1. Anatomy and Physiology
Marieb’s Human
Anatomy and Physiology
Ninth Edition
Marieb w Hoehn
Chapter 18
Heart
Lecture 3
Slides 1-15; 80 min (with review of syllabus and Web sites) [Lecture 1]
Slides 16 – 38; 50 min [Lecture 2]
118 min (38 slides plus review of course Web sites and syllabus)

2. Lecture Overview Physiology of cardiac muscle contraction
The electrocardiogram
Cardiac Output
Regulation of the cardiac cycle and cardiac output

3. Comparison of Skeletal and Cardiac Muscle
Cardiac and skeletal muscle differ in:
Nature of action potential
Source of Ca2+
Duration of contraction
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001
Let’s look at this more closely

4. The Cardiac Muscle Action Potential
Ca2+ ions enter from
Extracellular fluid (20%)
Sarcoplasmic reticulum (80%)
** Cardiac muscle is very sensitive to Ca2+ changes in extracellular fluid
Voltage-gated Na channels have two states (like neurons) and close after the voltage becomes positive. Na channels are inactivated until well into the repolarization phase.
Recall that tetanic contractions usually cannot occur in a normal cardiac muscle cell
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

5. Electrocardiogram
recording of electrical changes that occur in the myocardium during the cardiac cycle
used to assess heart’s ability to conduct impulses, heart enlargement, and myocardial damage
Important points to remember:
- Depolarization precedes contraction - Repolarization precedes relaxation
Emil Du Bois-Reymond German physiologist described an "action potential" accompanying each muscular contraction. He detected the small voltage potential present in resting muscle and noted that this diminished with contraction of the muscle. To accomplish this he had developed one of the most sensitive galvanometers of his time. His device had a wire coil with over 24,000 turns - 5 km of wire. Du Bois Reymond devised a notation for his galvanometer which he called the 'disturbance curve'. "o" was the stable equilibrium point of the astatic galvanometer needle and p, q, r and s (and also k and h) were other points in its deflection. Du Bois-Reymond, E. Untersuchungen uber thierische Elektricitat. Reimer, Berlin: 1848.
Why PQRST and not ABCDE? The four deflections prior to the correction formula were labelled ABCD and the 5 derived deflections were labelled PQRST. The choice of P is a mathematical convention (as used also by Du Bois-Reymond in his galvanometer's 'disturbance curve' 50 years previously) by using letters from the second half of the alphabet. N has other meanings in mathematics and O is used for the origin of the Cartesian coordinates. In fact Einthoven used O X to mark the timeline on his diagrams. P is simply the next letter. A lot of work had been undertaken to reveal the true electrical waveform of the ECG by eliminating the damping effect of the moving parts in the amplifiers and using correction formulae. If you look at the diagram in Einthoven's 1895 paper you will see how close it is to the string galvanometer recordings and the electrocardiograms we see today. The image of the PQRST diagram may have been striking enough to have been adopted by the researchers as a true representation of the underlying form. It would have then been logical to continue the same naming convention when the more advanced string galvanometer started creating electrocardiograms a few years later.
P wave – atrial depolarization
QRS wave – ventricular depolarization
T wave – ventricular repolarization
Three waves per heartbeat

6. Electrocardiogram PR Interval: 0.12 – 0.20 sec
P-R interval – Time between the onset of depolarization of the atria and onset of ventricular depolarization ( sec)
Q-T interval – Length of ventricular depolarization and repolarization (corresponds to action potential duration) ( sec) – QTc (QT/√RR) normally < 0.44 sec.
ST segment – Isoelectric period following the QRS during which the entire ventricle is depolarized. Elevation or depression can indicate nonuniform membrane potentials in ventricular cells signaling some damage from ischemia.
PR Interval: 0.12 – 0.20 sec
QT Interval: 0.20 – 0.40 sec
QRS Interval: < 0.10 sec
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

