Electrical Activity & Regulation Of Heart Pt 2

Front 1

As one of the mechanisms that decreases firing frequency of the pacemaker cells, what are the direct effects of Ca++ channel blockers?

Back 1

(A) reducing the slope of phase 4
-thereby decreasing the rate of spontaneous depolarization

(B) decreasing the slope of phase 0
-which slows conduction velocity within the AV node

(C) increasing the threshold potential level

Front 2

As one of the mechanisms that decreases firing frequency of the pacemaker cells, what is the effect of blockers of the delayed rectifier K+ channel?

Back 2

increasing the length of phase 3 repolarization

Front 3

As one of the mechanisms that decreases firing frequency of the pacemaker cells, what does the activation of G-protein-coupled K+ channels increase?

Back 3

increases the maximal negative potential

Front 4

As one of the mechanisms that decreases firing frequency of the pacemaker cells, what is the effect of decreasing the Na+ "funny" current (I,f)?

Back 4

Decreasing the slope of phase 4 (A)

Front 5

As part of the factors that affect generation of action potentials in the conducting and contracting myocytes, what are the common causes of ABNORMAL electrical activity in the heart?

Back 5

-Inadequate myocardial blood flow (myocardial hypoxia)

-Changes in ion concentrations in the ECF ([K+]o, [Ca+ +]o, [Na+]o,)

-Changes in membrane ionic conductances (ion channels, exchangers)

-Changes in the ATPase (Na,K-ATPase, Ca-ATPase)

Front 6

What are the common consequences of abnormal electrical activity in the conducting and contracting myocytes?

Back 6

-Transformation of non-pacemaker into pacemaker cell action potential
---Ectopic beats

-Alteration of duration of the refractory period
---Abnormal myocardial contractility and rate of contraction

Front 7

What is myocardial hypoxia?

Back 7

Is a primary cause of abnormal electrical activity in cardiac patients
-This may lead to irregular heart beat

(Myocardial hypoxia causes transformation of non-pacemaker into pacemaker cell action potential)

Front 8

What is myocardial hypoxia caused by?

Back 8

Myocardial hypoxia is caused by inadequate myocardial blood flow due to:
-Low O2 supply (atherosclerosis, stenosis, spasm)
-Increased O2 demands (increased myocardial contractility)

Front 9

How can patients with coronary artery disease develop myocardial hypoxia?

Back 9

-in response to exercise or at rest (in more severe cases)

Front 10

What does inadequate O2 supply in myocardial hypoxia cause?

Back 10

-A decrease in ATP synthesis (impairment of ATPases activity)

-Local accumulation of tissue metabolites

-Impaired Na, K-ATPase activity
--[K+]o is elevated

Front 11

What happens to nonpacemaker APs when there is an increase in [K+]o?

Back 11

*An increased [K+]o contributes to transformation of non-pacemaker into pacemaker cell action potential *


When [K+]o is increased :
--The resting Vm becomes less negative
--The amplitude, duration of the AP and the steepness of the upstroke all diminish
--Conduction velocity is diminished

Front 12

An increase in [K+]o in nonpacemaker cell APs has what effect on the fast Na+ channels?

Back 12

-All the fast Na+ channels are inactivated
-Slow response (pacemaker potentials), mediated by the Ca++ inward current

*slide 35, panels D and E*

Front 13

What happens to the membrane in response to myocardial hypoxia?

Back 13

In response to hypoxia the membrane depolarizes and closes fast Na+ channels (at a membrane potential of about –50 mV all the fast Na + channels are inactivated)

Front 14

How can action potentials be elicited in myocardial hypoxia?

Back 14

-By the inward Ca++ current

-Similar to those found in pacemaker cells located in the SA or AV nodes

-Sometimes spontaneously

Front 15

What is the effect of myocardial hypoxia in ischemic heart disease?

Back 15

In ischemic heart disease this mechanism may serve as the electrophysiological mechanism behind certain types of ectopic beats and irregular heart rate
-Decreasing cardiac output

Front 16

True or False: Transformation of non-pacemaker into pacemaker cells can be also triggered by a decrease in Na+ conductance through the voltage-gated Na+ channels.

Back 16

True

Front 17

What effect does Tetrodotoxin have on voltage-gated Na+ channels?

Back 17

-Tetrodotoxin (TOXIN!!!!) blocks the voltage-gated Na+ channels

---(slide 37) The concentration of tetrodotoxin [Ttx] in micro mole (microM)
-[Ttx]D = [Ttx]E, but panel E was recorded later than panel D
-leads to slow response AP and low cardiac output

Front 18

What is the effect of K+ and Na+ channel blockers on the effective refractory period (ERP)?

Back 18

Many antiarrhythmic drugs increase the ERP, thereby altering cellular excitability:
-(a) K+ channel blockers delays phase 3 repolarization and increase the action potential duration
-(b) Na+ channel blockers decrease slope of the phase 0, depress the peak of the AP, and increase the inactivation state of fast-Na channels (voltage-gated Na-channels)

Front 19

What can alter the normal sequence of excitation in the conduction system of the heart?

Back 19

Normal sequence of excitation may be altered by:
-Disorders of impulses conduction:
--Block and reentry

-Disorders of impulses generation:
--Abnormal automaticity
--Triggered activity

Front 20

What is a conduction block (a type of disturbance of impulse and conduction)?

Back 20

failure of propagation in a cardiac fiber

Front 21

What is reentry (a type of disturbance of impulse conduction)?

