Heart

Myocyte electrical properties

Excitability, conductivity, and automaticity

Excitability

RMP and regenerative AP

Fast and slow response

Cells with a fast response

Atria, ventricles, and fast conduction network

Phases of Fast Cardiac AP: 0 - 4

Phase 0 of Fast Cardiac AP

Upstroke due to very rapid increase in Na⁺ permeability (V_Na⁺ channels) but close quickly

Initiated by current from neighbouring cells

Phase 1 of Fast Cardiac AP

Early repolarisation to near 0mV due to inward Cl^- channels and outward transient K⁺ channels

Close off quickly

Phase 2 of Fast Cardiac AP

Plateau due to slow inward V_Ca²⁺ channels → Ca²⁺ mediated Ca²⁺ release but balanced by outward I_K1 current

Background currents are 3Na⁺/Ca²⁺ exchanger

Phase 3 of Fast Cardiac AP

Repolarisation due to Time dependent V_K⁺ channels (activated in phase 1), more I_K1 open, and V_Ca²⁺ channels close

Closes off as RMP is restored

Phase 4 of Fast Cardiac AP

RMP (~-85mV) defined by I_K1 being fully on at rest

Background pumps

Ca²⁺ ATPase pump (Outward current)

3Na⁺/Ca²⁺ exchanger (Electrogenic, depolarisation, or repolarisation)

Na⁺/K⁺ ATPase

Cells with a slow response

SA and AV nodes

Ca²⁺ upstroke instead of Na⁺ so slower

Higher RMP ~-60mV

Pathology that can change Fast AP → Slow

Angina, heart attacks, ischemia

Areas of slow conduction can cause arrhythmias

Refractoriness

Ensures rythmn of heart

Full recovery time = Absolute refractory period + Relative refractory period + Supernormal period

RRP

Can stimulate myocyte at higher a higher threshold

SNP

Stimulation results in abnormal AP

Conductivity

Myogenic activation (cell - cell conduction) through intercalated discs for mechanical and electrical connection

Automaticity

SA and AV nodes, and parts of His-Purkinje network

Combination of decreasing outward currents (I_K (mostly on and varies in strength) and I_K1) and increasing inward currents (I_f and I_ca (Continues into diastole))

I_f

Funny current and mainly inward Na⁺ current

Activated by hyperpolarisation

How to alter intrinsic rate of pacemaker discharge

Altering rate of depolarisation, threshold potential, and maximum diastolic potential

PNS affect on HR

Slows HR by release of ACh at vagal endings by binding to I_KACh found at SAN to increase K⁺ permeability = hyperpolarisation and decreased pacemaker slope

Also slows conduction through AVN (Very strong stimulation can stop SAN/AVN)

SNS affect on HR

Speeds HR by release of NA at SAN which phosphorylates and increases opening probability of Ca²⁺ channels to increase slope of pacemaker depolarisation

Internodal tracts

Cells connected and aligned so that rapid conduction does occur

Faster conduction along cells compared to across

Overdrive suppression

Keeps other cells from attempting to take over the pacemaker via hyperpolarisation

ECG

Sum of electrical activity of heart (Voltage/Time)

Recorded by electrodes at different sites to measure potential difference between sites

P wave

Atrial depolarisation

Relatively small and wide so slow event

PR segment

Atria have depolarised (isoelectric)

Reflects time taken to pass through AVN, AVB, and BB, small mass not seen

QRS complex

Ventricular depolarisation

Greater magnitude (more tissue) and skinnier (Purkinje fibres) than P wave

Q - Ventricular septum depolarising

R - Ventricular apex depolarising

S - Ventricular base depolarising

PR interval

Total time for wave to pass from atria to ventricles

ST segment

Isoelectric and all ventricular myocytes depolarised so no moving wavefront

Plateu of ventricular AP

T wave

Asynchronous ventricular repolarisation which is slower than depolarisation

U wave

Uncertain origin

QT interval

Reflection of AP duration

Dipole from wavefront

Direction of vector = direction of dipole ( - → + )

