Cardiac Muscle. Figure 1.02. The cardiac cycle in terms of time

Cardiac MuscleCardiac Muscle

Figure 1.02. The cardiac cycle in terms of time

Figure 1.02B. Left heart pressures

during one cardiac cycle

Figure 1.02C. Ventricular blood

volume during one cardiac cycle

Figure 1.02D. Aortic blood flow during one complete cardiac cycle

Figure 1.02E. ECG and heart sounds during one cardiac cycle

Figure 1.02F. Right heart pressures

during one cardiac cycle

Figure 1.05. Normal blood pressure and oxygen saturation values

Length-tension curves (diagrams) for skeletal and cardiac muscle

Figure 12M0. The effect of norepinephrine in augmenting tension and rate of tension development (Inotropicity)

produced during isometric muscle twitches

Figure 14. Bowditch effect (ie., Treppe, Staircase, force frequency relationship)

Refractory Period:

Long, compared to skeletal muscle

Prevents tetanus, guarantees a period of filling

Prevents ineffective tachycardia

Prevents re-entry ("circus" movement)

Two Kinds of Myocardial Cells:

Pacemaker - exhibit automaticity (rising phase 4 prepotential)

primary - SA nodal reserve - SA nodal, purkinje, AV nodal

Follower - no automaticity (stable phase 4 potential; atrium, ventricle)

Figure 3. The various ion pumps of the cell.

Figure 2M0. The three slow Ca++ channel states: resting, active, inactive.

"d" and "f" are upper and lower gates in the channel.

Ion Channels:

Fast - initial rapid inward Na+ current. - secondary outward K+ movement repolarization

Slow* - Ca++ moves inward, responsible for maintained depolarization of the "plateau phase" (Phase 2)

* An increase in contraction frequency increases Ca++ movement inward, giving the "staircase" phenomenon (Treppe, Bowditch) in cardiac muscle.

Figure 4M0. The fast sodium and slow calcium channels. The fast channel is in its "resting" mode;

the slow channel is in its depolarization mode, ie. active state (Ca++ ions moving through). The black dot indicates Nifedipine attachment site.

TTX = Tetrodotoxin, Nifedipine = a medically-used Ca++ channel blocker."m" and "h" are upper and lower gates in the Na+ channel."d" and "f" are upper and lower gates in the Ca++ channel.

Figure 5M0. Changes in transmembrane potential before and during depolarization in various types of

myocardial cells.Not all the depolarization / repolarizations look like

that in Figure 1.

Mechanisms for Changing Pacemaker Cell Automaticity:

Hyperpolarize/hypopolarize overdrive suppression Alteration of slope (rate of rise) of pre-potential (diastolic potential) Alteration of threshold; e.g. epinephrine increases gCa++ (hypopolarizes), acetylcholine increases gK+ (hyperpolarizes)

Factors Determining Action Potential

Conduction Velocity: Amplitude & rate of change of action potential -

increasing velocity, decreasing time - if large, more likely to depolarize adjacent cells

Anatomy of conducting cells - increased diameter, increases conduction velocity

- number of interconnections - longer nexus junctions (Purkinje cells)

"Cable Properties" of the conducting system

Factors Affecting Conduction Through the

AV Junction: Speeds -

Catecholamines * Atropine - blocks Acetylcholine Quinidine - inhibits vagal effects

Slows Acetylcholine * * Digitalis - central vagal (parasympathetic) stimulation Inhibitors of acetylcholine esterase, Ca++ antagonists (e.g. verapamil) An increased number of impulses arriving at AV junction increases

refractoriness

Various Conditions of Muscle Contraction:

Isotonic

Unloaded

Preloaded

Afterloaded (to less than isometric)

Isometric

Comparing isotonic and isometric muscle contractions.

