Cardiac Electrophysiology & Ion Movement

• Systole is the mechanical event of myocardial muscle contraction resulting from electrochemical events.
• Electrophysiology is the study of a single cell's electrical behavior at rest, during stimulation, and through recovery.

Intrinsic Conduction System

• Cardiac autorhythmic cells generate action potentials that spread to contractile cells.
• Action potentials from autorhythmic cells spread to contractile cells through gap junctions.

Ion Movement

• Cations are positively charged, and anions are negatively charged particles that transmit current.
• Extracellular and intracellular fluids contain specific concentrations of electrolytes.
• Passive ion transport requires no energy, moving from high to low concentration areas.
• Sodium and potassium pumps actively transport ions across the membrane, requiring ATP.
• Changes in membrane permeability cause electrolyte movement, altering electrical charge and creating current.
• Myocardial cells maintain a constant MRP until electrically stimulated, existing at phase 4 of the action potential curve.
• Pacemaker cells undergo slow diastolic depolarization instead of maintaining a constant MRP.

Electrochemical Events

• A cell membrane is polarized when neither responding to nor recovering from electrical stimulus.
• Membrane resting potential (MRP) is the electrical potential gradient across the cell membrane at rest.
• Polarized myocardial cells contain high intracellular potassium and low intracellular sodium.
• Extracellular space has high sodium and low potassium.
• MRP develops due to high intracellular K+, high extracellular Na+ and Ca2+, and greater membrane permeability to K+ than Na+.

Ion Movement and Channels

• Ion movement depends on energetic favorability and membrane permeability.
• Non-gated (leak) channels are always open.
• Chemically gated channels open in response to chemical signals.
• Voltage-gated channels open in response to changes in membrane potential.

Depolarization

• Phase 0 is when the curve occurs on the cell membrane.
• Increased sodium permeability causes sodium to diffuse into the cell and potassium to diffuse out.
• This makes the cell voltage less negative.

Repolarization

• Brief, early repolarization in Phase 1 is due to the partial closing of fast sodium channels, decreasing sodium influx.
• Phase 2, a slow repolarization "plateau," maintains ionic balance via slow calcium ion influx.
• Rapid repolarization in Phase 3 involves reduced inward flow of sodium and calcium and rapid potassium outflow via active transport.
• Phase 4 brings a constant resting MRP for non-pacemaker cells or automaticity for pacemaker cells.
• Muscle cells maintain a membrane potential of -90mV during this phase.
• Ion concentrations are restored using sodium-potassium pumps and ATP.

Cardiac Action Potential

• Cardiac AP represents the change in cardiac intracellular voltage over time due to depolarization and repolarization. has fast and slow responses.
• Fast response is more negative and slow conduction increases rhythm disturbances.

Refractory Period

• Action potential curve contains 3 periods.
• The absolute refractory period prevents response to any stimulus, during phases 0, 1, 2, and the start of 3.
• A stronger stimulus can depolarize the cell membrane in the relative refractory period, which includes the end of phase 3.
• Weaker impulses may cause depolarization during the supernormal period, when the cell is close to the threshold potential.
• A long refractory period prevents continuous impulse circulation in the heart.

Fast response action potentials

• Have a MRP of about – 90 mV, the most negative of all the cardiac cells.
• Have a constant membrane potential in phase 4 until stimulated.
• Rapid phase 0 rise allows for rapid conduction.
• Phase 1 overshoots into the positive potential range to +20mV
• Phase 2 contains the plateau phase with slow repolarization
• Phase 3 is when rapid repolarization occurs

Ionic basis of the fast response:

• Phase 0 is due to Na influx: rapid depolarization.
• Phase 1 is caused by efflux of K through a voltage gated channel : early rapid repolarization
• Phase 2 is mediated by the balance of outward K current in competition with an inward Ca current : plateau phase
• Phase 3 occurs when K efflux exceeds influx of Ca : final rapid repolarization
• Phase 4 is when Na and Ca channels are closed: establishes resting membrane potential

Slow response AP – Autorhythmic cells:

• Have a MRP of – 60mV the least negative of all cardiac cells.
• Phase 4 has the steepest slope.
• Phase 0 has the slowest rate of rise due to fast sodium channels being inactive.
• Phase 1 has a diminished or absent overshoot, does not move into positive range.
• Phases 2 and 3 have a gradual and even repolarization with a diminished plateau phase.

