IBHS 527 lecture 5

• 1. specialized muscle cells of the conducting system
• -controls and coordinate heartbeat
• 2. contractile cells (muscle cells of heart)
• -produce contractions that propel blood

TRUE

• ability to contract on it own without neural or hormonal stimulation (which usually is used to regulate the speed either increase or decrease)
• this is unique property to cardiac muscle

• 1. sinoatrial (SA) node
• 2. atrioventricular (AV) node
• 3. conducting cells:
• -internodal pathways, AV bundle, right and left bundle branches, Purkinje fibers (stimulate directly on the ventricular cardiac muscle cells)

after each repolarization the membrane drifts towards threshold and cannot maintain stable resting membrane potential (RMP)

FALSE. "different" rates

• 1. Sinoatrial (SA) node has fastest rate of spontaneous depolarization with 80-100 per minute
• 2. Atrioventricular (AV) node generates 40-60 action potential per minute
• 3. Purkinje fibers 20-40 action potential per minute
• *the fastest rate dominates because it occurs the quickest
• -SA node dominates usually, unless it's damaged and then AV node is next to dominate (back-up plan) ... however it's harder if it moves to Purkinje fibers

• 1. SA node
• 2. AV node
• 3. AV bundle (bundle of His)
• 4. Right and left AV bundle branches
• 5. Purkinje fibers

• step 1
• -located in posterior wall of right atrium
• -contains pacemaker cells
• -referred to as the cardiac pacemaker
• -connected to AV by internodal pathways
• ------
• T = 0
• SA node activity and atrial activation begins

• step 2
• -located in the floor of right atrium
• -impulse conduction slows when passing through AV node because the atria has to contract before the ventricles to get the extra blood into the ventricles first.
• ------
• T = 50 msec
• stimulus spreads across the atrial surfaces and reaches the AV node

• step 3
• only electrical connection between atria and ventricles
• ------
• T = 150 msec
• there is a 100-msec delay at the AV node. Atrial contraction begins

• step 4
• -left branch is larger because it meets the need of the left ventricle which is also large
• -both extend toward apex and fan out
• ------
• T = 175 msec
• the impulse travels along the interventricular septum within the AV bundle and the bundle branches to the Purkinje fibers and, via the moderator band, to the papillary muscles of the right ventricle

• step 5
• -conduct action potentials very rapidly to ventricular muscle (contractile) cells
• ------
• T = 225 msec
• the impulse is distributed by Purkinje fibers and relayed throughout the ventricular myocardium. Atrial contraction is complete, and ventricular contraction begins.

• ECG or EKG
• -recording of the electrical events in the heart (depolarization and repolarization)

• 3 parts on graph:
• 1. P wave: depolarization of atria
• 2. QRS complex: ventricular depolarization
• 3. T wave: ventricular repolarization
• *don't see atria repolarization --> masked by ventricular depolarization
• 2 measurable intervals:
• 1. P-R interval:
• -start of atrial depolarization (P) to start of ventricular depolarization (actually measured at start of QRS complex - but close to the R wave)
• -if P-R interval increases to over 200 msec, this can indicate damage to conducting pathways or AV node
• 2. Q-T interval:
• -one complete cycle of ventricular depolarization and repolarization
• -usually measured from end of P-R interval instead of from the bottom of the Q wave
• -prolonged Q-T interval can indicate electrolyte disturbances, conduction problems, coronary ischemia, myocardial damage, and some drugs can cause this
• 

• diagnosing cardiac arrhythmias
• -may indicate damage to myocardium (muscle tissue of heart), injuries to the pacemakers or conduction pathways, exposure to drugs, or abnormalities in electrolyte composition of extracellular fluids

digoxin, antiarrhythmics classes I-IV, tricyclic antidepressants, H₁ antagonists, methylxanthines, doxorubicin, lithium, catecholamines, diuretics

abnormal rhythm/pattern of electrical activity of the heart

• 1. bradycardia
• 2. tachycardia
• 3. atrial fibrillation
• 4. ventricular fibrillation

• less than 60 BPM with exceptions to athletes who may have lower at rest
• - caused by damage to conduction pathway or damage to SA node or damage to AV node (slower) - heart block (SA fire but AV is bad so that the atria still depolarizes of P wave but no QRST sometimes)
• TREATMENT (general): chronic and require pacemaker rather than drugs

• greater than 100 BPM at rest -caused by part of conduction system being overactive or overstimulated (overacting of nervous system. ex- hyperthyroidism and thyroid hormone
• TREATMENT (general): drugs like beta blockers and lowering heart rate.