+ indicates it occurs; - does not occur

Figure 6M0. Isometric and isotonic skeletal muscle twitches following a single action potential

Figure 9M0. Isometric twitch tension as it is influenced by preload (ie. initial length, Frank-Starling mechanism)

Figure 10M0. Velocity of muscle shortening and power output as each is influenced by increasing afterload

Figure 8M0. Velocity of shortening (isotonic contraction) as it is altered by afterload and preload

Effects of Increased Preload on Velocity of

Shortening, etc: Increased velocity of shortening (isotonic) at any given afterload

Unaltered Vmax at zero afterload

Increased muscle length

Increased tension development (isometric)

Effects of Afterload on Velocity of Shortening:

Maximum at no load

Zero at maximum load (isometric)

Intermediate with some, not maximum load

Effects of Increased Inotropicity on Velocity

of Shortening, etc.:

Increased velocity of shortening (isotonic) at any given afterload

Increased Vmax at zero afterload

Same muscle length

Increased tension development (isometric), and increased rate of contraction and relaxation

Figure 13M0. Velocity of muscle shortening and the influence of a catecholamine such as norepinephrine (

Inotropicity) in modifying the relationship

Figure 7M0. Mechanisms for altering isometric tension in cardiac muscle vs skeletal muscle

Factors Affecting Heart Rate:

Leading to an INCREASE: decreased activity of baroreceptors in the arteries, LV, and pulm. circ. (1) inspiration (2) excitement, anger, most painful stimuli (1) hypoxia (1?) exercise (1) norepinephrine (1) , epinephrine thyroid hormones fever Bainbridge reflex Leading to a DECREASE: increased activity of baroreceptors in the arteries, LV, and pulm. circ. (2) expiration (1) fear, grief (2) stimulation of pain fibers in trigeminal nerve increased intracranial pressure (Cushing Reflex) (1)

Actions of Vagal Parasympathetic Neurons to the Heart (through release of acetylcholine)

...... Site ................................ Action .......................................... Affecting ......

sino-atrial node ................... decreases heart rate ........... chronotropicity

atrio-ventricular node ............ slowed AV conduction ..... chronotropicity

atrio-ventricular node .. delayed conduction / increased refractoriness ……………………………………………………………..chronotropicity

Note: There are few/no parasympathetic nerve endings on the ventricular myocardium, so while acetylcholine is a potential negative inotrope for the ventricles, it is not released there.

Figure 2.01. Schematic of vagal escape. Acetylcholine release from parasympathetic ends on the SA node

and AV node & Junctional tissue increases refractoriness and depresses conduction velocity.

Intense stimulation will stop ventricular depolarization, ie. contraction. Reserve pacemakers come into play.

Control of Cardiac Performance: STROKE

VOLUME: Extrinsic:

Release of the following substances from the sympathetic and parasympathetic sympathetic branches of the autonomic nervous system, affect inotropicity:

norepinephrine (+) - neural acetylcholine (-) - neural* epinephrine (+) - blood borne These actions are mediated through cardiopulmonary receptors, such as the

carotid sinus (aortic) baroreceptors, carotid (aortic) body chemoreceptors, central chemo-receptors, venae cavae/atrial volume receptors (Bainbridge), and the ventricular volume receptors.

Attention: Inotropicity (ie. contractility) and strength of contraction are not synonomous. Increased / decreased strength of contraction can be achieved by changing preload(ie. Frank-Starling) with no change in inotropicity. Inotropicity reflects the biochemical state within the muscle (eg. Ca<SUP++< sup>, ATP), not simply the positioning of the thick and thin

myofilaments as determined by stretch. Intrinsic:

Frank-Starling - through preload (heterometric autoregulation) afterload - through increased / decreased arterial blood pressure acting on aortic valve. Anrep effect - laboratory curiousity? Bowditch effect } (homeometric autoregulation) (Treppe, Staircase) environment - ischemia, O2, CO2 cardiac hypertrophy - longterm effect

* In actual fact, there are few parasympathetic fibers in the ventricular myocardium, so ACH has little practical effect physiologically on ventricular inotropicity (contractility).