Ionic basis of the slow response:

• Phase 4 has an upward slope represents spontaneous gradual depolarization.
• The pacemaker current causes spontaneous depolarization; predominantly carried by Na ions.
• The inward flow of positive charged Na causes the membrane to become les negative during phase 4, depolarizing cell to threshold voltage.

Excitation – Contraction Coupling

• The process is where an electrical action potential leads to contraction of myocardial cells

Action Potentials- Non pacemaker cells

• Phase 4: stable resting membrane potential.
• Phase 0: a transient increase in fast Na channel conductance occurs
• Phase 1: K channel opens
• Phase 2: calcium channels open and delay repolarization
• Phase 3: K increases, Calcium decreases

Action Potentials – pacemaker cells:

• Phase 4 : slow Na currents and changes in Ca and K are responsible
• Phase 0: Ca increases due to Ca channels.
• Phase 3: K channels open and repolarize the cell as Ca channels inactivate

Myosin:

• Thick filaments with globular heads evenly spaced along their length, and contain myosin ATPase.
• Myosin heads bind to actin, bend/straighten during contraction, and break down ATP to release energy.

Actin:

• Is a smaller molecule, and contain thin filaments of two strands, woven between myosin filaments.

Tropomyosin:

• is a double helix that lies in the groove between actin filaments and prevents contraction in the resting state, it inhibits the interaction between myosin heads and actin.

Troponin:

• 3 subunits that sits at regular intervals along the actin strands.
• Troponin T ties troponin to actin and tropomyosin molecules
• Troponin I inhibits activity of ATPase in actin myosin interaction
• Troponin C binds calcium ions that regulate contractile process

Calcium Induced Calcium Release:

• Amplifies the signal.

Contractile Cycle:

• Calcium binds to TnC, inhibits TnI, conformational change in tropomyosin exposes active site between actin and myosin.
• Myosin head and actin interaction triggers myosin head firing, pulling along actin filament in the power stroke.
• ADP is released from the myosin head, which then binds a new ATP, releasing the actin filament.

Calcium and Force Production:

• Shortening of the sarcomere and ratcheting of actin myosin occurs

Automaticity:

• Myocardial electrical cells spontaneously initiate electrical impulses.
• Important functions include acting as a pacemaker and forming the conductive system.

Locations of autorhythmic cells:

• SA node is a specialized region in right atrial wall near opening of superior vena cava.
• AV node is a small bundle of specialized cardiac cells located at base of right atrium near septum.
• Bundle of His: cells originate at AV node and enters interventricular septum, divides to form right and left bundle branches, curve around tip of ventricular chambers, travel back toward atria along outer walls.
• Purkinje fibers: small, terminal fibers that extend from bundle of His and spread throughout ventricular myocardium.

Mechanisms of automaticity:

• Autorhythmic cells do not have stable resting membrane potential.
• This is due to Natural leakiness to Na and Ca which causes spontaneous and gradual depolarization
• Their unstable resting membrane potential leads to gradual depolarization, which reaches threshold.

Excitability:

• The ability of an electrical cell to acknowledge and respond to an electrical impulse.
• Certain cells possess greater excitability than others.
• SA and AV node have relatively poor responsiveness to stimulation by an electrical impulse.

Conductivity:

• Is the ability of myocardial cells to transmit the electrical impulses onto the next cell.

Contractility:

• Is the ability of a cell to shorten and lengthen its muscle fibre in response to electrical stimulation.

Spread of Cardiac Excitation:

• Cardiac impulse originates at SA node.
• AP spreads throughout right and left atria
• Impulse passes from atria into ventricles through AV node
• AP briefly delayed at AV node.
• Impulse travels rapidly down interventricular septum by means of bundle His
• Impulse rapidly disperses throughout myocardium by means of purkinje fibers.
• Rest of ventricular cells activated by cell to cell spread of impulse through gap junctions.

Variances in Cardiac Conduction

SV x HR = CO SV is dependent on filling time, adequate volume, and myocardial muscle function. HR is dependent on electrical stimulus, autonomic NS, parasympathetic NS.