Back 21

A cardiac impulse may reenter previously excited tissue when the impulse is conducted slowly around the loop and the impulse is blocked unidirectionally in some sections of the loop

Front 22

In disorders of impulses conduction (conduction block and reentry), what is the sequence of events in the disorder that leads up to depolarization being extinguished at the zone of collision?

Back 22

An excitation wave traveling down a single bundle (S) of fibers continues down the left (L) and right (R) branches. The depolarization wave enters the connecting branch (C) from both ends and is extinguished at the zone of collision.

Front 23

In disorders of impulses conduction (conduction block and reentry), can the depolarization wave be blocked in the L and R branches?

Back 23

Yes!

Front 24

In disorders of impulses conduction (conduction block and reentry), antegrade and retrograde (bidirectional) block exists in what branch?

Back 24

right branch

Front 25

In disorders of impulses conduction (conduction block and reentry), when unidirectional block exists in the right branch, what happens to the antegrade and retrograde impulse?

Back 25

-The antegrade impulse is blocked.

-The retrograde impulse in R arrives at this region later after excitability has recovered and is conducted through and reenters bundle S

Front 26

What happens in abnormal automaticity (a disorder of impulse generation)?

Back 26

Increased or depressed normal firing rate of pacemaker cells in the SA or/and AV nodes.

Front 27

What is abnormal automaticity due to?

Back 27

Due to:
Abnormal autonomic regulation
Other factors (metabolic, pharmacological, mechanical):
Hypo/hyper – kalemia , cardiac fiber stretch, β-adrenergic receptor activation, tissue injury
Ectopic pacemaker activity:
Increased automaticity of pacemakers outside of the SA

Front 28

What is triggered activity ( a disorder of impulse generation) always coupled to?

Back 28

a preceding action potential

Front 29

What is triggered activity caused by?

Back 29

It is caused by after depolarization:
--Early afterdepolarization (EAD) occurs at the end of phase 2 or about midway phase 3 (ionic mechanism is not clearly understood)

--Late afterdepolarization (LAD) occurs at the end or just after full repolarization ( associated with elevated [Ca++]i)

Front 30

What are the three main reasons for tachycardia (according to Ioudina...)?

Back 30

-Increased automaticity: anything that increases rate of the pacemaker. (Drugs, sympathetic stimulation)

-Spontaneous depolarizations: can occur during phase 3 or 4 of AP and referred to as triggered tachycardias. (This can be caused by mutation in ion channels)

-An ectopic pacemaker (ectopic focus): a single beat or series of beats that occurs outside the normal pacemaker region (premature systole).

Front 31

What are the main reasons for bradycardia (according to Ioudina...)?

Back 31

-Depressed impulse formation: pacemaker problem in the SA node.
--Abnormal autonomic influences (due to excessive parasymapthetic tone)

-Impaired impulse conduction: A block in the conduction pathway slows the electrical signal
--Tissue damage, change in anatomy
--Drugs

Front 32

The original ECG lead system (devised by Einthoven who won a Nobel Prize) measured what?

Back 32

Measures electrical difference between two surface electrodes placed near the heart.

(won The Nobel Prize in Physiology or Medicine 1924)

Front 33

How can the spread of cardiac excitation be recorded by electrocardiography (ECG)?

Back 33

-ECG is a measure of voltage and time
--ECG, surface electrodes, the heart electrical activity
--Leads:
---Bipolar: I,II, and III
--Unipolar:
---Limbs: LA, LL, RA
---Chest leads: V1-V6

Front 34

What is the sequence of excitation?

Back 34

-SA node generates impulse; atrial excitation begins
-Impulse delayed at AV node
-Impulse passes to heart apex, ventricular excitation begins
-Ventricular excitation complete

Front 35

In an ECG, what does Phase 0 of ventricular AP correspond to?

Back 35

Phase 0 (upstroke) of ventricular AP corresponds to the R wave in the ECG

Front 36

In an ECG, what does Phase 2 of ventricular AP correspond to?

Back 36

Phase 2 (plateau) of ventricular AP corresponds to the ST segment of the ECG

Front 37

n an ECG, what does Phase 4 of ventricular AP correspond to?

Back 37

Phase 3 (repolarization) of the ventricular AP corresponds to the T wave (ventricular repolarization) in the ECG

Front 38

What 5 structures can the ECG NOT show the electrical activity of?

Back 38

SA node, AV node, bundle of His, bundle branches, Purkinje fibers

Front 39

What even occurs at the PR interval of a normal ECG?

Back 39

Atrial depolarization and conduction thru AV node
(0.12-0.20 secs)

Front 40

What event occurs at the QRS interval of a normal ECG?

Back 40

Ventricular depolarization
Atrial repolarization
(0.08-0.10 secs)

Front 41

What event occurs at the QT interval in a normal ECG?

Back 41

Ventricular depolarization
Ventricular repolarization
(0.4-0.43 secs)

Front 42

What event occurs at the ST interval in a normal ECG?

Back 42

Ventricular repolarization
(QT minus QRS)
(0.32 secs)

Front 43

In an ECG, what interval do you use for the heart rate?

Back 43

For the heart rate: use R-R interval (1 beat) during time interval

Front 44

When does the heart have a normal sinus rhythm (normal P wave and PR interval)?

Back 44

if the heart follows normal conduction, SA node, AV node and activates ventricle:
-Normal heart rate (HR) : 60 bpm < HR < 100 bpm

-Tachycardia: HR > 100 bpm
(Can be normal in frightened or stressed individuals or exercise)

-Bradycardia: HR < 60 bpm
(Can be normal especially in endurance athletes)

Front 45

What is sinus arrhythmia?

Back 45

subtle change in HR with respiratory cycle. Inspiration accelerates, expiration slows