Figure 2.02. Frank-Starling (or ventricular function) curve. See cardiac muscle length-tension curve.The black curve defines a single inotropic state.

Major Factors Determining Myocardial

Stretch:Total blood volume Body position relative to the earth and

gravity pull Intrathoracic pressure Intrapericardial pressure Venous tone Pumping action of the skeletal muscle Atrial contribution to ventricular filling

Figure 2.03. Some factors contributing to afterload. What are shown here are the effects of increased vascular resistance and vascular compliance. Another major factor not shown is heart dimension, ie. a dilated heart sustains greater afterload at the same arterial or ventricular pressure than a smaller heart (a

larger heart has larger radii of curvature and through the Law of Laplace is at greater mechanical disadvantage relative to internal

pressure than a smaller heart).

Major factors determining myocardial contractile state (ie. inotropicity)

Sympathetic nerve impulses (normal) Circulating catecholamines (normal) Force-frequency relation (Bowditch, Treppe, Staircase) Normal) Various natural inotropic agents (normal) Digitalis, other non-natural inotropic agents (medical) Anoxia, hypercapnia, acidosis (pathologic) Pharmacologic depressants (medical / pathologic) Loss of myocardium (pathologic) Intrinsic depressants (normal / pathologic)

Attention: Inotropicity (ie. contractility) and strength of contraction are not synonomous. Increased / decreased strength of contraction can be achieved by changing preload(ie. Frank-Starling) with no change in inotropicity. Inotropicity reflects the biochemical state within the muscle (eg. Ca<SUP++< sup>, ATP), not simply the positioning of the thick and thin

myofilaments as determined by stretch.

Figure 2.04. Two Frank-Starling curves demonstrating altered inotropicity; Blue - lower inotropicity; Green -

higher inotropicity.

Inotropic agents:

Positive: Catecholamines (epinephrine, norepinephrine,

isoproterenol) Ca++ Cardiac glycosides (digitalis) Negative:

Ischemia/hypoxia Acetylcholine Heart Failure

Stages of the cardiac cycle

The cardiac cycle as a loop, independent of time

Figure 2.05. Changing pump conditions: A, changing preload; B, changing afterload; C, changing contractile

state

Note: Review loop-display.

changing afterload, preload remains constant

Alterations in contractile state: using systolic reserve volume (more complete emptying), through enhanced

inotropicity

Figure 2.07. Major factors contributing to cardiac output - Summary

Figure 2.06. Mechanisms of cardiac hypertrophy. Concentric and Eccentric

Hypertrophy

Changes in Gene Expression in Cardiac

Overload:Quantitative changes: Coordinated increase in protein (myosin, actin, myoglobin, Ca++ channels, mitochondria, surface membrane) and RNA (m, r and t) synthesis.

Regulated at a transcriptional and at the translational level.

Adaptational, because it multiplies contractile units and decreases wall stress. Qualitative changes: Several shifts in isoforms (myosin, creatine kinase, actin, tropomyosin, LDH, Na+-K+, ATPase, and SR protein).

Due to an isogene change in expression (myosin).

Adaptational because it decreases Vmax. and improves heat production.

Figure 10. Velocity of muscle shortening and power output as each is influenced by increasing afterload

Ejection Fraction

EF = (EDV - ESV) / EDV

or EF = SV / EDV, e.g. EF = 100 ml / 150 ml = 0.66

Note: SV = EDV - ESV

Figure 2.09. Assessment of ventricular performance. PEP,

LVET, and the ratio of PEP / LVET.

Figure 2.08. Factors affecting pre-ejection period

Figure 2.10. Range of ejection fractions. The normal range may extend to 0.82 or 0.84.

Values below 0.15 are usually incompatible with life. Note: The heart wall may be said to display normal kinesis, hypokinesis, hyperkinesis, akinesis (no motion), dyskinesis

(paradoxical wall motion).