Arrhythmia Symptoms

• Palpitations
• Dizziness
• Chest pain
• Dyspnea
• Fainting, syncope
• Sudden cardiac death

Effects of an altered action potential curve:

• External influences can alter one or more components of an action potential curve. Sympathetic or parasympathetic nervous system influence
• Acid/ base imbalance
• Meds
• HR changes
• Cell damage
• Myocardial cooling
• Myocardial stretching
• Hormones

Disorders of Automaticity

• When the slope of phase 4 becomes more steep, impulses are being generated with increased frequency
• This is because the rate of rise to threshold potential is faster.
• The opposite is true if the slope of phase 4 is more gradual.

Disorders of conductivity:

• The velocity at which an impulse is conducted will be faster if:
• The rate of rise of phase 0 is more perpendicular.
• MRP is more negative.
• The amplitude of phase 0 is greater, with more positive overshoot.
• There is less difference between MRP and TP

Disorders of excitability:

• The greater the difference membrane potential and threshold potential, the more depressed will be cell excitability.

Failure of impulse generation:

• Failure of SA node automaticity, resulting in an insufficient number of electrical emanating from the SA node: sinus bradycardia
• Symptomatic sinus bradycardia is called sick sinus syndrome.

Failure of impulse propagation:

• Failure of electrical impulses generated by the SA node or by subsidiary atrial pacemakers to conduct normally to the ventricles.

Heart block or AV block:

• Implies an abnormality of conduction velocity and/ or refractoriness in the conducting system.
• Ventricles depend on the function of the AV node for conduction of the electrical impulse.

Tachyarrhythmias:

• Acceleration of phase 4, abnormal focus in the atria, AV junction or ventricles
• Re entrant tachycardias are sudden onset, rapid heart arrhythmias that occur in people who have extra electrical connections in their heart.
• Triggered activity occurs early after depolarization and delayed after depolarization.

Reentry:

• Abnormal connections can create an electrical circuit that is not present in a normal heart.
• A re-entrant tachycardia occurs when under just the right conditions.
• SVT , VT , and VF are re-entrant tachycardias
• SVT’s are congenital usually seen in healthier, younger people, SVT can cause significant symptoms but is almost never dangerous or life threatening
• VT and VF are a result from scarring of heart muscle.

Triggered activity:

• Occurs when abnormal AP are triggered by a preceding AP, resulting in either atrial or ventricular tachycardia.
• The abnormal impulses are seen as spontaneous depolarizations that occur during either phase 3 or 4 of an action potential called afterdepolarizations.
• It is more likely to occur when the action potential duration is abnormally long.
• Early afterdepolarizations occur during late phase of 2 or 3 and can lead to several rapid action potentials or a prolonged series of action potentials.
• Delayed afterdepolarizations occur in late phase 3 or early phase 4 when the AP is nearly or fully repolarized.

Left Ventricular Hypertrophy:

• The LVH in response to pressure overload secondary to conditions such as aortic stenosis and hypertension
• The thickened LV wall leads to prolonged depolarization and delayed repolarization in the lateral leads.
• May lead to distortion and disruption of the conduction system, creating a widened QRS complex and an incomplete LBBB.

Right ventricular hypertrophy:

• With RVH, the pattern of the R wave progression is reversed and now the ventricle is the dominant area, resulting in an increased magnitude of depolarization

Right atrial enlargement:

• Often results in a disruption or slowing of conduction.
• The RA is depolarized earlier than the left atrium.

Left atrial enlargement:

• As the atrium expands and conduction is disrupted, P waves increase in duration.

Long QT syndrome:

• Involve an abnormal repolarization of the heart.
• Abnormal repolarization causes differences in the refractory period of the myocytes.

Conduction and ECG:.

• A vector is the visual representation of the summation of the millions of individual depolarizations.
• Vector travelling in the same direction will be positive.
• Vector is travelling in the opposite direction will be negative.
• Vector is travelling on an angle to the axis will have less amplitude.
• Vector off current flow will be biphasic.
• Biphasic deflection has both positive and negative components.

ECG paper:

• Small box is 1mm and 0.04sec
• Large box is 5mm and 0.20 sec.
• Paper speed is 25mm/sec.