7. Electrocardiogram and Heart Events
Figure from: Hole’s Human A&P, 12th edition, 2010

8. Electrocardiogram and Heart Events
Figure from: Hole’s Human A&P, 12th edition, 2010

9. Different Leads for a 12-Lead ECG

10. Different Leads Can Help Localize Abnormalities
EKG leads
Location of MI
Coronary Artery
II, III, aVF
Inferior MI
Right Coronary Artery
V1-V4
Anterior or Anteroseptal MI
Left Anterior Descending Artery
V5-V6, I, aVL
Lateral MI
Left Circumflex Artery
ST depression in V1, V2
Posterior MI
Left Circumflex Artery or Right Coronary Artery

11. Normal and Pathological ECGs
Figures from: Saladin, Anatomy & Physiology, McGraw Hill, 2007

12. Review of Events of the Cardiac Cycle
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2004
Atrial contraction begins
Atria eject blood into ventricles
Atrial systole ends; AV valves close (S1)
Isovolumetric ventricular contraction
Ventricular ejection occurs
Semilunar valves close (S2)
Isovolumetric relaxation occurs
AV valves open; passive atrial filling S2 S1

13. Cardiodynamics – Important terms
End-diastolic volume (EDV) – amount of blood present in the ventricles at end of ventricular diastole (~ 120 ml)
End-systolic volume (ESV) – amount of blood left in ventricles at end of ventricular systole (~ 50 ml)
Stroke volume (SV) – amount of blood pumped out of each ventricle during a single beat (SV = EDV – ESV) (~ 70 ml)
Ejection fraction – Percentage of EDV represented by the SV (SV/EDV) (~ 55%)
Ejection fraction is normally greater than 55% (0.55).

14. Cardiac Output (CO)
The volume of blood pumped by each ventricle in one minute
CO = heart rate (HR) x stroke volume (SV)
ml/min beats/min ml/beat
Changes in heart rate are usually more effective at increasing CO since hr may increase by %, e.g., during exercise, whereas SV increases by only about 50% during exercise.
A change in hr without accompanying change in SV can actually decrease CO (due to decreased duration of diastole and, consequently, decrease filling time).
Example: CO = 72 bpm x 75ml/beat  5,500 ml/min
Normal CO  5-6 liters (5,000-6,000 ml) per minute

15. Regulation of Cardiac Output
CO = heart rate (HR) x stroke volume (SV)
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001
SV = EDV – ESV
physical exercise
body temperature
concentration of various ions
calcium
potassium
parasympathetic impulses (vagus nerves) decrease heart action
sympathetic impulses increase heart action; epinephrine
CO peaks when the heart rate is bpm. (Max heart rate is about 230 bpm, set by the refractory period of the SA node) Above this, filling time is drastically decreased so CO begins to fall.

16. Regulation of Cardiac Rate
Autonomic nerve impulses alter the activities of the S-A and A-V nodes
Rising blood pressure stimulates baroreceptors to reduce cardiac output via parasympathetic stimulation
Stretching of vena cava near right atrium leads to increased cardiac output via sympathetic stimulation
Chronotropy -> heart rate. Positive chronotropy = increasing heart rate, negative chronotropy = decreasing heart rate.
Inotropy -> change contractility of heart muscle
Most important control of heart rate is the ANS. Most sensory input comes from baroreceptors.
- Sympathetic stim – causes threshold to be reached sooner and enhances Ca entry into cardiocytes.
Parasympathetic stim – hyperpolarizes effector cell membranes by opening K+ channels. Not much innervation in ventricles so contractility is not affected. Parasymp is responsible for the normal vagal tone of the heart, i.e., heart rate is slower than it would be without parasymp stim (Cutting vagal nerves would result in about a 25 bpm increase in heart rate.
Chemical regulation
Hormones; epi same effect as NE (see ANS above)
Thyroxine; Large quantities cause a sustained increase in heart rate and enhances the effect of NE/Epi. (upreg. Receptors for NE/Epi)
Ions; Hypocalcemia, depress heart; hypercalcemia increase heart rate and force and cause irritability: hypernatremia inhibits txport of Ca into cells blocking heart contraction: hyperkalemia interferes with depolarizing by lowering resting potential and may lead to heart block and cardiac arrest; hypokalemia leads to feeble beating and arrythmias.
Figure from: Hole’s Human A&P, 12th edition, 2010

