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)

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

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

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

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 1843 - 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

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 (0.12-0.20 sec) Q-T interval – Length of ventricular depolarization and repolarization (corresponds to action potential duration) (0.20-0.40 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

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

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

Different Leads for a 12-Lead ECG

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

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

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

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).

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 100-200%, 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

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 160-180 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.

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

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

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

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.

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 (~120-140 ml)

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

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)

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

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

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

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

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

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

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