Figure 3.01. Blood flow distribution and arteriovenous oxygen differences. The term "oxygen content" actually means "oxygen concentration".Arterial O2 concentration is constant, while venous O2

concentration varies from organ to organ, tissue to tissue

Ischemia

Increased A-V O2 diff. at rest usually indicates ischemia. Ischemia is relieved by: increasing blood flow decreasing O2 consumption Increased A-V

lactate indicates inadequate flow; heart usually uses lactate, in ischemia it produces lactate

The concept of Cardiac Reserve

Figure 3.02. The concept of cardiovascular reserve. Cardiac Output is

in units of liters

Fick Equation:

Cardiac output (L/min.) = O2 uptake (ml O2/min.) / A-V O2 diff. (ml O2/L blood) For Example: C.O. = 250/ (0.19 - 0.14) = 5100

ml/min.

O2 uptake = 250 ml/min.; Arterial O2 content = 0.19 ml/ml; Venous O2 content = 0.14 ml/ml

Figure 3.03. A dye-dilution curve

Figure 3.04. Effects of different levels of

exercise (work) on cardiovascular function

Figure 3.05. Redistribution of cardiac output with increased exercise / workload

Figure 3.06. Specific blood flow in various organs and

tissues

Figure 3.07. The coronary vessels

Figure 3.11. An angiogram of normal coronary vessels in an opened heart preparation (vessels filled with radiopaque material). On right is the horizontal main right coronary artery with small dscending twigs. On the left is the major left descending ramus and the horizontal major left circumflex ramus. Between these two are several large diagonal branches. The vessels show progressively diminishing lumina with no irregular narrowings or obstructions.

Thallium StudyExamine the images below obtained during exercise stress

and at rest for a normal patient. Note the uniform distribution in the walls of both right and left ventricle

Figure 1. The conduction system for the cardiac action potential. Normally the SA node depolarizes first and then the rest of the atria. After a delay at the AV junctional tissue, the action potential is conducted down the AV node, to the AV bundle, to the bundle branches, to the Purkinje fibers, and

then to the right and left ventricles.

Figure 1M0. Electrophysiologic changes during the cardiac cycle, including threshold current,

transmembrane potential and ion conductances over time. The circled numbers identify the

five phases of the process.

The 5 Phases of Myocardial Cell

Electrophysiology (follower cells only): Phase 4 -Polarized Cell; (-) inside, (+) outside; due mainly to Na+ & K+ ion positioning and higher permeability of membrane to K+, allowing loss of intracellular (+) charge. Phase 0 -Cell Depolarization; greatly increased membrane permeabilty to Na+ ions, which rush in through fast channels, down conc. gradient, reversing cell polarity (fast current). Phase 1 -Partial Repolarization; loss of Na+ conductance, & transient influx of Cl- ions and outflow K+ ions. Phase 2 -Plateau; due to the slow inward flow of Ca++ ions through slow channels (i.e. increased Ca++ conductance) (also some inward movement of Na+ through slow channels and outward movement of K+). Phase 2 includes most of the absolute refractory period. Phase 3 -Rapid Repolarization; decreased Ca++ conductance and increased K+ conductance, thus K+ moves out; inside of cell again becomes (-) relative to outside; Na+/K+ pump re-establishes distribution of ions. Supranormal excitabilty present early in phase 3, thus greatest chance of ectopic beat.

Table 6. HIERARCHY OF PACEMAKERS

BASED ON INTRINSIC FIRING RATES

_______________________________________________________ Sinoatrial Node .............................. 70 per min. Atrioventricular Node .................. 60 per min. Ventricle ....................................... 30-40 per min.

_______________________________________________________

Figure 7. Sequence of depolarization / repolarization of

the heart.

Figure 2. Sequence of cardiac excitation and associated changes

in the ECG.

Figure 3. The Einthoven Triangle, showing Leads I, II and III.

Figure 4. A moving dipole and how it is "sensed" in front, behind and at oblique

angles

Figure 11. Configuration of the standard limb leads, situated in the frontal (coronal) plane.