17. Regulation of Cardiac Rate
Tachycardia > 100 bpm Bradycardia < 60 bpm
Parasympathetic impulses reduce CO, sympathetic impulses increase CO
**ANS activity does not ‘make’ the heart beat, it only regulates its beat
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2004

18. Additional Terms to Know…
Preload
Degree of tension on heart muscle before it contracts (i.e., length of sarcomeres)
The end diastolic pressure (EDP)
Afterload
Load against which the cardiac muscle exerts its contractile force
Pressure in the artery leading from the ventricle

19. The Frank-Starling Mechanism
Amount of blood pumped by the heart each minute (CO) is almost entirely determined by the venous return
Frank-Starling mechanism
Intrinsic ability of the heart to adapt to increasing volumes of inflowing blood
Cardiac muscle reacts to increased stretching (venous filling) by contracting more forcefully
Increased stretch of cardiac muscle causes optimum overlap of cardiac muscle (length-tension relationship)
Figure from: Understanding Pathophysiology, Heuther & McCance, 5th ed, Elsevier, 2011.

20. Factors Affecting Cardiac Output
Figure adapted from: Aaronson & Ward, The Cardiovascular System at a Glance, Blackwell Publishing, 2007
ANS Parasympathetic Sympathetic HR
Contractility CO
= HR x SV
ESV
Afterload SV
= EDV - ESV
EDV
CVP
CO – Cardiac Output (~5L/min). Dependent upon Stroke Volume (SV; ~70 ml) and Heart Rate (HR)
CVP – Central Venous Pressure; Pressure in vena cava near the right atrium (affects preload; Starling mechanism)
Contractility – Increase in force of muscle contraction without a change in starting length of sarcomeres
Afterload – Load against which the heart must pump, i.e., pressure in pulmonary artery or aorta
ESV – End Systolic Volume; Volume of blood left in heart after it has ejected blood (~50 ml)
EDV – End Diastolic Volume; Volume of blood in the ventricle before contraction (~ ml)

21. Regulation of Cardiac Output
Recall: SV = EDV - ESV
Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001
Three major factors influence SV: preload, afterload, and contractility (inotropy).
Preload correlates to the degree of stretch of the cardiac muscle fibers before contraction. The resting length of cardiac muscle is shorter than optimal (unlike skeletal muscle where the resting length is optimal). The stretch of cardiac muscle during ventricular filling places the cardiac muscle sarcomeres at a more optimal length. Therefore, an increased rate of venous return (like a slow heart rate that allows more filling time, or exercise that increases the rate of venous blood flow back to heart), or an increased amount of venous return will cause an increased SV and, thus, and increased CO.
Contractility is an increased force of contraction independent of muscle stretch and EDV. Direct result of greater Ca influx into the cytoplasm from the extracellular fluid which is a result of sympathetic stimulation. Other factors include glucagon, thyroid hormone, epinephrine, and digitalis. These are positive inotropic agents. Factors that decrease contractility (negative inotropic agents) include acidosis, hyperkalemia, and Ca channel blockers.
Afterload is the pressure that the ventricles have to overcome in order to eject blood (back pressure on semilunar valves due to presence of blood in vessels; about 80 mm Hg in systemic circuit, 8 mm Hg in pulmonary circuit). Hypertension had a great effect on increasing afterload and consequently reducing SV (increasing ESV) and CO.
CO = heart rate (HR) x stroke volume (SV)
Be sure to review, and be able to use, this summary chart