• another cause of arrhythmias (another cell on its own causing async. contraction)
• -when a Purkinje or ventricular muscle cell depolarizes to threshold and triggers an abnormal conduction pathway or premature ventricular contraction (PVC)

• -impulses move over atrial surfaces in uncoordinated fashion (like a bag of worms - no distinct P wave and no pattern with QRST
• -heart can still pump blood
• -ventricles can still contract
• -and one can live with this because it affects the atria only contribute little whereas most blood is in the ventricles

• -impulses travel around ventricles in uncoordinated fashion
• -premature ventricular contractions (PVCs) and ventricular tachycardia can precede/lead to fibrillation
• -can lead to cardiac arrest (heart stops pumping blood)
• *you can't live with this! so you would need treatment: defibrillator - shocks heart --> depolarize entire heart at once --> SA take control again --> normal rhythm

classes

• 1. class I: sodium channel blockers
• 2. class II: beta-clockers
• 3. class III: potassium channel blockers
• 4. class IV: calcium channel blockers

• sodium channel blockers
• -lidocaine (not top 200)
• -quinidine (not top 200)
• *when having an abnormal rhythm, slow down the depolarization rate to get to unison

• beta-blockers
• -atenolol
• -carvedilol
• -metoprolol
• *when having tachycardia, slow the heart rate

• potassium channel blockers
• -amiodarone (can also block calcium and sodium channels)
• *slow down repolerization --> extend refractory period so that it is hard to stimulate again -- slow down for the SA node to take over again

• calcium channel blockers
• -diltiazem
• -verapamil
• *block/slow action potentials (AP)

• process:
• (1) action potential leads to appearance of Ca²⁺ among the myofibrils --> (2) binding of Ca²⁺ to troponin on thin filaments initiates contraction --> (3) actin-myosin cross-bridges form, filament slides, contraction occurs

nature and duration of action potential

• process:
• (1) depolarization to threshold initiates action potential [AP] --> depolarization pharse of AP due to Na⁺ influx --> repolarization phase of AP due to K⁺ efflux
• *lasts 1-2 msec during entire AP
• 

• 1. rapid depolarization (still like skeletal muscle):
• -causes Na⁺ entry
• -duration is 3-5 msec
• -ends with closure of voltage-regulated (fast) sodium channels
• 2. plateau (MAIN DIFFERENCE):
• -causes Ca²⁺ entry (K⁺ goes out)
• -duration is ~175 msec
• -ends with closure of slow calcium channels (net flux of ions is 0 because it balances with K⁺)
• 3. repolarization:
• -causes K⁺ loss
• -duration is 75 msec
• -ends with closure of slow potassium channels
• *graph looks different and there is a longer refractory period due to plateau and longer action potential (AP) - longer contraction
• 

• skeletal:
• (1) action potential (AP) travels down T tubules --> (2) changes in membrane potential opens Na⁺ channels --> (3) Ca²⁺ released from sarcoplasmic reticulum (SR) initiates contraction --> (4) actin, myosin filaments interact
• *AP lasts ~1-2 msec.

• cardiac:
• (1) action potential (AP) travels down T tubules --> (2) changes in membrane potential opens Na⁺ channels (fast) and Ca²⁺ channels (slow - slight delay) {extracellular Ca²⁺ concentration affects strength (INC.) of contraction (T tubules: 5x diameter vs skeletal) which means more Ca²⁺ in addition to SR Ca²⁺} --> from out to in is Ca²⁺ inducing Ca²⁺ release from SR, initiates contraction --> actin, myosin filaments interact
• *AP lasts ~250-300 msec (lasts longer than skeletal)

highlight = 3 differences between skeletal vs cardiac muscle

• 1. no plateau phase (Ca²⁺) in SA node action potential (the calcium is responsible only for conduction and so no need for more calcium)
• 2. Phase 4 (picture)
• -SA node has a drifting membrane potential (prepotential or pacemaker potential)
• 

from the start of one heartbeat to the beginning of the next

• 1. atrial systole and diastole
• 2. ventricular systole and diastole
• *systole = contraction
• *diastole = relaxation

FALSE. from "higher" to "lower"

TRUE. has to deal with systemic circulation

FALSE. "same" time (it's different between atria and ventricles)

• start = atrial systole
• isotonic - moving and changing muscle length
• 2 phases of ventricular systole
• 2 phases of ventricular diastole (early and late)
• ventricles fill passively in step f
• 

• stethoscope --> listen for normal/abnormal heart sound
• S₁: closing of AV valves = "Lubb"
• S₂: closing of semilunar valves = "Dubb"
• S₃ and S₄ = not often audible in healthy adults
• -S₃: blood flowing into ventricles
• -S₄: atrial contraction
• heart murmur: AV valve regurgitation (rushing, gurgling sound)

• 1. myocardial infarction (MI)
• 2. congestive heart failure (CHF)