P wave:

• Atrial contraction or depolarization

QRS complex:

• Time for ventricular contraction or depolarization

T wave:

• Ventricular repolarization “recharging”

PR interval:

• Time between atrial depolarization to ventricular depolarization

QT interval:

• Represents one complete ventricular depolarization and repolarization.

ST segment:

• Beginning of ventricular repolarization

Long QT interval:

• Can be caused by certain drugs, electrolyte disturbances, hypothermia, ischemia, infarction, subarachnoid hemorrhage

Short QT interval:

• Drugs or hypercalcemia can cause this.

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

Phases of the cardiac cycle:

• Contraction forces blood through the open AV valves into ventricles (active filling)
• Atrial systole pumps only about 20% of blood into ventricles
• Atrial systole contributes a final 25mL.
• Ventricular filling: mid to late diastole, 80% of blood enters ventricles passively.
• Rising ventricular pressure results in closing of AV valves (1st heart sound – lubb)
• For about 5 seconds both the SL and AV valves are closed
• Isovolumetric contraction phase means that the ventricles are contracting but no blood is leaving and the pressure isn’t great enough to open semilunar valves
• Ventricular ejection phase opens semilunar valves.
• Volume of blood remaining in ventricle at the end of systole is about 60mL : end systolic volume
• Stroke volume is the volume ejected per beat from each ventricle, equals end-diastolic volume minus end-systolic volume.
• At rest stroke volume is about 130mL – 60mL = 70mL
• Semilunar valves are closed (2nd sound dub)
• Dicrotic notch is the brief rise in aortic pressure caused by backflow of blood rebounding off semilunar valves.

Antiarrhythmic Drugs

Class I:

• Block sodium channels which reduce phase 0 slope and peak of action potential.

Class II:

• Block beta receptors which reduces the rate and conduction of sympathetic activity.

Class III:

• Block potassium channels which delay repolarization (phase 3) and thereby increase action potential duration and effective refractory period.

Class IV:

• Block calcium channels and L type calcium channels specifically which is most effective at SA and AV nodes; reduces rate and conduction.

Heart Disease

• Heart failure, also known as congestive heart failure, is a condition that develops after the heart becomes damaged or weakened.
• Occurs when the pumping action of the heart is not strong enough to move blood around.
• This can cause fluid to back up in the lungs and in other parts of the body.
• Typically begins in the Left ventricle and has no cure.

Left sided heart failure:

• The heart may back up in the lungs, causing shortness of breath.

Right sided heart failure:

• The heart may back up into abdomen, legs and feet, causing swelling.

Systolic heart failure:

• The left ventricle can’t contract vigorously, indicating a pumping problem.

Diastolic heart failure:

• The left ventricle can’t relax or fill fully, indicating a filling problem.

Symptoms of HF:

• Shortness of breath (SOB).
• Fatigue and weakness
• Swelling in your legs, ankles, and feet
• Rapid or irregular heartbeat
• Reduced ability to exercise
• Persistent cough or wheezing
• Increased need to urinate at night.
• Sudden weight gain from fluid retention
• Lack of appetite and nausea

Causes of HF:

• The most common is damage to the heart muscle caused by a heart myocardial infarction.
• The second most common cause of HF is hypertension.

High BP:

• The heart works harder than it has to if BP is high.

Coronary Artery Disease:

• Narrowed arteries may limit the heart’s supply of oxygen rich blood, resulting in weakened heart muscle.

Heart attack:

• Damage to the heart muscle from a heart attack may mean the heart can no longer pump as well as it should.

Diabetes:

• Having diabetes increases risk of high BP and CAD
• Sleep apnea:
• The inability to breathe properly at night results in low blood oxygen levels and increased risk of abnormal heart rhythms.
• Congenital heart defects: H

Kidney damage or failure:

• HF can reduce the blood flow to kidneys, eventually causes kidney failure if left untreated, kidney damage from HF can require dialysis for treatment.

Heart Valve Problems:

• The valves of the heart may not function properly if the heart is enlarged, or if the pressure in the heart is very high due to HF.

Liver damage:

• HF can lead to buildup of fluid that puts too much pressure on the liver, this fluid backup can lead to scarring, which makes it more difficult for the liver to function properly.

Stroke:

• Because blood flow through the heart is slower in HF than in a normal heart, blood clots may develop, increases risk of stroke.