22. Summary of Factors Influencing Cardiac Output
Effect on HR and/or SV
Effect on Cardiac Output
 DECREASE
Parasympathetic activity (vagus nerves)
 HR 
 K+ (hyperkalemia)
 HR and SV (weak, irreg. beats)
 K+ (hypokalemia)
Irritability
 Ca2+ (hypocalcemia)
 SV (flaccidity)
Decreased temperature
 INCREASE
Sympathetic activity
 HR and SV 
Epinephrine
Norepinephrine
 HR
Thyroid hormone
 Ca2+ (hypercalcemia)
 SV (spastic contraction)
Rising temperature
Increased venous return
Rapid onset hyperkalemia – outward diffusion of K+ is reduced, more K remains in the cell, resting potential is less negative and cell is closer to threshold. Causes hyperexcitability.
Slow onset hyperkalemia (aldosterone hyposecretion, renal failure, acidosis) – causes SLOW depolarization of cell which causes inactivation of Na+ channels and causes inability to produce action potentials. Results in hyPOexcitability.
The heartbeat increases by 10 bpm for every oF increase in temp (up to about 105oF)

23. Summary of Factors Influencing CO – Table Form
Effect on CO
How?
Affect HR, SV, or both?
INCREASE
Atrial reflex
 HR HR
Sympathetic stimulation
 HR, SV
HR and SV
Epinephrine, thyroxin
 Preload (Frank-Starling Mechanism)
 EDV,  ESV SV
 Contractility
 ESV
 Venous return,  CVP
 Preload,  atrial reflex
 Ca2+ (hypercalcemia)
 Contractility,  ESV
 Temperature
DECREASE
Parasympathetic stimulation (vagus nerves)
 HR
 Afterload
 ESV
 Ca2+ (hypocalcemia)
 Contractility,  ESV
 K+ (hyperkalemia)
Arrhythmia, cardiac arrest
HR, SV
 K+ (hypokalemia)
 Temperature

24. Life-Span Changes deposition of cholesterol in blood vessels
cardiac muscle cells die
heart enlarges
fibrous connective tissue of heart increases
adipose tissue of heart increases
blood pressure increases
resting heart rate decreases

25. Review
Cardiac muscle contraction differs in several important ways from skeletal muscle contraction
Duration of the action potential is longer
Ca2+ for contraction is derived from the extracellular fluid as well as the sacroplasmic reticulum
Length of contraction is longer
Tetany cannot develop due to length of the absolute refractory period
The electrocardiogram
Measures the electrical changes occurring in the heart
Is used to assess heart’s ability to conduct impulses, heart enlargement, and myocardial damage
Depolarization -> contraction, repolarization -> relaxation

26. Review There are three major events (waves) in the ECG
P wave = atrial depolarization
QRS complex = ventricular depolarization
T wave = ventricular repolarization
The different leads of an ECG can be used to localize heart muscle abnormalities
Abnormalities in ECG presentation can be indicative of heart damage
Several common cardiac abnormalities
Arrhythmia
Tachycardia (and bradycardia)
Atrial flutter

27. Review Important cardiodynamic terminology
End-diastolic volume (EDV) – amount of blood left in ventricles at end of ventricular diastole
End-systolic volume (ESV) – amount of blood left in ventricles at end of ventricular systole
Stroke volume (SV) – amount of blood pumped out of each ventricle during a single beat (EDV – ESV = SV)
Ejection fraction – Percentage of EDV represented by the SV

28. Review Cardiac output (CO) Factors Affecting CO
Amount of blood pumped by the heart in one minute
CO = stroke volume x heart rate
Normal (resting) CO  5-6 L/min
Factors Affecting CO
Autonomic activity
Hormones
K+, Ca2+
Venous return

29. Review Regulation of Cardiac Output Heart Rate Stroke Volume
Autonomic tone
Hormones
Venous return
Stroke Volume
Afterload