - period  of  contraction

7. Diastole: Passive ventricular filling. The AV valves open and
Beginning just after a
ventricular contraction
Semilunar
valves closed
AV valves
opened
Diastole: Passive ventricular filling. The AV valves open and
blood flows into the relaxed ventricles, accounting for most of the
ventricular filling.

8. Diastole: Active ventricular filling.
Semilunar
valves closed
AV valves
opened
Diastole: Active ventricular filling.
Semilunar
valves closed
AV valves
opened
Diastole: Passive ventricular
filling.

9. Semilunar
valves closed
AV valves
opened
Diastole: Active ventricular filling. The atria contract and complete ventricular filling.

10. Systole: Period of isovolumic contraction.
Semilunar
valves closed
AV valves
closed
Systole: Period of isovolumic contraction.
Semilunar
valves closed
AV valves
opened
Diastole: Active ventricular filling.

11. Semilunar
valves closed
AV valves
closed
Systole: Period of isovolumic contraction. Ventricular contraction causes the AV valves to close, which is the beginning of ventricular systole. The semilunar valves were closed in the previous diastole and remain closed during this period.

12. isovolumic contraction. ejection.
Semilunar
Semilunar
valves opened
valves closed
AV valves closed
AV valves closed
Systole: Period of
Systole: Period of
isovolumic contraction.
ejection.

13. Semilunar
valves opened
AV valves
closed
Systole: Period of ejection. Continued ventricular contraction pushes blood out of the ventricles, causing the semilunar valves to open.

14. Systole: Period of ejection.
Semilunar
valves opened
AV valves
closed
Systole: Period of ejection.
Semilunar
valves closed
AV valves
closed
Diastole: Period of isovolumic relaxation.

15. Semilunar
valves closed
AV valves
closed
Diastole: Period of isovolumic relaxation. Blood flowing back toward the relaxed ventricles causes the semilunar valves to close, which is the beginning of ventricular diastole. Note that the AV valves
closed, also.

16. isovolumic relaxation.
Semilunar
valves closed
AV valves
closed
Semilunar
Diastole: Period of
valves closed
isovolumic relaxation.
AV valves opened
Diastole: Passive ventricular filling.

17. Cardiac  Cycle  in  Left  Side

18. Mechanical Events:
The Cardiac Cycle

19. The Cardiac Cycle
Cardiac cycle refers to all events associated with blood flow through the heart from the start of one heartbeat to the beginning of the next
During a cardiac cycle
Each heart chamber goes through systole and diastole
Correct pressure relationships are dependent on careful timing of contractions

20. Phases of the Cardiac Cycle
Atrial diastole and systole -
Blood flows into and passively out of atria (80% of total)
AV valves open
Atrial systole pumps only about 20% of blood into ventricles
Ventricular filling: mid-to-late diastole
Heart blood pressure is low as blood enters atria and flows into ventricles
80% of blood enters ventricles passively
AV valves are open, then atrial systole occurs
Atrial systole pumps remaining 20% of blood into ventricles

21. Phases of the Cardiac Cycle
Ventricular systole
Atria relax
Rising ventricular pressure results in closing of AV valves (1st heart sound – “lubb”)
Isovolumetric contraction phase
Ventricles are contracting but no blood is leaving
Ventricular pressure not great enough to open semilunar valves
Ventricular ejection phase opens semilunar valves
Ventricular pressure now greater than pressure in arteries (aorta and pulmonary trunk)

22. Phases of the Cardiac Cycle
Ventricular diastole
Ventricles relax
Backflow of blood in aorta and pulmonary trunk closes semilunar valves (2nd hear sound - “dubb”)
Dicrotic notch – brief rise in aortic pressure caused by backflow of blood rebounding off semilunar valves
Blood once again flowing into relaxed atria and passively into ventricles

23. Normal Volume of Blood in Ventricles
After  atrial  contraction,    ml  in  each ventricle  (end-diastolic  volume)
Contraction  ejects  ~70  ml  (stroke  volume output)
Thus,  40-50  ml  remain  in  each  ventricle  (End‐ systolic  volume)
The  fraction  ejected  is  then  ~60%  (ejection fraction)

