Basic / Cellular EP

Question 1

Mutations in what ion channel cause LQT type II

Answer 1

Ikr (KCNH2, HERG)

Question 2

Mutations in IKr gene cause what type of LQTS

Answer 2

LQT Type II

Question 3

Mutations in the IKs gene cause what type of LQTS

Answer 3

LQT Type I

Question 4

Mutations in what ion channel cause LQT Type I

Answer 4

Iks

Question 5

All QT prolonging drugs delay current in which ion channel?

Answer 5

Ikr (KNCH2, HERG)

Question 6

Mutations in what ion channel cause LQT type I

Answer 6

Iks (coded for by KCNQ1 & minK (kvLQT1) & KCNE1

Question 7

There are 3 delayed rectifiers in the human heart. What are they

Answer 7

Ikur (ultra rapid), Ikr (rapid) and Iks (slow)

Question 8

Which delayed rectifier is found only in atrial tissue

Answer 8

Ikur

Question 9

Which type of after depolarization is blunted by an increase in heartbeat?

Answer 9

Early after depolarization

Question 10

Torsades de pointe is usually triggered by what kind of triggered activity?

Answer 10

Early after depolarization

Question 11

Which type of triggered activity is cause by a net inward phase III current?

Answer 11

Early after depolarization

Question 12

Overdose of what drug is associated with delayed after depolarization?

Answer 12

Digoxin

Question 13

Which type of after depolarization is caused by inappropriate calcium handling?

Answer 13

Delayed after depolarization

Question 14

What is the conduction velocity in healthy myocardium?

Answer 14

0.6 - 0.7 m/s (from Kyoko Soejima’s N+1 paper published in JACC 2001).

Question 15

How is bidirectional VT like ping-pong?

Answer 15

During slow rate no triggered activity. As heart rate increases - the right bundle activates the RV (DAD) and subsequently the LV retrograde. The left bundle sees sinus activation and the activation from the DAD on the right, which causes a triggered beat that will activate the RV. Alex A. Baher & James N. Weiss HRS 2014

Question 16

In humans, what part of the myocardium is most sensitive to the effects of ischemia during VF? How does that impact the clinical rx of a VF cardiac arrest?

Answer 16

In humans (in contrast to pigs), the epicardium is much more vulnerable to the effects of ischemia. The effect of this is that in late VF the epicardium becomes unexcitable and thus a shock may not work. Reperfusion with chest compressions may “reactivate” areas of the epicardium and allow defibrillation to be successful.

Question 17

In the context of VF, what are “mother rotors”

Answer 17

This concept challenges the idea that VF is random varying loops of ventricular activation but instead can be the consequence of a dominant rotor of electrical activity.

Question 18

How might myofibroblasts be important in arrhythmogenesis?

Answer 18

According to a study in heart rhythm 2009 by Stephan Rohr, Myofibroblasts are capable of passive conduction across the distance of 300 µm. This observation might explain slow conduction through The anastomosis in a transplanted heart, for example. It also may explain the conduction across a surgical scar in the maze procedure.

Question 19

Initial attempts at creating a biologic pacemaker focused on overexpression of individual ion channels in working myocardium. What were the drawbacks of this approach and what is the current (in 2013) approaches to creating a biological pacemaker)

Answer 19

Initial constructs involving overexpression of specific ion channels tended to have problems with proarrhythmia. More recent efforts have focused on transcription factors TBX3 & TBX18. These seem to regulate multiple gene expression downstream. Dobrzynski H 2013 - review article

Question 20

What are some of the hurdles that stem cell therapy must overcome before it can be implemented as common clinical therapy?

Answer 20

1. rejection and the need for immunosuppression, 2. a better understanding of malignant potential, 3. long term sustainability of the cells or their effect

Question 21

How are the SA and AV nodes anatomically and functionally similar?

Answer 21

1. Both have transition zones with hybid cellular properties between working myocardium and nodal tissue
2. Both are Ca+ dependent action potentials
3. Both have iKf and normal automaticity
4. Both demonstrate slow conduction due to a paucity of gap junctions (low Cx43 expression)

Question 22

The conduction velocity of normal working myocardium is 0.6-0.7 m/s. What is the conduction velocity of the His-Purkinje system?

Answer 22

2.3 m/s - more than 3x the speed!

Question 23

Name 3 reasons for the increased conduction velocity of the H-P system compared to normal myocardium

Answer 23

1. large and medium conductance connexins (Cx40 and Cx43 rather than small conductance Cx45)
2. Rapid AP upstroke
3. longer duration APs

Question 24

Name 3 cellular electrophysiologic properties of Purkinje fibers that promote arrhythmia

Answer 24

1. long action potential duration contributes to torsades de pointes
2. PF’s long action potentials are prone to DAD’s which can trigger VT
3. PF’s have 2 stable resting potential, one near−90 mVand one near−50 mV. These different states have different conduction properties which can promote bundle branch reentry.

Halina Dobrzynski - Pharmacology & Therapeutics 139 (2013) 260–288

Question 25

True or False: valve leaflets are composed exclusively of fibrous tissue

Answer 25

False: several studies have shown the presence of myocardial cells with intrinsic pacemaker activity. In the hearts of a number of species, there are sparsely arranged myocytes in the AV valve leaflets. Halina Dobrzynski

Pharmacology & Therapeutics 139 (2013) 260–288

Question 26

What is a raidan? How many radians make a full circle?

Answer 26

A radian is an angle in which the arc of the circle subtended by the angle equals the radius of the circle. Because the circumference of a circle is 2piR, the number of radians in 360 degrees is 2pi raidans.

Question 27

When the effective refractory period of a site distal in conduction is longer than the RRP of a more proximal site, what can result?

Answer 27

Gap Phenomenon. A longer extrastimuli, there is block to the distal site. At shorter extrastimuli coupling intervals, below the RRP of the proximal site, the delay to the proximal site allows recovery of conduction to the distal site creating a “gap phenomenon”.

Question 28

Name 5 potential mechanisms that might underlie functional BBB

Answer 28

1. First / Second degree BBB
2. Linking
3. Bradycardia Phase IV BBB
4. QRS alternans due to rate related aberration
5. Supernormal conduction