• when a region of the coronary circulation is blocked and cardiac muscle cells die from lack of oxygen
• -caused (often): by coronary artery disease (CAD)
• *approximately every minute an American dies from a coronary event (MI is just one of them)

region of damaged nonfunctional tissue

FALSE. they "cannot" be replaced unlike skeletal satellite cells

• 1. diagnostic blood tests
• -lactate dehydrogenase (LDH), creatine phosphokinase specific to cardiac muscle (CK-MB), cardiac troponin I, cardiac troponin T
• *if you have MI, those cells that die then go to the bloodstream and release these enzymes and proteins --> they are not normally found in the bloodstream = damage occurred
• 2. ECG findings
• -elevated/longer than normal S-T segment
• -enlargement of T waves

• 1. vasodilators
• 2. anticoagulants
• 3. fibrinolytics
• *depends on the cause

• 1. smoking
• 2. high blood pressure (BP)
• 3. high blood cholesterol levels
• 4. high LDLs
• 5. diabetes: it's own risk factor - INC. mortality
• 6. male gender (below 70 yrs) - although risk of MI is lower in females under 70 (with hormone levels), mortality rate is higher if you have one
• 7. severe emotional stress
• 8. obesity
• 9. genetic predisposition
• 10. sedentary lifestyle

• -inability for heart to function
• condition in which heart is unable to eject the volume of blood delivered to it; decreased cardiac output (amount of blood pumped per minute ~5L)

• 1. heart becomes engorged with blood
• 2. increased pressure, blood backs up into pulmonary or systemic circulation
• 3. typically due to cardiac muscle damage
• 4. initially compensates for the damage
• 5. eventually becomes decompensated (dHF)

• 1. coronary artery disease (CAD)
• 2. myocardial infarction
• 3. hypertension
• 4. valve disease

• 1. compensated CHF
• 2. decompensated CHF

• -cardiac hypertrophy (heart enlarges and increases in muscle size to increase contraction and not increase in numbers because cardiac muscle cells can't regenerate)
• -heart attempts to maintain cardiac output for short term
• -increased sympathetic nervous system output
• -release of adrenal hormones (epi/norepinephrine)
• -clinically asymptomatic

• after compensated stage
• -dilation and thinning of ventricular wall (chambers in heart enlarges)
• -heart can't maintain cardiac output
• -decreased blood flow to organs
• -venous congestion (backup of flow to heart)
• -clinical symptoms observed

• 1. right heart failure
• 2. left heart failure

• right ventricular dilation
• DEC. cardiac output
• INC. pressure in venous circulation (more blood back up in veins)
• systemic edema:
• -swelling of ankles and feet
• -distension of veins in neck
• *often caused by left heart failure

• left ventricular dilation
• DEC. cardiac output
• INC. pressure in pulmonary circulation (inc. back up in pulmonary)
• pulmonary edema
• breathlessness
• acidosis (due to accumulation of CO₂ and not enough O₂)
• *often caused by cardiac tissue damage

TRUE

• *making matters worse ...
• process:
• DEC. in renal/kidneys/body blood flow --> renin-angiotensin-aldosterone system (RAAS) stimulated --> angiotensin II --> (1) INC. blood pressure (BP) to increase blood flow while heart is already having hard time, (2) production of aldosterone --> aldosterone causes INC. Na⁺ and H₂O retention to increase blood volume to increase blood pressure which is worse for heart
• 

• 1. positively inotropic drugs
• 2. Beta-adrenergic receptor antagonists
• 3. diuretics
• 4. vasodilators
• 5. aldosterone receptor antagonists

• 1. Digitalis glycosides: Digoxin (top 200 - inhibit Na⁺/K⁺ ATPase --> INC. [Na⁺] --> INC. Ca²⁺ influx --> INC. fiber shortening = INC. strength of contraction)
• -INC. Ca²⁺ in cardiac muscle cells (INC. strength of contractility)
• -INC. cardiac output
• 2. adrenergic Beta-receptor agonists: dobutamine
• -acute
• -INC. contractility
• -INC. heart rate

• beta-blockers block effects of sympathetic nervous system
• -chronic
• top 200:
• 1. carvedilol (Coreg)
• 2. metoprolol (Toprol XL)

• DEC. fluid volume
• DEC. edema
• top 200:
• 1. loop diuretics: furosemide (most efficacious - larger extent in DEC. edema)
• 2. Thiazide diuretics: hydrochlorothiazide

• 1. ACE inhibitors:
• top 200:
• -Enalapril
• -Lisinopril
• *inhibits conversion of angiotensin I to angiotensin II (active form)
• 2. angiotensin receptor antagonists/blockers (ARBs)
• -Valsartan (DIOVAN; top 200)
• *blocks angiotensin II receptors

• top 200:
• spironolactone
• *act to INC. Na⁺ excretion (INC. water excretion) - like a diuretic