24. Left Ventricle Volume-­‐Pressure Curve
Be able to use these pressure
and volume values
Aortic valve closes
Aortic valve opens
Mitral valve opens
Mitral valve closes
End-systolic volume
End-diastolic volume

25. Preload  and  Afterload
Preload  - tension  on  muscle  when  it  begins  to contract  (end-diastolic  pressure)
Afterload  - load  against  which  the  muscle exerts  its  contractile  force,  which  is  the
pressure  in  the  artery  leading  from  the
ventricle.    Phase  III  on  volume-pressure
diagram

26. Cardiac Output and Venous Return
Cardiac  output  is  the  quantity  of  blood pumped  into  the  aorta  each  minute.
Cardiac  output  =  stroke  volume  x  heart  rate
Venous  return  is  the  quantity  of  blood  flowing from  the  veins  to  the  right  atrium.
Except  for  temporary  moments,  the  cardiac output  should  equal  the  venous  return

27. Normal Cardiac Output Normal resting cardiac output:
- Stroke  volume  of  70 ml
- Heart  rate  of  72 beats/minute - Cardiac  output  ~ 5 litres/minute
During  exercise,  cardiac  output  may  increase to  >  20  liters/minutes
You  should  be  able  to  get  stroke  volume  and heart  rate  from  volume-­‐pressure  curves  and
ECG  recordings,  respectively

28. Cardiac Output
Stroke Volume = the vol of blood pumped by either the right or left ventricle during 1 ventricular contraction.
SV = EDV – ESV
70 = 125 – 55
CO = SV x HR
5,250 = 70 ml/beat x 75 beats/min
CO = 5.25 L/min

29. Cardiac Output Regulation of Stroke volume
Preload: Degree of stretch of heart muscle (Frank-Starling) – greatest factor influencing stretch is venous return (see Below)
Contractility – Strength of contraction
Increased Ca2+ is the result of sympathetic nervous system

30. A Simple Model of Stroke Volume

31. Cardiac Output Other chemicals can affect contractility:
- Positive inotropic agents: glucagon, epinephrine, thyroxine, digitalis.
- Negative inotropic agents: acidoses, rising K+, Ca channel blockers.
Afterload: Back pressure exerted by arterial blood.
Regulation of Heart Rate
Autonomic nervous system
Chemical Regulation: Hormones (e.g., epinephrine, thyroxine) and ions.

32. Regulation of Cardiac Output
Frank-Starling  Mechanism  -­‐ Cardiac  output changes  in  response  to  changes  in  venous return.
Autonomic  control  -­‐ Control  of  heart  rate  and strength  of  heart  pumping  by  the  autonomic
nervous  system.

33. Chemical Regulation of the Heart
The hormones epinephrine and thyroxine increase heart rate
Intra- and extracellular ion concentrations must be maintained for normal heart function

34. Regulation of Stroke Volume
SV: volume of blood pumped by a ventricle per beat
SV= end diastolic volume (EDV) minus end systolic volume (ESV); SV = EDV - ESV
EDV = end diastolic volume
amount of blood in a ventricle at end of diastole
ESV = end systolic volume
amount of blood remaining in a ventricle after contraction
Ejection Fraction - % of EDV that is pumped by the ventricle; important clinical parameter
Ejection fraction should be about 55-60% or higher

35. Factors Affecting Stroke Volume
EDV - affected by
Venous return - vol. of blood returning to heart
Preload – amount ventricles are stretched by blood (=EDV)
ESV - affected by
Contractility – myocardial contractile force due to factors other than EDV
Afterload – back pressure exerted by blood in the large arteries leaving the heart

36. Frank-Starling Law of the Heart
Preload, or degree of stretch, of cardiac muscle cells before they contract is the critical factor controlling stroke volume; EDV leads to stretch of myocardium.
preload  stretch of muscle  force of contraction  SV
Unlike skeletal fibers, cardiac fibers contract MORE FORCEFULLY when stretched thus ejecting MORE BLOOD (SV)
If SV is increased, then ESV is decreased!!
Slow heartbeat and exercise increase venous return (VR) to the heart, increasing SV.
VR changes in response to blood volume, skeletal muscle activity, alterations in cardiac output
VR  EDV and in VR   in EDV
Any  in EDV   in SV
Blood loss and extremely rapid heartbeat decrease SV.