Class I HF:

• No limitation of physical activity

Class II HF:

• Slight limitation of physical activity

Class III HF:

• Marked limitation of physical activity

Class IV HF:

• Unable to carry on any physical activity without discomfort.

Treatments:

Angiotensin- converting enzyme (ACE) inhibitors:

• A type of vasodilator, widens blood vessels to lower BP, improve blood flow and decrease the workload on the heart.

Angiotensin II receptor blockers:

• Have many of the same benefits at ACE inhibitors, just more tolerable

Beta blockers:

• Not only slows the heart rate and reduces BP but also limits or reverses some of the damage to the hart if there is systolic HF.

Diuretics

• Decrease rate and force
• Lose electrolytes so pt may need to take K supplements

Coronary bypass surgery:

• Used if severely blocked arteries are contributing to HF.

Cardiomyopathy:

• Is a disease of the heart muscle that includes dilated, hypertrophic, and restrictive forms.
• Makes it harder for the heart to pump and deliver blood to the rest of the body.
• Has treatment and occurs in several forms.
• Ischemic cardiomyopathy is the most common form, it is the loss or weakening of heart muscle tissue caused by ischemia which usually results from CAD and MI’s

Dilated cardiomyopathy:

• Affects the chambers of the heart by weakening their walls, it may be caused y viral infection of the heart muscle, excessive alcohol consumption, cocaine and abuse of antidepressant drugs, the cause is usually unknown.

Hypertrophic cardiomyopathy:

• Causes a thickening of the heart’s walls, which makes it harder for it to pump, mainly occurs when the wall between the bottom chambers of the heart becomes enlarges and blocks the flow of blood.

Symptoms of cardiomyopathy:

• Palpitations
• Fainting
• Light headedness
• Breathlessness upon exertion
• Arrhythmias
• Hypertrophic cardiomyopathy may cause dizziness.
• Restrictive cardiomyopathy can cause swelling.

Causes of cardiomyopathy:

• Long term high BP
• Heart valve problems
• Heart tissue damage
• Chronic rapid HR
• Metabolic disorders
• Nutritional deficiencies
• Pregnancy
• Drinking too much
• Use of cocaine
• Use of chemo drugs

Risk factors of cardiomyopathy:

• Family history
• Obesity
• Alcoholism
• Illicit drug use
• Cancer treatments

Complications of cardiomyopathy:

• HF, blood clots, valve problems, cardiac arrest or sudden death

Left ventricular hypertrophy:

• Is the enlargement of the muscle tissue that makes up the wall of the heart’s main pumping chamber.
• Develops in response to some factor.
• Usually develops gradually.
• Causes SOB, CP, palpitations, dizziness or fainting.
• Causes include hypertension, aortic valve stenosis, hypertrophic cardiomyopathy,and athletic training.
• LVH changes both the structure and function of the chamber

Pulmonary Hypertension:

• Is a type of high BP that affects the arteries in the lungs and the right side of the heart.
• Begins when pulmonary arteries, and capillaries become narrowed, blocked or destroyed, it makes it harder for blood to flow through the lungs, and raises pressure within the lungs arteries.
• Is a serious illness that becomes progressively worse and is sometimes fatal.
• Is not curable.
• Class I : no symptoms
• Class II : no symptoms at rest, fatigue, SOB or chest pain with normal activity
• Class III : comfortable at rest, symptoms occur when physically active
• Class IV : symptoms even at rest
• Causes dyspnea, fatigue, syncope, chest pressure or pain, edema in your ankles and legs, cyanosis, palpitations.

Idiopathic pulmonary hypertension:

• This is when an underlying cause for high BP in the lungs can’t be found

Secondary pulmonary hypertension:

• Pulmonary hypertension that’s caused by another medical problem.
• Causes include blood clots in the lungs, COPD, sleep apnea, congenital heart defects, sickle cell anemia, AIDS,

Eisenmenger syndrome and pulmonary hypertension:

• A type of congenital heart defect, causes pulmonary hypertension.
• Most commonly caused by a large hole in your heart between the two lower chambers

Primary Hypertension:

• Tends to develop gradually over time.

Secondary Hypertension:

• Tends to appear suddenly and cause higher BP.
• Kidney problems, adrenal gland tumors, certain defects your born with, certain meds, and drugs can lead to secondary hypertension.