Figure 12. Configuration of the augmented limb leads, situated in the frontal (coronal)

plane.

Figure 13. Configuration of the precordial (chest) leads, situated in the transverse (horizontal) plane.

Figure 5. Standard terminology for the ECG (Lead aVf, 75

beats/min.).

Figures 9. Method for accurately determining mean electrical axis of the

heart (ventricles) - Step 1.

Figures 10. Method for accurately determining mean electrical axis of the heart (ventricles) - Step

2. Go to Step 1

Figure 8. Electrocardiograms of two individuals, one sedentary and one an endurance athlete (Standard paper speed 25 mm/sec., large horizontal squares 200 msec.,

small squares 40 msec.)

Figure 6. Comparison of the ECG's of an office worker and an athlete. (Standard paper speed 25 mm/sec., large horizontal squares 200 msec., small squares 40 msec.)

Figure 14. Normal sinus rhythm. Impulses originate at the SA node at the normal rate. All complexes are evenly spaced; rate 60 - 100/min. PR interval 120 -

200 msec

Figure 15. Sinus bradycardia. Impulses originate at the SA node at a slow rate. All complexes are normal, evenly spaced; rate <60/min. PR interval 120 - 200 msec.

Figure 16. First degree AV block. Fixed but prolonged PR interval. P wave precedes each QRS complex but PR interval, although uniform, is >0.2

sec. (>5 small boxes).

Figure 17. Second-degree heart block: Mobitz I or Wenchebach. Progressive lengthening of the PR interval with intermittent dropped beats.

Figure 21. Third-degree (complete) heart (AV) block. There is no relationship between P waves and QRS complexes: QRS rate is slower than P wave rate. Impulses originate at both the SA node (P waves) and below the site of block in the AV node (junctional rhythm) conducting to the ventricles. Atria and ventricles depolarize independently, QRS complexes are less frequent;

regular at 20 to 40/min but normal in shape

Figure 22. Third-degree (complete) heart (AV) block. There is no relationship between P waves and QRS complexes: QRS rate is slower than P wave rate. Impulses originate at SA node (P waves) and also below the site of block in ventricles (idioventricular rhythm). Atria and ventricles depolarize independently, QRS complexes are less frequent; regular at 20 to 40/min but wide and abnormal in shape.

Figure 18. Junctional rhythm. Impulses originate in the AV node or AV junctional tissue, with retrograde and antegrade transmission. In this example, retrograde transmission is taking place into the atria, giving an inverted P wave. The ventricular rate is slower than with sinus rhythm and the QRS is narrow. If there is also sinus node depolarization, a normal-appearing P wave may be present. If a wandering pacemaker is present in the

atria, inverted P waves can precede the QRS complex

Figure 19. Idioventricular rhythm. No P waves (ventricular impulse origin). Rate <40 / min.; QRS >

0.10 sec.

Figure 20. Intraventricular conduction defect (IVCD), including right or left bundle branch block. Wide QRS (2-1/2 small boxes), often notched, preceded by P wave with normal PR interval.

Figure 23. Wandering atrial pacemaker. Impulses originate from varying points in atria. Variation in

wave contour, PR interval, PP and thus RR intervals.

Figure 24. Atrial flutter. Impulses travel in circular course in atria, setting up regular, rapid (220 to 300/min.) flutter (F) waves without any isoelectric baseline. Ventricular rate (QRS) is regular or irregular and slower depending upon the degree of block.

Figure 25. Atrial fibrillation - impulses take random, chaotic pathways in atria. Baseline coarsely or finely irregular; P waves absent. Ventricular

response (QRS) irregular, slow or rapid

Figure 26. Ventricular tachycardia. Arrow shows slowed conduction in the margin of the ischemic area, which permits a circular course of impulses and re-entry with rapid repetitive depolarization.

Figure 27. Ventricular fibrillation.

Figure 28. The effect of increases in

serum K concentration on the ECG

the endthe end