37. Frank-Starling Law of the Heart
Relationship between EDV, contraction strength, and SV.
Intrinsic mechanism:
As EDV increases:
Myocardium is increasingly stretched.
Contracts more forcefully.
As ventricles fill, the myocardium stretches:
Increases the number of interactions between actin and myosin.
Allows more force to develop.
Explains how the heart can adjust to rise in TPR.
Figure 14.3

38. Extrinsic Control of Contractility
Strength of contraction at any given fiber length.
Sympathoadrenal system:
NE and Epi produce an increase in contractile strength.
+ inotropic effect:
More Ca2+ available to sarcomeres.
Parasympathetic stimulation:
Does not directly influence contraction strength.
Figure 14.2

39. Frank-Starling Mechanism
The force of cardiac muscle contraction
increases as the muscle stretches, within limits.
Due to more optimal overlap of actin and myosin filaments during stretch - same in skeletal muscle
So, with increase venous return and increased stretching, the force of contraction increases and the stroke volume increases.
Moreover, stretching of the SA node increasing the firing rate of the pacemaker (increasing heart rate).

40. Frank-­‐Starling Summary: within physiological limits, the heart
pumps  all  the  blood  that  returns  to  it  from  the veins.
Venous  return  increases  when  there  is  an
increase  in  the  blood  flow  through  peripheral
organs.    So,  peripheral  blood  flow  is  a  major determinant  of  cardiac  output

41. Factors Affecting Stroke Volume

42. Extrinsic Factors Influencing Stroke Volume
Contractility is the increase in contractile strength, independent of stretch and EDV
Referred to as extrinsic since the influencing factor is from some external source
Increase in contractility comes from:
Increased sympathetic stimuli
Certain hormones
Ca2+ and some drugs
Agents/factors that decrease contractility include:
Acidosis
Increased extracellular K+
Calcium channel blockers

43. Effects of Autonomic Activity on Contractility
Sympathetic stimulation
Release norepinephrine from symp. postganglionic fiber
Also, EP and NE from adrenal medulla
Have positive ionotropic effect
Ventricles contract more forcefully, increasing SV, increasing ejection fraction and decreasing ESV
Parasympathetic stimulation via Vagus Nerve -CNX
Releases ACh
Has a negative inotropic effect
Hyperpolarization and inhibition
Force of contractions is reduced, ejection fraction decreased

44. Contractility and Norepinephrine
Sympathetic stimulation releases norepinephrine and initiates a cyclic AMP 2nd-messenger system
Figure 18.22

45. Preload and Afterload
Figure 18.21

46. Effects of Hormones on Contractility
Epi, NE, and Thyroxine all have positive ionotropic effects and thus contractility
Digitalis elevates intracellular Ca++ concentrations by interfering with its removal from sarcoplasm of cardiac cells
Beta-blockers (propanolol, timolol) block beta-receptors and prevent sympathetic stimulation of heart (neg. chronotropic effect)

47. Autonomic Control of Cardiac Output
Sympathetic increases cardiac output
‡Can increase heart rate 70 to BPM ‡Can double force of contraction
Sympathetic nerves release norepinephrine
‡Believed to increase permeability of Ca2+ and Na+.
Parasympathetic (vagal) decreases cardiac
output
‡Can decrease heart rate to BPM
‡Can decrease force of contraction by 20-30%
Parasympathetic nerves release acetylcholine ‡Increases permeability to K+

48. Cardiac Output and Peripheral Resistance
Increasing the peripheral resistance decreases cardiac output.
arterial pressure total peripheral resistance
cardiac output =

50. Other Factors Affecting Cardiac Output
Age
Gender
Exercise/body temperature