Length of vector ≈ strength of dipole

+ve deflection when +ve pole faces +ve electrode

How do you increase a dipole

Recruiting more muscle

More efficient conduction/distance between

What determines the final vector

Magnitude of charges (true size of dipole)

Distance between dipole and electrodes

Orientation of dipole and electrodes

Vector properties

Length represents magnitude

Angle represents direction

Polarity represents direction of wavefront

ECG lead systems

Bipolar, unipolar (frontal plane), and precordial (horizontal plane)

Bipolar lead system

Uses Einthoven’s triangle

Lead 1 = LA - RA, Lead 2 = LL - RA , Lead 3 = LL - LA

Einthoven’s triangle

Uses the RA ( -,-), LL ( +,+ ), and LA ( +,-)

Equivalent to 3 corners of an equilateral triangle with heart at centre

Einthoven’s law

At any instant during the cardiac cycle: Lead 1 + Lead 3 = Lead 2

Unipolar lead system

Uses Wilson’s Central Terminal as the reference lead and an indifferent/exploring electrode

Limb leads are aV_R, aV_L, aV,_F

Wilson’s Central Terminal

Connects RA, LA, and LL to average them out which allows you to look at ‘heart from centre of chest’

Precordial leads

V1 - V6

Looks at heart from front and side

Good at looking at ventricular abnormalities

ECG abnormalities

Widened QRS - slow depolarisation of ventricles

Prolonged PR segment - delayed conduction form atria to ventricles

QRS - ischemia and infarction causes many (Q wave)

ST segments - elevation/depression from baseline

T wave - inversion

Wolff-Parkinson-White syndrome

Shortened PR interval, wide QRS complex, and delta wave

Mean QRS vector

Points from base → apex

Dipole consistent with all leads

Maximum deflection - maximum deflection in opposite direction

Deflection ≈ -30^o to +110^o (0^o = horizontal)

Left axis deviation

Mean QRS vector less than -30^o

Right axis deviation

Mean QRS vector more than 110^o

Cardiac myocytes

Always have maximum actin-myosin overlap

Contains lots of CT

No descending limb (impossible in normal physiology)

Has length dependent activation property

Length dependent activation

Increased Ca²⁺ sensitivity of Troponin-C at greater sarcomere lengths

Increased Ca²⁺ entry through stretch activated channels at greater SL

Calcium movement in cardiac muscle

Contraction: Ca⁺ in through V_Ca²⁺ via T-tubule/AP → Ca²⁺ mediated Ca²⁺ release from SR/SSS

Relaxation: Ca²⁺ reuptake in SSS/SR via Ca²⁺ ATPase, Ca²⁺ ATPase on SL, and 3Na⁺/Ca²⁺ exchanger on SL

Inotropic state

Degree of activation of contractile proteins by Ca²⁺

Factors that increase inotropic state

∆AP - Increased plateau → Increased Ca²⁺ influx

External ion conc. - Increased Ca²⁺ external conc. → Increased Ca²⁺ influx
Lower external Na⁺ → slows 3Na⁺/Ca²⁺ x → Increased intracellular Ca²⁺

Force frequency relationship - Increase stimulation frequency → Increased Ca²⁺ influx

Neurotransmitters (activation of G-protein pathways) - α/ß-adrenergic agonist → Opens V_Ca²⁺ longer, upregulates Ca²⁺ ATPase into SR, and phosphorylates Troponin-C

Xanthines - inhibits breakdown of cAMP

Cardiac Glycosides - Inhibit Na⁺/K⁺ pump → Diminish Na⁺ gradient → slow 3Na⁺/Ca²⁺ x → Increased intracellular Ca²⁺ (Temporary as it causes dying heart to work harder)

Factors that decrease inotropic state

AChnergic muscarinic agonist - Decrease Ca²⁺ influx

Ca²⁺ channel blockers → Reduce Ca²⁺ entry across SL

Ischaemia and heart failure

Potential pressure

The highest possible amount of pressure the heart can reach

LaPlace’s law

The larger the radius, the larger the wall tension required to withstand a given internal fluid pressure

Stroke work

= Pressure x Volume ≈ MAP x SV

VSW = Area in pressure volume loop

ASW = Area under passive pressure within the same volume