Complications of hypertension:

• MI or stroke: cause atherosclerosis
• Aneurysm
• HF
• Weakened or narrowed vessels in your kidneys.
• Thickened or narrowed or torn blood vessels in the eyes.
• Metabolic syndrome
• Trouble with memory or understanding.

Pulmonary edema:

• Is a condition caused by excess fluid in the lungs, the fluid collects in the numerous air sacs in the lungs, making it difficult to breathe.
• If it continues, it can raise pressure in the pulmonary artery and eventually the right ventricle begins to fail.
• The RV has a much thinner wall of muscle than the LV, the increased pressure backs up into the right atrium and then into various parts of your body where it can cause edema, congestion and welling of the liver, etc

Varicose Veins:

• Age, gender, family history, obesity, standing or sitting for long periods of time, ulcers, and blood clots are all factors that increase the risk of having varicose veins.

Peripheral artery disease:

• Is a common circulatory problem in which narrowed arteries reduce blood flow to limbs.
• Extremities don’t receive enough blood flow to keep up with demand.
• Is also likely to be a sign of more widespread accumulation of fatty deposits in arteries.
• This may reduce blood flow to the heart, brain, and legs.

Cardiac Output

• The amount of blood pumped by each ventricle in one minute.
• CO = HR x SV

Heart Rate:

• Is modified by autonomic, immune, and local factors.
• An increase in parasympathetic activity via M2 cholinergic receptors in the heart will decrease the heart rate.
• An increase in sympathetic activity via B1 and B2 adrenergic receptors throughout the heart will increase the HR.

Stroke Volume:

• Is determines by 3 factors; preload, afterload, and contractility.
• Preload gives the volume of blood the ventricle has available to pump.
• Contractility refers to the ability of the myocardium to contract normally, it is influenced by preload. The greater the stretch the more forceful the contraction.
• Stronger contraction = larger SV
• Afterload is the arterial pressure against which the muscle will contract.
• Volume of blood pumped by a ventricle per beat.
• SV = end diastolic volume – end systolic volume

Preload:

• The stretching of muscle fibers in the ventricle
• The most important determining factor for preload is venous return; skeletal muscle pump, respiratory pump, atrial suction.

Afterload:

• Refers to the pressure the ventricular muscles generate to overcome the higher pressure in the aorta to get the blood out of the heart.

Frank Starling Principle:

• The relationship between cardiac output and left ventricular end diastolic volume.
• Cardiac output os directly related to venous return.
• The contraction and therefore stroke volume in response to changes in venous return is called the frank starling mechanism.

Neural Regulation of the heart:

• Parasympathetic stimulation: a negative chronotropic factor
• Sympathetic stimulation : a positive chronotropic factor, increases HR and force of contraction

Hormonal Regulation:

• Epinephrine and norepinephrine from the adrenal medulla is a response to increased physical activity, emotional excitement, and stress.

Extrinsic factors influencing stroke volume:

• Contractility is the increase in contractile strength, independent of stretch and EDV which comes from certain hormones, Ca and drugs.

EDV:

• EDV is affected by venous return, which is the volume of blood returning to heart.
• Preload also affects EDV by the amount ventricles are stretched by blood.

ESV:

• ESV is affected by contractility, which is myocardial contractile force due to factors.other than EDV
• Afterload also affects ESV by the back pressure exerted by blood in the large arteries leaving the heart.

Vascular system

• Total blood flow through any level of the circulation is equal to the cardiac output.
• Total peripheral resistance= (Mean arterial pressure – Mean Venous Pressure) / Cardiac Output

Aorta:

• Absorbs pulse pressure.

Large arteries:

• conduct and distribute blood to regional areas.

Arterioles:

• Regulate flow to tissues and regulate MAP.

Capillaries:

• Allow for exchange.

Venules:

• Collect and direct blood to the veins

Veins:

• returns blood to heart and acts as a blood reservoir and have one way valves..

Blood flow:

• Blood flow through the vascular system is directly proportional to the pressure gradient.
• If the pressure gradient increases, flow increased.
• The tendency of the vascular system to oppose blood flow is called its resistance and is inversely proportional to flow.
• If the resistance increases, the flow decreases.

Pulse Pressure:

• Applies only applies to arteries.